Simulation training in urology.

PURPOSE OF REVIEW: This review outlines recent innovations in simulation technology as it applies to urology. It is essential for the next generation of urologists to attain a solid foundation of technical and nontechnical skills, and simulation technology provides a variety of safe, controlled environments to acquire this baseline knowledge. RECENT FINDINGS: With a focus on urology, this review first outlines the evidence to support surgical simulation, then discusses the strides being made in the development of 3D-printed models for surgical skill training and preoperative planning, virtual reality models for different urologic procedures, surgical skill assessment for simulation, and integration of simulation into urology residency curricula. SUMMARY: Simulation continues to be an integral part of the journey towards the mastery of skills necessary for becoming an expert urologist. Clinicians and researchers should consider how to further incorporate simulation technology into residency training and help future generations of urologists throughout their career.

Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.

Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.

Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies.

Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate. Further, K562 cells overexpress transferrin receptors (TfR) and have been used as a model for targeting cytotoxic therapies, via receptor-mediated endocytosis. Here, we have characterized K562 cells focusing on the karyotype of cells in prolonged culture, regulation of expression of TfR in wildtype (WT) and doxorubicin-resistant cells, and responses to histone deacetylase inhibition (HDACi). Karyotype analysis indicates novel chromosomes and gene expression analysis suggests a shift of cultured K562 cells away from patient-derived leukemic cells. We confirm the high expression of TfR on K562 cells using immunofluorescence and cell-surface receptor binding radioassays. Importantly, high TfR expression is observed in patient-derived cells, and we highlight the persistent expression of TfR following doxorubicin acquired resistance. Epigenetic analysis indicates that permissive histone acetylation and methylation at the promoter region regulates the transcription of TfR in K562 cells. Finally, we show relatively high expression of HDAC enzymes in K562 cells and demonstrate the chemotoxic effects of HDACi, using the FDA-approved hydroxamic acid, vorinostat. Together with a description of morphology, infrared spectral analysis, and examination of metabolic properties, we provide a comprehensive characterization of K562 cells. Overall, K562 cell culture systems remain widely used for the investigation of novel therapeutics for CML, which is particularly important in cases of imatinib-mesylate resistance.

Investigation of the Anti-Inflammatory Properties of Bioactive Compounds from Olea europaea: In Silico Evaluation of Cyclooxygenase Enzyme Inhibition and Pharmacokinetic Profiling.

In a landmark study, oleocanthal (OLC), a major phenolic in extra virgin olive oil (EVOO), was found to possess anti-inflammatory activity similar to ibuprofen, involving inhibition of cyclooxygenase (COX) enzymes. EVOO is a rich source of bioactive compounds including fatty acids and phenolics; however, the biological activities of only a small subset of compounds associated with Olea europaea have been explored. Here, the OliveNetTM library (consisting of over 600 compounds) was utilized to investigate olive-derived compounds as potential modulators of the arachidonic acid pathway. Our first aim was to perform enzymatic assays to evaluate the inhibitory activity of a selection of phenolic compounds and fatty acids against COX isoforms (COX-1 and COX-2) and 15-lipoxygenase (15-LOX). Olive compounds were found to inhibit COX isoforms, with minimal activity against 15-LOX. Subsequent molecular docking indicated that the olive compounds possess strong binding affinities for the active site of COX isoforms, and molecular dynamics (MD) simulations confirmed the stability of binding. Moreover, olive compounds were predicted to have favorable pharmacokinetic properties, including a readiness to cross biological membranes as highlighted by steered MD simulations and umbrella sampling. Importantly, olive compounds including OLC were identified as non-inhibitors of the human ether-à-go-go-related gene (hERG) channel based on patch clamp assays. Overall, this study extends our understanding of the bioactivity of Olea-europaea-derived compounds, many of which are now known to be, at least in part, accountable for the beneficial health effects of the Mediterranean diet.

Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein-peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet.

The Potential Antidepressant Compound Org 34167 Modulates HCN Channels Via a Novel Mode of Action.

Org 34167 is a small molecule hyperpolarization-activated cyclic nucleotide-gated (HCN) channel modulator that has been trialed in humans for its potential antidepressant activity. The precise action of Org 34167 is not fully understood. Here we use two-electrode voltage clamp recordings and an allosteric model to explore the interaction of Org 34167 with human HCN1 channels. The impact of Org 34167 on channel function included a hyperpolarizing shift in activation voltage dependence and a slowing of activation kinetics. Furthermore, a reduction in the maximum open probability at extreme hyperpolarization argued for an additional voltage-independent mechanism. Org 34167 had a similar impact on a truncated HCN1 channel lacking the C-terminal nucleotide binding domain, thus ruling out an interaction with this domain. Fitting a gating model, derived from a 10-state allosteric scheme, predicted that Org 34167 strongly reduced the equilibrium constant for the voltage-independent pore domain to favor a closed pore, as well as reducing the voltage sensing domain-pore domain coupling and shifting the zero voltage equilibrium constant of the voltage sensing domain to favor the inactive state. SIGNIFICANCE STATEMENT: The brain penetrant small molecule Org 34167 has been reported to have an antidepressant action by targeting HCN channels; however, its mode of action is unknown. We used heterologously expressed human HCN1 channels to show that Org 34167 inhibits channel activity by modulating kinetic parameters associated with the channel pore domain, voltage sensing domain, and interdomain coupling.

A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort Study.

PURPOSE: We explored the accuracy of a urine-based epigenetic test for detecting upper tract urothelial carcinoma. MATERIALS AND METHODS: Under an Institutional Review Board-approved protocol, urine samples were prospectively collected from primary upper tract urothelial carcinoma patients before radical nephroureterectomy, ureterectomy, or ureteroscopy between December 2019 and March 2022. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and 2 internal control loci using methylation-sensitive restriction enzymes coupled with quantitative polymerase chain reaction. Results were reported as the Bladder CARE Index score and quantitatively categorized as positive (>5), high risk (2.5-5), or negative (<2.5). The findings were compared with those of 1:1 sex/age-matched cancer-free healthy individuals. RESULTS: Fifty patients (40 radical nephroureterectomy, 7 ureterectomy, and 3 ureteroscopy) with a median (IQR) age of 72 (64-79) years were included. Bladder CARE Index results were positive in 47, high risk in 1, and negative in 2 patients. A significant correlation was found between Bladder CARE Index values and tumor size. Urine cytology was available for 35 patients, of whom 22 (63%) results were false-negative. Upper tract urothelial carcinoma patients had significantly higher Bladder CARE Index values compared to the controls (mean 189.3 vs 1.6, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the Bladder CARE test for detecting upper tract urothelial carcinoma were 96%, 88%, 89%, and 96%, respectively.Conclusions:Bladder CARE is an accurate urine-based epigenetic test for the diagnosis of upper tract urothelial carcinoma, with much higher sensitivity than standard urine cytology.

Molecular modeling of lactoferrin for food and nutraceutical applications: insights from in silico techniques.

Lactoferrin is a protein, primarily found in milk that has attracted the interest of the food industries due to its health properties. Nevertheless, the instability of lactoferrin has limited its commercial application. Recent studies have focused on encapsulation to enhance the stability of lactoferrin. However, the molecular insights underlying the changes of structural properties of lactoferrin and the interaction with protectants remain poorly understood. Computational approaches have proven useful in understanding the structural properties of molecules and the key binding with other constituents. In this review, comprehensive information on the structure and function of lactoferrin and the binding with various molecules for food purposes are reviewed, with a special emphasis on the use of molecular dynamics simulations. The results demonstrate the application of modeling and simulations to determine key residues of lactoferrin responsible for its stability and interactions with other biomolecular components under various conditions, which are also associated with its functional benefits. These have also been extended into the potential creation of enhanced lactoferrin for commercial purposes. This review provides valuable strategies in designing novel nutraceuticals for food science practitioners and those who have interests in acquiring familiarity with the application of computational modeling for food and health purposes.

Sulforaphane prevents and reverses allergic airways disease in mice via anti-inflammatory, antioxidant, and epigenetic mechanisms.

Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced epithelial thickening, collagen deposition, goblet cell metaplasia, and inflammation. Well-known antioxidant and anti-inflammatory mechanisms contribute to the beneficial effects of LSF. Fourier transform infrared microspectroscopy revealed altered composition of macromolecules, following OVA sensitization, which were restored by LSF. RNA sequencing in human peripheral blood mononuclear cells highlighted the anti-inflammatory signature of LSF. Findings indicated that LSF may alter gene expression via an epigenetic mechanism which involves regulation of protein acetylation status. LSF resulted in histone and α-tubulin hyperacetylation in vivo, and cellular and enzymatic assays indicated decreased expression and modest histone deacetylase (HDAC) inhibition activity, in comparison with the well-known pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Molecular modeling confirmed interaction of LSF and LSF metabolites with the catalytic domain of metal-dependent HDAC enzymes. More generally, this study confirmed known mechanisms and identified potential epigenetic pathways accounting for the protective effects and provide support for the potential clinical utility of LSF in allergic airways disease.

Exploring the Use of Artificial Intelligence in the Management of Prostate Cancer.

PURPOSE OF REVIEW: This review aims to explore the current state of research on the use of artificial intelligence (AI) in the management of prostate cancer. We examine the various applications of AI in prostate cancer, including image analysis, prediction of treatment outcomes, and patient stratification. Additionally, the review will evaluate the current limitations and challenges faced in the implementation of AI in prostate cancer management. RECENT FINDINGS: Recent literature has focused particularly on the use of AI in radiomics, pathomics, the evaluation of surgical skills, and patient outcomes. AI has the potential to revolutionize the future of prostate cancer management by improving diagnostic accuracy, treatment planning, and patient outcomes. Studies have shown improved accuracy and efficiency of AI models in the detection and treatment of prostate cancer, but further research is needed to understand its full potential as well as limitations.

Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying K+ Channel 4 Mutant: In Silico Investigation in the Context of Drug Discovery for Hypertension.

Genetic abnormalities have been associated with primary aldosteronism, a major cause of secondary hypertension. This includes mutations in the KCNJ5 gene, which encodes G protein-gated inwardly rectifying K+ channel 4 (GIRK4). For example, the substitution of glycine with glutamic acid gives rise to the pathogenic GIRK4G151E mutation, which alters channel selectivity, making it more permeable to Na+ and Ca2+. While tertiapin and tertiapin-Q are well-known peptide inhibitors of the GIRK4WT channel, clinically, there is a need for the development of selective modulators of mutated channels, including GIRK4G151E. Using in silico methods, including homology modeling, protein-peptide docking, ligand-binding site prediction, and molecular docking, we aimed to explore potential modulators of GIRK4WT and GIRK4G151E. Firstly, protein-peptide docking was performed to characterize the binding site of tertiapin and its derivative to the GIRK4 channels. In accordance with previous studies, the peptide inhibitors preferentially bind to the GIRK4WT channel selectivity filter compared to GIRK4G151E. A ligand-binding site analysis was subsequently performed, resulting in the identification of two potential regions of interest: the central cavity and G-loop gate. Utilizing curated chemical libraries, we screened over 700 small molecules against the central cavity of the GIRK4 channels. Flavonoids, including luteolin-7-O-rutinoside and rutin, and the macrolides rapamycin and troleandomycin bound strongly to the GIRK4 channels. Similarly, xanthophylls, particularly luteoxanthin, bound to the central cavity with a strong preference towards the mutated GIRK4G151E channel compared to GIRK4WT. Overall, our findings suggest potential lead compounds for further investigation, particularly luteoxanthin, that may selectively modulate GIRK4 channels.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.

Analgesic α-Conotoxin Binding Site on the Human GABAB Receptor.

The analgesic α-conotoxins Vc1.1, RgIA, and PeIA attenuate nociceptive transmission via activation of G protein-coupled GABAB receptors (GABABRs) to modulate N-type calcium channels in primary afferent neurons and recombinantly coexpressed human GABABR and Cav2.2 channels in human embryonic kidney 293T cells. Here, we investigate the effects of analgesic α-conotoxins following the mutation of amino acid residues in the Venus flytrap (VFT) domains of the GABABR subunits predicted through computational peptide docking and molecular dynamics simulations. Our docking calculations predicted that all three of the α-conotoxins form close contacts with VFT residues in both B1 and B2 subunits, comprising a novel GABABR ligand-binding site. The effects of baclofen and α-conotoxins on the peak Ba2+ current (IBa) amplitude were investigated on wild-type and 15 GABABR mutants individually coexpressed with human Cav2.2 channels. Mutations at the interface of the VFT domains of both GABABR subunits attenuated baclofen-sensitive IBa inhibition by the analgesic α-conotoxins. In contrast, mutations located outside the putative peptide-binding site (D380A and R98A) did not. The key GABABR residues involved in interactions with the α-conotoxins are K168 and R207 on the B2 subunit and S130, S153, R162, E200, F227, and E253 on the B1 subunit. The double mutant, S130A + S153A, abolished inhibition by both baclofen and the α-conotoxins. Depolarization-activated IBa mediated by both wild-type and all GABABR mutants were inhibited by the selective GABABR antagonist CGP 55845. This study identifies specific residues of GABABR involved in the binding of the analgesic α-conotoxins to the VFT domains of the GABABR. SIGNIFICANCE STATEMENT: This study defines the binding site of the analgesic α-conotoxins Vc1.1, RgIA, and PeIA on the human GABAB receptor to activate Gi/o proteins and inhibit Cav2.2 channels. Computational docking and molecular dynamics simulations of GABABR identified amino acids of the Venus flytrap (VFT) domains with which the α-conotoxins interact. GABABR alanine mutants attenuated baclofen-sensitive Cav2.2 inhibition by the α-conotoxins. We identify an allosteric binding site at the interface of the VFT domains of the GABABR subunits for the analgesic α-conotoxins.

Tailored Feedback Based on Clinically Relevant Performance Metrics Expedites the Acquisition of Robotic Suturing Skills-An Unblinded Pilot Randomized Controlled Trial.

PURPOSE: Previously, we identified 8 objective suturing performance metrics highly predictive of urinary continence recovery after robotic-assisted radical prostatectomy. Here, we aimed to test the feasibility of providing tailored feedback based upon these clinically relevant metrics and explore the impact on the acquisition of robotic suturing skills. MATERIALS AND METHODS: Training surgeons were recruited and randomized to a feedback group or a control group. Both groups completed a baseline, midterm and final dry laboratory vesicourethral anastomosis (VUA) and underwent 4 intervening training sessions each, consisting of 3 suturing exercises. Eight performance metrics were recorded during each exercise: 4 automated performance metrics (derived from kinematic and system events data of the da Vinci® Robotic System) representing efficiency and console manipulation competency, and 4 suturing technical skill scores. The feedback group received tailored feedback (a visual diagram+verbal instructions+video examples) based on these metrics after each session. Generalized linear mixed model was used to compare metric improvement (Δ) from baseline to the midterm and final VUA. RESULTS: Twenty-three participants were randomized to the feedback group (11) or the control group (12). Demographic data and baseline VUA metrics were comparable between groups. The feedback group showed greater improvement than the control group in aggregate suturing scores at midterm (mean Δ feedback group 4.5 vs Δ control group 1.1) and final VUA (Δ feedback group 5.3 vs Δ control group 4.9). The feedback group also showed greater improvement in the majority of the included metrics at midterm and final VUA. CONCLUSIONS: Tailored feedback based on specific, clinically relevant performance metrics is feasible and may expedite the acquisition of robotic suturing skills.

Investigation of small molecule inhibitors of the SARS-CoV-2 papain-like protease by all-atom microsecond modelling, PELE Monte Carlo simulations, and in vitro activity inhibition.

The SARS-CoV-2 papain-like (PLpro) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PLpro inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro. Although not potent as GRL-0617 (45.8 vs 1.6 µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PLpro protease and deubiquitinating activities. Given its use in supplementations and the FDA conditional approval of a synthetic version, further evaluation of hypericin as a potential SARS-CoV-2 antiviral is warranted.

Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking.

Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. A total of 12 previously reported bromotyrosine-derived alkaloids were isolated from the marine sponge species Pseudoceratina durissima, and the compound, (+)-aeroplysinin-1 (1) displayed activity against the MRSA pathogen (MIC: <32 µg/mL). The compounds (1−3, 6 and 9) were assessed for their central nervous system (CNS) interaction and behavioral toxicity to zebrafish (Danio rerio) larvae, whereby several of the compounds were shown to induce significant hyperactivity. Anthelmintic activity against the parasitic nematode Haemonchus contorutus was also evaluated (2−4, 6−8).

Robotic and robot-assisted skull base neurosurgery: systematic review of current applications and future directions.

OBJECTIVE: The utility of robotic instrumentation is expanding in neurosurgery. Despite this, successful examples of robotic implementation for endoscopic endonasal or skull base neurosurgery remain limited. Therefore, the authors performed a systematic review of the literature to identify all articles that used robotic systems to access the sella or anterior, middle, or posterior cranial fossae. METHODS: A systematic review of MEDLINE and PubMed in accordance with PRISMA guidelines performed for articles published between January 1, 1990, and August 1, 2021, was conducted to identify all robotic systems (autonomous, semiautonomous, or surgeon-controlled) used for skull base neurosurgical procedures. Cadaveric and human clinical studies were included. Studies with exclusively otorhinolaryngological applications or using robotic microscopes were excluded. RESULTS: A total of 561 studies were identified from the initial search, of which 22 were included following full-text review. Transoral robotic surgery (TORS) using the da Vinci Surgical System was the most widely reported system (4 studies) utilized for skull base and pituitary fossa procedures; additionally, it has been reported for resection of sellar masses in 4 patients. Seven cadaveric studies used the da Vinci Surgical System to access the skull base using alternative, non-TORS approaches (e.g., transnasal, transmaxillary, and supraorbital). Five cadaveric studies investigated alternative systems to access the skull base. Six studies investigated the use of robotic endoscope holders. Advantages to robotic applications in skull base neurosurgery included improved lighting and 3D visualization, replication of more traditional gesture-based movements, and the ability for dexterous movements ordinarily constrained by small operative corridors. Limitations included the size and angulation capacity of the robot, lack of drilling components preventing fully robotic procedures, and cost. Robotic endoscope holders may have been particularly advantageous when the use of a surgical assistant or second surgeon was limited. CONCLUSIONS: Robotic skull base neurosurgery has been growing in popularity and feasibility, but significant limitations remain. While robotic systems seem to have allowed for greater maneuverability and 3D visualization, their size and lack of neurosurgery-specific tools have continued to prevent widespread adoption into current practice. The next generation of robotic technologies should prioritize overcoming these limitations.

An Objective Assessment of Performance during Robotic Partial Nephrectomy: Validation and Correlation of Automated Performance Metrics with Intraoperative Outcomes.

PURPOSE: Automated performance metrics provide a novel approach to the assessment of surgical performance. Herein, we present a construct validation of automated performance metrics during robotic assisted partial nephrectomy. MATERIALS AND METHODS: Automated performance metrics (instrument motion tracking/system events) and synchronized surgical videos from da Vinci® Si systems during robotic assisted partial nephrectomy were recorded using a system data recorder. Each case was segmented into 7 steps: colon mobilization, ureteral identification/dissection, hilar dissection, exposure of tumor within Gerota's fascia, intraoperative ultrasound/tumor scoring, tumor excision, and renorrhaphy. Automated performance metrics from each step were compared between expert (≥150 cases) and trainee (<150 cases) surgeons by Mann-Whitney U test (continuous variables) and Pearson's chi-squared test (categorical variables). Clinical outcomes were collected prospectively and correlated to automated performance metrics and R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score by Spearman's correlation coefficients (r). RESULTS: A total of 50 robotic assisted partial nephrectomy cases were included for analysis, performed by 7 expert and 10 trainee surgeons. Automated performance metric profiles significantly differed between experts and novices in the initial 5 steps (p <0.05). Specifically, experts exhibited faster dominant instrument movement and greater dominant instrument usage (bimanual dexterity) than trainees in select steps (p ≤0.045). Automated performance metrics during tumor excision and renorrhaphy were significantly correlated with R.E.N.A.L. score (r ≥0.364; p ≤0.041). These included metrics related to instrument efficiency, task duration, and dominant instrument use. CONCLUSIONS: Experts are more efficient and directed in their movement during robotic assisted partial nephrectomy. Automated performance metrics during key steps correlate with objective measures of tumor complexity and may serve as predictors of clinical outcomes. These data help establish a standardized metric for surgeon assessment and training during robotic assisted partial nephrectomy.

A Novel Dissection Gesture Classification to Characterize Robotic Dissection Technique for Renal Hilar Dissection.

PURPOSE: Deconstruction of robotic surgical gestures into semantic vocabulary yields an effective tool for surgical education. In this study we disassembled tissue dissection into basic gestures, created a classification system, and showed its ability to distinguish between experts and novices. MATERIALS AND METHODS: Videos of renal hilum preparation during robotic assisted partial nephrectomies were manually reviewed to identify all discrete surgical movements. Identified dissection movements were classified into distinct gestures based on the consensus of 6 expert surgeons. This classification system was then employed to compare expert and novice dissection patterns during the renal hilum preparation. RESULTS: A total of 40 robotic renal hilum preparation videos were reviewed, representing 16 from 6 expert surgeons (100 or more robotic cases) and 24 from 13 novice surgeons (fewer than 100 robotic cases). Overall 9,819 surgical movements were identified, including 5,667 dissection movements and 4,152 supporting movements. Nine distinct dissection gestures were identified and classified into the 3 categories of single blunt dissection (spread, peel/push, hook), single sharp dissection (cold cut, hot cut and burn dissect) and combination gestures (pedicalize, 2-hand spread, and coagulate then cut). Experts completed 5 of 9 dissection gestures more efficiently than novices (p ≤0.033). In consideration of specific anatomical locations, experts used more peel/push and less hot cut while dissecting the renal vein (p <0.001), and used more pedicalize while dissecting the renal artery (p <0.001). CONCLUSIONS: Using this novel dissection gesture classification system, key differences in dissection patterns can be found between experts/novices. This comprehensive classification of dissection gestures may be broadly applied to streamline surgical education.

Multi-institutional validation of a perfused robot-assisted partial nephrectomy procedural simulation platform utilizing clinically relevant objective metrics of simulators (CROMS).

OBJECTIVE: To conduct a multi-institutional validation of a high-fidelity, perfused, inanimate, simulation platform for robot-assisted partial nephrectomy (RAPN) using incorporated clinically relevant objective metrics of simulation (CROMS), applying modern validity standards. MATERIALS AND METHODS: Using a combination of three-dimensional (3D) printing and hydrogel casting, a RAPN model was developed from the computed tomography scan of a patient with a 4.2-cm, upper-pole renal tumour (RENAL nephrometry score 7×). 3D-printed casts designed from the patient's imaging were used to fabricate and register hydrogel (polyvinyl alcohol) components of the kidney, including the vascular and pelvicalyceal systems. After mechanical and anatomical verification of the kidney phantom, it was surrounded by other relevant hydrogel organs and placed in a laparoscopic trainer. Twenty-seven novice and 16 expert urologists, categorized according to caseload, from five academic institutions completed the simulation. RESULTS: Clinically relevant objective metrics of simulators, operative complications, and objective performance ratings (Global Evaluative Assessment of Robotic Skills [GEARS]) were compared between groups using Wilcoxon rank-sum (continuous variables) and parametric chi-squared (categorical variables) tests. Pearson and point-biserial correlation coefficients were used to correlate GEARS scores to each CROMS variable. Post-simulation questionnaires were used to obtain subjective supplementation of realism ratings and training effectiveness. RESULTS: Expert ratings demonstrated the model's superiority to other procedural simulations in replicating procedural steps, bleeding, tissue texture and appearance. A significant difference between groups was demonstrated in CROMS [console time (P < 0.001), warm ischaemia time (P < 0.001), estimated blood loss (P < 0.001)] and GEARS (P < 0.001). Six major intra-operative complications occurred only in novice simulations. GEARS scores highly correlated with the CROMS. CONCLUSIONS: This perfused, procedural model offers an unprecedented realistic simulation platform, which incorporates objective, clinically relevant and procedure-specific performance metrics.