Phylogenetic and evolutionary analysis of foot-and-mouth disease virus A/ASIA/Sea-97 lineage.

Foot-and-mouth disease virus (FMDV) A/ASIA/Sea-97 is a predominant lineage in Southeast Asia and East Asia. However, Sea-97 lineage has not been well studied since its first outbreak in Thailand in 1997. Thus, we conducted phylogenetic and evolutionary analysis of Sea-97 using 224 VP1 sequences of FMDV A/ASIA during 1960 and 2018. Phylogenetic analysis revealed that Sea-97 lineage can be classified into five groups (G1-G5). After the emergence of G2 from G1, the genetic diversity of Sea-97 increased sharply, causing divergence into G3, G4 and G5. During this evolutionary process, Sea-97 lineage, which was initially found only in some countries in Southeast Asia, gradually spread to East Asia. The evolution rate of this lineage was estimated to be 1.2 × 10-2 substitutions/site/year and there were many differences in amino acid residues compared to vaccine strain. Substitutions at antigenically important sites may affect the efficacy of the vaccine, suggesting the need for appropriate vaccine strains. Our results could provide meaningful information to understand comprehensive characteristic of Sea-97 lineage.

Physicochemical and biological characterization of SB2, a biosimilar of Remicade® (infliximab).

A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor-α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy.

Impact of initial glycosylated hemoglobin level on cardiovascular outcomes in prediabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: The prognostic value of the glycemic control level, as measured using glycosylated hemoglobin (HbA1c) level, in prediabetic patients with acute coronary syndrome is still undetermined. The aim of this study was to demonstrate the influence of HbA1c level at admission on the incidence of major adverse cardiac events (MACE) in prediabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: Using data from the Korea Working Group on Myocardial Infarction (February 2008-December 2011), this observational study included 2470 STEMI patients undergoing primary PCI who had not been diagnosed with diabetes mellitus either before or after admission (HbA1c at admission <6.5%). Patients were divided into two groups based on HbA1c at admission: prediabetic (5.7% ≤ HbA1c ≤ 6.4%, n=1475, 59.5%) and nondiabetic (HbA1c<5.7%, n=995, 40.5%). After analyzing the matched cohort, 1-year cumulative MACE incidence, defined as a composite of mortality, nonfatal myocardial infarction, repeated PCI, or coronary artery bypass graft, MACE was not found to differ significantly between the two groups (6.7 vs. 6.0%, P=0.616). Using multivariate logistic analysis, HbA1c level at admission was not significantly associated with the occurrence of MACE (odds ratio 0.925, 95% confidence interval 0.618-1.384, P=0.925). CONCLUSION: This study demonstrated that HbA1c level at admission was not significantly associated with cardiovascular outcomes in prediabetic Korean populations with STEMI undergoing primary PCI.