Accuracy of Several Lung Ultrasound Methods for the Diagnosis of Acute Heart Failure in the ED: A Multicenter Prospective Study.

BACKGROUND: Early appropriate diagnosis of acute heart failure (AHF) is recommended by international guidelines. This study assessed the value of several lung ultrasound (LUS) strategies for identifying AHF in the ED. METHODS: This prospective study, conducted in four EDs, included patients with diagnostic uncertainty based on initial clinical judgment. A clinical diagnosis score for AHF (Brest score) was quantified, followed by an extensive LUS examination performed according to the 4-point (BLUE protocol) and 6-, 8-, and 28-point methods. The primary outcome was AHF discharge diagnosis adjudicated by two senior physicians blinded to LUS measurements. The C-index was used to quantify discrimination. RESULTS: Among the 117 included patients, AHF (n = 69) was identified in 27.4%, 56.2%, 54.8%, and 76.7% of patients with the 4-point (two bilateral positive points), 6-point, 8-point (≥ 1 bilateral positive point), and 28-point (B-line count ≥ 30) methods, respectively. The C-index (95% CI) of the Brest score was 72.8 (65.3-80.3), whereas the C-index of the 4-, 6-, 8-, and 28-point methods were 63.7 (58.5-68.8), 72.4 (65.0-79.8), 74.0 (67.1-80.9), and 72.4 (63.9-80.9). The highest increase in the C-index on top of the BREST score was observed with the 8-point method in the whole population (6.9; 95% CI, 1.6-12.2; P = .010) and in the population with an intermediate Brest score, followed by the 6-point method. CONCLUSIONS: In patients with diagnostic uncertainty, the 6-point/8-point LUS method (using the 1 bilateral positive point threshold) improves AHF diagnosis accuracy on top of the BREST score. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03194243; URL: www.clinicaltrials.gov.

Structural insight into the inhibition of tubulin by vinca domain peptide ligands.

The tubulin vinca domain is the target of widely different microtubule inhibitors that interfere with the binding of vinblastine. Although all these ligands inhibit the hydrolysis of GTP, they affect nucleotide exchange to variable extents. The structures of two vinca domain antimitotic peptides--phomopsin A and soblidotin (a dolastatin 10 analogue)--bound to tubulin in a complex with a stathmin-like domain show that their sites partly overlap with that of vinblastine and extend the definition of the vinca domain. The structural data, together with the biochemical results from the ligands we studied, highlight two main contributors in nucleotide exchange: the flexibility of the tubulin subunits' arrangement at their interfaces and the residues in the carboxy-terminal part of the beta-tubulin H6-H7 loop. The structures also highlight common features of the mechanisms by which vinca domain ligands favour curved tubulin assemblies and destabilize microtubules.