Assessment of circulatory/respiratory status, other parameters, and clinical courseAt the time of though enrollment (day 0), the clinical conditions, cause of respiratory insufficiency, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Lung Injury Scale score were assessed [41,42]. Echocardiography was performed to measure the left ventricular ejection fraction, left ventricular end-diastolic dimension, interventricular septum thickness, E/A ratio, left atrial dimension, inferior vena cava diameter and its respiratory variation, presence of hypo/akinesis, valvular abnormality, left ventricular systolic/diastolic function, and the thermodilution hemodynamic assessment validity. Chest computed tomography was also conducted on the day of enrollment.

B-type natriuretic peptide (BNP) or N-terminal pro-BNP was measured on the day of enrollment and daily thereafter.From the day of enrollment to day 2, the circulatory/respiratory status and other parameters except for routine clinical workup were assessed; the clinical course, including respirator settings, Lung Injury Scale score [43], Sequential Organ Failure Assessment score, antithrombin activity level, serum procalcitonin level, daily fluid intake/output and balance, and therapeutic interventions (surgery, antibiotics, steroids, diuretics, renal replacement therapy, and so forth) were recorded daily.All patients were followed for 28 days after enrollment and assessed for 28-day all-cause mortality.

Determination of pathophysiological diagnostic differential of respiratory insufficiencyAt least three experts (intensive care, respiratology, and cardiology) retrospectively determined the pathophysiological mechanism of respiratory insufficiency: ALI/ARDS, increased pulmonary vascular permeability without or with increased pulmonary vascular hydrostatic pressure; cardiogenic edema, increased pulmonary capillary hydrostatic pressure without increased vascular permeability; and pleural effusion with atelectasis, no evidence of lung edema secondary to increased hydrostatic pressure or vascular permeability, as previously reported [7,44]. For this purpose, the experts particularly considered the patients’ medical history, clinical presentation and the course, chest computed tomography and radiography findings, echocardiography findings, and serum BNP or N-terminal pro-BNP and procalcitonin concentrations, and systemic inflammatory status.

The pulmonary capillary wedge pressure was not routinely Entinostat obtained in this study and any pressures measured depended on the attending physicians’ discretion and was only obtained for selected patients. The physicians also considered in particular the time course of all the preceding findings, including daily fluid intake/output and balance, hemodynamic parameters obtained from the thermodilution method, the requirement for systemic management and respiratory therapy, and the clinical responses to these treatments.