Bentiromide

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal chronic disease. One of the Food and Drug Administration (FDA)-approved therapies for IPF, oral pirfenidone (PFD), has limited clinical applications owing to its systemic side effects. In contrast to oral administration, inhaled therapy offers enhanced therapeutic efficacy at the target organ while minimizing systemic side effects. However, its application has challenges, such as limited drug delivery to the distal lung region and rapid clearance. In this study, we developed pulmonary surfactant (PS)-based PFD-loaded nanovesicles (PFD-PSNVs) for targeted delivery to the lung area and prolonged retention and examined their safety, stability, and antifibrotic efficacy. PFD-PSNVs were prepared using the thin-film hydration and extrusion method. The mean size and zeta potential of PFD-PSNVs were 149.7 ± 10.1 nm and - 31.3 ± 2.3 mV, respectively. An in vitro antifibrotic study showed that PFD-PSNVs inhibited the expression of fibrotic factors such as p-ERK, p-SMAD2/3, and α-SMA proteins on fibroblasts activated by transforming growth factor-β1. When inhaled in mice using a nebulizer, the PFD-PSNVs remained in lung tissues for 24 h, whereas Arikayce, an FDA-approved liposomal formulation for inhalation, was eliminated within 6 h. In a bleomycin sulfate-induced IPF mouse model, inhalation treatment with PFD-PSNVs significantly reduced collagen deposition (76.2 ± 4.1 %, p < 0.01) and α-SMA expression (60.8 ± 3.7 %, p < 0.05) compared with inhalation treatment with the PFD-loaded CtrlNV (PFD-CNVs) formulation and oral administration of PFD. These results indicate that PSNVs have great potential as an inhaled drug delivery system for the treatment of IPF.

This study assessed the predictive value of pericarotid fat density (PFD) on carotid computed tomography angiography (CTA) for recurrent ischemic stroke or transient ischemic attack (TIA).

In total, 739 patients who underwent CTA between January 2014 and December 2021 were retrospectively included in this study. The PFD was evaluated using carotid CTA. The clinical endpoint was recurrent ischemic stroke or transient ischemic attack (TIA). The association between PFD and the endpoint was examined using Kaplan-Meier and Cox analyses. The combination model was established using significant clinical imaging risk factors and PFD. The predictive performance of the model was assessed using the receiver operating characteristic curve (ROC).

A total of 739 patients (mean age: 64.28±9.44 years old, 496 males) completed a median of 3.31 years of follow-up (interquartile range, 2.11-4.05). During the follow-up period, 166 patients reached the clinical end point. The event-free survival (EFS) rate was lower in the high-PFD group than in the low-PFD group (log-rank P＜0.001). Multivariate Cox analyses showed that the PFD was associated with recurrent stroke or TIA (all P＜0.05). The combination model demonstrated excellent performance in predicting the clinical endpoint (area under the curve = 0.89). In addition, the endpoint event prognostic value was significantly improved by adding the PFD to the baseline model (C-statistic improvement: 0.61-0.84).

CTA-assessed PFD is an independent predictor of recurrent stroke or TIA.