Síndrome de neurotoxicidad asociada a células inmunoefectoras: un enfoque terapéutico en el paciente crítico / Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill

La inmunoterapia con células T modificadas con receptor quimérico antígeno-específico (chimeric antigen receptor conocida como [CAR-T]) está emergiendo como un tratamiento prometedor para enfermedades hematológicas. Así, las CAR-T dirigidas contra el complejo de diferenciación 19 han demostrado gran eficacia antitumoral contra neoplasias de células B resistentes a terapias convencionales. Sin embargo, la activación dirigida de la respuesta inmunitaria desata en ciertos casos complicaciones específicas graves y potencialmente mortales. Entre ellas cabe destacar el síndrome de liberación de citoquinas y el síndrome de toxicidad neurológica asociado a la terapia con células inmunoefectoras (Immune-effector cell associated neurotoxicity syndrome conocido como ICANS), siendo este último el objetivo de nuestra revisión. Aunque los mecanismos fisiopatológicos que conducen al ICANS son poco conocidos, existen factores clínicos y biológicos que aumentan el riesgo de desarrollo de neurotoxicidad asociada a la terapia CAR-T. El tratamiento se basa en medidas de monitorización y soporte, tratamiento con anticonvulsivantes, corticosteroides e ingreso en los servicios de medicina intensiva de forma precoz. Este artículo proporciona una revisión exhaustiva de la literatura disponible sobre el ICANS desde una perspectiva multidisciplinar, incluyendo recomendaciones de intensivistas, neurólogos y hematólogos formados en el cuidado de adultos críticamente enfermos (AU)

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults (AU)

Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill.

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.

Estudio de mortalidad de pacientes en desconexión progresiva del ventilador / Mortality study in patients at weaning from mechanical ventilation

OBJETIVO: Explicar la mortalidad de pacientes con ventilación mecánica invasiva en el Servicio de Medicina Intensiva (SMI) y en el hospital. DISEÑO: Prospectivo de cohortes. Duración: 9 meses. ÁMBITO: SMI. PACIENTES: En ventilación mecánica en el SMI, desde la intubación hasta el alta del hospital. INTERVENCIONES: Ninguna. VARIABLES DE INTERÉS: Fecha de ingreso, día de la primera prueba de desconexión de la ventilación, días de ventilación mecánica, día de extubación final, días de estancia en el SMI y en el hospital, día de muerte o traslado del SMI, SAPS-3, clasificación del estudio WIND, día de muerte o alta del hospital. RESULTADOS: De 266 pacientes, 40 eran del grupo 0 de la clasificación WIND (15%; IC 95% 11-20%); 166 del grupo 1 (62%; IC 95% 56-68%); 38 del grupo 2 (14%; IC 95% 11-19%); y 22 del grupo 3 (8%; IC 95% 6-12%). Usando regresión logística, el grupo 3 tiene la más alta probabilidad de muerte en el hospital: grupo 3 vs. 1 (odds ratio 4,0; IC 95% 1,5-10,8; p = 0,007). Sin embargo, no se observaron diferencias en la mortalidad del grupo 3 vs. 1 empleando el método de regresión de Cox (hazard ratio 1,6; IC 95% 0,7-3,4; p=ns). CONCLUSIÓN: En nuestro estudio, y teniendo en cuenta el tiempo de exposición, la mortalidad es la misma entre los 3 diferentes grupos de pacientes que se han sometido a una prueba de desconexión de la ventilación

OBJECTIVE: To explain mortality in the ICU and in hospital among patients subjected to invasive mechanical ventilation. DESIGN: A prospective, 9-month observational cohort study was carried out. SETTING: A Department of Intensive Care Medicine. PATIENTS: Consecutive patients requiring invasive mechanical ventilation were followed-up on until hospital discharge or death. INTERVENTIONS: None. INTEREST VARIABLES: Date of admission, day of first spontaneous breathing test, length of mechanical ventilation, final extubation date, days in ICU, days in hospital or discharge from ICU, SAPS-3 score, WIND study classification, day of death, hospital discharge. RESULTS: There were 266 patients: 40 in group 0 of the WIND classification (15%; 95% CI 11-20%); 166 in group 1 (62%; 95% CI 56-68%); 38 in group 2 (14%; 95% CI 11-19%); and 22 in group 3 (8%; 95% CI 6-12%. Logistic regression analysis showed group 3 to have the highest hospital mortality (group 3 vs. group 1; odds ratio 4.0; 95% CI 1.5-10.8; P=.007). However, Cox regression analysis showed no significant differences (hazard ratio group 3 vs. group 1, 1.6; 95% CI 0.7-3.4; P=ns). CONCLUSION: In our study, considering exposure time, the probability of mortality was the same among the 3 different groups of patients with at least one spontaneous breathing test

Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill. / Síndrome de neurotoxicidad asociada a células inmunoefectoras: un enfoque terapéutico en el paciente crítico.

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.

Mortality study in patients at weaning from mechanical ventilation. / Estudio de mortalidad de pacientes en desconexión progresiva del ventilador.

OBJECTIVE: To explain mortality in the ICU and in hospital among patients subjected to invasive mechanical ventilation. DESIGN: A prospective, 9-month observational cohort study was carried out. SETTING: A Department of Intensive Care Medicine. PATIENTS: Consecutive patients requiring invasive mechanical ventilation were followed-up on until hospital discharge or death. INTERVENTIONS: None. INTEREST VARIABLES: Date of admission, day of first spontaneous breathing test, length of mechanical ventilation, final extubation date, days in ICU, days in hospital or discharge from ICU, SAPS-3 score, WIND study classification, day of death, hospital discharge. RESULTS: There were 266 patients: 40 in group 0 of the WIND classification (15%; 95% CI 11-20%); 166 in group 1 (62%; 95% CI 56-68%); 38 in group 2 (14%; 95% CI 11-19%); and 22 in group 3 (8%; 95% CI 6-12%. Logistic regression analysis showed group 3 to have the highest hospital mortality (group 3 vs. group 1; odds ratio 4.0; 95% CI 1.5-10.8; P=.007). However, Cox regression analysis showed no significant differences (hazard ratio group 3 vs. group 1, 1.6; 95% CI 0.7-3.4; P=ns). CONCLUSION: In our study, considering exposure time, the probability of mortality was the same among the 3 different groups of patients with at least one spontaneous breathing test.

El futuro de la Medicina Intensiva / The future of intensive medicine

Resumen Aunque una especialidad joven en comparación con otras disciplinas médicas, laMedicina Intensiva ocupa en la actualidad un papel clave en el proceso asistencial de muchospacientes. La experiencia ha demostrado que, para ofrecer una asistencia de calidad a lospacientes críticos, es necesario disponer de profesionales con una formación específica enMedicina Intensiva. En Europa se han dado pasos importantes hacia la homogeneización delos programas formativos de los distintos Estados miembros, pero es necesario dar un paso más,que es la creación de una especialidad primaria de Medicina Intensiva. La atención al enfermocrítico debe ser liderada por especialistas que hayan recibido una formación específica y completa,y posean las competencias profesionales necesarias para prestar una asistencia de lamáxima calidad a sus pacientes. El futuro de la especialidad presenta retos que habrá queafrontar con determinación, teniendo como objetivo principal satisfacer las necesidades de lapoblación (AU)

Abstract Although Intensive Care Medicine is a young specialty compared with other medicaldisciplines, it currently plays a key role in the process of care for many patients. Experiencehas shown that professionals with specific training in Intensive Care Medicine are needed toprovide high quality care to critically ill patients. In Europe, important steps have been takentowards the standardization of training programs of the different member states. However, itis now necessary to take one more step forward, that is, the creation of a primary specialtyin Intensive Care Medicine. Care of the critically ill needs to be led by specialists who havereceived specific and complete training and who have the necessary professional competencesto provide maximum quality care to their patients. The future of the specialty presents challengesthat must be faced with determination, with the main objective of meeting the needsof the population (AU)

[The future of intensive medicine]. / El futuro de la Medicina Intensiva.

Although Intensive Care Medicine is a young specialty compared with other medical disciplines, it currently plays a key role in the process of care for many patients. Experience has shown that professionals with specific training in Intensive Care Medicine are needed to provide high quality care to critically ill patients. In Europe, important steps have been taken towards the standardization of training programs of the different member states. However, it is now necessary to take one more step forward, that is, the creation of a primary specialty in Intensive Care Medicine. Care of the critically ill needs to be led by specialists who have received specific and complete training and who have the necessary professional competences to provide maximum quality care to their patients. The future of the specialty presents challenges that must be faced with determination, with the main objective of meeting the needs of the population.

Código ético de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) / Code of ethics of the Spanish Society of Intensive Care, Critical and Coronary Units (SEMICYUC)

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Adult respiratory distress syndrome caused by acute systemic lupus erythematosus.

A 34-year-old man, previously diagnosed as having an idiopathic diffuse glomerulonephritis, developed an acute, fulminating pulmonary disease which fulfilled clinical, radiological and physiological criteria for ARDS. He also fulfilled criteria for the diagnosis of systemic lupus erythematosus. High-dose corticosteroid therapy, artificial respiration and hemodialysis were instituted and were followed by marked clinical, radiological and physiological improvement, returning to normal 15 days after admission. We discuss here the role of immune complexes in the pathogenesis of acute pulmonary vasculitis of lupus erythematosus and suggest a role of corticosteroid pulse therapy in treating ARDS of this etiology.