Identification of Factors Affecting Tacrolimus Trough Levels in Latin American Pediatric Liver Transplant Patients

Tacrolimus is the cornerstone in pediatric liver transplant immunosuppression. Despite close monitoring, fluctuations in tacrolimus blood levels affect safety and efficacy of immunosuppressive treatments. Identifying the factors related to the variability in tacrolimus exposure may be helpful in tailoring the dose. The aim of the present study was to characterize the clinical, pharmacological, and genetic variables associated with systemic tacrolimus exposure in pediatric liver transplant patients. De novo transplant patients with a survival of more than 1 month were considered for inclusion and were genotyped for cytochrome P450 3A5 (CYP3A5). Peritransplant clinical factors and laboratory covariates were recorded retrospectively between 1 month and 2 years after transplant, including alanine aminotransferase (ALT), aspartate aminotransferase, hematocrit, and tacrolimus predose steady-state blood concentrations collected 12 hours after tacrolimus dosing. A linear mixed effect (LME) model was used to assess the association of these factors and the log-transformed tacrolimus dose-normalized trough concentration (logC0/D) levels. Bootstrapping was used to internally validate the final model. External validation was performed in an independent group of patients who matched the original population. The developed LME model described that logC0/D increases with increases in time after transplant (β = 0.019, 95% confidence interval [CI], 0.010-0.028) and ALT values (β = 0.00030, 95% CI, 0.00002-0.00056), whereas logC0/D is significantly lower in graft CYP3A5 expressers compared with nonexpressers (β = −0.349, 95% CI, −0.631 to −0.062). In conclusion, donor CYP3A5 genotype, time after transplant, and ALT values are associated with tacrolimus disposition between 1 month and 2 years after transplant. A better understanding of tacrolimus exposure is essential to minimize the occurrence of an out-of-range therapeutic window that may lead to adverse drug reactions or acute rejection.Fil: Riva, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Woillard, Jean Baptiste. Inserm; FranciaFil: Distefano, Maximiliano. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Moragas, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dip, Marcelo Fabian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Halac, Esteban Tomas. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cáceres Guido, Paulo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Licciardone, Nieves. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bosaleh, Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: de Davila, María Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Imventarza, Oscar Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Artistas sobre outras Obras

Entre a pele da pintura e a pele do pintor, existe uma continuidade interrompida pelo encerramento da peça, em que o autor se despede e abre caminho aos novos participantes. Estes são seres políticos, pois são público, são relação. As quinze propostas de abordagem à obra de outros tantos artistas que aqui são apresentadas, neste número 35 da Revista Estúdio, transportam um desejo interior de uma expansão para os vivos, para novas relações, novos trânsitos, no círculo aberto das artesinfo:eu-repo/semantics/publishedVersio

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Detection and characterization of N-glycolyated gangliosides in Wilms tumor by immunohistochemistry

Gangliosides are glycolipids present on the cell surface. The N-glycolylated ganglioside NeuGc-GM3 has been described in some neoplasms, such as breast carcinoma and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in Wilms tumor by immunohistochemistry. Postchemotherapy tumors were grouped into different histologic subtypes considering the main preserved component. Formalin-fixed, paraffin-embedded tumor samples were cut into 5-mm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Sections from breast carcinoma were employed as positive controls. Presence of NeuGc-GM3 was evident in 22 of 25 (88%) cases. The staining was stronger in the epithelial component, with a membrane pattern and cytoplasmic diffusion. The stromal component expressed cytoplasmic NeuGc-GM3 in cells with rhabdomyoblastic differentiation. Tubules of adjacent renal tissue were also positive, but no expression of NeuGc-GM3 was detected in nontumoral fetal kidney. Until now, the expression of N-glycolylated gangliosides in pediatric solid tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of Wilms tumors, suggesting its potential utility as a specific target of immunotherapy.Fil: Scursoni, Alejandra M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Galluzzo, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Camarero, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Pozzo, Norma. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gabri, Mariano Rolando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Acosta, Cristina Mateo. Centro de Inmunología Molecular; CubaFil: Vázquez, Ana María. Centro de Inmunología Molecular; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Davila, María Teresa G.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Coaching Para El Aprendizaje Universitario - HU604 - 202100

Descripción: El curso Coaching para el Aprendizaje cuenta con dos unidades. La primera explora los servicios para el estudiante que ofrece la UPC, las normas que rigen los estudios en pregrado y las plataformas digitales a disposición de la comunidad académica de la universidad. Se busca la exploración y el descubrimiento, por parte del alumno, de las preguntas y respuestas más frecuentes que se hacen los jóvenes que se disponen a iniciar estudios de pregrado. De esta manera, el curso facilita el acceso a las condiciones de soporte externo al proceso de enseñanza - aprendizaje que brinda la universidad. En la segunda unidad del curso, se aplican técnicas de estudio para la organización de los materiales de enseñanza digitales, tomar apuntes durante las sesiones síncronas, hacer sumillas a documentos digitales, contar con un lugar adecuado para el estudio y organizar el tiempo para llevar una vida equilibrada. Mediante el uso de estas técnicas se busca promover hábitos de organización y estudio que faciliten el desarrollo de recursos personales orientados al aprendizaje activo y reflexivo. Mediante estos comportamientos, el curso promueve buenas prácticas de estudio. Propósito: El curso Coaching para el Aprendizaje ha sido diseñado con el propósito de permitir al futuro estudiante de 1pregrado contar con acceso a los recursos y servicios que brinda la universidad y desarrollar prácticas que facilita la inserción universitaria del ingresante a pregrado. El curso contribuye al desarrollo de la competencia Aprendizaje Autónomo, específicamente en la dimensión Contexto y Comportamiento a nivel ingresante

Rotaciones en Prácticas Psicológicas I - PS264 - 202102

Rotaciones en Prácticas Psicológicas I curso dirigido a estudiantes del 8° ciclo de la carrera de Psicología, es de índole teórico practico, mediante el cual se busca consolidar el desarrollo de competencias generales y específicas aplicadas al campo de la psicología. En este periodo el estudiante aplicará sus conocimientos en situaciones simuladas y reales, en intervenciones a nivel individual o grupal. Propósito: El curso permite integrar conocimientos teórico-prácticos, a través de la intervención basada en evidencia en 1diversos contextos. De igual manera, el curso le faculta desarrollar tres competencias: Pensamiento Crítico, Pensamiento innovador e Intervención todos en nivel 3. Pre‐Requisito: PS386 Externado en Procesos Laborales; PS396 Externado en Procesos Sociales y Promoción de la Salud; PS393 Intervenciones Psicológicas en la infancia y la Adolescencia El curso busca que el estudiante integre los aprendizajes previos, evalúe, diseñe y realice intervenciones basadas en evidencia científica, en el campo de su especialidad. Es relevante que la rotación del futuro profesional psicólogo le permita analizar la interacción de la persona en el entorno de la salud, enseñanza aprendizaje o de una organización. Es por ello, que corresponde al nivel de logro 3 de la competencia específica: Intervención. Competencia General: Pensamiento Crítico Nivel de logro: Nivel 3 Definición: Capacidad para explorar de manera exhaustiva problemas, ideas o eventos para formular conclusiones u opiniones sólidamente justificadas. Competencia General: Pensamiento innovador Nivel de logro: Nivel 3 Definición: Capacidad para detectar necesidades y oportunidades para generar proyectos o propuestas innovadoras, viables y rentables. Planifica y toma decisiones eficientes orientadas al objetivo del proyecto. Competencia Específica: Intervención Nivel de logro: Nivel 3 Definición: Aplica el plan de intervención psicológica diseñado como respuesta a las necesidades, complejidad y diversidad de los sistemas humanos