Usefulness of brain natriuretic peptide for predicting left atrial appendage thrombus in patients with unanticoagulated nonvalvular persistent atrial fibrillation

AbstractBackgroundThe CHADS2 scoring system is simple and widely accepted for predicting thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Although congestive heart failure (CHF) is a component of the CHADS2 score, the definition of CHF remains unclear. We previously reported that the presence of CHF was a strong predictor of left atrial appendage (LAA) thrombus. Therefore, the present study aimed to elucidate the relationship between LAA thrombus and the brain natriuretic peptide (BNP) level in patients with unanticoagulated NVAF.MethodsThe study included 524 consecutive patients with NVAF who had undergone transesophageal echocardiography to detect intracardiac thrombus before cardioversion between January 2006 and December 2008, at Hiroshima City Asa Hospital. The exclusion criteria were as follows: paroxysmal atrial fibrillation, unknown BNP levels, prothrombin time international normalized ratio ≥2.0, and hospitalization for systemic thromboembolism.ResultsReceiver operating characteristic analysis yielded optimal plasma BNP cut-off levels of 157.1pg/mL (area under the curve, 0.91; p<0.01) and 251.2pg/mL (area under the curve, 0.70; p<0.01) for identifying CHF and detecting LAA thrombus, respectively. Multivariate analyses demonstrated that a BNP level >251.2pg/mL was an independent predictor of LAA thrombus (odds ratio, 3.51; 95% confidence interval, 1.08–10.7; p=0.046).ConclusionsIn patients with unanticoagulated NVAF, a BNP level >251.2pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF

Lenvatinib for Anaplastic Thyroid Cancer

Background: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. Patients and methods: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. Results: At data cutoff, 17 patients with ATC were enrolled. All experienced >= 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%. Conclusion: In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC

High‐Density Lipoprotein Engineering for Eye‐Drop Treatment of Age‐Related Macular Degeneration

Eye-drop treatments of age-related macular degeneration (AMD) are desirable; however, no clinically approved eye drop has been reported to date. This study aim to evaluate the therapeutic activity of eye-drop instillation of a high-density lipoprotein (HDL) variant bearing a cell-penetrating peptide and neovasculature-targeted peptide (AsnGlyArg [NGR] peptide) in a mouse model at a dose of 0.6–0.85 µg protein/eye drop. The results reveal that the activity of the abovementioned variant was >10-fold higher than that of the previous variant lacking an NGR peptide. In addition, the anti-inflammatory activity, cholesterol-efflux capacity, and antiangiogenic activity of reconstituted HDL are significantly augmented by the attachment of these two peptides. The mechanism underlying this dramatic improvement is likely the expression of CD13, an NGR peptide receptor, on the cornea and conjunctiva in mice. CD13 mRNA/protein expression is also detected in cultured human corneal and conjunctival cells. These results demonstrate that NGR peptide is an unprecedented class of an absorption enhancer on the eye surface. Thus, HDL engineering is a potential strategy for developing eye drops to treat neovascular AMD by enhancing the ocular surface absorption and HDL functionalities