The SIMULATE ureteroscopy training curriculum: educational value and transfer of skills.

OBJECTIVE: Different simulation modalities may be utilised in a curricular fashion to benefit from the strengths of each training model. The aim of this study is to evaluate a novel multi-modality ureterorenoscopy (URS) simulation curriculum in terms of educational value, content validity, transfer of skills and inter-rater reliability. METHODS: This international prospective study recruited urology residents (n = 46) with ≤ 10 URS experience and no prior simulation training. Participants were guided through each phase of the expert-developed SIMULATE URS curriculum by trainers and followed-up in the operating room (OR). Video recordings were obtained during training. A post-training evaluation survey was distributed to evaluate content validity and educational value, using descriptive statistics. Performance was evaluated using the objective structured assessment of technical skills (OSATS) scale to measure improvement in scores throughout the curriculum. Pearson's correlation coefficient and Cohen's kappa tests were utilised to investigate correlation and agreement between raters. RESULTS: Participants reported gaining OR-transferrable skills (Mean: 4.33 ± 0.67) and demonstrated marked improvement in throughout the curriculum, transferred to the OR for both semi-rigid URS (p = 0.004) and flexible URS (p = 0.007). 70% of participants were successfully followed-up in the OR (n = 32). No differences were identified with the additional use of fresh frozen cadavers (p = 0.85, p = 0.90) and the URO Mentor VR simulator (p = 0.13, p = 0.22). A moderate level of correlation was noted on the video OSATS assessments, between two expert assessors (r = 0.70), but a poor agreement with the live rating. CONCLUSION: The SIMULATE URS training curriculum received high educational value from participants, who demonstrated statistically significant improvement with consecutive cases throughout the curriculum and transferability of skills to the OR in both semi-rigid and flexible URS.

Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development.

Glycosaminoglycans (GAGs) play a central role in embryonic development by regulating the movement and signaling of morphogens. We have previously demonstrated that GAGs are the co-receptors for Fgf10 signaling in the lacrimal gland epithelium, but their function in the Fgf10-producing periocular mesenchyme is still poorly understood. In this study, we have generated a mesenchymal ablation of UDP-glucose dehydrogenase (Ugdh), an essential biosynthetic enzyme for GAGs. Although Fgf10 RNA is expressed normally in the periocular mesenchyme, Ugdh mutation leads to excessive dispersion of Fgf10 protein, which fails to elicit an FGF signaling response or budding morphogenesis in the presumptive lacrimal gland epithelium. This is supported by genetic rescue experiments in which the Ugdh lacrimal gland defect is ameliorated by constitutive Ras activation in the epithelium but not in the mesenchyme. We further show that lacrimal gland development requires the mesenchymal expression of the heparan sulfate N-sulfation genes Ndst1 and Ndst2 but not the 6-O and 2-O-sulfation genes Hs6st1, Hs6st2 and Hs2st. Taken together, these results demonstrate that mesenchymal GAG controls lacrimal gland induction by restricting the diffusion of Fgf10.

An allelic series at the paired box gene 6 (Pax6) locus reveals the functional specificity of Pax genes.

The advent of the ocular and nervous system in metazoan evolution coincides with the diversification of a single ancestral paired box (Pax) gene into Pax6, Pax6(5a), and Pax2. To investigate the role of these Pax genes in neural development, we have generated an allelic series of knock-in models at the Pax6 locus. We showed that although Pax6(5a) and Pax2 could not replace Pax6 for its autoregulation in lens induction or for neural differentiation in retina, Pax6(5a) was sufficient for corneal-lenticular detachment. In brain development, cell proliferation in the cerebral cortex and dorsoventral patterning of the telencephalon and neural tube were partially rescued in either knock-in mutant. Contrary to the previous belief, our genetic studies showed that the Pax6 isoform Pax6(5a) could potentially play a role in neuronal differentiation in brain development. Importantly, Pax2 showed greater rescue efficiency than Pax6(5a) in the telencephalon even though the latter was identical to Pax6 outside the paired domain. In studying Ngn2, a Pax6 direct target gene in telencephalon, we showed that the level of Ngn2 expression correlated with the in vitro binding of Pax2, Pax6, and Pax6(5a) paired domain on its enhancer. Our results show that Pax6 is uniquely required for eye development, but in brain development, Pax6 can be functionally substituted by related Pax family genes that share a similar paired domain binding specificity.

Septic and febrile kidney stone presentations during the COVID-19 pandemic What is the effect of reduced access to care during pandemic restrictions?

INTRODUCTION: During the early stages of the COVID-19 pandemic, hospitals shifted their resources and focus toward COVID-19 care and non-deferrable conditions. Renal colic is one of the most common urologic presentations to the emergency department (ED ). In our study, we examined whether there was an increase in septic/febrile stone presentations to the ED requiring ureteral stent insertion after the public health restrictions during the COVID-19 pandemic. METHODS: We carried out a retrospective cohort study and reviewed charts of septic/febrile stone patients requiring ureteral stent insertion from January 1, 2019, to March 16, 2020 (pre-COVID) and July 1, 2020, to December 31, 2021 (intra-COVID) at the Queen Elizabeth II Health Sciences Centre in Halifax, NS. The incidence of septic/febrile stone presentation, baseline characteristics, and perioperative outcomes were captured. RESULTS: There were 54 patients in the pre-COVID group and 74 patients in the intra- COVID group. There were no statistically significant differences found in baseline or stone characteristics between the two groups (p>0.05). Patients in the intra-COVID group were found to have a longer presentation to operating room time when compared to the pre- COVID cohort (U=961.00, p=0.04). The intra-COVID group had 20 more cases of septic stone presentations compared to the pre-COVID group at the 15-month mark (pre-COVID, n=54; intra-COVID, n=74). CONCLUSIONS: We found increased time to operative intervention in the intra-COVID cohort compared to the pre-COVID cohort. The overall number of urgent and/or critically ill ureteric stone patients increased between cohorts but was not statistically significant.

Incidence and trends in the treatment of kidney stones in Canada A population-based cohort study.

INTRODUCTION: Our objective was to assess the incidence of kidney stones requiring acute care, trends in the surgical treatment of stones, and the demographics of stone formers in Canada. METHODS: We conducted a population-based, retrospective cohort study using administrative data from the Canadian Institute for Health Information. We included Canadian residents age >18 years, outside of Quebec, who presented between January 1, 2013, and December 31, 2018, with a kidney stone episode. This was defined as a kidney stone resulting in hospital admission, emergency department visit, or stone intervention, specifically shockwave lithotripsy (SWL), ureteroscopy (URS), or percutaneous nephrolithotomy (PCNL). RESULTS: There were 471 824 kidney stone episodes, including 184 373 interventions. The number of kidney stone episode increased from 277/100 000 in 2013 to 290/100 000 in 2018. The median age was 53 (interquartile range 41-65) years and 59.9% were male. The crude rate for stone intervention was 877/100 000. The age- and gender-standardized rate for interventions was highest in Nova Scotia and Newfoundland and Labrador, and lowest in Prince Edward Island. The most common intervention in Canada was URS (73.5%), followed by SWL (19.8%) and PCNL (6.7%). The percent utilization of SWL was highest in Manitoba, whereas for URS, it was highest in Prince Edward Island and Alberta. CONCLUSIONS: Our study provides the first population-based data on the demographics of stone formers and treatment trends across Canada. There has been a 4.7% increase in kidney stone episodes over the study period. Those presenting to hospital or requiring intervention for a kidney stone are more likely to be male, aged 41-65, and undergo URS.

Sprouty2-modulated Kras signaling rescues Shp2 deficiency during lens and lacrimal gland development.

Shp2/Ptpn11 tyrosine phosphatase is a general regulator of the RTK pathways. By genetic ablation, we demonstrate that Shp2 is required for lacrimal gland budding, lens cell proliferation, survival and differentiation. Shp2 deletion disrupted ERK signaling and cell cycle regulation, which could be partially compensated by activated Kras signaling, confirming that Ras signaling was the main downstream target of Shp2 in lens and lacrimal gland development. We also showed that Sprouty2, a general suppressor of Ras signaling, was regulated by Shp2 positively at the transcriptional level and negatively at the post-translational level. Only in the absence of Sprouty2 could activated Kras signaling robustly rescue the lens proliferation and lacrimal-gland-budding defects in the Shp2 mutants. We propose that the dynamic regulation of Sprouty by Shp2 might be important not only for modulating Ras signaling in lens and lacrimal gland development, but also for RTK signaling in general.

Lacrimal gland development and Fgf10-Fgfr2b signaling are controlled by 2-O- and 6-O-sulfated heparan sulfate.

Heparan sulfate, an extensively sulfated glycosaminoglycan abundant on cell surface proteoglycans, regulates intercellular signaling through its binding to various growth factors and receptors. In the lacrimal gland, branching morphogenesis depends on the interaction of heparan sulfate with Fgf10-Fgfr2b. To address if lacrimal gland development and FGF signaling depends on 2-O-sulfation of uronic acids and 6-O-sulfation of glucosamine residues, we genetically ablated heparan sulfate 2-O and 6-O sulfotransferases (Hs2st, Hs6st1, and Hs6st2) in developing lacrimal gland. Using a panel of phage display antibodies, we confirmed that these mutations disrupted 2-O and/or 6-O but not N-sulfation of heparan sulfate. The Hs6st mutants exhibited significant lacrimal gland hypoplasia and a strong genetic interaction with Fgf10, demonstrating the importance of heparan sulfate 6-O sulfation in lacrimal gland FGF signaling. Altering Hs2st caused a much less severe phenotype, but the Hs2st;Hs6st double mutants completely abolished lacrimal gland development, suggesting that both 2-O and 6-O sulfation of heparan sulfate contribute to FGF signaling. Combined Hs2st;Hs6st deficiency synergistically disrupted the formation of Fgf10-Fgfr2b-heparan sulfate complex on the cell surface and prevented lacrimal gland induction by Fgf10 in explant cultures. Importantly, the Hs2st;Hs6st double mutants abrogated FGF downstream ERK signaling. Therefore, Fgf10-Fgfr2b signaling during lacrimal gland development is sensitive to the content or arrangement of O-sulfate groups in heparan sulfate. To our knowledge, this is the first study to show that simultaneous deletion of Hs2st and Hs6st exhibits profound FGF signaling defects in mammalian development.

A high-fidelity, virtual-reality, transurethral resection of bladder tumor simulator: Validation as a tool for training.

INTRODUCTION: Simulation-based training is used to help trainees learn surgical procedures in a safe environment. The objective of our study was to test the face, content, and construct validity of the transurethral resection of bladder tumor (TURBT) module built on the Simbionix TURP Mentor simulator. METHODS: Participants performed five standardized cases on the simulator. Domains of the simulator were evaluated on a five-point Likert scale to establish face and content validity. Construct validity was assessed through the simulator's built-in scoring metrics, as well as video recordings of the simulator screen and an anonymized view of participants' hands and feet, which were evaluated using an objective structured assessment of technical skills (OSATS) tool. RESULTS: Ten experienced operators and 15 novices participated. Face validity was somewhat acceptable (mean realism 3.8/5±1.03 standard deviation [SD]; mean appearance 4.1/5±0.57), as was content validity, represented by simulation of key steps (mean 3.9±0.57). The simulator failed to achieve construct validity. There was no difference in mean simulator scores or OSATS scoring between experienced operators and novices. Novices significantly improved their mean simulator scores (305.9 vs. 332.4, p=0.006) and OSATS scoring (15.8 vs. 18.1, p=0.001), while 87% felt their confidence to perform TURBT improved. Overall, 92% of participants agreed that the simulator should be incorporated into residency training. CONCLUSIONS: Our study suggests a role for the TURBT module of the Simbionix TURP Mentor simulator as an introduction to TURBT for urology trainees. Strong support was found from both experienced operators and novices for its formal inclusion in resident education.

Effect of Tranexamic Acid on Bleeding Outcomes After Percutaneous Nephrolithotomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Purpose: We performed a systematic review and meta-analysis of the literature to evaluate the efficacy of the routine use of tranexamic acid (TXA) during percutaneous nephrolithotomy (PCNL). Methods: This systematic review was conducted following the updated reporting guidelines from PRISMA 2020. Results: In total, 275 titles and abstracts were reviewed, of which 20 were screened to be eligible for full text review. Of these 20 articles, 11 were selected for inclusion after full article evaluations. Seven of these 11 studies were seen as having a low risk of bias with a Jadad score of ≥3. These studies were included for data extraction. Once data were extracted, 964 patients were included. The primary outcome, blood transfusion rate, showed significant reduction with a ratio for transfusion rate of 0.34 [95% confidence interval (CI) (0.19 to 0.61), z = 3.61, p = 0.0003]. Mean hemoglobin (Hgb) drop and operative time were both shown to be reduced with the use of TXA. The mean difference for Hgb drop was -0.86 [95% CI (-1.26 to -0.46), z = 4.23, p < 0.0001]. Reduction in operative time showed a mean difference of -8.45 minutes [95% CI (-15.04 to -1.86), z = 2.51, p = 0.01]. Stone clearance was not shown to differ significantly between experimental and control groups, with a risk ratio of 1.28 [95% CI (0.89 to 1.84), z = 1.31, p = 0.19]. Conclusions: This meta-analysis revealed that the routine use of TXA at time of PCNL reduces the rates of blood transfusion, mean Hgb drop, and operative time. With the low cost of TXA and strong safety profile, stronger consideration should be given to the routine use of TXA during PCNL by endoscopic surgeons.

Effect of Simulation-based Training on Surgical Proficiency and Patient Outcomes: A Randomised Controlled Clinical and Educational Trial.

BACKGROUND: It is hypothesised that simulation enhances progression along the initial phase of the surgical learning curve. OBJECTIVE: To evaluate whether residents undergoing additional simulation, compared to conventional training, are able to achieve proficiency sooner with better patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: This international, multicentre, randomised controlled trial recruited 94 urology residents with experience of zero to ten procedures and no prior exposure to simulation in ureterorenoscopy, selected as an index procedure. INTERVENTION: Participants were randomised to simulation or conventional operating room training, as is the current standard globally, and followed for 25 procedures or over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of procedures required to achieve proficiency, defined as achieving a score of ≥28 on the Objective Structured Assessment of Technical Skill (OSATS) scale over three consecutive operations, was measured. Surgical complications were evaluated as a key secondary outcome. This trial is registered at www.isrctn.com as ISCRTN 12260261. RESULTS AND LIMITATIONS: A total of 1140 cases were performed by 65 participants, with proficiency achieved by 21 simulation and 18 conventional participants over a median of eight and nine procedures, respectively (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.72-2.75). More participants reached proficiency in the simulation arm in flexible ureterorenoscopy, requiring a lower number of procedures (HR 0.89, 95% CI 0.39-2.02). Significant differences were observed in overall comparison of OSATS scores between the groups (mean difference 1.42, 95% CI 0.91-1.92; p < 0.001), with fewer total complications (15 vs 37; p = 0.003) and ureteric injuries (3 vs 9; p < 0.001) in the simulation group. CONCLUSIONS: Although the number of procedures required to reach proficiency was similar, simulation-based training led to higher overall proficiency scores than for conventional training. Fewer procedures were required to achieve proficiency in the complex form of the index procedure, with fewer serious complications overall. PATIENT SUMMARY: This study investigated the effect of simulation training in junior surgeons and found that it may improve performance in real operating settings and reduce surgical complications for complex procedures.

Stakeholder perspectives and status of surgical simulation and skills training in Canadian urology residency program.

INTRODUCTION: With the shift to competency-based training, surgical skills lab training (SSLT) may become a mandatory part of Canadian urology residency programs (CURPs). This study aims to identify: 1) the status of SSLT in CURP; 2) stakeholder perspectives on the utility of SSLT; 3) barriers to developing and implementing SSLT; and 4) how to address these barriers. METHODS: Surveys were developed and issued to three groups of stakeholders: 1) SSLT directors at all 13 CURPs (response rate 100%); 2) teaching faculty (response rate 33%); and 3) urology residents (response rate 24%). Surveys 2 and 3 were sent to 10 English CURPs. Results were collected through email and SurveyMonkey®. RESULTS: Nine of 13 CURPs have a dedicated SSLT; 46% of CURP have 1-3 sessions per year, 8% have 5-7, and 30% >7. Most residents have independent lab access, but 80% do so less than once monthly. Over 90% of stakeholders find SSLT useful, of which high-fidelity models are most preferred (faculty rated 3.66/4, residents 3.18/4). Program directors (PDs) identified lack of protected faculty time, funding, and infrastructure as the top three barriers to SSLT implementation. Residents found lack of faculty time, protected academic time, and infrastructure as barriers. PDs viewed protecting faculty time and more funding as potential solutions, while residents suggested protected faculty and academic time, and after-hours lab access. CONCLUSIONS: Residents, faculty, and PDs in CURPs view SSLT as useful. Most CURPs have defined SSLT; programs without this have labs for resident use but are underused. To continue to develop and progress SSLT, more time, participation, and funding must be made available.

Urological issues in pregnancy: A review for urologists.

Urological issues in the pregnant patient present a unique clinical dilemma. These patients may be challenging to treat due to risks associated with medications and surgical procedures. This review aims to provide an update on the physiological changes and surgical risks in pregnancy. In addition, we review the approach for management of urolithiasis and urinary tract infections in pregnancy. Lastly, we highlight the importance of a multidisciplinary approach to placenta percreta, a condition not commonly addressed in urological education.

Stable knockout of lanthionine synthase C-like protein-1 (LanCL1) from HeLa cells indicates a role for LanCL1 in redox regulation of deubiquitinating enzymes.

Lanthionine synthase C-like protein-1 (LanCL1) is a glutathione (GSH)-binding protein of uncertain function, widely expressed in mammalian cells. Recent data suggests that LanCL1 has glutathione S-transferase (GST)-like activity, while other reports claim that LanCL1 suppresses mitogen-activated kinase (MAPK) phosphorylation. In the present study, recombinant human LanCL1 had less than 10% the specific activity of GST. When CRISPR-Cas9 was used to stably ablate LanCL1 from HeLa cells, the resulting line was sensitized to H2O2 toxicity. [GSH], [GSSG], [GSH]/[GSSG] and GST activity were unaltered by LanCL1 knockout but glutathione reductase and glutathione peroxidase activities were significantly elevated. LanCL1-KO cells did not differ in basal or H2O2-induced p38-MAPK, ERK p42/p44 or JNK phosphorylation; however, MAPK-targeted transcription factor regulators c-Jun and IκBα were significantly decreased. Because c-Jun and IκBα levels are ubiquitin regulated, experiments addressed the hypothesis that LanCL1 affects ubiquitination dynamics. In the presence of the 26S proteasome inhibitor bortezomib, ubiquitinated proteins accumulated faster in LanCL1-KO cells, suggesting that LanCL1 positively regulates deubiquitination. The activity of ubiquitin C-terminal hydrolase (UCH), a major deubiquitinase (DUB) subclass, was significantly decreased in LanCL1-KO cells while protein levels of A20/TNFAIP3, USP9X and USP10 DUBs were significantly reduced. UCH activity in HeLa cell lysates was lost upon treatment with H2O2 and significantly recovered by addition of recombinant LanCL1 plus GSH. Taken together these data suggest that LanCL1 likely does not act as a GST-like enzyme in vivo, but rather modulates ubiquitin-dependent cell signaling pathways through positive regulation of redox-sensitive DUBs.

Routine Preoperative Electrocardiograms in Patients at Low Risk for Cardiac Complications During Shockwave Lithotripsy: Are They Useful?

INTRODUCTION: Routine preoperative electrocardiogram (ECG) before shockwave lithotripsy (SWL) is frequently performed despite recommendations against its use in asymptomatic patients undergoing low-risk surgical procedures. This study assesses whether routine preoperative ECG before SWL is useful in patients at low risk for cardiac complications. MATERIALS AND METHODS: A retrospective study of SWL at our center (2003-2013) reviewed all cardiac-related preoperative cancellations, intraoperative complications, postoperative admissions, and emergency department presentations in patients at low risk for cardiac complications. Patients received SWL with sedation and continuous five-lead ECG monitoring. RESULTS: Of 30,892 referrals, preoperative ECG triggered 13 (0.04%) cancelations in low-risk patients (1 with new atrial fibrillation and 12 with ischemia/previous infarction). Of these patients, 1 had a subsequent abnormal cardiac work-up and 11 underwent uncomplicated SWL without cardiac intervention (2 had unknown history). Of 27,722 treatments, 5 (0.02%) were stopped prematurely in low-risk patients because of arrhythmia (3 had normal preoperative ECG, 1 had abnormal ECG, and 1 did not complete ECG). Three patients developed an arrhythmia with sedation and 2 patients were admitted postoperatively because of cardiac complications (1 for atrial fibrillation and 1 for hypertension), of whom all had normal preoperative ECG. No patients presented to our emergency department with cardiac complications after SWL. CONCLUSIONS: In patients at low risk for cardiac complications, preoperative ECG triggered very few cancellations and did not predict early termination of treatment or cardiac complications after SWL. These findings suggest that in low-risk patients, routine preoperative ECG has little effect on treatment or complication rate and should be omitted.

Evaluation of Optimal Timing of Expert Feedback in a Simulated Flexible Ureteroscopy Course.

Introduction: Simulation-based training (SBT) has become an increasingly popular modality to train novice surgical residents in the face of rapidly increasing innovative surgical techniques across all surgical disciplines. Recent studies have already demonstrated SBT to be effective in helping overcome the learning curve associated with new surgical techniques, especially in junior residents and endoscopic procedures. In addition, it is known that trainees benefit significantly from expert feedback; however, there is a paucity of data looking into the optimal timing of this feedback during SBT. To address this knowledge deficit, an SBT curriculum was developed for junior urology residents to assess optimal timing of feedback during SBT for flexible ureteroscopy (fURS). Materials and Methods: The SBT course consisted of a pretraining assessment, three independent practice sessions, and a post-training assessment, with residents receiving expert feedback right after their pretraining assessment (early feedback [EF]) or after their final independent training session (late feedback [LF]). Results: Fifteen trainees with similar baseline fURS experience and precourse fURS task performance score participated in the study. There was a significant difference between the pre- and post-task completion times overall (15.2 minutes vs 9.1 minutes, p < 0.001), with no difference between the early or LF groups (p = 0.884). The mean performance scores improved for both groups (18.2 vs 24.2, p < 0.001) with the EF group having a more statistically significant improvement in performance scores than the LF group (p = 0.05), and most (73%) of residents preferred EF. Conclusions: This study demonstrates that an SBT curriculum for fURS is effective for technical skills development among junior trainees, and that EF resulted in marginally better overall scores and was preferred by residents.