Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy.

OBJECTIVES: We sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). MATERIALS AND METHODS: Patients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. RESULTS: Median follow-up was 12.9 months (1.3 - 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was -3.8 kg (-14.1 - 5.1) for VMAT and -3 kg (-16.8 - 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. CONCLUSIONS: Cutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Pathways to paediatric urology subspecialisation: a study of casemix, incumbent attitudes and opinions.

OBJECTIVE: To identify any self-reported differences or attitudes towards certification, publication, or practice patterns between adult urology and paediatric general surgery-trained paediatric urology providers. There are no known published differences in clinical/operative/research outcomes in either group. METHODS: An 18-item cross-sectional survey was compiled through the EAU Young Academic Urologists (YAU) office and disseminated to a trans-Atlantic convenience sample of current practising paediatric urologists. This was created using a mini-Delphi method to provide current semi-quantitative data relating to current opinions and attitudes of this cohort. RESULTS: A total of 228 respondents completed the survey, with female respondents representing 37% and 34% for urology and paediatric general surgery, respectively. Nearly 90% overall respondents felt that a full 2-year paediatric fellowship program was very important and 94% endorsed a collaborative dedicated paediatric urology on call service, with 92% supporting the joint development of transitional care. Urology managed higher numbers of bedwetting (p = 0.04), bladder bowel dysfunction (p = 0.02), endourological procedures (p = 0.04), and robotics (p = 0.04). Paediatric general surgery managed higher numbers of laparoscopic reconstruction (p = 0.03), and posterior urethral valve ablation (p = 0.002). CONCLUSION: This study represents the first time that a cross-sectional cohort of paediatric urologists from different training backgrounds were compared to assess their productivity, practice patterns and attitudes. Paediatric urology is in a unique position to have two contributing specialities, with the ability to provide optimal transitional and lifelong care. We believe that there should be a strong emphasis on collaboration and to remove any historically-created barriers under policies of equity, diversity and inclusivity.

Bones and guts - Why the microbiome matters.

The importance of the gut microbiota in human health has become increasingly apparent in recent years, especially when the relationship between microbiota and host is no longer symbiotic. It has long been appreciated that gut dysbiosis can be detrimental to human health and is associated with numerous disease states. Only within the last decade, however, was the gut microbiota implicated in bone biology. Dubbed osteomicrobiology, this emerging field aims to understand the relationship between the gut microbiome and the bone microenvironment in both health and disease. Importantly, the key to one of the major clinical challenges facing both bone and cancer biologists: bone metastasis, may lie in the field of osteomicrobiology; however the link between gut bacteria and bone metastasis is only beginning to be explored. This review will discuss (i) osteomicrobiology as an emerging field, and (ii) the current understanding of osteomicrobiology in the context of cancer in bone.

Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response.

BACKGROUND: Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. METHODS: Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo-keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed. RESULTS: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = -0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo-keto reductases, or epoxide hydrolase protein expression. CONCLUSION: These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.

Metastatic non-small-cell lung cancer without driver mutations: projections by therapy line in Western Europe, 2021-2026.

Aim: To estimate the incidence, prevalence and treated prevalence by line of therapy (LOT) for non-small-cell lung cancer (NSCLC) patients without driver mutations from 2021 to 2026. Materials & methods: Country-specific registry data for Western Europe were used to project incidence and prevalence of NSCLC; LOT information was obtained from CancerMPact® Treatment Architecture physician surveys. Results: Incidence, prevalence and treated prevalence across LOTs for NSCLC are projected to increase across five WE countries, including for stage IV patients without driver mutations (184,966 cases [2021] to 197,925 [2026]). Pembrolizumab monotherapy is utilized by ∼50% of NSCLC patients with programmed death-ligand 1 expression ≥50%. Conclusion: Improved treatment options for NSCLC patients without known driver mutations are important for combating the projected increase in prevalence.

Lung cancer is the leading cause of cancer-related death in Europe. This study estimated how the number of patients living with, and being treated for, lung cancer is projected to change between 2021 and 2026 in Western Europe by collecting past data on lung cancer in France, Germany, Italy, Spain and the UK, and analyzing the trends to create estimates for the future. The number of new cases of lung cancer is projected to increase each year from 2021 to 2026, and in line with this, the number of patients receiving treatment for their disease will increase. Improving treatment options for lung cancer will be an important step to combat the expected increase in cancer cases.

Real-world treatment patterns and clinical outcomes after introduction of immune checkpoint inhibitors: Results from a retrospective chart review of patients with advanced/metastatic non-small cell lung cancer in the EU5.

BACKGROUND: Real-world evidence is increasingly used to guide treatment and regulatory decisions for non-small cell lung cancer (NSCLC). Real-world treatment patterns and clinical outcomes among patients with advanced/metastatic NSCLC in France, Germany, Italy, Spain, and the UK (EU5) were assessed. METHODS: This retrospective physician-completed patient chart review assessed treatment patterns (regimen, duration of treatment [DOT], time to discontinuation), and clinical outcomes (duration of response [DOR], progression-free survival [PFS], and overall survival [OS]) of patients with stage IIIB/C or IV NSCLC who received pembrolizumab-based first-line induction chemotherapy. RESULTS: Overall, 322 patients were included; at first-line maintenance (1LM), 92% had stage IV NSCLC, 68% had nonsquamous histology, and 89% had no central nervous system (CNS)/brain metastasis. The two most common 1LM regimens were pembrolizumab monotherapy (76% overall) and pembrolizumab + pemetrexed (21% overall). Docetaxel monotherapy was the most common second-line regimen in all countries except Germany (54% overall). For 1LM therapy, the overall median DOT and DOR were 5 and 10 months, respectively; PFS was 7 months and OS was 8 months. Germany had a longer duration of each outcome except for DOR which was longer in Spain. Clinical outcomes were generally poorer for patients with squamous histology and CNS/brain metastases. CONCLUSIONS: This study demonstrated differences in treatment patterns and clinical outcomes in NSCLC across the EU5 and patient subgroups. Improved survival was generally associated with response to first-line therapy, nonsquamous histology, and CNS/brain metastases absence. These real-world data provide valuable insights which may aid treatment decision-making and clinical trial design.

The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

A cross-sectional analysis of paediatric urologists' current practices, opinions and areas of perceived importance in the delivery of adolescent & transitional care.

INTRODUCTION: Complex urological anomalies often require continued care as patients reach adulthood. Adequate transition for adolescents with ongoing urological care needs is critical to allow for seamless care in adult hospitals. Studies have shown that this can lead to improved patient and parental satisfaction, and lower utilisation of unplanned inpatient beds and emergency department visits. There is currently no ESPU-EAU consensus on the adequate mechanism and very few individual papers examining the role of urological transition for these patients in a European setting. This study aimed to identify current practice patterns in paediatric urologists providing adolescent/transitional care, to assess their opinions towards formal transition and to look for variations in care. This has implications for long-term patient health and specialist care. METHODS: An 18-item cross-sectional survey was compiled and pre-approved through the EAU-EWPU and ESPU board offices prior to dissemination to all registered ordinary members affiliated with the ESPU. This was created using a mini-Delphi method through the EWPU research meetings to provide current semi-quantitative data relating to current opinions and attitudes of this cohort. RESULTS: A total of 172 respondents (55% paediatric general surgery; 45% urology) across 28 countries completed the survey. The majority of respondents were in practice >10 years and spent >80% time in paediatric urology. There was no formal transition process according to 50% respondents and over half of those that did have less than 1/month, with <10% using validated questionnaires. More than two-thirds respondents continued to provide care after transition, as >70% units had no designated corresponding adult service. Furthermore, 93% paediatric believe a formal transition service to be very important, using a multidisciplinary framework. A pareto chart demonstrated 10 specific conditions to be of most interest in transition to adulthood. CONCLUSION: This is the first study to assess the requirements of paediatric urologists for adequate transitional care, however due to the nature of the survey's distribution, this was a non-scientific poll based on a convenience sample of respondents. It is critical that dual-trained or adult-trained urologists with a specific interest in paediatric urology work with current paediatric urologists in a multidisciplinary fashion to facilitate early transition based on the adolescent's developmental and biopsychosocial requirements. National urological and paediatric surgical societies need to make transitional urology a priority. The ESPU and EAU should collaboratively consider developing transitional urology guidelines to allow a framework by which this can occur.

Adapting lean methodology towards surgical tray rationalisation in inguinoscrotal day case surgery in the republic of Ireland.

INTRODUCTION: Lean methodologies have been used successfully in both industry and healthcare to reduce waste. The operating room (OR) and central supplies department (CSD) are areas associated with high hospital costs. The aim of this study was to employ Lean methodologies to support the rationalisation of surgical trays in paediatric inguinoscrotal surgery in order to reduce instrument wastage, processing times and overall costs in a European setting. METHODS: This was a prospective, pilot observation and implementation study using Lean methodology including DMAIC (Define, Measure, Analyse, Improve and Control) cycles. Relevant tray set-up included trays for boys ≥12 months age undergoing open elective inguinoscrotal surgery. A comparative analysis of two phases, pre and post-standardization was then carried out with respect to operating times, instrument set-up times, tray weights, and costs. Instruments that were used <40% of the time were eliminated from the surgical tray. RESULTS: Rationalization of the inguinoscrotal tray led to a 34.7% reduction in tray size, with a concomitant time-reduction of >2 min per case. The average overall instrument utilisation rate increased from 56% to 80% across users. Cost savings were projected at €5380.40 per annum based on current changes. There were no differences in operative time, or adverse outcomes. DISCUSSION: At the hospital level, the reduction in variation, and rationalisation of this single surgical tray could lead to both operational (Tray assembly process; Operating rooms; Ergonomic functionality) as well as economic (Sterilisation; Instrument repair; Purchases) financial and ergonomic improvements for the healthcare system. The reduction in time taken to count and sterilise instruments can lead to a potential manpower saving involving a redistribution of activities to other areas which may require them. CONCLUSION: Surgical tray rationalisation is emerging Lean concept with overlap across a number of specialities, and represents a technique by which to manage costs, and improve supply chain efficiency without any adverse effect in patient healthcare outcomes.

Women in Irish urology: An examination of female representation amongst attendees of the Irish Society of Urology annual meeting (2008-2020).

BACKGROUND: There is underrepresentation of women at surgical conferences. We examine the representation of women in Irish urology by looking at gender balance within the Irish Society of Urology (ISU) conference. AIMS: ISU programmes over thirteen years from 2008 to 2020 were assessed and female representation in session chairs, guest speakers, poster and oral presentations identified. Gender distributions of authors for each year was examined. To investigate changes in female representation temporally, the period of this study (2008-2020) was subdivided and compared: 2008-2013 and 2014-2020. RESULTS: 76 sessions were presided over by 138 chairs, of which 6 (4.3%) were female. Eight conferences had zero female chairs. 62 guest lectures were given, 6 (9.6%) by women. Of total 340 poster and 434 oral presentations, women delivered 24.9% (0-47.5%) of posters and 31.6% (10.3-59.4%) of oral presentations. We found no significant difference in the percentage of female poster presentations between the time periods 2008-2013 (m = 18.2, sd = 13.7) and 2014-2020 (m = 34.3, sd = 17.8), t(11) = -1.4, p > 0.05. However, we found a significant difference in the percentage of female oral presentations between the periods 2008-2013 (m = 18.7, sd = 14.2) and 2014-2020 (m = 40.6, sd = 14.5), t(11) = -2.8, p < 0.05. CONCLUSIONS: Our study is the second to examine female representation in Irish urology. Session chairs and guest speakers were grossly overrepresented by males as were oral and poster presentations. Despite lacking female influence overall, in more recent years there was an increased representation of women. Societies should strive to increase female representation, as this perpetuates a positive feedback loop, encouraging future female trainees to pursue urological surgery.

Regionalization of Head and Neck Oncology Tumor Boards: Perspectives of Collaborating Physicians.

Objectives: To survey academic and community physician preferences regarding the virtual multidisciplinary tumor board (MTB) for further improvement and expansion. Study Design: This anonymous 14-question survey was sent to individuals that participated in the head and neck virtual MTBs. The survey was sent via email beginning August 3, 2021, through October 5, 2021. Setting: The University of Maryland Medical Center and regional practices in the state of Maryland. Methods: Survey responses were recorded and presented as percentages. Subset analysis was performed to obtain frequency distributions by facility and provider type. Results: There were 50 survey responses obtained with a response rate of 56%. Survey participants included 11 surgeons (22%), 19 radiation oncologists (38%), and 8 medical oncologists (16%), amongst others. More than 96% of participants found the virtual MTB to be useful when discussing complex cases and impactful to future patient care. A majority of respondents perceived a reduction in time to adjuvant care (64%). Community and academic physician responses strongly agreed that the virtual MTB improved communication (82% vs 73%), provided patient-specific information for cancer care (82% vs 73%), and improved access to other specialties (66% vs 64%). Academic physicians, more so than community physicians, strongly agreed that the virtual MTB improves access to clinical trial enrollment (64% vs 29%) and can be useful in obtaining CME (64% vs 55%). Conclusion: Academic and community physicians view the virtual MTB favorably. This platform can be adapted regionally and further expanded to improve communication between physicians and improve multidisciplinary care for patients.

Immunotherapy as a potential treatment approach for currently incurable bone metastasis.

Once cancer metastasizes to the bone, the prognosis of cancer patients becomes extremely poor. Unfortunately, the current most successful treatment for bone metastasis can extend their survival by only a few months. Although recent studies have revealed promising impacts of cancer immunotherapies, their treatment efficacy on bone metastatic diseases remains controversial. Therefore, in this review, we discussed (i) preclinical and clinical evidence of the immunotherapeutic strategies for cancer bone metastasis, mainly focusing on cell-based immunotherapy, cytokine-based immunotherapy, and immune checkpoint blockade, and (ii) current shortcomings of immunotherapy for bone metastasis and their potential future directions. Although the evidence on treatment efficacy and safety, as well as long-term effects, is limited, immunotherapies could induce partial or complete remissions in a few cancer patients with bone metastasis. However, there are still hurdles, such as the immunosuppressive nature of the bone marrow microenvironment and poor distribution of cell-based immunotherapies to bone, that need to be overcome to enhance the treatment efficacy of immunotherapies on bone metastasis. While it is apparent that further investigation is needed regarding immunotherapeutic treatment efficacy in patients with bone metastasis, this therapy may prove to be clinically novel in this subset of cancer patients.

Prevalence, Risk Factors, and Sequelae of Asymptomatic Clostridioides difficile Colonization in Children with Cystic Fibrosis.

Patients with CF (pwCF) have high antibiotic use and an altered intestinal microbiome, known risk factors for infection with Clostridioides difficile. However, in adults with CF, C. difficile infection (CDI) is uncommon and asymptomatic colonization with C. difficile occurs frequently, for reasons that remain unclear. We investigated the rate, risk factors, and sequelae of asymptomatic C. difficile colonization in children with CF (cwCF). We identified that 32% of cwCF were colonized with C. difficile without acute gastrointestinal symptoms. Higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) were significantly associated with C. difficile colonization. No children developed symptomatic CDI in 90-days following enrollment.

Adherence to Screen Time and Physical Activity Guidelines is Associated with Executive Function in US Toddlers Participating in the STRONG Kids 2 Birth Cohort Study.

OBJECTIVE: To test the hypothesis that healthy weight status and adherence to American Academy of Pediatrics (AAP) guidelines for diet and physical activity would extend to greater executive function (EF) at age 24 months. STUDY DESIGN: Parents of 24-month-old children from the STRONG Kids 2 cohort study (n = 352) completed the Behavioral Rating Inventory of Executive Function for Preschoolers (BRIEF-P) and reported physical activities, diet, and screen time. Toddlers met AAP guidelines if they consumed at least 5 servings of fruits and vegetables, were physically active, refrained from sugar-sweetened beverages, and limited daily screen time to <60 minutes. Relationships between EF, 24-month weight status, and meeting AAP guidelines were tested independent of child sex, ethnicity, socioeconomic status, weight status at birth, and maternal pregnancy weight status. RESULTS: Weight-for-length z-score had no effect on EF. Toddlers meeting the screen time guideline had greater EF (ß, -0.125; 95% CI, 0.234 to -0.008), inhibitory self-control (ß, -0.142; 95% CI, -0.248 to -0.029), and emergent metacognition (ß, -0.111; 95% CI, -0.221 to 0.002), indicated by lower BRIEF-P scores. Those with more minutes of screen time had poorer overall EF (ß, 0.257; 95% CI, 0.118-0.384), inhibitory self-control (ß, 0.231; 95% CI, 0.099-0.354), cognitive flexibility (ß, 0.217; 95% CI, 0.082-0.342), and emergent metacognition (ß, 0.257; 95% CI, 0.120-0.381). Daily physical activity was associated with greater emergent metacognition (ß, -0.116; 95% CI, -0.225 to -0.005). CONCLUSIONS: Meeting AAP guidelines for physical activity and screen time was related to greater EF in a demographically homogenous sample of toddlers. Future randomized control trials and more diverse samples are needed to confirm the directionality of this relationship. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03341858.

The impacts of exosomes on bone metastatic progression and their potential clinical utility.

Bone is one of the most common sites of cancer metastasis. Once cancer metastasizes to the bone, the mortality rate of cancer patients dramatically increases. Although the exact mechanisms for this observation remain elusive, recent studies have revealed that the complex crosstalk between bone marrow microenvironment and bone metastatic cancer cells is responsible for the induction of treatment resistance. Consequently, bone metastasis is currently considered incurable. Bone metastasis not only impairs the patients' survival, but also negatively affects their quality of life by causing painful complications. It has recently been implicated the regulatory role of exosomes in cancer development and/or progression as a delivery biomaterial between cancer cells and tumor microenvironment. However, little is known as to how exosomes contribute to the progression of bone metastasis by impaction on the crosstalk between bone metastatic cancer cells and bone marrow microenvironment. Here, we highlighted the emerging roles of cancer-derived exosomes in (i) the process of dissemination and bone colonization of bone metastatic cancer cells, (ii) the enhancement of crosstalk between bone marrow microenvironment and bone metastatic cancer cells, (iii) the development of its resultant painful complications, and (iv) the clinical applications of exosomes in the bone metastatic setting.

Skull Base Regeneration During Treatment With Chemoradiation for Nasopharyngeal Carcinoma: A Case Report.

Background: Advanced cases of nasopharyngal carcinoma can present with skull base invasion. Treatment of these advanced cases with radiotherapy poses a challenge given proximity of tumor to critical neural structures as well as concern that a skull base defect and associated complications could develop with tumor regression. Case Presentation: A 34-year-old male patient presented with a 7-cm nasopharyngeal tumor invading the skull base with destruction of the clivus and intracranial extension. He underwent a course of definitive chemoradiation, requiring use of adaptive radiotherapy, that resulted in complete tumor regression and is free of disease 5 years posttreatment. Imaging done during treatment demonstrated that significant regeneration of bone occurred simultaneously with tumor regression. Conclusions: This case demonstrates that it is possible for bony regeneration to occur simultaneously with tumor regression in a patient with skull base invasion by tumor, precluding the need for neurosurgical intervention.

External validation of a low fidelity dry-lab platform to enhance loupes surgical skills techniques for hypospadias repair.

INTRODUCTION: Hypospadias repair is an index pediatric urology procedure that requires trainee familiarity with surgical loupes. A previous low-fidelity, 6-step curriculum was proposed that deconstructed the most important steps of loupe surgery. We expanded on this curriculum with an intermediate-fidelity silicone hypospadias model and designed an abbreviated version of the 6-step curriculum to precede the hypospadias repair simulation. OBJECTIVE: To assess the validity of our prior, low-fidelity conceptual model using the metric of improved performance on the intermediate-fidelity silicone hypospadias model. STUDY DESIGN: A silicone model was first prototyped with the design software Solidworks™, and then fabricated using a cast made of a mixture of silicone rubbers designed to function like skin and soft tissue (Mold Star 20T, Dragon skin FX-pro and Slacker). Casts were used to create the penile shaft model and the dorsal hooded foreskin model. The urethral plate was cast separately on a flat surface. The model was then assembled by hand. The model used for simulation included the penile shaft and urethral plate, while the dorsal-hooded foreskin was prepared to simulate the penile anatomy separately. Trainees were then divided into two groups. Group 1 practiced the low-fidelity curriculum (3 tasks) and then performed dissection of the urethral plate and suturing using the intermediate-fidelity hypospadias model. Group 2 practiced hypospadias repair prior to the low-fidelity curriculum. Both groups' models were scored by 3 blinded urologists. Trainees were then asked to complete a post simulation satisfaction survey. Data analysis was performed in IBM SPSS Statistics for Macintosh (Version 28.0 Armonk, NY: IBM Corp). RESULTS: Twenty-two candidates across Wisconsin, USA, and Dublin, Ireland participated in the study. This included 7 s-year residents, 9 third-year residents, 2 fourth-year residents, and 3 fifth-year residents. Both Groups 1 and 2 had a similar distribution of trainees (p = 0.60). Group 1 outperformed group 2 in all tasks (p < 0.05, Table 1). Trainees reported that the platform was very useful (91%). DISCUSSION: Our curriculum showed improvement in trainee ability and comfort to perform hypospadias repair. Advantages of such a simulated curriculum include improving current resident training in microsurgery, improving surgical ergonomics for trainees prior to real-time experience, and decreasing the learning curve for trainees pursuing pediatric urology. CONCLUSION: An intermediate-fidelity hypospadias platform externally validates the conceptual model implemented in the low-fidelity loupes curriculum. This appears to lead to improvement in loupe surgical skills regardless of trainee level.

Efectos de la danza en adultos mayores con riesgo de caídas. Revisión exploratoria / Effects of dance in older adults at risk of falls. Exploratory review

Resumen Introducción: Las caídas se consideran un problema de salud pública en los adultos mayores y su abordamiento debería ser multidimensional. La danza surge como una opción de intervención que permite integrar diferentes esquemas en la potenciación del movimiento. Objetivo: Determinar los efectos de la danza a nivel de equilibrio, función motora y actividades de la vida diaria en adultos mayores con riesgo de caer. Métodos: Revisión exploratoria en torno a cuáles son los efectos de la danza en adultos mayores con riesgo de caer para mejor el equilibrio, la marcha, la función motora y las actividades de la vida diaria. Las búsquedas se llevaron a cabo en PubMed, LILACS, Registro Central Cochrane de Ensayos Clínicos Controlados, PEDro, OTSeeker, artículos en texto completo en las diferentes bibliotecas virtuales (ProQuest, Ovid, Ebsco, Science Direct) y búsqueda manual. Resultados: Se encontraron 19 estudios que reportan sesiones de 45 a 60 minutos durante 12 semanas. La danza puede considerarse una intervención segura que disminuye significativamente la intervención de control para equilibrio y marcha en adultos mayores. Conclusiones: Los resultados de este trabajo sustentan que se puede emplear la danza como una opción interventiva en adultos mayores que presentan riesgo de caer.

Abstract Introduction: Falls are considered a public health problem in older adults, and their approach should be multidimensional. Dance emerges as an intervention option that allows different schemes to be integrated in movement enhancement. Objective: To determine the effects of dance on balance, motor function and activities of daily living in older adults at risk of falling. Methods: Exploratory review of the effects of dance in older adults at risk of falling in terms of balance, gait, motor function and activities of daily living. Searches were carried out in PubMed, LILACS, Cochrane Central Register of Controlled Trials, PEDro, OTSeeker, full text articles were searched in different virtual libraries (ProQuest, Ovid, Ebsco, Science Direct) and manual search was also carried out. Results: Nineteen studies were found, which report sessions of 45 to 60 minutes for 12 weeks. Dance can be considered a safe intervention that significantly decreases control intervention for balance and gait in older adults Conclusions: The results of this work support that dance can be used as an interventional option in older adults at risk of falling.

Sex Differences in Kappa Opioid Receptor Agonist Mediated Attenuation of Chemotherapy-Induced Neuropathic Pain in Mice.

Chemotherapy-induced neuropathic pain is a common side effect for cancer patients which has limited effective treatment options. Kappa opioid receptor (KOR) agonists are a promising alternative to currently available opioid drugs due to their low abuse potential. In the current study, we have investigated the effects of Salvinorin A (SalA) analogues, 16-Ethynyl SalA, 16-Bromo SalA and ethyoxymethyl ether (EOM) SalB, and in a preclinical model of paclitaxel-induced neuropathic pain in male and female C57BL/6J mice. Using an acute dose-response procedure, we showed that compared to morphine, 16-Ethynyl SalA was more potent at reducing mechanical allodynia; and SalA, 16-Ethynyl SalA, and EOM SalB were more potent at reducing cold allodynia. In the mechanical allodynia testing, U50,488 was more potent in males and SalA was more potent in females. There were no sex differences in the acute cold allodynia testing. In the chronic administration model, treatment with U50,488 (10 mg/kg) reduced the mechanical and cold allodynia responses to healthy levels over 23 days of treatment. Overall, we have shown that KOR agonists are effective in a model of chemotherapy-induced neuropathic pain, indicating that KOR agonists could be further developed to treat this debilitating condition.