RESUMEN
Sarcomas are rare malignancies with over 100 distinct histological subtypes. Their rarity and heterogeneity pose significant challenges to identifying effective therapies, and approved regimens show varied responses. Novel, personalized approaches to therapy are needed to improve patient outcomes. Patient-derived tumor organoids (PDTOs) model tumor behavior across an array of malignancies. We leverage PDTOs to characterize the landscape of drug resistance and sensitivity in sarcoma, collecting 194 specimens from 126 patients spanning 24 distinct sarcoma subtypes. Our high-throughput organoid screening pipeline tested single agents and combinations, with results available within a week from surgery. Drug sensitivity correlated with clinical features such as tumor subtype, treatment history, and disease trajectory. PDTO screening can facilitate optimal drug selection and mirror patient outcomes in sarcoma. We could identify at least one FDA-approved or NCCN-recommended effective regimen for 59% of the specimens, demonstrating the potential of our pipeline to provide actionable treatment information.
RESUMEN
Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient out-comes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from tissue collection. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how PDTO drug screening can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we were able to identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline. Highlights: Standardized organoid culture preserve unique sarcoma histopathological featuresDrug screening on patient-derived sarcoma organoids provides sensitivity information that correlates with clinical features and yields actionable information for treatment guidanceHigh-throughput screenings provide orthogonal information to genetic sequencingSarcoma organoid response to treatment correlates with patient response to therapyLarge scale, functional precision medicine programs for rare cancers are feasible within a single institution.
RESUMEN
Propósito: elaborar una propuesta técnica para mejorar el desempeño laboral del profesional de Enfermería. Objetivo: analizar el desempeño laboral del profesional de enfermería del Hospital Nacional "San Pedro", Departamento de Usulután, febrero a septiembre del 2019. Materiales y Métodos: se realizó un estudio descriptivo, transversal y cualitativo. Resultados: inadecuadas relaciones interpersonales, mal manejo del estrés y desconocimiento de la base legal de su rol función, desconocimiento de las cualidades técnicas y personales del profesional en enfermería. Conclusiones: los factores problemas de enfermería son influenciados por las relaciones interpersonales, el mal manejo del estrés y la falta de recursos, lo que inciden en la sobrecarga laboral. La mayoría del personal desconoce los instrumentos técnicos y jurídicos necesarios para ejercer su función como profesional. Todos los profesionales en enfermería conocen las cualidades técnicas y personales que deben de poseer. Un bajo porcentaje desconoce las funciones y responsabilidades en el ejercicio de su profesión. Recomendaciones: realizar capacitación continua de base legal, brindando información del marco legal vigente. Promover la comunicación efectiva entre todos los niveles. Identificación de problemas que impiden el desarrollo de sus obligaciones. Fomentar el trabajo en equipo, manejo del estrés, fortalecimiento de cualidades técnicas, y personales, así como el reforzamiento de sus funciones y responsabilidades como profesionales de enfermería
