Probability of weaning success in patients with different hemoglobin levels (<i>P</i> = 0.06 by the log-rank test).

<p>Probability of weaning success in patients with different hemoglobin levels (<i>P</i> = 0.06 by the log-rank test).</p

Study flow.

<p>Study flow.</p

A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease

<p>Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (<i>n</i> = 93) or placebo (<i>n</i> = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (−0.49%; <i>p</i> = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.</p

Cautious Application of Pleural N-Terminal Pro-B-Type Natriuretic Peptide in Diagnosis of Congestive Heart Failure Pleural Effusions among Critically Ill Patients

<div><p>Background and Objective</p><p>Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.</p><p>Methods</p><p>NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.</p><p>Results</p><p>One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001).</p><p>Conclusions</p><p>Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings.</p></div

Boxplots showing the minimum, 25th, 50th, and 75th percentiles, and the maximum pleural N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, by etiologies of pleural effusions.

<p>Outliers (open circles) and extremes (stars) are plotted separately.</p

Receiver operating characteristic curve of pleural N-terminal pro-B-type natriuretic peptide levels comparing patients with pleural effusions caused by congestive heart failure to those with pleural effusions attributable to other reasons.

<p>The area under the curve was 0.87 (95% confidence interval 0.81–0.92).</p

Characteristics of the study population.

<p>Data are presented as No. (%) or mean ± standard deviation.</p><p>*APACHE, Acute Physiology and Chronic Health Evaluation.</p>†<p>NT-proBNP, N-terminal pro-B-type natriuretic peptide.</p><p>Characteristics of the study population.</p

Etiologies of pleural effusions.

<p>*Effusions due to atelectasis, hepatic hydrothorax, or nephrotic syndrome.</p>†<p>Effusions due to chylothorax, connective tissue disease, hypothyroidism, lymphangioleiomyomatosis, subphrenic abscess, tuberculosis, or uremia.</p><p>Etiologies of pleural effusions.</p

Diagnostic information for pleural N-terminal pro-B-type natriuretic peptide concentrations in the diagnosis of pleural effusions caused by congestive heart failure.

<p>*NT-proBNP, N-terminal pro-B-type natriuretic peptide.</p>†<p>Optimal cutoff value determined by Youden index.</p><p>Diagnostic information for pleural N-terminal pro-B-type natriuretic peptide concentrations in the diagnosis of pleural effusions caused by congestive heart failure.</p