Efficient and Accurate Computed Tomography-Based Stone Volume Determination: Development of an Automated Artificial Intelligence Algorithm.

PURPOSE: Given the shortcomings of current stone burden characterization (maximum diameter or ellipsoid formulas), we sought to investigate the diagnostic accuracy and precision of a University of California, Irvine-developed artificial intelligence (AI) algorithm for determining stone volume determination. MATERIALS AND METHODS: A total of 322 noncontrast CT scans were retrospectively obtained from patients with a diagnosis of urolithiasis. The largest stone in each noncontrast CT scan was designated the "index stone." The 3D volume of the index stone using 3D Slicer technology was determined by a validated reviewer; this was considered the "ground truth" volume. The AI-calculated index stone volume was subsequently compared with ground truth volume as well with the scalene, prolate, and oblate ellipsoid formulas estimated volumes. RESULTS: There was a nearly perfect correlation between the AI-determined volume and the ground truth (R=0.98). While the AI algorithm was efficient for determining the stone volume for all sizes, its accuracy improved with larger stone size. Moreover, the AI stone volume produced an excellent 3D pixel overlap with the ground truth (Dice score=0.90). In comparison, the ellipsoid formula-based volumes performed less well (R range: 0.79-0.82) than the AI algorithm; for the ellipsoid formulas, the accuracy decreased as the stone size increased (mean overestimation: 27%-89%). Lastly, for all stone sizes, the maximum linear stone measurement had the poorest correlation with the ground truth (R range: 0.41-0.82). CONCLUSIONS: The University of California, Irvine AI algorithm is an accurate, precise, and time-efficient tool for determining stone volume. Expanding the clinical availability of this program could enable urologists to establish better guidelines for both the metabolic and surgical management of their urolithiasis patients.

Initial Clinical Experience With a Novel Robotically Assisted Platform for Combined Mini-Percutaneous Nephrolithotomy and Flexible Ureteroscopic Lithotripsy.

PURPOSE: We sought to evaluate the technical feasibility of performing a combined robotically assisted mini-percutaneous nephrolithotomy (PCNL) and flexible ureteroscopy (URS) procedure by a single urologist using the MONARCH Platform, Urology (Johnson & Johnson MedTech, Redwood City, California). MATERIAL AND METHODS: In this prospective, first-in-human clinical trial, 13 patients underwent robotically-assisted PCNL for renal calculi at the University of California-Irvine, Department of Urology. Successful completion of the procedure was assessed as the primary endpoint. Postoperative adverse events were monitored for 30 days following the completion of the procedure. Stone ablation efficiency was evaluated on postoperative day 30 with low-dose 2-3 mm slice CT scans. Patients were classified according to the maximum length of their residual stone fragments as either absolute stone-free (Grade A), < 2 mm remnants (Grade B), or 2.1-4.0 mm remnants (Grade C). RESULTS: The combined robotic mini-PCNL and URS procedure was successfully completed in 12 of 13 procedures. No robotic device-related adverse events occurred. Preoperative stone burden was quantified by both maximum linear measurement (median 32.8 mm) as well as by CT-based volume (median 1645.9 mm3). Using the unique robotically assisted targeting system, percutaneous access was gained directly through the center of the renal papilla in a single pass in all cases. Median operative time was 187 minutes (range: 83-383 minutes). On postoperative day 30, a 98.7% (range: 72.9%-100.0%) volume reduction was achieved, with 5 Grade A (38.5%), 1 Grade B (7.7%), and 2 Grade C (15.4%). Three patients experienced complications (2 grade 1 and one grade 2 Clavien-Dindo). CONCLUSIONS: Our preliminary investigation demonstrates the safety, efficacy, and feasibility of a unique robotic-assisted combined mini-PCNL and URS platform.

Alkaline Water: Help or Hype for Uric Acid and Cystine Urolithiasis?

PURPOSE: The consumption of alkaline water, water with an average pH of 8 to 10, has been steadily increasing globally as proponents claim it to be a healthier alternative to regular water. Urinary alkalinization therapy is frequently prescribed in patients with uric acid and cystine urolithiasis, and as such we analyzed commercially available alkaline waters to assess their potential to increase urinary pH. MATERIALS AND METHODS: Five commercially available alkaline water brands (Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration) underwent anion chromatography and direct chemical measurements to determine the mineral contents of each product. The alkaline content of each bottle of water was then compared to that of potassium citrate (the gold standard for urinary alkalinization) as well as to other beverages and supplements used to augment urinary citrate and/or the urine pH. RESULTS: The pH levels of the bottled alkaline water ranged from 9.69 to 10.15. Electrolyte content was minimal, and the physiologic alkali content was below 1 mEq/L for all brands of alkaline water. The alkali content of alkaline water is minimal when compared to common stone treatment alternatives such as potassium citrate. In addition, several organic beverages, synthetic beverages, and other supplements contain more alkali content than alkaline water, and can achieve the AUA and European Association of Urology alkali recommendation of 30 to 60 mEq per day with ≤ 3 servings/d. CONCLUSIONS: Commercially available alkaline water has negligible alkali content and thus provides no added benefit over tap water for patients with uric acid and cystine urolithiasis.

Preoperative Immersive Virtual Reality (iVR) Applied to Percutaneous Nephrolithotomy: A Prospective Randomized Clinical Study of Surgical Planning and Clinical Outcomes.

PURPOSE: Percutaneous nephrolithotomy (PCNL) is the procedure of choice for the management of complex or large renal stones. A major challenge for the surgeon, however, is the need to assimilate the nearly 2000 static images from a CT scan into a functional mental image to enable surgical planning. Accordingly, we investigated the potential of immersive virtual reality (iVR) to enhance surgical planning and its impact on the outcomes among patients undergoing PCNL. MATERIALS AND METHODS: Between 2019-2023, 175 patients undergoing PCNL were pre-operatively randomized into a CT-only group (N=89) or a CT+iVR group (N=86). CT scans were rendered into iVR models that allowed the surgeon not only to visualize and manipulate each patient's relevant anatomy, but also simulate the percutaneous approach to the proposed calyx. Post-operative CT scans were defined as absolute stone-free, <2mm remnants or 2.1-4mm remnants. RESULTS: Pre-operative visualization of the iVR model resulted in a changed calyx of entry in 30% of cases. The CT+iVR group had a significant improvement in absolute stone-free rate (33.70% vs. 20.22%, p=0.043) and overall <4mm remnant rate (62.79% vs. 48.20%, p=0.044). Clavien-Dindo II+IIIa complications were less in the iVR group (3.48% vs. 12.30%, p=0.03). The results were independent of the surgeon's years of PCNL experience. CONCLUSIONS: Pre-operative iVR model visualization benefited surgeons and patients alike. From a surgical standpoint, viewing the iVR model resulted in a safer, more effective percutaneous stone removal procedure.

Clinical determination of the natural distensibility of the human ureter: initial study.

OBJECTIVES: To define the natural distensibility of the human ureter and evaluate the impact of other possibly favourable factors on ureteric distensibility. PATIENTS AND METHODS: A total of 101 patients undergoing ureteroscopic stone removal or percutaneous nephrolithotomy underwent ureteric sizing using sequential passage of 37-cm urethral dilators in 2-F increments while attached to a unique force sensor. Insertion forces were limited to 6 N. After 6 N was attained, an appropriately sized ureteric access sheath was passed. At the conclusion of each procedure, Post-Ureteroscopic Lesion Scale score was determined. RESULTS: Urethral dilators were passed in 61% of patients at ≤14 F; 39% of patients accepted urethral dilators of ≥16 F. The mean dilator size was 14 F. Multivariate logistic regression analysis revealed that preprocedural ureteric stenting and antibiotic use favoured passage of 16-F dilators (odds ratio [OR] 5.16, 95% confidence interval [CI] 1.70-15.62 [P = 0.004] and OR 5.15, 95% CI 1.743-15.243 [P = 0.003], respectively). Neither tamsulosin nor prior urinary tract infection had an impact on ureteric size (OR 0.765, 95% CI 0.281-2.084 [P = 0.601], OR 1.049, 95% CI 0.269-4.089 [P = 0.945], respectively). CONCLUSION: Using continuous insertion force monitoring and a 6-N threshold, the majority of unstented adult human ureters within our patient population safely accommodated a 14-F dilator. Safe passage of a 16-F dilator at the 6-N threshold was more likely among patients with a preexisting indwelling ureteric stent or patients who were treated with antibiotics within a week of the procedure.

A Nanocavitation Approach to Understanding Water Capture, Water Release, and Framework Physical Stability in Hierarchically Porous MOFs.

Chemically stable metal-organic frameworks (MOFs) featuring interconnected hierarchical pores have proven to be promising for a remarkable variety of applications. Nevertheless, the framework's susceptibility to capillary-force-induced pore collapse, especially during water evacuation, has often limited practical applications. Methodologies capable of predicting the relative magnitudes of these forces as functions of the pore size, chemical composition of the pore walls, and fluid loading would be valuable for resolution of the pore collapse problem. Here, we report that a molecular simulation approach centered on evacuation-induced nanocavitation within fluids occupying MOF pores can yield the desired physical-force information. The computations can spatially pinpoint evacuation elements responsible for collapse and the chemical basis for mitigation of the collapse of modified pores. Experimental isotherms and difference-electron density measurements of the MOF NU-1000 and four chemical variants validate the computational approach and corroborate predictions regarding relative stability, anomalous sequence of pore-filling, and chemical basis for mitigation of destructive forces.

Visible light-assisted chemistry of vinyl azides and its applications in organic synthesis.

Vinyl azides have emerged as highly versatile precursors in organic synthesis due to their rich reactivity driven by the excellent leaving-group ability of molecular nitrogen. Over the years, significant advancement has been achieved in the manipulation of vinyl azides for the construction of C-C and C-X bonds. Typical methods involve the application of transition metals and strong oxidants for the conversion of vinyl azides into useful compounds employing harsh reaction conditions coupled with intense product purification. In this regard, visible light chemistry has become one of the most exciting fields in organic synthesis for being mild, sustainable, and often orthogonal to conventional approaches. Visible light-induced reactions involving vinyl azides generate either 2H-azirines or iminyl radicals as key intermediates, which may undergo further useful transformations to form the desired cyclic or acyclic products. Herein, we provide the most significant transformations of vinyl azides as versatile synthetic precursors or transient intermediates for compounds of synthetic and biological significance under visible light photocatalysis. We have classified this review into two parts: (i) formation of an iminyl radical intermediate and (ii) formation of 2H-azirine intermediate-based reactions.

Sulfated Zirconium Metal-Organic Frameworks as Well-Defined Supports for Enhancing Organometallic Catalysis.

Understanding heterogeneous catalysts is a challenging pursuit due to surface site nonuniformity and aperiodicity in traditionally used materials. One example is sulfated metal oxides, which function as highly active catalysts and as supports for organometallic complexes. These applications are due to traits such as acidity, ability to act as a weakly coordinating ligand, and aptitude for promoting transformations via radical cation intermediates. Research is ongoing about the structural features of sulfated metal oxides that imbue the aforementioned properties, such as sulfate geometry and coordination. To better understand these materials, metal-organic frameworks (MOFs) have been targeted as structurally defined analogues. Composed of inorganic nodes and organic linkers, MOFs possess features such as high porosity and crystallinity, which make them attractive for mechanistic studies of heterogeneous catalysts. In this work, Zr6-based MOF NU-1000 is sulfated and characterized using techniques such as single crystal X-ray diffraction in addition to diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The dynamic nature of the sulfate binding motif is found to transition from monodentate, to bidentate, to tridentate depending on the degree of hydration, as supported by density functional theory (DFT) calculations. Heightened Brønsted acidity compared to the parent MOF was observed upon sulfation and probed through trimethylphosphine oxide physisorption, ammonia sorption, in situ ammonia DRIFTS, and DFT studies. With the support structure benchmarked, an organoiridium complex was chemisorbed onto the sulfated MOF node, and the efficacy of this supported catalyst was demonstrated for stoichiometric and catalytic activation of benzene-d6 and toluene with structure-activity relationships derived.

Simultaneously Enhanced Hydrophilicity and Stability of a Metal-Organic Framework via Post-Synthetic Modification for Water Vapor Sorption/Desorption.

With increasing demands for high-performance water sorption materials, metal-organic frameworks (MOFs) have gained considerable attention due to their high maximum uptake capacities. In many cases, however, high overall capacity is not necessarily accomplishing high working capacity under operating conditions, due to insufficient hydrophilicity and/or water stability. Herein, we present a post-synthetic modification (PSM) of MOF-808, with di-sulfonic acids enhancing simultaneously its hydrophilicity and water stability without sacrificing its uptake capacity of ≈30 mmol g-1 . Di-sulfonic acid PSM enabled a shift of the relative humidity (RH) associated with a sharp step in water vapor sorption from 35-40 % RH in MOF-808 to below 25 % RH. While MOF-808 lost uptake capacity and crystallinity over multiple sorption/desorption cycles, the di-sulfonic acid PSM MOF-808 retained >80 % of the original capacity. PSM MOF-808 exhibited good hydrothermal stability up to 60 °C and high swing capacity.

Qualitative Review of Clinical Guidelines for Medical and Surgical Management of Urolithiasis: Consensus and Controversy 2020.

PURPOSE: Many major guidelines across the globe address the medical and surgical management of urolithiasis. We elected to compare and contrast the recommendations among the 5 most highly cited guidelines on stone disease to offer insights on where evidence has created a consensus and where there remains ongoing controversy and hence a need for the pursuit of studies that will provide a higher level of evidence. MATERIALS AND METHODS: We reviewed the American Urological Association 2019 medical and 2016 surgical guidelines, the 2016 Canadian Urological Association guidelines, the 2020 European Association of Urology guidelines, the 2019 National Institute for Health and Care Excellence and the 2019 Urological Association of Asia guidelines. Tables correlating guideline statements by topic were created, and a comparative analysis was conducted to ascertain consensus and discordance. RESULTS: Comparative analysis of recommendations from the American Urological Association guidelines to the Canadian Urological Association, European Association of Urology, National Institute for Health and Care Excellence guidelines and Urological Association of Asia revealed a high consensus surrounding the medical management of stones. In terms of the surgical management of stones, there is high consensus regarding the treatment of ureteral stones including medical expulsive therapy using alpha blockers, not prestenting for uncomplicated ureteroscopy and employment of either ureteroscopy or shockwave lithotripsy as first line treatment. There is high consensus among the American Urological Association, European Association of Urology, National Institute for Health and Care Excellence and Urological Association of Asia guidelines regarding renal stone treatment. The Canadian Urological Association does not have guidelines on the management of renal stones. Unlike the American Urological Association and National Institute for Health and Care Excellence, the Canadian Urological Association and European Association of Urology make specific recommendations regarding selection of patients for shockwave lithotripsy procedures, including stone density, skin-to-stone distance, treatment rate, acoustic coupling and postshockwave lithotripsy use of medical expulsive therapy. CONCLUSIONS: There are many areas of consensus and only minor areas of conflict among the most up-to-date American Urological Association, Canadian Urological Association, European Association of Urology, National Institute for Health and Care Excellence and Urological Association of Asia guidelines on the medical and surgical management of stone disease. Conflicts among guidelines and areas of low evidence, such as followup imaging strategies and stone surveillance, the use of a ureteral access sheath in ureteroscopy and guidance on the use of miniaturized percutaneous nephrolithotomy, are opportunities for novel, impactful high grade clinical studies.

Determining the Safety Threshold for the Passage of a Ureteral Access Sheath in Clinical Practice Using a Purpose-Built Force Sensor.

PURPOSE: Ureteral injury is a frequent complication of ureteral access sheath deployment. We sought to define the safe threshold of force for the passage of a ureteral access sheath using a novel ureteral access sheath force sensor. MATERIALS AND METHODS: Ureteral access sheath-force sensor measurements were recorded in 210 renal units. A 16Fr ureteral access sheath was deployed initially based on a prior porcine study. If 6 N was reached, the surgeon was advised to downsize the 16Fr ureteral access sheath. In each case, a post-ureteroscopic lesion scale was recorded. Regression models were used to estimate the impact of adjusted variables on post-ureteroscopic lesion scale grade, 16Fr ureteral access sheath deployment, and peak force. RESULTS: A 16Fr ureteral access sheath was deployed in 127 (61%) renal units with a mean peak force of 5.7 N. Two high-grade ureteral injuries occurred; in both cases >6 N of force was recorded. Post-ureteroscopic lesion scale grade correlated directly with peak insertion force (p <0.01). Bacteriuria within 60 days of the procedure (OR 2.009, p=0.034), combination of preoperative stent plus oral tamsulosin (OR 2.998, p=0.045), and prior ipsilateral stone surgery (OR 2.13, p=0.01) were independent predictors of successful 16Fr ureteral access sheath deployment. Among patients with neither prior ipsilateral stone surgery nor preoperative stent, preoperative tamsulosin facilitated passage of a 16Fr ureteral access sheath (OR 2.750, p=0.034). CONCLUSIONS: Ureteral access sheath associated ureteral injury can be averted by limiting the insertion force to ≤6 N. Prior stone surgery, preoperative indwelling ureteral stent plus oral tamsulosin, and recently treated bacteriuria favored passage of a 16Fr ureteral access sheath. In the naïve, unstented patient, preoperative tamsulosin favored deployment of a 16Fr ureteral access sheath.

Comparison of Conventional and Triple Bolus Computerized Tomographic Urography Protocols for Radiation Dose Reduction in Hematuria Evaluation: A Randomized Controlled Trial.

PURPOSE: Computerized tomographic urography is the diagnostic tool of choice for evaluating hematuria. In keeping with the ALARA (As Low As Reasonably Achievable) principle, we evaluated a triple bolus computerized tomography protocol designed to reduce radiation exposure. MATERIALS AND METHODS: Patients with macroscopic or microscopic hematuria were prospectively randomized to conventional computerized tomography (100) or triple bolus computerized tomography (100). The triple bolus computerized tomography protocol entails 2 scans: pre-contrast scan followed by 3 contrast injections at 40 seconds, 60 seconds and 20 minutes prior to the second scan to capture all 3 phases. The conventional computerized tomography protocol requires 4 scans: pre-contrast scan, and 3 post-contrast scans at the corticomedullary, nephrographic and excretory phases. Radiation exposure and the detection of urological pathology were recorded based on radiology reports. RESULTS: There were no differences in patient demographics or body mass index between the 2 groups. Triple bolus computerized tomography exposed patients to 33% less radiation (1,715 vs 1,145 mGy*cm for conventional vs triple bolus computerized tomography; p <0.001). For macroscopic hematuria, the pathology detection rates were 70% for triple bolus and 73% for conventional computerized tomography (p=0.72). For microscopic hematuria, the detection rates were 59% for triple bolus and 50% for conventional computerized tomography (p=0.68). In both groups, the rates of detection of urolithiasis, renal cysts, urological masses, bladder pathology and prostate pathology were no different between triple bolus and conventional computerized tomography. CONCLUSIONS: In both the settings of macroscopic and microscopic hematuria evaluation, triple bolus computerized tomography significantly reduces radiation exposure while providing equivalent detection of genitourinary pathology compared to conventional computerized tomography. The ability to detect upper tract filling defects was not specifically tested.

Characterization of intracalyceal pressure during ureteroscopy.

PURPOSE: To provide the first report of measuring intracalyceal pressures during ureteroscopy (URS). METHODS: A prospective single-center clinical study using a cardiac pressure guidewire to measure intracalyceal pressure during flexible URS was performed. Eight patients (45 calyces) undergoing URS for nephrolithiasis were included. A Verrata® pressure guide wire was passed through the working channel of a dual lumen flexible ureteroscope and into the calyces while irrigation was maintained at 150 mmHg. Pressure was measured in the renal pelvis, upper pole, interpolar, and lower pole calyces both with and without a ureteral access sheath (UAS). The pressure in each location with and without a UAS was compared. The correlation between calyceal pressure and infundibular dimensions (width, length) was determined. RESULTS: Intracalyceal pressure was significantly lower in each region when a UAS was used. Compared to patients with a 12/14Fr UAS, those with a 14/16Fr UAS had significantly lower pressure in the interpolar (25.3 ± 13.1 vs. 44.0 ± 27.5 mmHg, p = 0.03) and lower pole (16.2 ± 3.5 vs. 49.2 ± 40.3 mmHg, p = 0.004) calyces. Interpolar calyceal pressure in the presence of a UAS was significantly higher than the renal pelvis pressure (RPP) (30.8 ± 19.6 vs. 17.9 ± 11.0 mmHg, p = 0.004). CONCLUSIONS: During flexible URS, RPP strongly correlates with, but does not uniformly represent, the intracalyceal pressure. With a 14/16Fr UAS and an inflow pressure of 150 mmHg, RPP and intracalyceal pressure never exceed the threshold for renal backflow.

Surface stability of perovskite oxides under OER operating conditions: a first principles approach.

The activity-stability conundrum has long been the Achilles' heel in the design of catalysts, in particular, for electrochemical reactions such as water splitting. Here, we use ab initio thermodynamics to delineate the surface stoichiometry of a group of perovskite oxides with different activities towards the oxygen evolution reaction (OER), in order to get a measure of their stability under OER operating conditions. In particular, we compare the surface stability of SrIrO3, SrRuO3 and SrTiO3, establishing atomistic insights into the stability and dissolution of these oxide surfaces.

Palpitation referrals from primary care to a secondary care cardiology outpatient clinic: assessing adherence to guidelines.

BACKGROUND AND AIMS: Palpitations are a common presentation in primary care. Guidelines have been developed to identify patients with palpitations who require further assessment by a cardiologist in secondary care. However, patients that do not meet guideline thresholds for referrals are still referred to secondary care services. This audit evaluated the adherence to referral guidelines at our trust and assessed the characteristics of patients who were referred appropriately versus those referred without meeting guideline referral thresholds (inappropriate referral). RESULTS: Palpitation referrals to a single cardiology outpatient clinic were assessed (n = 66). Half the patients referred for palpitations were referred inappropriately (n = 34, 51.5%). Patients referred inappropriately were more likely to have a benign diagnosis after assessment (91.2%). These patients also had significantly fewer investigations [mean difference of 1.1 (confidence interval: 0.6-1.6)]. Specialist investigations, such as cardiac event recorders (P < 0.05) and cardiac magnetic resonance imaging (P < 0.05) were less likely to be used in inappropriately referred patients. CONCLUSIONS: The results from this audit provide early evidence that there are a significant number of patients who are being referred that could be managed in primary care. Further studies are needed to confirm our findings in larger cohorts and to establish the underlying reasons for inappropriate referrals.

Office-Based Renal Tumor Biopsy: a Paradigm Change in the Management of a Small Renal Mass?

PURPOSE OF REVIEW: The goal of this paper is to evaluate the use of an office-based renal mass biopsy (RMB), whose feasibility could represent a paradigm shift in clinical practice. RECENT FINDINGS: Despite the earlier diagnosis of patients with renal masses, the lack of evidence showing a reduction in cancer-specific mortality warrants an examination in treatment practices. RMB is underutilized when compared to biopsy practice for all other neoplasms in every other solid organ (except testis), and the majority of RMB performed are outsourced to interventional radiologists. Performing an ultrasound-guided, office-based RMB is safe, reproducible, and has a meaningful impact on management decisions. The use of percutaneous RMB in clinical practice is growing, and the use of RMB has meaningful impact on management decisions for renal masses. Incorporating ultrasound-guided biopsy of a renal mass into clinical practice is feasible, and in contemporary practice, the urologist has the skill set to perform the procedure reliably, with low morbidity, and with minimal patient discomfort.

Smartphone technology and its applications in urology: a review of the literature.

PURPOSE: Smartphone technology has propelled the evolution of health-related mobile technology, referred to as mobile health (mHealth). With the rise of smartphone ownership and the growing popularity of health-related smartphone usage, mHealth offers potential benefits for both patients and health care providers. The objective of this review is to assess the current state of smartphone technology in urology. METHODS: A literature search of PubMed database was conducted to identify articles reporting on smartphone technology in urology. Publications were included if they focused on smartphone mHealth technology pertinent to the field of urology or included an evaluation of urological applications in digital stores. RESULTS: We identified 50 publications focused on the use of smartphones in urology. Studies were then grouped into the following categories: smartphones employing the built-in camera and light source, applications specific to prostate cancer, urolithiasis, pediatric urology, and as educational tools for urologists. In 23/50 (46%) studies, smartphone technology/intervention was compared to a control group or to standard of care. In this regard, smartphone technology did not demonstrate benefit over standard of care in 13 studies. In contrast, in 10 studies, smartphone interventions were proven beneficial over current practice. CONCLUSIONS: Smartphone technology is constantly evolving and has the potential to improve urological care and education. Of concern to consumer and urologist alike is that these downloadable programs are limited due to the accuracy of their content, risk of confidentiality breach, and the lack of central regulation and professional involvement in their development.

A Novel Unified Approach to Predict Human Hepatic Clearance for Both Enzyme- and Transporter-Mediated Mechanisms Using Suspended Human Hepatocytes.

The accurate prediction of human pharmacokinetics is critically important in modern drug discovery since it drives both pharmacological and toxicological effects. Although significant progress has been made in predicting drug disposition by hepatic drug-metabolizing enzymes, predicting transporter-mediated clearance is still highly uncertain. Furthermore, different approaches are often used to predict clearance with and without transporter involvement, hence the major clearance pathway for a compound must first be determined to know which approach to use. As a result of these challenges, a novel unified method has been developed using cryopreserved suspended human hepatocytes to predict human hepatic clearance for both enzyme- and transporter-mediated mechanisms. This method hypothesizes that, once in vitro metabolic stability is scaled by partition coefficients between hepatocytes and buffer with 4% bovine serum albumin, in vivo clearance can be better predicted. With this method, good in vitro-in vivo correlation of human hepatic clearance has been obtained for a set of 32 structurally diverse compounds, including such transporters as organic anion-transporting polypeptide substrates. The clearance predictions for most compounds are within 3-fold of observed values. This is the first time that multiple compounds result in good in vitro-in vivo extrapolation using an entirely "bottom-up" approach without any empirical scaling factor when transporter-mediated clearance is involved. Potential exceptions are compounds with significant biliary and/or extra-hepatic clearance. The method offers an alternative approach to more accurately predict human hepatic clearance when multiple complex mechanisms are involved.

Effect of positioning on ureteric stone retropulsion: 'gravity works'.

OBJECTIVE: To evaluate the potential impact of alterations in 'patient' position on laser-induced ureteric stone retropulsion in an in vitro model. MATERIALS AND METHODS: A ceramic (phantom) stone was placed in a water-filled clear polymer tube and subjected to continuous laser energy until the stone had retropulsed a distance of 10 cm. The trial was stopped after 60 s if the stone had not reached 10 cm. The time and total energy needed to cause 10 cm of retropulsion were recorded at incline angles of 0°, 10°, 20°, and 40°; 10 trials at each angle were completed. The study was then repeated with pure calcium phosphate brushite stones. RESULTS: Retropulsion decreased with increasing incline angle of the saline-filled clear polymer tube. At 0° of incline the phantom stone reached a distance of 10 cm after 7.4 s. At 10°, 20° and 40°, the phantom stone migrated a mean maximum distance of 3.1, 1.2 and 0.7 cm, respectively, and the trial was stopped after 60 s. For the calcium phosphate stone, at 0° and 10° of incline, the stone reached 10 cm after 6.9 and 42.8 s, respectively (P < 0.05). At 20° and 40°, the calcium phosphate stone moved a mean maximum distance of 2.4 and 1 cm, and the trial was stopped after 60 s. CONCLUSION: Alterations in the angle of inclination reduced stone retropulsion during ureteroscopic lithotripsy in an in vitro model to <1 cm. Increasing the incline angle of a patient may effectively preclude retropulsion when performing laser lithotripsy of ureteric stones.

Intraoperative Management by a Craniofacial Team Anesthesiologist is Associated With Improved Outcomes for Children Undergoing Major Craniofacial Reconstructive Surgery.

The benefits of using a dedicated team for complex surgeries are well established for certain specialties, but largely unknown for others. The aim of this study was to determine whether management by a dedicated craniofacial team anesthesiologist would impact perioperative outcomes for children undergoing major surgery for craniosynostosis. Sixty-two children undergoing complex cranial vault reconstruction were identified. Fifty-four patients were managed by the craniofacial anesthesia team, while 8 patients were not. Primary outcome measures were calculated blood loss, red blood cell transfusion volume, blood donor exposures, extubation rate, and postoperative complication rate. Secondary outcome measures included intraoperative opioid administration, crystalloid and colloid administration, intraoperative complication rate, and intensive care unit (ICU) and hospital length of stay. Children cared for by the craniofacial team had significantly lower calculated blood loss, reduced red blood cell transfusion volume, fewer blood donor exposures, less crystalloid administration, higher rate of postoperative extubation, fewer postoperative complications, and decreased ICU and hospital length of stay than patients who were managed by noncraniofacial team anesthesiologists. There were no significant differences in demographics, opioid administration, colloid volume administration, or intraoperative complication rates between the 2 groups. Management by a craniofacial team anesthesiologist was associated with improved outcomes in children undergoing major craniofacial reconstructive surgery. While some variability can be attributed to provider-volume relationship, these findings suggest that children may benefit from a subspecialty anesthesia team-based approach for the management of craniofacial surgery, and potentially other similar high-risk cases.