Temperature management in acute brain injury: A narrative review.

Temperature management has been used in patients with acute brain injury resulting from different conditions, such as post-cardiac arrest hypoxic-ischaemic insult, acute ischaemic stroke, and severe traumatic brain injury. However, current evidence offers inconsistent and often contradictory results regarding the clinical benefit of this therapeutic strategy on mortality and functional outcomes. Current guidelines have focused mainly on active prevention and treatment of fever, while therapeutic hypothermia (TH) has fallen into disuse, although doubts persist as to its effectiveness according to the method of application and appropriate patient selection. This narrative review presents the most relevant clinical evidence on the effects of TH in patients with acute neurological damage, and the pathophysiological concepts supporting its use.

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study.

BACKGROUND: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. METHODS: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. RESULTS: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection.

BACKGROUND: Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited understanding of the mechanistic pathways linked to post-acute pulmonary sequelae. AIM: To identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS. METHODS: Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO<60%) and age- and sex-matched individuals with mild-normal lung function (DLCO≥60%). A transcriptomic signature for optimal classification was constructed using random forest. Transcriptomic data were analyzed for biological pathway enrichment, cellular deconvolution, cell/tissue-specific gene expression and candidate drugs. RESULTS: RNA-seq identified 1357 differentially expressed transcripts. A model composed of 14 mRNAs allowed the optimal discrimination of survivors with severe diffusion impairment (AUC=0.979). Hallmarks of lung sequelae involved cell death signaling, cytoskeleton reorganization, cell growth and differentiation and the immune response. Resting natural killer (NK) cells were the most important immune cell subtype for the prediction of severe diffusion impairment. Components of the signature correlated with neutrophil, lymphocyte and monocyte counts. A variable expression profile of the transcripts was observed in lung cell subtypes and bodily tissues. One upregulated gene, TUBB4A, constitutes a target for FDA-approved drugs. CONCLUSIONS: This work defines the transcriptional programme associated with post-acute pulmonary sequelae and provides novel insights for targeted interventions and biomarker development.

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection.

Introduction: Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making. Aim: To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS. Methods: Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance. Results: After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-α were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1α, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a protein-based prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively. Conclusion: BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BAS-based protein testing emerges as a novel tool for risk assessment in the ICU.

Factores de riesgo de reingreso en UCI y análisis de la mortalidad intrahospitalaria / Risk factors for readmission to ICU and analysis of intra-hospital mortality

IntroducciónLos pacientes críticos, a pesar de la recuperación inicial en la unidad de cuidados intensivos (UCI), pueden precisar reingreso en UCI o incluso fallecer en el mismo episodio hospitalario. Los objetivos son: conocer la incidencia e identificar factores de riesgo de reingreso en UCI, y determinar la mortalidad hospitalaria.MétodosEstudio de cohortes observacional de todos los pacientes ingresados consecutivamente más de 24h en la UCI del Hospital Universitario de Getafe entre el 1-04-2018 y el 30-09-2018 y dados de alta vivos de su primer ingreso en UCI.ResultadosDe los 164 pacientes vivos al alta de UCI, 14 (8,5%) fueron reingresados en UCI (2,4% en≤48h). El riesgo ajustado de reingreso en UCI fue mayor en los pacientes con déficit neurológico discapacitante previo al ingreso en UCI (odds ratio [OR]: 7,96; intervalo de confianza del 95% [IC 95%]: 1,55-40,92) o que recibieron fármacos vasoactivos (OR: 5,07; IC 95%: 1,41-18,29) durante su estancia en UCI. Los pacientes reingresados tuvieron mayor mortalidad hospitalaria (4 de 14 [29%] versus 5 de 150 [3%], p<0,001) y mayor estancia hospitalaria (74,5 [37,5-99,75] días versus 16 [9-34] días, mediana [rango intercuartílico], p=0,001).ConclusionesLos pacientes con déficit neurológico discapacitante previo al ingreso hospitalario o que recibieron fármacos vasoactivos durante la estancia en UCI tienen mayor riesgo de reingreso en UCI, lo que aumenta la estancia y la mortalidad hospitalaria.

Risk factors for readmission to ICU and analysis of intra-hospital mortality. / Factores de riesgo de reingreso en UCI y análisis de la mortalidad intrahospitalaria.

INTRODUCTION: Critical patients, despite initial recovery in the intensive care unit (ICU), may require readmission to the ICU or even die in the same hospital episode. The objectives are to determine the incidence and to identify risk factors for ICU readmission, and to determine hospital mortality. METHODS: Observational cohort study of all patients admitted consecutively for more than 24hours to the ICU of the University Hospital of Getafe between April 1, 2018 and September 30, 2018 and discharged alive from their first ICU admission. RESULTS: Of the 164 patients alive at ICU discharge, 14 (8.5%) were readmitted to ICU (2.4% at≤48hours). The adjusted risk of ICU readmission was higher in patients with disabling neurological deficits prior to ICU admission [odds ratio (OR) 7.96, 95% confidence interval (CI) 1.55-40.92] or who received vasoactive drugs (OR 5.07, 95% CI 1.41-18.29) during their ICU stay. Readmitted patients had higher hospital mortality (4 of 14 [29%] versus 5 of 150 [3%], P<.001) and longer hospital stay (74.5 [37.5-99.75] days versus 16 [9-34] days, median [interquartile range], P=.001). CONCLUSIONS: Patients with disabling neurological deficits prior to hospital admission or who received vasoactive drugs during their ICU stay have a higher risk of readmission to the ICU, which increases hospital stay and mortality.

CIBERESUCICOVID: un proyecto estratégico para una mejor comprensión y manejo clínico de la COVID-19 en pacientes críticos / CIBERESUCICOVID: A strategic project for a better understanding and clinical management of COVID-19 in critical patients

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