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 LC-MS/MS method for the simultaneous quantitation of 1ß-OH DCA and its glycine and taurine conjugates in human plasma with the LLOQ 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-, 10.3-fold increases of AUCLST, AUC24h, Cmax 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%, 81% reductions of AUCLST, AUC24h, Cmax and mean concentrations for total 1ß-OH DCA, respectively. This preliminary data demonstrates 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 We have reported the use of total 1ß-Hydroxydeoxycholic Acid (1ß-OH DCA) (sum of 1ß-OH DCA and its glycine and taurine conjugates) plasma concentration as a biomarker for CYP3A activity. Itraconazole inhibition led to an 81-85% decrease of total 1ß-OH DCA plasma exposures, while rifampin induction led to a 6.8-10.3 fold increase of total 1ß-OH DCA plasma exposures. Using 1ß-OH DCA exposures in plasma also provides benefit of allowing PK and biomarker assessment using the same matrix, thus simplify collection procedures.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Do Illuminated Foot Pedals Improve the Speed and Accuracy of Pedal Activation During Endoscopic Procedures?

PURPOSE: Endourologic procedures such as percutaneous nephrolithotomy (PCNL) employ the use of foot pedals in low-light operating room (OR) settings. These pedals can be especially difficult to locate or distinguish when several pedals are present during a single operation. Improper instrument activation in the OR has led to serious complications ranging from unintentional electrocautery to patient burns and even an intraoperative explosion. This study evaluates the impact of color-coded illumination on speed and efficiency of foot pedal activation. MATERIALS AND METHODS: During a simulated PCNL procedure, the foot pedals for a C-arm, laser, and ultrasonic lithotripter (USL) were placed in random positions. Ten participants performed pedal activation in a randomized sequence. Objective outcomes included time to instrument activation, number of attempted pedal presses, number of incomplete pedal presses, and number of incorrect pedal presses. Subjective preferences for pedal illumination were also determined. Data were analyzed using Mann-Whitney U, Wilcoxon signed-rank, and Chi-square tests with p < 0.05 indicating statistical significance. RESULTS: Illuminated foot pedals were associated with decreases in the average activation time for all instruments collectively (3.95 seconds vs 6.49 seconds; p = 0.017) and individually (C-arm: 3.07 seconds vs 4.21 seconds; p = 0.006; laser: 13.04 seconds vs 15.18 seconds; p < 0.001; USL: 3.28 seconds vs 4.91 seconds; p < 0.001) compared with nonilluminated pedals. Illuminated pedals were associated with fewer attempted pedal presses (33.5 vs 39.5; p = 0.007) and incomplete pedal presses (1.5 vs 8.5; p = 0.002). The number of incorrect pedal presses decreased with illumination, but this did not reach statistical significance (0 vs 0.5; p = 0.08). Participants reported that illumination simplified pedal activation and recommended its use (p < 0.01). CONCLUSION: Color-coded illumination improved the speed and efficiency of foot pedal activation during simulated PCNL. Participants subjectively preferred using illuminated foot pedals for endourologic procedures and felt that they improved safety and efficiency.

Highly selective and sensitive measurement of active forms of FGF21 using novel immunocapture enrichment with LC-MS/MS.

AIM: Recombinant FGF21 analogs are under wide ranging investigations as a potential therapeutic agent for Type 2 diabetes, as well as other metabolic disorders. The endogenous FGF21 is often used as a surrogate pharmacodynamic(PD) biomarker to assess drug efficacy and safety. Results & methodology: Immunocapture was performed using a monoclonal antibody which had been generated to bind to specific domain of native FGF21 as the capture reagent. After immunocapture, enzymatic digestion was performed and a native FGF21-specific tryptic peptide was monitored using LC-MS/MS by selective reaction monitoring. CONCLUSION: We have successfully developed and validated a bioanalytical assay which provides the specificity to differentiate the endogenous FGF21 from the recombinant therapeutic agent which has nearly identical sequence to the endogenous molecule.

A multiplexed immunocapture liquid chromatography tandem mass spectrometry assay for the simultaneous measurement of myostatin and GDF-11 in rat serum using an automated sample preparation platform.

Myostatin, also known as growth differentiation factor 8 (GDF-8), is a protein acting as a negative regulator in skeletal muscle growth. Inhibition of myostatin by therapeutic agents provides opportunities for current unmet medical needs. In order to better understand drug engagement to aid the drug development, we have developed a hybrid LC-MS/MS method which can differentially measure myostatin and another protein from the same GDF family, GDF-11. Although the two proteins share high homology, the LC-MS/MS assay provided the specificity based on monitoring of unique surrogate peptide generated from enzymatic digestion. An automated sample preparation platform, Agilent AssayMap Bravo, was used for automated immunocapture. Capture antibody that is non-competing with our investigational drug and has similar binding affinity to both myostatin and GDF-11 was used. Therefore, total myostatin and GDF-11 including both free form and drug-bound form were captured and measured. The enriched sample was digested after reduction and alkylation. Two surrogate peptides (IPAMVVDR for myostatin and IPGMVVDR for GDF-11) were monitored and the lower limit of quantitation (LLOQ) was established at 1.0 ng/mL for myostatin and 0.1 ng/mL for GDF-11. The accuracy was demonstrated with recovery for IPAMVVDR between 99.2% and 103.1% and for IPGMVVDR between 90.3% and 114.5%. The developed hybrid assay exhibits sufficient sensitivity, accuracy and specificity to differentiate between the highly structurally similar myostatin and GDF-11. This analytical approach was successfully applied to a rat toxicology study, and was demonstrated to be a powerful tool for biomarker measurement in the present of a therapeutic agent.

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.

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.

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.

Percutaneous Externally Assembled Laparoscopic vs Laparoendoscopic Single-Site Nephrectomy in a Porcine Model: A Prospective, Randomized, Blinded, Study.

OBJECTIVE: To compare the outcomes between laparoendoscopic single-site (LESS) and a novel percutaneous externally assembled laparoscopic (PEAL) nephrectomy in an in vivo porcine model. MATERIALS AND METHODS: Ten female farm pigs were randomized to LESS nephrectomy (5) or PEAL nephrectomy (5). Operative times, estimated blood loss, and intraoperative and postoperative complications were compared. The surgeons used a Likert scale to grade difficulty of peritoneal access, port placement, tool assembly, hilar dissection, closure, and overall difficulty of surgery. Scar assessment was performed by a blinded plastic surgeon using the Vancouver Scar Scale. Descriptive statistics were reported as median and range. The Mann-Whitney U test was used for continuous and ordinal variables. A p value <0.05 was considered significant. RESULTS: Median operative time was significantly shorter in the PEAL group vs the LESS group (85 minutes vs 127 minutes, p = 0.03). Median Likert scores showed overall hilar dissection and nephrectomy to be significantly easier using PEAL compared with LESS (2 vs 9, p < 0.01 for both). The PEAL instruments left no visible scar at 5 feet in any animal, and only 1 out of 10 scars could be identified on physical examination. CONCLUSIONS: The PEAL surgical paradigm demonstrates nearly scarless outcomes while providing shorter operative times and easier performance than LESS nephrectomy in a porcine model.

Bench-Top Feasibility Testing of a Novel Percutaneous Renal Access Technique: The Laser Direct Alignment Radiation Reduction Technique (DARRT).

INTRODUCTION: Traditional techniques for obtaining percutaneous renal access utilize continuous fluoroscopy. In an attempt to minimize radiation exposure, we describe a novel laser direct alignment radiation reduction technique (DARRT) for percutaneous access and test it in a bench-top model. METHODS: In this randomized-controlled bench-top study, 20 medical personnel obtained renal accesses using both the conventional bullseye technique and the laser DARRT. The primary endpoint was total fluoroscopy time. Secondary endpoints included insertion time, puncture attempts, course corrections, and subjective procedural difficulty. In the laser DARRT, fluoroscopy was used with the C-arm positioned with the laser beam at a 30° angle. The access needle and hub were aligned with the laser beam. Effective caliceal puncture was confirmed with fluoroscopy and direct vision. The Paired samples Wilcoxon signed rank test was used for statistical analysis with significance at p < 0.05. RESULTS: A total of 120 needle placements were recorded. Fluoroscopy time for needle access using the laser DARRT was significantly lower than the bullseye technique in all groups as follows: attendings (7.09 vs 18.51 seconds; p < 0.001), residents (6.55 vs 13.93 seconds; p = 0.001), and medical students (6.69 vs 20.22 seconds; p < 0.001). Students rated the laser DARRT easier to use (2.56 vs 4.89; p < 0.001). No difference was seen in total access time, puncture attempts, or course corrections between techniques. CONCLUSION: The laser DARRT reduced fluoroscopy time by 63%, compared with the conventional bullseye technique. The least experienced users found the laser DARRT significantly easier to learn. This novel technique is promising and merits additional testing in animal and human models.