Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease.

BACKGROUND AND AIMS: Phenylacetylglutamine (PAG), a gut microbiota metabolite, has recently been found to be associated with major adverse cardiovascular events. In this study, we analyzed the relationship between plasma PAG and coronary atherosclerotic severity assessed by coronary computed tomographic angiography (CCTA). METHODS: We enrolled consecutive patients with suspected coronary artery disease (CAD) who underwent CCTA. Plasma PAG was measured by mass spectrometry. Coronary atherosclerotic severity was evaluated based on plaque burden and plaque vulnerability. Plaque burden was quantified as percent atheroma volume (PAV), CCTA-derived SYNTAX score (CT-SYNTAX) and CAD reporting and data system score (CAD-RADS). Plaque vulnerability was evaluated by the presence of adverse characteristics. RESULTS: A total of 686 patients were enrolled. The patients were divided into two groups based on median plasma PAG (3.25 µM). A correlation was found between plasma PAG and PAV (r = 0.499, p < 0.01). Patients with obstructive CAD (CAD-RADS>3) and high coronary lesion complexity (CT-SYNTAX≥23) had higher plasma PAG (2.04 vs. 3.8 µM and 2.85 vs. 4.49 µM, respectively; p < 0.01 for all). After adjustment for confounding factors, plasma PAG remained associated with PAV (ß: 0.98, p < 0.01), and patients in the higher PAG group had higher risks of obstructive CAD (odds ratio [OR]: 1.88, p < 0.01) and high coronary lesion complexity (OR: 1.47; p < 0.01). In addition, a high plasma PAG level (≥3.25 µM) was not an independent predictor of the presence of high-risk plaques. CONCLUSIONS: There was an independent association between plasma PAG levels and the coronary atherosclerotic burden among patients with suspected CAD.

Hypoxic targeting and activating TH-302 loaded transcatheter arterial embolization microsphere.

The tumor-derived and transcatheter arterial chemoembolization (TACE) induced hypoxia microenvironment is closely related to the poor prognosis of hepatocellular carcinoma (HCC). In this study, hypoxia-activated prodrug TH-302 loaded poly(lactic-co-glycolic acid) (PLGA)-based TACE microspheres were prepared to treat HCC through localized and sustained drug delivery. TH-302 microspheres with three different sizes were fabricated by an oil-in-water emulsion solvent evaporation method and characterized by scanning electron microscopy (SEM), infrared spectra (IR), X-ray diffractometer (XRD), and drug release profiles. The in vitro antitumor potential was firstly evaluated in an HepG2 cell model under normoxic and hypoxic conditions. Then, a VX-2 tumor-bearing rabbit model was established and performed TACE to investigate the in vivo drug tissue distribution and antitumor efficiency of TH-302 microspheres. Blood routine examination and histopathological examinations were also conducted to evaluate the safety of TH-302 microspheres. TH-302 microspheres with particle size 75-100 µm, 100-200 µm, and 200-300 µm were prepared and characterized by sphere morphology and sustained drug release up to 360 h. Compared with TH-302, the microspheres exhibited higher cytotoxicity, cell apoptosis, and cell cycle S phase retardation in HepG2 cells under hypoxic conditions. The microspheres also displayed continuous drug release in the liver tissue and better anti-tumor efficiency compared with TH-302 injection and lipiodol. Meanwhile, no serious toxicity appeared in the duration of treatment. Therefore, TH-302 microspheres showed to be feasible and effective for TACE and hold promise in the clinical for HCC chemoembolization therapy.

Diagnostic Value of Dual-input Computed Tomography Perfusion on Detecting Bronchial-Pulmonary Artery Fistula in Tuberculosis Patients with Massive Hemoptysis.

RATIONALE AND OBJECTIVES: This prospective study aimed to evaluate the diagnostic performance of dual-input computed tomography perfusion technique (DI-CTP) in identifying the bronchial-pulmonary artery fistula in patients tuberculosis with massive hemoptysis. MATERIAL AND METHODS: Twenty patients with tuberculosis with massive hemoptysis were enrolled from January 2015 to December 2015. The association between DI-CTP parameters and the diagnostic outcomes of digital subtraction angiography was assessed. Diagnostic efficacy of DI-CTP was evaluated by receiver operating curve (ROC) analyses using the diagnostic outcomes of digital subtraction angiography, which is the gold standard for identifying bronchial-pulmonary artery fistula. RESULTS: Compared to lung segments with normal blood flow (n = 304), those with bronchial-pulmonary artery fistula (n = 164) had a reduced pulmonary flow value, perfusion index (PI) value, and an elevated bronchial artery (BF) value in the DI-CTP scan, which was further confirmed by multivariate logistic regression. ROC analysis showed that PI and bronchial artery has an excellent diagnostic performance (both area under the ROC curve > 0.9, P < .001) and high sensitivity and specificity (from 0.79 to 0.95 at the optimal cutoff). PI has the best diagnostic performance, with an overall diagnostic accuracy of 0.91. CONCLUSIONS: DI-CTP scan possesses the diagnostic value for detecting bronchial-pulmonary artery fistula in patients with tuberculosis with massive hemoptysis, providing an alternative diagnostic method.