MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction.

Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twenty-seven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality.

MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival.

MicroRNAs (miRNAs) have remarkable potential as diagnostic and prognostic markers because of their roles in disease pathogenesis. miRNAs can be released into the bloodstream, where they are sufficiently stable to be detected noninvasively. Here, we prospectively evaluated serum levels of miR-21, miR-34a, miR-122, miR-181b, and miR-885-5p in patients with stable cirrhosis. Total RNA was extracted from the sera of patients with cirrhosis and healthy individuals, and the expression levels of the target miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction. Serum miRNAs levels were correlated with liver function parameters, etiology, and complications of cirrhosis. Circulating miR-34a, miR-122, and miR-885-5p levels were higher in patients with cirrhosis than in healthy individuals. These miRNAs were positively correlated with alanine aminotransferase and aspartate aminotransferase levels, and the relative expression levels were higher in hepatitis C virus-infected patients and lower in patients with Child-Pugh C cirrhosis. miR-122 and miR-885-5p levels were also positively correlated with γ-glutamyl transpeptidase concentrations. miR-21 was associated with transplant-free survival in univariate Cox regression analysis and remained independently associated with survival after adjustment for age, Child-Pugh classification, Model for End-stage Liver Disease score, and history of previous decompensation in multivariate Cox regression analysis. These data suggested that miR-34a, miR-122, and miR-885-5p levels may be more related to the inflammatory process and ongoing hepatocyte damage in patients with cirrhosis. Moreover, miR-21 levels were independently associated with shorter transplant-free survival and may be used as a prognostic tool in outpatients with stable cirrhosis.

From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis.

INTRODUCTION: Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis. METHODS: This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group. RESULTS: Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF. CONCLUSIONS: The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.

Avaliação prognóstica precoce da asma aguda na sala de emergência / Early prognosis of acute asthma in the emergency room

OBJETIVO: Estudar medidas clínicas e funcionais pulmonares utilizadas nos primeiros quinze minutos de manejo da asma aguda em um serviço de emergência, para predição prognóstica. MÉTODOS: Estudo de coorte, prospectivo, que incluiu pacientes consecutivos com asma aguda, com idades entre doze e 55 anos e medida do pico de fluxo expiratório menor ou igual a 50 por cento do previsto. Realizaram-se avaliações na admissão, aos quinze minutos e em quatro horas após o início do tratamento. O tratamento incluiu salbutamol e ipratrópio, administrados por aerossol dosimetrado com espaçador, e 100 mg de hidrocortisona intravenosa. O desfecho favorável foi definido pelo pico de fluxo expiratório maior ou igual a 50 por cento do previsto após a quarta hora de tratamento, e o desfecho desfavorável pelo pico de fluxo expiratório menor que 50 por cento do previsto. RESULTADOS: Tiveram desfecho favorável 27 pacientes e desfavorável 24. A análise multivariada identificou o pico de fluxo expiratório em porcentagem do previsto aos quinze minutos como variável mais preditiva. O pico de fluxo expiratório maior ou igual a 40 por cento aos quinze minutos mostrou significativa contribuição em predizer desfecho favorável (sensibilidade = 0,74, especificidade = 1,00 e valor preditivo positivo = 1,00). O pico de fluxo expiratório menor que 30 por cento aos quinze minutos contribuiu para predizer desfecho desfavorável (sensibilidade = 0,54, especificidade = 0,93 e valor preditivo positivo = 0,87). CONCLUSÃO: O estudo sugeriu que a medida do pico de fluxo expiratório aos quinze minutos do manejo da asma aguda em um serviço de emergência é um instrumento útil para avaliação prognóstica.

Early prognosis of acute asthma in the emergency room.

OBJECTIVE: To evaluate clinical and pulmonary function measurements taken in the first fifteen minutes of the assessment of acute asthma in the emergency room and used for prognostic purposes. METHODS: A prospective cohort study involving consecutive patients with acute asthma. Only patients who were between the ages of 12 and 55 and presented peak expiratory flow rates < or = 50% of predicted were included. Evaluations were performed upon admission, then again at 15 minutes and 4 hours after the initiation of treatment. Treatment included albuterol and ipratropium delivered by metered-dose inhaler with a spacer, together with 100 mg of intravenous hydrocortisone. Favorable outcomes were defined as peak expiratory flow > or = 50% of predicted after 4 hours of treatment, and unfavorable outcomes were defined as peak expiratory flow < 50% after 4 hours of treatment. RESULTS: Favorable outcomes were seen in 27 patients, and unfavorable outcomes were seen in 24 patients. In the multivariate analysis, peak expiratory flow as percentage of predicted was identified as the variable with the highest predictive value. A peak expiratory flow > or = 40% after 15 minutes of treatment showed significant power in predicting a favorable outcome (sensitivity = 0.74, specificity = 1.00, and positive predictive value = 1.00). A peak expiratory flow < 30% after 15 minutes of treatment was predictive of a poor outcome (sensitivity = 0.54, specificity = 0.93, and positive predictive value = 0.87). CONCLUSION: Our results suggest that measuring peak expiratory flow after 15 minutes of management in the emergency room is a useful tool for predicting outcomes in cases of acute asthma.

Incidência de infecção viral do trato respiratório em asma aguda atendida em sala de emergência / Incidence of viral infection of the respiratory tract in acute asthma patients treated in the emergency room

OBJETIVO: Avaliar a incidência de infecção viral em asma aguda em pacientes atendidos em setor de adultos de um serviço de emergência. MÉTODOS: Conduzimos um estudo de coorte de pacientes que se apresentaram com asma aguda no setor de adultos do Serviço de Emergência do Hospital de Clínicas de Porto Alegre (idade > 12 anos). Um aspirado nasofaríngeo foi obtido para detecção de antígenos com a técnica de coloração de imunofluorescência indireta para os vírus sincicial respiratório, adenovírus, influenza e parainfluenza tipos 1, 2, 3 e 4. Foram coletados dados referentes a características demográficas, história médica pregressa, crise que levou à atual visita ao serviço de emergência e desfechos da crise. RESULTADOS: No período de março a julho de 2004, 49 pacientes foram examinados para infecção viral do trato respiratório. Foram identificados vírus respiratórios em 6 pacientes (3 com adenovírus, 2 com influenza A e 1 com parainfluenza tipo 1). Os pacientes com infecção viral do trato respiratório apresentaram média de idade de 61,7 ± 11,5 anos, enquanto que os pacientes sem infecção viral apresentaram média de idade de 41,7 ± 20,9 anos (p = 0,027). Não houve outras diferenças significativas quanto às características clínicas e desfechos. CONCLUSÃO: Este estudo mostra uma incidência de 12,24 por cento de infecção viral do trato respiratório na asma aguda em pacientes com idade igual ou maior que doze anos atendidos em sala de emergência, o que confirma a infecção viral como um desencadeante nessa faixa etária.