Comparison of Mortality and Amputation after Lower Extremity Bypass vs. Peripheral Vascular Intervention in Patients with Chronic Limb-Threatening Ischemia and Comorbid Chronic Kidney Disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data is limited for lower extremity bypass (LEB) vs. peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate 1) 30-day all-cause mortality and amputation and 2) 5-year all-cause mortality and amputation for LEB vs. PVI in patients with comorbid CKD. METHODS: Individuals undergoing LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs. PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, 69.0% were male. Irrespective of CKD status, 30-day mortality (HR 0.94, 95% CI 0.63-1.42, p=0.78) was similar for LEB vs. PVI, but LEB was associated with a lower risk of 30-day amputation (sHR 0.66, CI 0.44-0.97, p=0.04). CKD status, however, did not modify these results. Similarly, LEB vs. PVI was associated with a lower risk of 5-year mortality (HR 0.79, 95% CI 0.71-0.88, p<0.001), but no difference in 5-year amputation (sHR 1.03, 95% CI 0.89-1.20, p=0.67). CKD status did not modify these results. CONCLUSION: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs. PVI. Results may help inform preference-sensitive treatment decisions on LEB vs. PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

Evaluation of short-term mortality in patients with Medicare undergoing endovascular interventions for chronic limb-threatening ischemia.

INTRODUCTION: Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI). METHODS: Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index. RESULTS: A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10). CONCLUSION: RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI.

Zebrafish as an Emerging Model for Sarcopenia: Considerations, Current Insights, and Future Directions.

Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to address the urgent need for practical solutions to reduce the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

Anesthesia in medical school: A simulation-based curriculum proposal

Introduction Most medical students are not familiar with Anesthesiology, as it is infrequently addressed properly in medical school curricula. However, anesthesiology skills are widely practiced across specialties and commonly performed by general practitioners. Currently, anesthesia curricula are often based on shadowing and lectures without emphasizing relevant skills, behaviors, and attitudes, whereas simulation-based curricula enable a holistic evaluation of the trainee. Objective To implement and assess the perceptions of students and professors of a novel simulation-based anesthesiology curriculum. Methods A descriptive study was planned for evaluating the new proposal. A simulation-based 3-week curriculum was organized using a blended course with skill laboratories. We designed flipped classroom-based lectures (2 weeks) combined with activities using standardized patients, manikins, and hybrid scenarios (1 week). After each activity, feedback was given by an anesthesiologist, as well as individual grading and a survey based on the Kirkpatrick levels. Results From June to November 2020, 53 students were enrolled in the clerkship. Each week, every group of 6-8 students was assigned to the same specialist to perform the activities and track individual progress. The response rate of the survey was 83%. Across the levels of Kirkpatrick, there was an excellent opinion of the activities, as well as a high similarity between the perception of both students and professors. Conclusion Our simulation-based curriculum, which was highly appraised by students and professors, was found to be feasible, appealing, and offered a good introduction to the principles and practices of anesthesiology to medical students.

Introducción: La mayoría de los estudiantes de medicina no están familiarizados con la Anestesiología, ya que la materia pocas veces se aborda adecuadamente en el programa académico de la facultad de medicina. Sin embargo, las habilidades en anestesiología son ampliamente utilizadas por los médicos generales. En la actualidad los currículos de anestesiología suelen basarse en prácticas y conferencias donde no se enfatizan las destrezas pertinentes, las conductas y las actitudes, mientras que los currículos basados en simulación permiten una evaluación integral del aprendiz. Objetivo: Implementar y evaluar las percepciones de estudiantes y de los profesores de un novedoso plan de estudios de anestesiología basado en la simulación. Métodos: Se diseñó un estudio descriptivo para valorar la nueva propuesta. Se organizó un plan de estudios de 3 semanas, basado en simulación, utilizando un curso mixto con habilidades de laboratorio. Diseñamos conferencias basadas en el modelo de aula invertida (2 semanas), combinadas con actividades basadas en pacientes estandarizados, maniquíes y escenarios híbridos (1 semana). Luego de cada actividad, un anestesiólogo ofrecía su retroalimentación, así como calificaciones individuales y una encuesta basada en los niveles de Kirkpatrick. Resultados: Se inscribieron 53 estudiantes en la pasantía de junio a noviembre de 2020. Cada semana se asignaba un grupo de 6-8 estudiantes a un mismo especialista para llevar a cabo las actividades y hacer un seguimiento al progreso alcanzado de manera individual. La tasa de respuesta de la encuesta fue de 83%. En todos los niveles de Kirkpatrick, hubo una excelente opinión sobre las actividades y una elevada similitud en la percepción, tanto de los estudiantes como de los profesores. Conclusión: Nuestro currículo basado en simulación fue muy bien valorado por estudiantes y profesores y se consideró factible, atractivo y que ofrecía a los estudiantes una buena introducción a los principios y prácticas de la anestesiología.

Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged gpr27 Knockout Zebrafish.

Throughout a vertebrate organism's lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy (p < 0.000001, q = 0.000002; p = 0.000004, q = 0.000006; p = 0.000867, q = 0.000683, respectively). Moreover, these same measurements exhibited strong correlations with an established morphometric parameter of muscle atrophy (myofiber cross-sectional area), as determined by histological-based morphometric analysis (r = 0.831, p = 2 × 10-12; r = 0.6959, p = 2 × 10-8; and r = 0.7220; p = 4 × 10-9, respectively). Finally, the genetic deletion of gpr27, an orphan G-protein coupled receptor (GPCR), exacerbated the atrophy of skeletal muscle in aged animals, as evidenced by both sEIM and histology. In conclusion, the data here show that surface EIM techniques can effectively discriminate between healthy young and sarcopenic aged muscle as well as the advanced atrophied muscle in the gpr27 KO animals. Moreover, these studies show how EIM values correlate with cell size across the animals, making it potentially possible to utilize sEIM as a "virtual biopsy" in zebrafish to noninvasively assess myofiber atrophy, a valuable measure for muscle and gerontology research.

Electrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish.

Age-related deficits in skeletal muscle function, termed sarcopenia, are due to loss of muscle mass and changes in the intrinsic mechanisms underlying contraction. Sarcopenia is associated with falls, functional decline, and mortality. Electrical impedance myography (EIM)-a minimally invasive, rapid electrophysiological tool-can be applied to animals and humans to monitor muscle health, thereby serving as a biomarker in both preclinical and clinical studies. EIM has been successfully employed in several species; however, the application of EIM to the assessment of zebrafish-a model organism amenable to high-throughput experimentation-has not been reported. Here, we demonstrated differences in EIM measures between the skeletal muscles of young (6 months of age) and aged (33 months of age) zebrafish. For example, EIM phase angle and reactance at 2 kHz showed significantly decreased phase angle (5.3 ± 2.1 versus 10.7 ± 1.5°; p = 0.001) and reactance (89.0 ± 3.9 versus 172.2 ± 54.8 ohms; p = 0.007) in aged versus young animals. Total muscle area, in addition to other morphometric features, was also strongly correlated to EIM 2 kHz phase angle across both groups (r = 0.7133, p = 0.01). Moreover, there was a strong correlation between 2 kHz phase angle and established metrics of zebrafish swimming performance, including turn angle, angular velocity, and lateral motion (r = 0.7253, r = 0.7308, r = 0.7857, respectively, p < 0.01 for all). In addition, the technique was shown to have high reproducibility between repeated measurements with a mean percentage difference of 5.34 ± 1.17% for phase angle. These relationships were also confirmed in a separate replication cohort. Together, these findings establish EIM as a fast, sensitive method for quantifying zebrafish muscle function and quality. Moreover, identifying the abnormalities in the bioelectrical properties of sarcopenic zebrafish provides new opportunities to evaluate potential therapeutics for age-related neuromuscular disorders and to interrogate the disease mechanisms of muscle degeneration.

A Case Series and Literature Review of Subacute Infective Endocarditis: A Clinical Challenge.

Endocarditis is a life-threatening, relatively rare disease caused by an infection of the endocardial epithelium of the heart. Its clinical presentation is highly variable, depending on whether it presents acutely, subacutely, or chronically. Also, the wide array of causal etiologies and pathogens makes its diagnosis and treatment complex and challenging. The main etiological agents are Staphylococci and Streptococci, while fastidious microorganisms are infrequent agents of this pathology. Advancements in the identification of microorganisms with novel molecular techniques have revealed new previously unidentified pathogens. Despite their low frequency, these fastidious pathogens are highly relevant, as they have been associated with a higher rate of complications and mortality. Therefore, it is necessary to be aware of the wide array of clinical presentations and important considerations for the management of patients with subacute endocarditis with atypical microorganisms. In this article, we present a case series involving three different clinical presentations of subacute endocarditis with fastidious microorganisms, which required extensive medical management and surgical valve repair with favorable and unfavorable outcomes. We also engage in a review of the literature on their microbiology, diagnosis, and treatment.

External validation of the ACC/AHA ASCVD risk score in a Colombian population cohort.

No cardiovascular risk score has included Latin American patients in its development. The ACC/AHA ASCVD risk score has not been validated in Latin America; consequently, its predictive capacity in the population of the region is unknown. The aim of this study is to evaluate the discrimination capacity and calibration of the ACC/AHA ASCVD score to predict the 10-year risk of a cardiovascular event in a primary prevention cohort followed in a Colombian hospital. A retrospective cohort study was conducted in primary prevention patients belonging to an intermediate/high-risk and low-risk cohort without established atherosclerotic disease. Cardiovascular risk was calculated at inclusion. The calibration was analyzed by comparing observed and expected events in the different risk categories. A discrimination analysis was made using the area under the ROC curve and C statistic. A total of 918 patients were included-202 from the intermediate/high-risk and 716 from the low-risk cohort. The median cardiovascular risk was 3.6% (IQR 1.7-8.5%). At the 10-year follow-up, 40 events (4,4%) occurred. The area under the ROC curve was 0.782 (95% CI 0.71-0.85). The Hosmer-Lemeshow test did not show differences between expected and observed events. The ACC/AHA ASCVD score is calibrated and has good discrimination capacity in predicting 10-year risk of cardiovascular events in a Colombian population.

Patient-Derived Xenotransplant of CNS Neoplasms in Zebrafish: A Systematic Review.

Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor's molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.