Serum amyloid a1/toll-like receptor-4 Axis, an important link between inflammation and outcome of TBI patients

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability world-wide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patientsThis work was supported by grants from Fundación Mutua Madrileña and Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet CP14/00008; CPII19/00005; PI16/00735; PI19/00082) to JE, RYC2019-026870-I to JMR and PI18/01387 to A

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Protocolo gerenciado de tratamento do potencial doador falecido reduz incidência de parada cardíaca antes do explante dos órgãos

OBJETIVO: Avaliar o efeito da aplicação de um protocolo gerenciado de manutenção de potenciais doadores falecidos de múltiplos órgãos em duas unidades hospitalares. MÉTODOS: Estudo antes (Fase 1)/depois (Fase 2) realizado em dois hospitais gerais que incluiu, consecutivamente, os potenciais doadores ingressados em duas unidades de terapia intensiva. Na Fase 1 (16 meses), os dados foram coletados retrospectivamente e as medidas de manutenção do potencial doador foram instituídas a critério do intensivista. Na Fase 2 (12 meses), a coleta de dados foi prospectiva e a manutenção foi guiada por um protocolo gerenciado. As duas fases foram comparadas entre si de acordo com variáveis demográficas, variáveis fisiológicas no diagnóstico da morte encefálica e ao final do processo, tempo necessário para realização do exame confirmatório de morte encefálica e final do processo, aderência aos conjuntos de medidas essenciais de manutenção (pacotes), perdas por parada cardíaca, perdas por negativa familiar, perdas por contraindicação e taxa de conversão de potenciais doadores em doadores reais. Foram aplicados os testes de t-Student e do qui-quadrado, e o valor de p<0,05 foi considerado significativo. RESULTADOS: Identificaram-se 42 potenciais doadores (18 na Fase 1 e 24 na Fase 2). Houve diminuição do tempo entre a primeira exploração clínica e o explante (Fase 1: 35,0±15,5 horas versus Fase 2: 24,6±6,2 horas; p=0,023). Houve aumento na aderência em 10 dos 19 itens essenciais de manutenção, e redução nas perdas por parada cardíaca (Fase 1: 27,8 versus 0% na Fase 2; p=0,006) com aumento de doadores reais (Fase 1: 44,4 versus 75% na Fase 2; p=0,044). Não houve mudança nas perdas por negativa familiar ou por contraindicação médica. CONCLUSÃO: A adoção de um protocolo gerenciado promove a aplicação de medidas essenciais no cuidado do potencial doador falecido e pode reduzir as perdas de potenciais doadores por parada cardíaca

Protocolo gerenciado de tratamento do potencial doador falecido reduz incidência de parada cardíaca antes do explante dos órgãos A managed protocol for treatment of deceased potential donors reduces the incidence of cardiac arrest before organ explant

OBJETIVO: Avaliar o efeito da aplicação de um protocolo gerenciado de manutenção de potenciais doadores falecidos de múltiplos órgãos em duas unidades hospitalares. MÉTODOS: Estudo antes (Fase 1)/depois (Fase 2) realizado em dois hospitais gerais que incluiu, consecutivamente, os potenciais doadores ingressados em duas unidades de terapia intensiva. Na Fase 1 (16 meses), os dados foram coletados retrospectivamente e as medidas de manutenção do potencial doador foram instituídas a critério do intensivista. Na Fase 2 (12 meses), a coleta de dados foi prospectiva e a manutenção foi guiada por um protocolo gerenciado. As duas fases foram comparadas entre si de acordo com variáveis demográficas, variáveis fisiológicas no diagnóstico da morte encefálica e ao final do processo, tempo necessário para realização do exame confirmatório de morte encefálica e final do processo, aderência aos conjuntos de medidas essenciais de manutenção (pacotes), perdas por parada cardíaca, perdas por negativa familiar, perdas por contraindicação e taxa de conversão de potenciais doadores em doadores reais. Foram aplicados os testes de t-Student e do qui-quadrado, e o valor de pOBJECTIVE: To assess the effect of the application of a managed protocol for the maintenance care of deceased potential multiple organ donors at two hospitals. METHODS: A before (Phase 1)/after (Phase 2) study conducted at two general hospitals, which included consecutively potential donors admitted to two intensive care units. In Phase 1 (16 months), the data were collected retrospectively, and the maintenance care measures of the potential donors were instituted by the intensivists. In Phase 2 (12 months), the data collection was prospective, and a managed protocol was used for maintenance care. The two phases were compared in terms of their demographic variables, physiological variables at diagnosis of brain death and the end of the process, time to performance of brain death confirmatory test and end of the process, adherence to bundles of maintenance care essential measures, losses due to cardiac arrest, family refusal, contraindications, and the conversion rate of potential into actual donors. Student's t- and chi-square tests were used, and p-value < 0.05 was considered to be significant. RESULTS: A total of 42 potential donors were identified (18 in Phase 1 and 24 in Phase 2). The time interval between the first clinical assessment and the recovery decreased in Phase 2 (Phase 1: 35.0±15.5 hours versus Phase 2: 24.6±6.2 hours; p = 0.023). Adherence increased to 10 out of the 19 essential items of maintenance care, and losses due to cardiac arrest also decreased in Phase 2 (Phase 1: 27.8 versus 0% in Phase 2; p = 0.006), while the convertion rate increased (Phase 1: 44.4 versus 75% in Phase 2; p = 0.044). The losses due to family refusal and medical contraindication did not vary. CONCLUSION: The adoption of a managed protocol focused on the application of essential measures for the care of potential deceased donors might reduce the loss of potential donors due to cardiac arrest

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave : the global UNITE-COVID study

Purpose To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality