A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Early postoperative mortality in liver transplant recipients involving indications other than hepatocellular carcinoma. A retrospective cohort study.

AIMS: To analyze the perioperative differences in a consecutive cohort of liver transplant recipients (LTRs) classified according to the indication of transplantation, and assess their impact upon early mortality 90 days after transplantation. DESIGN: A retrospective cohort study was carried out. SCOPE: A single university hospital. PATIENTS: A total of 892 consecutive adult LTRs were included from January 1995 to December 2017. Recipients with acute liver failure, retransplantation or with grafts from non-brain death donors were excluded. Two cohorts were analyzed according to transplant indication: hepatocellular carcinoma (HCC-LTR) versus non-carcinoma (non-HCC-LTR). MAIN VARIABLES OF INTEREST: Recipient early mortality was the primary endpoint. The pretransplant recipient and donor characteristics, surgical time data and postoperative complications were analyzed as independent predictors. RESULTS: The crude early postoperative mortality rate related to transplant indication was 13.3% in non-HCC-LTR and 6.6% in HCC-LTR (non-adjusted HR=2.12, 95%CI=1.25-3.60; p=0.005). Comparison of the perioperative features between the cohorts revealed multiple differences. Multivariate analysis showed postoperative shock (HR=2.02, 95%CI=1.26-3.24; p=0.003), early graft vascular complications (HR=4.01, 95%CI=2.45-6.56; p<0.001) and multiorgan dysfunction syndrome (HR=18.09, 95%CI=10.70-30.58; p<0.001) to be independent predictors of mortality. There were no differences in early mortality related to transplant indication (adjusted HR=1.60, 95%CI=0.93-2.76; p=0.086). CONCLUSIONS: The crude early postoperative mortality rate in non-HCC-LTR was higher than in HCC-LTR, due to a greater incidence of postoperative complications with an impact upon mortality (shock at admission to intensive care and the development of multiorgan dysfunction syndrome).

Pretransplant predictors of early mortality in adult recipients of liver transplantation in the MELD-Na Era. / Predictores pretrasplante de mortalidad precoz en receptores adultos de trasplante hepático en la era MELD-Na.

AIMS: To identify pretransplant predictors of early mortality (90 days after transplantation) and evaluate their discriminating capacity in adult liver transplant recipients (LTR). DESIGN: An observational, retrospective, nested cases-controls study from a consecutive cohort of LTRs was carried out. SETTING: University hospital. PATIENTS: All consecutive LTR between January 2003 and December 2016 were eligible for inclusion. Patients with acute liver failure, previous graft dysfunction, simultaneous multiple organ transplantation, non-heart beating donors, and those needing urgent retransplantation during the study period were excluded. The analysis comprised 471 patients. MAIN VARIABLES OF INTEREST: Pretransplant characteristics were the main variables of interest. The LTR were grouped according to the dependent variable (early mortality). Multivariate logistic regression analysis was conducted to identify predictors of early mortality. The discriminating capacity of the models obtained was evaluated by comparing ROC curves (models versus MELD-Na). RESULTS: The MELD-Na score (OR = 1.069, 95% CI = 1.014-1.127), age > 60 years (OR = 2.479, 95% CI = 1.226-5.015), and LTR height < 163cm (OR = 4.092, 95% CI = 2.115-7.917) were identified as independent predictors of early mortality. The cause of transplantation (hepatocellular carcinoma or decompensated cirrhosis) was identified as a confounding factor. CONCLUSIONS: In LTR due to decompensated cirrhosis, the MELD-Na score, age > 60 years, and height < 163cm are independent predictors of early mortality. These factors provide a better classification model than the MELD-Na score for early post-transplant mortality.

Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence.

OBJECTIVE: The goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of post-transplant tumor relapse and factors related to this complication. DESIGN: Retrospective study of a consecutive series of patients having had liver transplant for HCC. PATIENTS AND METHODOLOGY: Transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. RESULTS: The survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR=1,7944) (IC 95%=1,1332-2,8413) and the vascular invasion (OR=6,6346) (IC 95%=1,4624-30,1003) as risk factors of relapse. CONCLUSIONS: The liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion.

Early postoperative mortality in liver transplant recipients involving indications other than hepatocellular carcinoma. A retrospective cohort study / Mortalidad postoperatoria precoz en los receptores de trasplante hepático por indicaciones distintas al carcinoma hepatocelular (non-HCC). Estudio retrospectivo de cohortes

Aims: To analyze the perioperative differences in a consecutive cohort of liver transplant recipients (LTRs) classified according to the indication of transplantation, and assess their impact upon early mortality 90 days after transplantation. Design: A retrospective cohort study was carried out.ScopeA single university hospital. Patients: A total of 892 consecutive adult LTRs were included from January 1995 to December 2017. Recipients with acute liver failure, retransplantation or with grafts from non-brain death donors were excluded. Two cohorts were analyzed according to transplant indication: hepatocellular carcinoma (HCC-LTR) versus non-carcinoma (non-HCC-LTR). Main variables of interest: Recipient early mortality was the primary endpoint. The pretransplant recipient and donor characteristics, surgical time data and postoperative complications were analyzed as independent predictors. ResultsThe crude early postoperative mortality rate related to transplant indication was 13.3% in non-HCC-LTR and 6.6% in HCC-LTR (non-adjusted HR=2.12, 95%CI=1.25–3.60; p=0.005). Comparison of the perioperative features between the cohorts revealed multiple differences. Multivariate analysis showed postoperative shock (HR=2.02, 95%CI=1.26–3.24; p=0.003), early graft vascular complications (HR=4.01, 95%CI=2.45–6.56; p<0.001) and multiorgan dysfunction syndrome (HR=18.09, 95%CI=10.70–30.58; p<0.001) to be independent predictors of mortality. There were no differences in early mortality related to transplant indication (adjusted HR=1.60, 95%CI=0.93–2.76; p=0.086). Conclusions: The crude early postoperative mortality rate in non-HCC-LTR was higher than in HCC-LTR, due to a greater incidence of postoperative complications with an impact upon mortality (shock at admission to intensive care and the development of multiorgan dysfunction syndrome). (AU)

Objetivos: Analizar las diferencias perioperatorias de una cohorte de trasplantados hepáticos (LTR) clasificados por la indicación de trasplante, y evaluar su impacto sobre la mortalidad precoz (90 días postrasplante). Diseño: Estudio de cohorte retrospectivo. Ámbito: Institución universitaria. Pacientes: Desde 1995 hasta 2017 fueron incluidos 892 LTR. Se excluyeron los receptores con fallo hepático agudo, retrasplante o de donantes sin muerte cerebral. Se analizaron 2 cohortes según el motivo del trasplante: carcinoma hepatocelular (HCC-LTR) vs. causas diferente al carcinoma (non-HCC-LTR).Principales variables de interés: La variable principal fue la mortalidad precoz. Las características pretrasplante de receptores, donantes, tiempo quirúrgico y complicaciones postoperatorias se estudiaron como predictores independientes. Resultados: La mortalidad postoperatoria temprana bruta relacionada con la indicación de trasplante fue del 13,3% en non-HCC-LTR y del 6,6% en HCC-LTR (HR no ajustada: 2,12; IC 95%: 1,25-3,60; p=0,005). La comparación de características perioperatorias entre las cohortes mostró múltiples diferencias. El shock postoperatorio (HR: 2,02; IC 95%: 1,26-3,24), complicaciones vasculares tempranas del injerto (HR: 4,01; IC 95%: 2,45-6,56) y síndrome de disfunción multiorgánica (HR: 18,09; IC 95%: 10,70-30,58) fueron predictores independientes de mortalidad. La indicación de trasplante no mostró significación en el análisis multivariante (HR ajustada: 1,60; IC 95%: 0,93-2,76; p=0,086). Conclusiones: La mortalidad postoperatoria temprana bruta en non-HCC-LTR fue mayor que en HCC-LTR debido a la mayor incidencia de complicaciones postoperatorias con impacto en la mortalidad (shock al ingreso en la UCI y aparición del síndrome de disfunción multiorgánica). (AU)

[Acute liver failure in a hospital with a liver transplantation program]. / Fallo hepático agudo en un hospital con programa de trasplante hepático.

INTRODUCTION: Acute hepatic failure (AHF) is an uncommon entity but with high mortality. Liver transplantation has improved prognosis but is an aggressive treatment with high risk. Currently, there are no accurate criteria to differentiate between irreversible AHF and the possibility of hepatic regeneration. The aim of this study is to review the clinical characteristics indicating transplantation and the outcome of AHF in patients at our institution. PATIENTS AND METHOD: Descriptive and retrospective study of cases of AHF at our institution in the last 3 years. RESULTS: Eleven patients were studied. Mortality was lower in transplant recipients (23%; 2 out of 8) than in non-transplanted patients (67%; 2 out 3). Hepatic regeneration occurred in one patient. Overall mortality was 36% with a perioperative mortality of 13%. CONCLUSION: The indication of hepatic transplantation in patients with a poor prognosis, early stage acute liver failure, and a low grade of encephalopathy, and prior to the development of multiorgan failure could improve the results of transplantation and reduce perioperative mortality.