Search

Background and objectivesThe optimal timing for complete revascularization (CR) in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) remain uncertain.MethodsThis post-hoc analysis of the FRAME-AMI trial included AMI patients with MVD (n = 549). They were classified into immediate (n = 329) and staged CR (n = 220) groups. All percutaneous coronary interventions were performed during inex hospitalization. The primary endpoint was a composite of all-cause death, acute myocardial infarction, and repeated revascularization. Secondary endpoints included each component of the primary endpoint. Additional comparisons for the outcomes in ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were also performed.ResultsThe incidence of the primary endpoint was not significantly different in any of the AMI patients [12.7% [immediate CR] vs. 17.4% [staged CR], p = 0.905, adjusted hazard ratio [HR] of staged CR = 0.81, 95% confidence interval = 0.43–1.53, p = 0.528]. Other secondary endpoints were also not significantly different. Analyses of STEMI and Neither the primary or secondary endpoints of NSTEMI patients were significantly different.ConclusionsIn this post-hoc analysis of the FRAME-AMI trial, no significant difference in clinical outcomes was observed between the immediate and staged CR strategies for AMI with MVD and the subgroups, such as STEMI or NSTEMI. However, the results should be interpreted carefully because of the many limitations, including a limited sample size and a lack of statistical power. Trial Registration: FRAME-AMI clinicaltrials.gov, identifier (NCT02715518).

BackgroundLeft ventricular ejection fraction (LVEF) is a crucial prognostic indicator of acute myocardial infarction (AMI). However, there is a lack of studies on the clinical characteristics and prognosis of patients with mildly reduced ejection fraction (EF) after AMI.MethodsWe categorized 6,553 patients with AMI from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) between November 2011 and December 2015 into three groups based on their EF, as assessed by echocardiography during index hospitalization: reduced EF (LVEF ≤40%), mildly reduced EF (LVEF 41%–49%), and preserved EF (LVEF ≥50%). The primary outcome was all-cause death within 2 years. The secondary outcomes included myocardial infarction (MI), revascularization, and patient-oriented composite endpoint (POCE), which was defined as a composite of all-cause death, any MI, or revascularization.ResultsOf the total 6,553 patients, 884 (13.5%) were classified into the reduced EF group, 1,749 (26.7%) into the mildly reduced EF group, and 3,920 (59.8%) into the preserved EF group. Patients with mildly reduced EF exhibited intermediate mortality (reduced EF, 24.7%; mildly reduced EF, 8.3%; preserved EF, 4.6%; p

Acetogenic bacteria can utilize C1 compounds, such as carbon monoxide (CO), formate, and methanol, via the Wood-Ljungdahl pathway (WLP) to produce biofuels and biochemicals. Two novel acetogenic bacteria of the family Eubacteriaceae ES2 and ES3 were isolated from Eulsukdo, a delta island in South Korea. We conducted whole genome sequencing of the ES strains and comparative genome analysis on the core clusters of WLP with Acetobacterium woodii DSM1030T and Eubacterium limosum ATCC8486T. The methyl-branch cluster included a formate transporter and duplicates or triplicates copies of the fhs gene, which encodes formyl-tetrahydrofolate synthetase. The formate dehydrogenase cluster did not include the hydrogenase gene, which might be replaced by a functional complex with a separate electron bifurcating hydrogenase (HytABCDE). Additionally, duplicated copies of the acsB gene, encoding acetyl-CoA synthase, are located within or close to the carbonyl-branch cluster. The serum bottle culture showed that ES strains can utilize a diverse range of C1 compounds, including CO, formate, and methanol, as well as CO2. Notably, ES2 exhibited remarkable resistance to high concentrations of C1 substrates, such as 100% CO (200 kPa), 700 mM formate, and 500 mM methanol. Moreover, ES2 demonstrated remarkable growth rates under 50% CO (0.45 h−1) and 200 mM formate (0.34 h−1). These growth rates are comparable to or surpassing those previously reported in other acetogenic bacteria. Our study introduces novel acetogenic ES strains and describes their genetic and physiological characteristics, which can be utilized in C1-based biomanufacturing.

BackgroundA strong association between elevated neutrophil extracellular trap (NET) levels and poor clinical outcomes in patients with coronavirus infection 2019 (COVID-19) has been reported. However, while acute kidney injury (AKI) is a common complication of COVID-19, the role of NETs in COVID-19-associated AKI is unclear. We investigated the association between elevated NETs and AKI and the prognostic role of NETs in COVID-19 patients.MethodsTwo representative markers of NETs, circulating nucleosomes and myeloperoxidase-DNA, were measured in 115 hospitalized patients. Serum levels of interleukin [IL]-6, monocyte chemotactic protein-1 [MCP-1], plasma von Willebrand factor (vWF) and urinary biomarkers of renal tubular damage (β2-microglobulin [β2M] and kidney injury molecule 1 [KIM-1]) were measured.ResultsAKI was found in 43 patients (37.4%), and pre-existing chronic kidney disease (CKD) was a strong risk factor for AKI. Higher circulating NET levels were a significant predictor of increased risk of initial ICU admission, in-hospital mortality (adjusted HR 3.21, 95% CI 1.08–9.19) and AKI (OR 3.67, 95% CI 1.30-10.41), independent of age, diabetes, pre-existing CKD and IL-6 levels. There were strong correlations between circulating nucleosome levels and urinary KIM-1/creatinine (r=0.368, p=0.001) and β2M (r=0.218, p=0.049) levels. NETs were also strongly closely associated with serum vWF (r = 0.356, p

BackgroundThe role of high-flow arteriovenous fistula (AVF) in cardiovascular morbidity in hemodialysis (HD) patients is very likely under-recognized. We assessed the relationship between high access flow (Qa) and myocardial fibrosis in HD patients.MethodsMyocardial fibrosis was assessed by native T1 relaxation times on non-contrast cardiac magnetic resonance imaging and a potential marker of fibrosis. Serum levels of galectin-3, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and monocyte chemoattractant protein 1 (MCP-1) were measured in 101 HD patients who underwent regular monitoring of AVF Qa. A high-flow AVF was defined as a Qa >2 L/min.ResultsHemodialysis patients showed significantly higher galectin-3 value and increased T1 relaxation time compared to healthy volunteers, suggesting increased myocardial fibrosis in uremic cardiomyopathy. In HD patients, 20 (19.8%) had a Qa > 2L/min, and they had significantly higher cardiac output, cardiac index, left ventricular mass, and increased T1 times than those with a Qa ≤ 2 L/min. Also, serum galectin-3 and NT-proBNP levels were much higher in the high Qa group, indicating a close relationship between the high Qa, increased myocardial fibrosis, and the risk of heart failure (HF) in HD patients. It is interesting that a higher AVF Qa for myocardial fibrosis was independent of several traditional cardiovascular risk factors as well as serum levels of NT-proBNP and MCP-1.ConclusionsA supra-physiologically high Qa can be related to myocardial fibrosis and increased risk of HF in HD patients. Regular Qa monitoring could allow early detection of a high-flow AVF that could arise cardiac complications.

The genome of the hyperthermophilic archaeon Thermococcus onnurineus NA1 contains three copies of the formate dehydrogenase (FDH) gene, fdh1, fdh2, and fdh3. Previously, we reported that fdh2, clustered with genes encoding the multimeric membrane-bound hydrogenase and cation/proton antiporter, was essential for formate-dependent growth with H2 production. However, the functionality of the other two FDH-coding genes has not yet been elucidated. Herein, we purified and characterized cytoplasmic Fdh3 to understand its functionality. The purified Fdh3 was identified to be composed of a tungsten-containing catalytic subunit (Fdh3A), an NAD(P)-binding protein (Fdh3B), and two Fe-S proteins (Fdh3G1 and Fdh3G2). Fdh3 oxidized formate with specific activities of 241.7 U/mg and 77.4 U/mg using methyl viologen and NADP+ as electron acceptors, respectively. While most FDHs exhibited NAD+-dependent formate oxidation activity, the Fdh3 of T. onnurineus NA1 showed a strong preference for NADP+ over NAD+ as a cofactor. The catalytic efficiency (kcat/Km) of Fdh3 for NADP+ was measured to be 5,281 mM−1 s−1, which is the highest among NADP-dependent FDHs known to date. Structural modeling suggested that Arg204 and Arg205 of Fdh3B may contribute to the stabilization of the 2′-phosphate of NADP(H). Fdh3 could also use ferredoxin as an electron acceptor to oxidize formate with a specific activity of 0.83 U/mg. Furthermore, Fdh3 showed CO2 reduction activity using reduced ferredoxin or NADPH as an electron donor with a specific activity of 0.73 U/mg and 1.0 U/mg, respectively. These results suggest a functional role of Fdh3 in disposing of reducing equivalents by mediating electron transfer between formate and NAD(P)H or ferredoxin.

A novel Klebsiella pneumoniae carbapenemase (KPC) variant, KPC-55, produced by a K. pneumoniae ST307 strain was characterized. K. pneumoniae strain BS407 was recovered from an active surveillance rectal swab of a patient newly admitted to a general hospital in Busan, South Korea. Carbapenemase production was confirmed by the modified Hodge test, and the MICs of β-lactams were determined by the broth microdilution method. The whole genome was sequenced. Cloning and expression of the blaKPC–55 gene in Escherichia coli and MIC determination were performed. The enzyme KPC-55 was used for kinetic assays against β-lactams and compared with the KPC-2 enzyme. The new allele of the blaKPC gene had a T794A alteration compared to the blaKPC–2 gene, resulting in the amino acid substitution Y264N in the middle of the β9-sheet. Compared to the KPC-2-producing strain, the KPC-55-producing strain exhibited a lower level of resistance to most β-lactam drugs tested, however, the KPC-55 enzyme catalyzed aztreonam and meropenem at an increased efficiency compared to the catalytic activity of KPC-2. KPC subtypes could have varied phenotypes due to alterations in amino acid sequences, and such an unexpected resistance phenotype emphasizes the importance of detailed characterizations for the carbapenemase-producing Enterobacterales.