ABSTRACT
The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport. Although brain endothelial cell function is crucial for brain homeostasis, their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia, astroglia, neurons, or even molecules such as amyloid beta, Tau, or alpha-synuclein. Alzheimer's disease is the most common neurodegenerative disease, and brain endothelial cell dysfunction has been reported by several groups. However, its impairment has barely been considered as a potential therapeutic target. Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease, highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment. Finally, we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.
ABSTRACT
Suspected or confirmed antibiotic allergy is a frequently encountered clinical circumstance that influences antimicrobial prescribing and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs (ASP) in several countries. This guidance document aims to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. A panel of eleven members of involved Scientific Societies with expertise in the management of patients with suspected or confirmed antibiotic allergy formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence and formulated graded recommendations when possible. The answers to all questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy is recommended to improve antibiotic selection and, consequently clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed β-lactam allergy were formulated. Recommendations on the implementation and monitoring of the impact of the guidelines were formulated. ASP and allergists should design and implement activities that facilitate the most adequate antibiotic use in these patients.(AU)
En la práctica clínica, un antecedente de alergia a los antibióticos, confirmada o sospechada, es frecuente y condiciona la selección de antibióticos, lo que requiere, con frecuencia, el uso de fármacos menos eficaces, más tóxicos o más caros que los antibióticos de primera línea. La optimización del uso de antibióticos en pacientes con este antecedente es una de las prioridades de los programas de optimización de uso de antibióticos (PROA) en varios países. Estas guías pretenden formular recomendaciones para evaluar de una manera sistemática a estos pacientes mediante una aproximación basada en la evidencia. Un panel multidisciplinar constituido por alergólogos, infectólogos, farmacéuticos hospitalarios e intensivistas formularon una serie de preguntas sobre el manejo de estos pacientes. Una documentalista realizó la revisión bibliográfica. Las preguntas se distribuyeron entre los miembros del grupo de trabajo, quienes seleccionaron las referencias más relevantes y formularon las correspondientes recomendaciones, que fueron revisadas y aprobadas por todos los miembros del grupo. Es necesaria una aproximación sistemática a los pacientes con antecedente de alergia a antibióticos para optimizar la selección del tratamiento antibiótico y mejorar los resultados clínicos de estos pacientes cuando precisan antibioterapia. El presente documento recomienda una estrategia de estratificación clínica del riesgo en 3 categorías. La recomendación de realizar evaluaciones complementarias se basa en el riesgo clínico y el antibiótico de primera línea necesario. Además, se formulan recomendaciones de tratamiento antibiótico empírico para los principales síndromes infecciosos en pacientes con alergia confirmada o sospechada. Finalmente se formulan recomendaciones sobre la implementación y monitorización del impacto de las recomendaciones de la guía. Los programas PROA y los alergólogos deben trabajar...(AU)
