Survey of Informed Consent Procedures in Urology: Disclosing Resident Participation to Patients.

AbstractThe American Urological Association (AUA) and American College of Surgeons (ACS) codes of professionalism require surgeons to disclose the specific roles and responsibilities of trainees to patients during the informed consent process. The objective of this study is to analyze how these requirements are met by urology training programs. An anonymous electronic survey was distributed to the program directors (PDs) of the 143 Accreditation Council for Graduate Medical Education urology residency programs in the United States in 2021. Information was collected regarding program demographics, aspects of the program's consent process, and the disclosure to patients of the role and participation of residents in their surgery. There were 49 responses to the survey (34.3% response rate). Nearly 70 percent of PDs reported that attending physicians lead the consent process. The topics covered during consent discussion include possible complications (25%), expected recovery time (23%), length of the surgery (22%), the people involved (18%), and their specific roles (7%). Many PDs do not explicitly discuss trainee involvement (48.8%) or when a resident is to perform the majority of the case (87.8%). The majority of PDs (78.8%) communicate medical student involvement, but 73.2 percent reported having a patient decline participation of a trainee after describing their role. Despite the AUA and ACS codes of professionalism, many urologists do not disclose resident involvement in surgery to patients. Further discussions are needed to explore how to better balance resident education and patient autonomy.

Prevention of Skin Cancers With Topical Calcipotriol and Fluorouracil in Patients With Xeroderma Pigmentosum.

This case report describes treatment regimens with topical calcipotriol plus fluorouracil for 2 patients with xeroderma pigmentosum.

Characteristics of Medical Schools in the United States Associated With Successful Match into Urology Residency Programs: Analysis of the 2016-2021 Urology Resident Cohort.

OBJECTIVE: To determine the characteristics of US medical schools associated with successful urology match applicants. MATERIALS AND METHODS: Using publicly available data, demographics and bibliometrics were collected for 1814 current urology residents who attend a US-based Accreditation Council for Graduate Medical Education (ACGME) Accredited program, reflecting matched applicants over a 6-year period from 2016-2021. A generated list of US feeder medical schools for urology was analyzed for correlative and predictive factors. Statistical analyses to characterize these factors included Pearson's Correlation Coefficient (PCC) and univariable and multivariable linear regression, respectively, as needed. RESULTS: There were 516 (28.45%) female residents and 58 (3.20%) international medical graduates. The mean number of published papers and abstracts ± SD pre-residency was 5.54 ± 7.20 with a mean h-index of 1.97 ± 2.24. The Cleveland Clinic Lerner College of Medicine had the highest percentage of successful matches into urology (n = 7, 3.65%), while the State University of New York Downstate Medical Center College of Medicine produced the highest absolute number (n = 41, 3.30%). The presence of a home urology program and pre-residency h-index had the strongest correlation with producing urology residents (PCC = 0.5769 and 0.3709, respectively, P<.0001). CONCLUSION: Understanding the characteristics of a successful urology match applicant and the medical schools that produce them will be vital as USMLE Step 1 exam becomes pass/fail. Further research into these schools' curricula is required to better understand the effect of early exposure to urology on matching into urology.

In vivo high-content imaging and regression analysis reveal non-cell autonomous functions of Shroom3 during neural tube closure.

During neural tube closure, neural ectoderm cells constrict their apical surfaces to bend and fold the tissue into a tube that will become the central nervous system. Recent data from mice and humans with neural tube defects suggest that key genes required for neural tube closure can exert non-cell autonomous effects on cell behavior, but the nature of these effects remains obscure. Here, we coupled tissue-scale, high-resolution time-lapse imaging of the closing neural tube of Xenopus to multivariate regression modeling, and we show that medial actin accumulation drives apical constriction non-autonomously in neighborhoods of cells, rather than solely in individual cells. To further explore this effect, we examined mosaic crispant embryos and identified both autonomous and non-autonomous effects of the apical constriction protein Shroom3.

Single-Port Robotic Radical Prostatectomy: Short-Term Outcomes and Learning Curve.

Introduction and Objective: In 2018, the U.S. Food and Drug Administration approved the da Vinci single-port (SP) system, in which four instruments are still utilized, but enter through a single-site access trocar. Herein, we report the largest case series for SP robot-assisted radical prostatectomy (RARP) to date. Our primary aim is to analyze the perioperative and short-term outcomes of this procedure. Our secondary aim is an assessment of the learning curve with this new platform. Methods: A total of 157 patients underwent SP RARP by two surgeons who have completed >3000 multiport robotic surgeries collectively. Institutional Review Board-approved prospectively collected data were used. Basic demographic preoperative variables and perioperative outcomes were analyzed. Results: Median patient age and prostate-specific antigen was 63 years and 6.3 ng/mL before treatment (interquartile range [IQR] 4.7-8.2 ng/mL). Average prostate weight was 47 g. The median operating time was 195 minutes (IQR 165-221.25 minutes) with a median estimated blood loss of 100 mL (IQR 100-200 mL). Surgeon 1's operating time stabilized around case #56, and Surgeon 2 around case #26. Surgeon 2 used the transperitoneal approach for the first 7 cases. There were no intraoperative complications. There were six total postoperative complications (3.8%) and four (2.5%) were Clavien-Dindo scale ≥IIIa. One hundred ten patients went home same day, 45 stayed 1 night at the hospital, with only 2 patients requiring stay in the hospital for more than 1 night (70%, 29%, and 1% respectively). With the median follow-up period of 9 months, rates of biochemical recurrence, pad-free, and potency preservation were 8.3%, 82.5%, and 64.4%, respectively. Conclusions: This case series confirms the safety and efficacy of SP RARP with acceptable short-term outcomes. There is a significant learning curve for this new modality. Shorter hospital stay appears to be an early benefit of the SP platform.

The Ideal Time to Administer Pre-operative Antibiotics: Current and Future Practices.

Background Preoperative antibiotic prophylaxis is a method of administering antibiotics prior to surgical procedures to decrease surgical site infections. The Center for Disease Control and Prevention (CDC) guidelines recommend administering the chosen antibiotic within 60 minutes prior to incision. However, further research can be conducted to explore and determine a more precise and ideal time for preoperative antibiotic prophylaxis. Methods This paper explores the most used antibiotics within the Department of Neurosurgery at Arrowhead Regional Medical Center, which are cefazolin and clindamycin, and pinpoints the ideal time of preoperative antibiotic prophylaxis based on peak serum levels. It will present and discuss findings by analyzing the pharmacokinetic profiles of each antibiotic, focusing on the minimal inhibitory concentration (MIC), time to peak in the tissue, and duration of action to determine the appropriate time for redosing. Results Our findings indicate that based on the pharmacological profiles, the ideal time to administer preoperative antibiotics for cefazolin is 40 minutes prior to incision, and for clindamycin is 45 minutes prior to incision. Conclusions This study may help guide clinical decision-making and lead to minimizing the rate of infections and decreasing hospital stay.

Impact of medical school responses during the COVID-19 pandemic on student satisfaction: a nationwide survey of US medical students.

PURPOSE: Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students' satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. METHODS: In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools' responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. RESULTS: The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools' response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. CONCLUSION: In future crises, schools can best improve student satisfaction by prioritizing timely communication.

Genomic analysis and long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy.

Purpose: Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy. Materials and methods: This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study. Results: Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group. Conclusion: Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa.

Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure.

Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure. This new analytical approach elucidates several differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3, and demonstrates the ability of tissue-level imaging and analysis to generate cell biological mechanistic insights into neural tube closure.

Massively parallel reporter assays discover de novo exonic splicing mutants in paralogs of Autism genes.

To determine the contribution of defective splicing in Autism Spectrum Disorders (ASD), the most common neurodevelopmental disorder, a high throughput Massively Parallel Splicing Assay (MaPSY) was employed and identified 42 exonic splicing mutants out of 725 coding de novo variants discovered in the sequencing of ASD families. A redesign of the minigene constructs in MaPSY revealed that upstream exons with strong 5' splice sites increase the magnitude of skipping phenotypes observed in downstream exons. Select hits were validated by RT-PCR and amplicon sequencing in patient cell lines. Exonic splicing mutants were enriched in probands relative to unaffected siblings -especially synonymous variants (7.5% vs 3.5%, respectively). Of the 26 genes disrupted by exonic splicing mutations, 6 were in known ASD genes and 3 were in paralogs of known ASD genes. Of particular interest was a synonymous variant in TNRC6C - an ASD gene paralog with interactions with other ASD genes. Clinical records of 3 ASD patients with TNRC6C variant revealed respiratory issues consistent with phenotypes observed in TNRC6 depleted mice. Overall, this study highlights the need for splicing analysis in determining variant pathogenicity, especially as it relates to ASD.

Dissecting the role of lymphadenectomy in the management of renal cell carcinoma: past, present, and future.

Lymph node involvement in renal cell carcinoma (RCC) portends a poor prognosis. However, the role of lymph node dissection (LND) at the time of tumor resection is not fully understood. Conflicting data have been published regarding the survival implications of LND during RCC surgery, and the optimal patient population for which LND might be beneficial has yet to be identified. Based on recent data characterizing the outcomes of node-positive RCC, some have advocated for revising the current staging guidelines to better reflect these findings. Given the paucity of high-quality evidence supporting or refuting the routine use of LND in RCC, further research is needed to shed light on this important topic. There are a number of ongoing clinical trials evaluating the role of perioperative (neoadjuvant and adjuvant) systemic therapy, which include patients with node-positive RCC, and will serve to guide changes in treatment practices for this patient population moving forward.

Prospective Analyses of Cytokine Mediation of Sleep and Survival in the Context of Advanced Cancer.

OBJECTIVE: The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in patients with advanced cancer. METHODS: A prospective study of 294 patients with gastrointestinal cancer administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including interleukin (IL)-1α, IL-1ß, tumor necrosis factor α, IL-10, IL-2, and interferon-γ were measured to assess biological mediation between sleep and survival. Survival was measured as time from diagnosis to death. RESULTS: Fifty-nine percent of patients reported poor sleep quality, 53% reported poor sleep efficiency, 39% reported sleep latency greater than 30 minutes, and 45% reported sleeping less than 6 hours or greater than 10 hours. We found a significant association between sleep duration and symptom burden. Shorter sleep duration was significantly associated with higher levels of fatigue (r = -0.169, p = .01), pain (r = -0.302, p = .01), anxiety (r = -0.182, p = .01), depression (r = -0.172, p = .003), and lower levels of quality of life (r = 0.240, p = .01). After adjustment for demographic, psychological, and disease-specific factors, short sleep duration was associated with reduced survival (hazard ratio [HR] linear = 0.485, 95% confidence interval = 0.275-0.857) and there was also evidence for a quadratic pattern (HR quadrati = 1.064, 95% confidence interval = 1.015-1.115) suggesting a curvilinear relationship between sleep duration and survival. Interleukin 2 was the only cytokine significantly related to survival (HR = 1.01, p = .003) and sleep duration (ß = -30.11, p = .027). When of IL-2 was added to the multivariable model, short and long sleep (ß = -0.557, p = .097; ß = 0.046, p = .114) were no longer significantly related to survival, suggesting mediation by IL-2. CONCLUSION: Sleep duration was associated with symptom burden and poorer survival and IL-2 was found to mediate the association between sleep and survival. Screening and treatment of sleep problems in patients diagnosed with cancer are warranted.

Characterization of Electrophysiological Propagation by Multichannel Sensors.

OBJECTIVE: The propagation of electrophysiological activity measured by multichannel devices could have significant clinical implications. Gastric slow waves normally propagate along longitudinal paths that are evident in recordings of serosal potentials and transcutaneous magnetic fields. We employed a realistic model of gastric slow wave activity to simulate the transabdominal magnetogastrogram (MGG) recorded in a multichannel biomagnetometer and to determine characteristics of electrophysiological propagation from MGG measurements. METHODS: Using MGG simulations of slow wave sources in a realistic abdomen (both superficial and deep sources) and in a horizontally-layered volume conductor, we compared two analytic methods (second-order blind identification, SOBI and surface current density, SCD) that allow quantitative characterization of slow wave propagation. We also evaluated the performance of the methods with simulated experimental noise. The methods were also validated in an experimental animal model. RESULTS: Mean square errors in position estimates were within 2 cm of the correct position, and average propagation velocities within 2 mm/s of the actual velocities. SOBI propagation analysis outperformed the SCD method for dipoles in the superficial and horizontal layer models with and without additive noise. The SCD method gave better estimates for deep sources, but did not handle additive noise as well as SOBI. CONCLUSION: SOBI-MGG and SCD-MGG were used to quantify slow wave propagation in a realistic abdomen model of gastric electrical activity. SIGNIFICANCE: These methods could be generalized to any propagating electrophysiological activity detected by multichannel sensor arrays.

Simulating a dual-array electrode configuration to investigate the influence of skeletal muscle fatigue following functional electrical stimulation.

A novel, anatomically-accurate model of a tibialis anterior muscle is used to investigate the electro-physiological properties of denervated muscles following functional electrical stimulation. The model includes a state-of-the-art description of cell electro-physiology. The main objective of this work is to develop a computational framework capable of predicting the effects of different stimulation trains and electrode configurations on the excitability and fatigue of skeletal muscle tissue. Utilizing a reduced but computationally amenable model, the effects of different electrode sizes and inter-electrode distances on the number of activated muscle fibers are investigated and qualitatively compared to existing literature. To analyze muscle fatigue, the sodium current, specifically the K+ ion concentrations within the t-tubule and the calcium release from the sarcoplasmic reticulum, is used to quantify membrane and metabolic fatigue. The simulations demonstrate that lower stimulation frequencies and biphasic pulse waveforms cause less fatigue than higher stimulation frequencies and monophasic pulses. A comparison between single and dual electrode configurations (with the same overall stimulation surface) is presented to locally investigate the differences in muscle fatigue. The dual electrode configuration causes the muscle tissue to fatigue quicker.

Silver nanoparticles induce apoptosis through the toll-like receptor 2 pathway.

OBJECTIVE: The objective of this study was to evaluate the effects of silver nanoparticles (AgNPs) on the Toll-like receptor 2 (TLR-2) pathway in cultured cells. STUDY DESIGN: Human chondrocytes, periodontal ligament (PDL) cells, and SCC-9 cells (squamous cell carcinoma from the tongue) were cultured and subjected to cytotoxicity assays. To evaluate the effects of AgNPs on the TLR-2 pathway, TLR-2 small interfering (si) RNA or TLR-2 antibodies were applied to the chondrocytes, followed by the application of AgNPs. RESULTS: AgNPs induced dose-dependent effects on the examined cell types in terms of both cytotoxicity and TLR-2 expression levels. AgNP-mediated apoptosis was reduced after treatment with TLR-2 siRNA in both PDL cells and chondrocytes. Furthermore, functional blocking of TLR-2 with anti-TLR2 antibodies inhibited AgNP-mediated cytotoxicity. AgNPs increased c-Jun phosphorylation, an effect that was reversed after treatment with TLR-2 siRNA. CONCLUSIONS: The results indicate that AgNP-mediated apoptosis most likely occurs via the TLR-2 pathway.