Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and children with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available.

Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and children with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available.

Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies / Resumen ejecutivo del Documento de consenso sobre diagnóstico y manejo de pacientes con inmunodeficiencias primarias

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and children with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available

Las inmunodeficiencias primarias (IDP) son unas enfermedades raras, frecuentemente infradiagnosticadas y potencialmente fatales. Las manifestaciones clínicas de las IDP pueden ser muy graves y ocasionar secuelas que empeoran la calidad de vida de los pacientes. Tradicionalmente, el tratamiento de las IDP ha sido fundamentalmente de soporte, con excepción del trasplante de progenitores hematopoyéticos y, más recientemente, la terapia génica. El descubrimiento de nuevos mecanismos patogénicos, el desarrollo de nuevas moléculas y fármacos biológicos y los avances en el conocimiento de las bases moleculares de estas enfermedades han abierto oportunidades para el tratamiento de esta afección. El objetivo de este documento es revisar el conocimiento actual y aportar recomendaciones para el diagnóstico y el tratamiento clínico de los pacientes adultos y pediátricos con IDP basado en la evidencia científica disponible y teniendo en cuenta la actual práctica y los retos futuros. Se realizó una revisión sistemática, que justifica los niveles de evidencia para cada recomendación

Infection in the process of organ donation

The difference between demand and supply has led transplant organizations to look for marginal donors, including those who could transmit infections to their recipients. This potential risk must be thoroughly evaluated to optimize the use of such organs without increasing the incidence of graft dysfunction and the morbidity and mortality of the recipient. This article aims to provide a general and up-to-date overview of this issue

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Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital / / Utilidad clínica de la determinación de concentraciones plasmáticas de voriconazol en un hospital universitario

INTRODUCTION: The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. METHODS: A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5 μg/mL. RESULTS: The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1 µg/mL in 10 (19.2%) and >5.5 µg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p = .005) and cystic fibrosis as the underlying disease (p = .04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1 µg/mL at the first TDM had a successful outcome (96%). CONCLUSIONS: Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics

INTRODUCCIÓN: Nuestro objetivo fue evaluar la utilidad clínica de la monitorización de la concentración plasmática (TMD) de voriconazol (VOR) en un hospital universitario. MÉTODOS: Revisión retrospectiva de las historias clínicas de 52 pacientes tratados con VOR en los que se realizó TDM. El intervalo terapéutico de la concentración plasmática de VOR fue definida entre 1 μg/mL y 5.5 μg/mL. RESULTADOS: Las condiciones subyacentes más frecuentes en la población de estudio fueron trasplante de pulmón (48,1%) y neoplasias hematológicas (26,9%). En la primera determinación de TMD de VOR estaban fuera del intervalo en 16 (30,7%) casos: < 1 µg/mL en 10 (19,2%) y > 5,5 µg/mL en 6 (11,5%). Once pacientes (21,2%) experimentaron debilidad muscular, éstos pacientes recibían tratamiento concomitante con corticosteroides. Los Factores asociados con bajos niveles de VOR observados fueron la edad menor a 30 años (p= 0,005) y la fibrosis quística (p = 0,04). Casi todos los pacientes que tenían concentraciones VOR > 1 µg/mL en la primera TDM tuvieron un resultado satisfactorio (96%). CONCLUSIONES: En 30% (16/52) de los pacientes, las concentraciones plasmáticas de VOR estaban fuera del intervalo terapéutico en la primera TDM. La edad menor a 30 años y la fibrosis quística fueron factores asociados con niveles bajos de VOR. Observamos una posible interacción entre corticoesteroides y voriconazol con debilidad muscular asociada en los pacientes tratados con ambos fármacos. Se necesitan estudios clínicos prospectivos en relación a las interacciones entre corticoesteroides y voriconazol

Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital.

INTRODUCTION: The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. METHODS: A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5µg/mL. RESULTS: The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1µg/mL in 10 (19.2%) and >5.5µg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1µg/mL at the first TDM had a successful outcome (96%). CONCLUSIONS: Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics.