MicroCycle: An Integrated and Automated Platform to Accelerate Drug Discovery.

We herein describe the development and application of a modular technology platform which incorporates recent advances in plate-based microscale chemistry, automated purification, in situ quantification, and robotic liquid handling to enable rapid access to high-quality chemical matter already formatted for assays. In using microscale chemistry and thus consuming minimal chemical matter, the platform is not only efficient but also follows green chemistry principles. By reorienting existing high-throughput assay technology, the platform can generate a full package of relevant data on each set of compounds in every learning cycle. The multiparameter exploration of chemical and property space is hereby driven by active learning models. The enhanced compound optimization process is generating knowledge for drug discovery projects in a time frame never before possible.

Factors associated with the adoption of minimally invasive radical prostatectomy in the United States.

PURPOSE: Minimally invasive radical prostatectomy has supplanted radical retropubic prostatectomy in popularity despite the absence of strong comparative effectiveness data demonstrating its superiority. We examined the influence of patient, surgeon and hospital characteristics on the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data we identified 11,732 men who underwent radical prostatectomy from 2003 to 2007. We assessed the contribution of patient, surgeon and hospital characteristics to the likelihood of undergoing minimally invasive radical prostatectomy vs radical retropubic prostatectomy using multilevel logistic regression mixed models. RESULTS: Patient factors (36.7%) contributed most to the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy, followed by surgeon (19.1%) and hospital (11.8%) factors. Among patient specific factors Asian race (OR 1.86, 95% CI 1.27-2.72, p = 0.001), clinically organ confined tumors (OR 2.71, 95% CI 1.60-4.57, p <0.001) and obtaining a second opinion from a urologist (OR 3.41, 95% CI 2.67-4.37, p <0.001) were associated with the highest use of minimally invasive radical prostatectomy while lower income was associated with decreased use of minimally invasive radical prostatectomy. Among surgeon and hospital specific factors, higher surgeon volume (OR 1.022, 95% CI 1.015-1.028, p <0.001), surgeon age younger than 50 years (OR 2.68, 95% CI 1.69-4.24, p <0.001) and greater hospital bed size (OR 1.001, 95% CI 1.001-1.002, p <0.001) were associated with increased use of minimally invasive radical prostatectomy, while solo or 2 urologist practices were associated with decreased use of minimally invasive radical prostatectomy (OR 0.48, 95% CI 0.27-0.86, p = 0.013). CONCLUSIONS: The adoption of minimally invasive radical prostatectomy vs radical retropubic prostatectomy is multifactorial, and associated with specific patient, surgeon and hospital related factors. Obtaining a second opinion from another urologist was the strongest factor associated with opting for minimally invasive radical prostatectomy.

Outcomes assessment in men undergoing open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted radical prostatectomy.

OBJECTIVES: To review the various methods of outcomes assessment used for effectiveness studies comparing retropubic radical prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), and robotic-assisted laparoscopic prostatectomy (RALP). METHODS: A review of the peer reviewed literature was performed for reported series of RRP, LRP, and RALP using Pubmed and MEDLINE with emphasis on comparing perioperative, functional, and oncologic outcomes. Common methods used for outcomes assessment were categorized and compared, highlighting the pros and cons of each approach. RESULTS: The majority of the literature comparing RRP, LRP, and RALP comes in the form of observational data or administrative data from secondary datasets. While randomized controlled trials are ideal for outcomes assessment, only one such study was identified and was limited. Non-randomized observational studies contribute to the majority of data, however are limited due to retrospective study design, lack of consistent endpoints, and limited application to the general community. Administrative data provide accurate assessment of operative outcomes in both academic and community settings, however has limited ability to convey accurate functional outcomes. CONCLUSIONS: Non-randomized observational studies and secondary data are useful resources for assessment of outcomes; however, limitations exist for both. Neither is without flaws, and conclusions drawn from either should be viewed with caution. Until standardized prospective comparative analyses of RRP, LRP, and RALP are established, comparative outcomes data will remain imperfect. Urologic researchers must strive to provide the best available outcomes data through accurate prospective data collection and consistent outcomes reporting.

Partial clamping of the renal artery during robot-assisted laparoscopic partial nephrectomy: technique and initial outcomes.

PURPOSE: We describe the feasibility of partial arterial clamping (PAC) during robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: We undertook a retrospective study of five patients who underwent PAC vs 17 who underwent complete hilar clamping (CHC). Estimated blood loss (EBL), transfusion rate, operative/console time, warm ischemia time (WIT), pathology, and postoperative glomerular filtration rate (GFR) were compared. RESULTS: PAC patients were older (P=0.002) and more likely to have had previous abdominal surgeries (P=0.032). PAC vs CHC was associated with higher median EBL (350 mL vs 75 mL, P=0.026), although there were no differences in blood transfusions (P=0.250). PAC was associated with shorter WIT (14 min vs 21 min, P=0.023). Positive margin rate and GFR change were similar. CONCLUSIONS: PAC offers a simple and reproducible technique that limits WIT during RAPN. PAC was not associated with more transfusions or positive margins. Further study is warranted to determine the utility of PAC with larger tumor size as well as the long-term benefits on renal function.

Stepwise approach for nerve sparing without countertraction during robot-assisted radical prostatectomy: technique and outcomes.

BACKGROUND: Although subtle technical variation affects potency preservation during robot-assisted laparoscopic radical prostatectomy (RARP), most prostatectomy studies focus on achieving the optimal anatomic nerve-sparing dissection plane. However, the impact of active assistant/surgeon neurovascular bundle (NVB) countertraction on sexual function outcomes has not been studied or quantified. OBJECTIVE: To illustrate technique and compare sexual function outcomes for nerve sparing without (NS-0C) versus with (NS-C) assistant and/or surgeon NVB countertraction. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study of 342 NS-0C versus 268 NS-C RARP procedures performed between August 2008 and February 2011. SURGICAL PROCEDURE: RARP. MEASUREMENTS: We used the Expanded Prostate Cancer Index Composite (EPIC) sexual function and potency scores, estimated blood loss (EBL), operative time, and positive surgical margin (PSM). RESULTS AND LIMITATIONS: In unadjusted analysis, men undergoing NS-0C versus NS-C were older, had worse baseline sexual function, higher biopsy and pathologic Gleason grade, and higher preoperative prostate-specific antigen (PSA) levels (all p ≤ 0.023). However, NS-0C versus NS-C was associated with higher 5-mo sexual function scores (20 vs 10; p < 0.001), and this difference was accentuated for bilateral intrafascial nerve sparing in preoperatively potent men (35.8 vs 16.6; p < 0.001). Similarly, 5-mo potency for preoperatively potent men was better with bilateral intrafascial NS-0C versus NS-C (45.0% vs 28.4%; p = 0.039). However, no difference in sexual function or potency was observed at 12 mo. In adjusted analyses, NS-0C versus NS-C was associated with improved 5-mo sexual function (parameter estimate: 10.90; standard error: 2.16; p < 0.001) and potency (odds ratio: 1.69; 95% confidence interval, 1.01-2.83; p = 0.046). NS-0C versus NS-WC was associated with shorter operative times (p = 0.001) and higher EBL (p = 0.001); however, there were no significant differences in PSM. Limitations include the retrospective, single-surgeon study design and smaller numbers for 12-mo comparison. CONCLUSIONS: Reliance on countertraction to facilitate dissecting NVB away from the prostate leads to neuropraxia and delayed recovery of sexual function and potency. Subtle technical modification to dissect the prostate away from the NVB without countertraction enables earlier return of sexual function and potency.

Health services research in urology.

OBJECTIVES: Health services research (HSR) is increasingly important given the focus on patient-centered, cost-effective, high-quality health care. We examine how HSR affects contemporary evidence-based urologic practice and its role in shaping future urologic research and care. METHODS: PubMed, urologic texts, and lay literature were reviewed for terms pertaining to HSR/outcomes research and urologic disease processes. RESULTS: HSR is a broad discipline that focuses on access, cost, and outcomes of Health care. Its use has been applied to a myriad of urologic conditions to identify deficiencies in access, to evaluate cost-effectiveness of therapies, and to evaluate structural, process, and outcome quality measures. CONCLUSIONS: HSR utilizes an evidence-based approach to identify the most effective ways to organize/manage, finance, and deliver high-quality urologic care and to tailor care optimized to individuals.

The impact of prostate size, median lobe, and prior benign prostatic hyperplasia intervention on robot-assisted laparoscopic prostatectomy: technique and outcomes.

BACKGROUND: Large prostate size, median lobes, and prior benign prostatic hyperplasia (BPH) surgery may pose technical challenges during robot-assisted laparoscopic prostatectomy (RALP). OBJECTIVE: To describe technical modifications to overcome BPH sequelae and associated outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: A retrospective study of prospective data on 951 RALP procedures performed from September 2005 to November 2010 was conducted. Outcomes were analyzed by prostate weight, prior BPH surgical intervention (n=59), and median lobes >1 cm (n=42). SURGICAL PROCEDURE: RALP. MEASUREMENTS: Estimated blood loss (EBL), blood transfusions, operative time, positive surgical margin (PSM), and urinary and sexual function were measured. RESULTS AND LIMITATIONS: In unadjusted analysis, men with larger prostates and median lobes experienced higher EBL (213.5 vs 176.5 ml; p<0.001 and 236.4 vs 193.3 ml; p=0.002), and larger prostates were associated with more transfusions (4 vs 1; p=0.037). Operative times were longer for men with larger prostates (164.2 vs 149.1 min; p=0.002), median lobes (185.8 vs 155.0 min; p=0.004), and prior BPH surgical interventions (170.2 vs 155.4 min; p=0.004). Men with prior BPH interventions experienced more prostate base PSM (5.1% vs 1.2%; p=0.018) but similar overall PSM. In adjusted analyses, the presence of median lobes increased both EBL (p=0.006) and operative times (p<0.001), while prior BPH interventions also prolonged operative times (p=0.014). However, prostate size did not affect EBL, PSM, or recovery of urinary or sexual function. CONCLUSIONS: Although BPH characteristics prolonged RALP procedure times and increased EBL, prostate size did not affect PSM or urinary and sexual function.

Athermal division and selective suture ligation of the dorsal vein complex during robot-assisted laparoscopic radical prostatectomy: description of technique and outcomes.

BACKGROUND: Apical dissection and control of the dorsal vein complex (DVC) affects blood loss, apical positive margins, and urinary control during robot-assisted laparoscopic radical prostatectomy (RALP). OBJECTIVE: To describe technique and outcomes for athermal DVC division followed by selective suture ligation (DVC-SSL) compared with DVC suture ligation followed by athermal division (SL-DVC). DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective study of prospectively collected data from February 2008 to July 2010 for 303 SL-DVC and 240 DVC-SSL procedures. SURGICAL PROCEDURE: RALP with comparison of DVC-SSL prior to anastomosis versus early SL-DVC prior to bladder-neck dissection. MEASUREMENTS: Blood loss, transfusions, operative time, apical and overall positive margins, urine leaks, catheterization duration, and urinary control at 5 and 12 mo evaluated using 1) the Expanded Prostate Cancer Index (EPIC) urinary function scale and 2) continence defined as zero pads per day. RESULTS AND LIMITATIONS: Men who underwent DVC-SSL versus SL-DVC were older (mean: 59.9 vs 57.8 yr, p<0.001), and relatively fewer white men underwent DVC-SSL versus SL-DVC (87.5% vs 96.7%, p<0.001). Operative times were also shorter for DVC-SSL versus SL-DVC (mean: 132 vs 147 min, p<0.001). Men undergoing DVC-SSL versus SL-DVC experienced greater blood loss (mean: 184.3 vs 175.6 ml, p=0.033), and one DVC-SSL versus zero SL-DVC were transfused (p=0.442). Overall (12.2% vs 12.0%, p=1.0) and apical (1.3% vs 2.7%, p=0.361) positive surgical margins were similar for DVC-SSL versus SL-DVC. Although 5-mo postoperative urinary function (mean: 72.9 vs 55.4, p<0.001) and continence (61.4% vs 39.6%, p<0.001) were better for DVC-SSL versus SL-DVC, 12-mo urinary outcomes were similar. In adjusted analyses, DVC-SSL versus SL-DVC was associated with shorter operative times (parameter estimate [PE]±standard error [SE]: 16.84±2.56, p<0.001), and better 5-mo urinary function (PE±SE: 19.93±3.09, p<0.001) and continence (odds ratio 3.39, 95% confidence interval 2.07-5.57, p<0.001). CONCLUSIONS: DVC-SSL versus SL-DVC improves early urinary control and shortens operative times due to fewer instrument changes with late versus early DVC control.

Bilateral congenital absence of the long head of the biceps tendon.

Absence of the long head of the biceps tendon is a rare anomaly particularly when it occurs bilaterally. We present the magnetic resonance and arthroscopy findings in a patient with bilateral congenital absence of the long head of the biceps who presented with bilateral shoulder pain. Identification of a shallow or absent intertubercular groove may aid in differentiating congenital absence of the long head of the biceps from a traumatic tendon rupture.