Cost-effectiveness of follow-up invasive coronary angiography after percutaneous coronary stenting: a real-world observational cohort study in Japan.

OBJECTIVES: Follow-up invasive coronary angiography (FUICA) after percutaneous coronary intervention (PCI) has been shown to increase the rate of early coronary revascularisation without reducing the incidence of subsequent myocardial infarction or death. However, no studies have evaluated the cost-effectiveness of FUICA in patients after coronary stenting. Therefore, this study aimed to evaluate the cost-effectiveness of FUICA after PCI. DESIGN: Retrospective observational cohort study. SETTING: 497 hospitals. PARTICIPANTS AND INTERVENTIONS: Overall, 558 patients who underwent coronary artery stenting between April 2014 and March 2015 were matched and included in the invasive angiographic follow-up (AF) group (n=279), in which patients underwent FUICA 6-12 months after PCI, or in the clinical follow-up alone group (CF; n=279) using propensity scores. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the composite outcome of death, myocardial infarction, urgent coronary revascularisation, stroke or hospitalisation for the heart failure. The secondary endpoints included all-cause death, non-fatal myocardial infarction, urgent revascularisation, coronary artery bypass grafting, stroke, hospitalisation for the heart failure and any coronary revascularisation after a minimum of 6 months of follow-up. RESULTS: Costs were calculated as direct medical expenses based on medical fee billing information. The cumulative 3-year incidence of the primary endpoint was 5.3% in the AF group and 4.7% in the CF group (HR 1.02; 95% CI 0.47 to 2.20; p=0.98). The total incremental cost at the 3-year endpoint in the AF group was US$1874 higher than that in the CF group (US$8947±US$5684 vs US$7073±US$6360; p≤0.001). CONCLUSIONS: FUICA increased the costs but did not improve clinical benefits. Thus, FUICA is not economically more attractive than CF alone. TRIAL REGISTRATION NUMBER: UMIN000039768.

Oxidative Ring Contraction by a Multifunctional Dioxygenase Generates the Core Cycloocatadiene in the Biosynthesis of Fungal Dimeric Anhydride Zopfiellin.

To elucidate the biosynthesis of a fungicidal dimeric anhydride zopfiellin, the putative biosynthetic gene cluster was identified. We conducted heterologous expression of candidate genes for the synthesis of maleic anhydride and its dimerization and identified the two isomeric dimers with 9-membered rings as products. Notably, α-ketoglutarate-dependent dioxygenase ZopK oxidized one of the dimers, giving the 8-membered ring of zopfiellin. The mechanism of oxidative rearrangement is proposed by analyzing the incorporation of 13C-labeled precursors.

Biosynthetic study of conidiation-inducing factor conidiogenone: heterologous production and cyclization mechanism of a key bifunctional diterpene synthase.

Conidiogenone, a diterpene with a unique structure, is known to induce the conidiation of Penicillium cyclopium. The biosynthetic pathway of (-)-conidiogenone has been fully elucidated by the heterologous expression of biosynthetic genes in Aspergillus oryzae and by in vitro enzyme assay with 13C-labeled substrates. After construction of deoxyconidiogenol by the action of bifunctional terpene synthase, one cytochrome P450 catalyzes two rounds of oxidation to furnish conidiogenone. Notably, similar biosynthetic genes are conserved among more than 10 Penicillium sp., suggesting that conidiogenone is a common conidiation inducer in this genus. The cyclization mechanism catalyzed by terpene synthase, which involves successive 1,2-alkyl shifts, was fully elucidated using 13C-labeled geranylgeranyl pyrophosphate (GGPP) as substrate. During the structural analysis of deoxyconidiogenol, we observed broadening of some of the 13C signals measured at room temperature, which has not been observed with other structurally related compounds. Careful examination using techniques including 13C NMR studies at -80 °C, conformational analysis and prediction of the 13C chemical shifts using density functional theory gave insights into this intriguing phenomenon.