ABSTRACT
RESUMEN Introducción: La utilidad de la resonancia magnética cardíaca (RMC) ha crecido ampliamente en los últimos años, en los cuales se han publicado distintos registros internacionales sobre su uso e impacto clínico. Sin embargo, no contamos con este tipo de información en Argentina. Objetivo: Evaluar indicaciones, protocolos utilizados, seguridad y consecuencias terapéuticas de la RMC en la República Argentina. Material y métodos: Se diseñó un registro prospectivo a nivel nacional con recolección de datos demográficos, indicaciones de RMC, complicaciones asociadas, diagnósticos y consecuencias terapéuticas. Resultados: Participaron 34 centros de 10 provincias de Argentina (85% centros privados, 59% centros con internación). Se incluyeron 1131 pacientes (edad 54 ± 18 años, 61% varones). Las principales indicaciones para el estudio de RMC fueron la miocardiopatía hipertrófica (13,9%) y la arritmia ventricular (12,3%). El 99,7% de los estudios fueron reportados sin complicaciones. Los resultados más frecuentes de la RMC fueron: normal (31,2%), miocardiopatía no isquémica (14,7%), miocardiopatía isquémico-necrótica (11,6%) y miocardiopatía hipertrófica (8,9%). La sospecha clínica fue confirmada en el 23,6% de los casos y la RMC generó un diagnóstico nuevo no sospechado en el 48,7% de los casos. Las consecuencias terapéuticas más frecuentes fueron el alta hospitalaria (31,6%) seguida por el cambio en la medicación (28,1%). Conclusiones: La RMC es un estudio ampliamente utilizado en Argentina, principalmente en centros privados, con un número muy bajo de complicaciones. Las principales indicaciones son las miocardiopatías (hipertrófica y dilatada) y la arritmia ventricular, y provee un diagnóstico nuevo no sospechado en casi la mitad de los casos. Se requieren de otros estudios en el futuro para evaluar las implicancias clínicas y terapéuticas.
ABSTRACT Background: The usefulness of cardiac magnetic resonance imaging (MRI) has greatly increased in the last years. Different international registries have been published on its use; however, there is no data available from Argentina. Objective: The aim of this study was to evaluate different indications, protocols, safety and therapeutic consequences of cardiac MRI in Argentina. Methods: A prospective national registry was designed with collection of demographic data, indications for cardiac MRI, associated complications, diagnoses and therapeutic consequences. Results: A total of 34 centers from 10 provinces of Argentina (85% private and 59% with inpatient capacity) participated in the study, including 1131 patients (mean age 54±18 years and 61% males). The main indications for cardiac MRI were hypertrophic cardiomyopathy (13.9%), and ventricular arrhythmia (12.3%). In 99.7% of cases, no study complications were reported. The most frequent results of cardiac MRI were: normal (31.2%), non-ischemic cardiomyopathy (14.7%), ischemic-necrotic cardiomyopathy (11.6%) and hypertrophic cardiomyopathy (8.9%). Clinical suspicion was confirmed in 23.6% of cases and cardiac MRI generated an unsuspected new diagnosis in 48.7% of cases. The main therapeutic consequences were hospital discharge (31.6%) followed by change in medication (28.1%). Conclusions: Cardiac MRI is widely used in Argentina, mainly in private centers with a very low incidence of complications. Cardiomyopathies (hypertrophic and dilated) and ventricular arrhythmia are its main indication, and it provides a new unsuspected diagnosis in almost half of the cases. Further studies are required to assess its clinical and therapeutic impact.
ABSTRACT
The CD40 receptor and its ligand CD40L is one of the most critical molecular pairs of the stimulatory immune checkpoints. Both CD40 and CD40L have a membrane form and a soluble form generated by proteolytic cleavage or alternative splicing. CD40 and CD40L are widely expressed in various types of cells, among which B cells and myeloid cells constitutively express high levels of CD40, and T cells and platelets express high levels of CD40L upon activation. CD40L self-assembles into functional trimers which induce CD40 trimerization and downstream signaling. The canonical CD40/CD40L signaling is mediated by recruitment of TRAFs and NF-κB activation, which is supplemented by signal pathways such as PI3K/AKT, MAPKs and JAK3/STATs. CD40/CD40L immune checkpoint leads to activation of both innate and adaptive immune cells via two-way signaling. CD40/CD40L interaction also participates in regulating thrombosis, tissue inflammation, hematopoiesis and tumor cell fate. Because of its essential role in immune activation, CD40/CD40L interaction has been regarded as an attractive immunotherapy target. In recent years, significant advance has been made in CD40/CD40L-targeted therapy. Various types of agents, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors and protein antagonist, have been developed and evaluated in early-stage clinical trials for treating malignancies, autoimmune diseases and allograft rejection. In general, these agents have demonstrated favorable safety and some of them show promising clinical efficacy. The mechanisms of benefits include immune cell activation and tumor cell lysis/apoptosis in malignancies, or immune cell inactivation in autoimmune diseases and allograft rejection. This review provides a comprehensive overview of the structure, processing, cellular expression pattern, signaling and effector function of CD40/CD40L checkpoint molecules. In addition, we summarize the progress, targeted diseases and outcomes of current ongoing and completed clinical trials of CD40/CD40L-targeted therapy.