Diagnostic performance of cardiopulmonary ultrasound performed by the emergency physician in the management of acute dyspnea.

OBJECTIVE: The etiologic diagnosis of acute dyspnea in the emergency department (ED) remains difficult, especially for elderly patients or those with previous cardiorespiratory medical history. This may lead to inappropriate treatment and potentially a higher mortality rate. Our objective was to evaluate the performance of cardiopulmonary ultrasound compared with usual care for the etiologic diagnosis of acute dyspnea in the ED. METHODS: Patients admitted to the ED for acute dyspnea underwent upon arrival a cardiopulmonary ultrasound performed by an emergency physician, in addition to standard care. The performances of the clinical examination, chest x-ray, N-terminal brain natriuretic peptide (NT-proBNP), and cardiopulmonary ultrasound were compared with the final diagnosis made by 2 independent physicians. RESULTS: One hundred thirty patients were analyzed. For the diagnosis of acute left-sided heart failure, cardiopulmonary ultrasound had an accuracy of 90% (95% confidence interval [CI], 84-95) vs 67% (95% CI, 57-75), P = .0001 for clinical examination, and 81% (95% CI, 72-88), P = .04 for the combination "clinical examination-NT-proBNP-x-ray". Cardiopulmonary ultrasound led to the diagnosis of pneumonia or pleural effusion with an accuracy of 86% (95% CI, 80-92) and decompensated chronic obstructive pulmonary disease or asthma with an accuracy of 95% (95% CI, 92-99). Cardiopulmonary ultrasound lasted an average of 12 ± 3 minutes. CONCLUSIONS: Cardiopulmonary ultrasounds performed in the ED setting allow one to rapidly establish the etiology of acute dyspnea with an accuracy of 90%.

CHK1 as a therapeutic target to bypass chemoresistance in AML.

The nucleoside analog cytarabine, an inhibitor of DNA replication fork progression that results in DNA damage, is currently used in the treatment of acute myeloid leukemia (AML). We explored the prognostic value of the expression of 72 genes involved in various aspects of DNA replication in a set of 198 AML patients treated by cytarabine-based chemotherapy. We unveiled that high expression of the DNA replication checkpoint gene CHEK1 is a prognostic marker associated with shorter overall, event-free, and relapse-free survivals and determined that the expression of CHEK1 can predict more frequent and earlier postremission relapse. CHEK1 encodes checkpoint kinase 1 (CHK1), which is activated by the kinase ATR when DNA replication is impaired by DNA damage. High abundance of CHK1 in AML patient cells correlated with higher clonogenic ability and more efficient DNA replication fork progression upon cytarabine treatment. Exposing the patient cells with the high abundance of CHK1 to SCH900776, an inhibitor of the kinase activity of CHK1, reduced clonogenic ability and progression of DNA replication in the presence of cytarabine. These results indicated that some AML cells rely on an efficient CHK1-mediated replication stress response for viability and that therapeutic strategies that inhibit CHK1 could extend current cytarabine-based treatments and overcome drug resistance. Furthermore, monitoring CHEK1 expression could be used both as a predictor of outcome and as a marker to select AML patients for CHK1 inhibitor treatments.