OLIG2 is an in vivo bookmarking transcription factor in the developing neural tube in mouse.

Cells possess intrinsic features that are inheritable via epigenetic regulation, such as DNA methylation and histone modification. These inheritable features maintain a unique gene expression pattern, underlying cellular memory. Because of the degradation or displacement of mitotic chromosomes, most transcription factors do not contribute to cellular memory. However, accumulating in vitro evidence indicates that some transcription factors can be retained in mitotic chromosomes called as bookmarking. Such transcription factors may contribute to a novel third mechanism of cellular memory. Since most findings of transcription factor bookmarking have been reported in vitro, little is currently known in vivo. In the neural tube of mouse embryos, we discovered that OLIG2, a basic helix loop helix (bHLH) transcription factor that regulates proliferation of neural progenitors and the cell fate of motoneurons and oligodendrocytes, binds to chromatin through every cell cycle including M-phase. OLIG2 chromosomal localization coincides with mitotic cell features such as the phosphorylation of histone H3, KI67, and nuclear membrane breakdown. Chromosomal localization of OLIG2 is regulated by an N-terminus triple serine motif. Photobleaching analysis revealed slow OLIG2 mobility, suggesting a high affinity of OLIG2 to DNA. In Olig2 N-terminal deletion mutant mice, motoneurons and oligodendrocyte progenitor numbers are reduced in the neural tube, suggesting that the bookmarking regulatory domain is important for OLIG2 function. We conclude that OLIG2 is a de novo in vivo bookmarking transcription factor. Our results demonstrate the presence of in vivo bookmarking in a living organism and illustrate a novel function of transcription factors.

AUF1, an mRNA decay factor, has a discordant role in Cpeb1 expression.

Cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates polyadenylation and subsequent translation of CPE-containing mRNAs involved in various physiological and pathological phenomena. Although the significance of CPEB1-mediated translational regulation has recently been reported, the detailed regulatory mechanism of Cpeb1 expression remains unclear. To elucidate the post-transcriptional regulatory mechanisms of Cpeb1 expression, we constructed reporter plasmids containing various deletions or mutations in the Cpeb1 mRNA 3' untranslated region (3'UTR). We investigated their expression levels in Neuro2a neuroblastoma cells. We found that Cpeb1 expression is regulated through an AU-rich element in its 3'UTR. Furthermore, the mRNA decay factor AU-rich binding factor 1 (AUF1) regulates Cpeb1 expression, and knockdown of AUF1 upregulates Cpeb1 mRNA expression but results in a decrease in CPEB1 protein levels. These findings indicate that AUF1 has a discordant role in the expression of Cpeb1.

Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor.

Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.

Public preferences and willingness to accept a hypothetical vaccine to prevent a pandemic in Japan: a conjoint analysis.

OBJECTIVES: Understanding public vaccine acceptability is critical to preparing for future pandemics. This research investigated Japanese individuals' willingness to be vaccinated against a hypothetical infectious disease. METHODS: A conjoint analysis was conducted with a general public panel via an Internet survey agency. Vaccine efficacy, vaccine safety, duration of immunity, and price were chosen as analysis attributes. Each respondent chose from 12 hypothetical scenarios using an online panel. RESULTS: From the 2,155 complete responses, 51,720 results were extracted and analyzed. Higher efficacy, lifetime immunity duration, and fear of the pandemic positively affected willingness to be vaccinated, while higher vaccination price and higher toxicity had negative effects. The number of infected individuals and deaths had no significant impact. A total of 69.2% of the study population reported being willing to receive a vaccine with 100% efficacy, lifetime immunity, and low toxicity and free of charge. CONCLUSIONS: This study assessed the preferences for vaccines against infectious diseases with the potential to become pandemics during the COVID-19 pandemic in Japan. This result can influence vaccine-related policy and pandemic preparedness and help governments consider public intention to prepare health communication campaigns that encourage vaccination.

Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3' Untranslated Region in Central Nervous System Neurons.

Fragile X syndrome (FXS) is an inherited intellectual disability caused by a deficiency in Fragile X mental retardation 1 (Fmr1) gene expression. Recent studies have proposed the importance of cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in FXS pathology; however, the molecular interaction between Fmr1 mRNA and CPEB1 has not been fully investigated. Here, we revealed that CPEB1 co-localized and interacted with Fmr1 mRNA in hippocampal and cerebellar neurons and culture cells. Furthermore, CPEB1 knockdown upregulated Fmr1 mRNA and protein levels and caused aberrant localization of Fragile X mental retardation protein in neurons. In an FXS cell model, CPEB1 knockdown upregulated the mRNA levels of several mitochondria-related genes and rescued the intracellular heat shock protein family A member 9 distribution. These findings suggest that CPEB1 post-transcriptionally regulated Fmr1 expression through the 3' untranslated region, and that CPEB1 knockdown might affect mitochondrial function.

Retrospective comparison of clinical and angiographic outcomes after sirolimus-eluting and bare-metal stent implantation in 312 consecutive, nonrandomized severely calcified lesions using a rotablator.

In order to compare the long-term clinical and angiographic outcomes after sirolimus-eluting stent (SES) and bare-metal stent (BMS) placement in severely calcified lesions using a rotablator under the widespread indication of SES, a nonrandomized examination of 312 consecutive lesions after successful implantation of a BMS (99 lesions in 84 patients; from January 2003) or SES (213 in 167; from September 2004) using a rotablator was conducted. The lesion-based primary endpoints (cardiac death and nonfatal recurrent myocardial infarction) and the secondary endpoint [binary restenosis (BR) (diameter stenosis > 50%) at follow-up angiography] were retrospectively determined in August 2010. The incidence of primary endpoint in the SES group (2.3%; mean follow-up period of 1289 ± 526 days) was significantly lower than that in the BMS group (7.1%; P = 0.043; 1803 ± 887 days), although the several variables related to the endpoints were present in the SES group. Cox proportional hazard model analysis revealed that SES was not significantly related to a primary endpoint [hazard ratio of 0.42 (95% CI, 0.073-2.42; P = 0.33)]. The incidence of BR in the SES group (21.3%) was not significantly different from that in the BMS group (27.1%) (P = 0.33). Multivariate logistic regression analysis revealed that SES was not a significant predictor of BR [Odds ratio of 0.78 (95% CI, 0.41-1.51; P = 0.47)]. Thus, although the results of the present retrospective nonrandomized study demonstrate the long-term safety of SES for calcified lesions using a rotablator in daily practice, SES did not show a benefit for the angiographic outcomes compared to BMS.

ICOSLG-mediated regulatory T-cell expansion and IL-10 production promote progression of glioblastoma.

BACKGROUND: Targeting immune checkpoint proteins has recently gained substantial attention due to the dramatic success of this strategy in clinical trials for some cancers. Inducible T-cell co-stimulator ligand (ICOSLG) is a member of the B7 family of immune regulatory ligands, expression of which in cancer is implicated in disease progression due to regulation of antitumor adaptive immunity. Although aberrant ICOSLG expression has been reported in glioma cells, the underlying mechanisms that promote glioblastoma (GBM) progression remain elusive. METHODS: Here, we investigated a causal role for ICOSLG in GBM progression by analyzing ICOSLG expression in both human glioma tissues and patient-derived GBM sphere cells (GSCs). We further examined its immune modulatory effects and the underlying molecular mechanisms. RESULTS: Bioinformatics analysis and GBM tissue microarray showed that upregulation of ICOSLG expression was associated with poor prognosis in patients with GBM. ICOSLG expression was upregulated preferentially in mesenchymal GSCs but not in proneural GSCs in a tumor necrosis factor-α/nuclear factor-kappaB-dependent manner. Furthermore, ICOSLG expression by mesenchymal GSCs promoted expansion of T cells that produced interleukin-10. Knockdown of the gene encoding ICOSLG markedly reduced GBM tumor growth in immune competent mice, with a concomitant downregulation of interleukin-10 levels in the tumor microenvironment. CONCLUSIONS: Inhibition of the ICOSLG-inducible co-stimulator axis in GBM may provide a promising immunotherapeutic approach for suppressing a subset of GBM with an elevated mesenchymal signature.

High-sensitive liquid chromatography-tandem mass spectrometry-based chiral metabolic profiling focusing on amino acids and related metabolites.

Metabolomics has been an evolving science with a wide range of applications in various fields. However, previous studies have rarely focused on metabolite chirality. In this study, to achieve metabolic profiling of chiral amino acids and related metabolites, we developed a high-throughput method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The combination of two types of chiral columns (with binaphthyl-based crown ether and cinchona alkaloid-derived zwitterionic stationary phases) enabled the analysis of 115 chiral and non-chiral metabolites. By finely optimizing MS/MS parameters, the method allowed the highly sensitive (0.001-50 nmol/mL) and wide dynamic range detection of targeted analytes in a standard solution without derivatization. We applied the method to food samples (cheese), and successfully quantified trace levels of metabolites such as d-amino acids in samples. Additionally, we performed principal component analysis on the metabolome data and obtained unique profiles that reflected metabolite chirality. These results demonstrated the applicability and feasibility of the LC-MS/MS method as an effective tool for wide-targeted chiral metabolome analysis.

High-Throughput LC-MS/MS Method for Chiral Amino Acid Analysis Without Derivatization.

D-Amino acids have recently attracted much attention in various research fields including medical, clinical, and food industry due to their important biological functions that differ from L-amino acid. Most chiral amino acid separation techniques require complicated derivatization procedures in order to achieve the desirable chromatographic behavior and detectability. This chapter describes a highly sensitive analytical method for the enantioseparation of chiral amino acids without any derivatization process using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method allows the simultaneous analysis of 18 D-amino acids with high sensitivity and reproducibility. Additionally, this chapter also focuses on the application of the method to real samples for the quantification of targeted amino acids.

Automatic switching valve system to minimize variation of liquid chromatography-tandem mass spectrometry-based chiral amino acid profiling.

Although d-amino acids are less prevalent in nature, they have been detected in mammals (including humans) and it is widely accepted that they might play important physiological roles. While an analytical method for chiral amino acid profiling is strongly required, it has not been well-established because of the difficulties associated with analysis. A high-sensitivity and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method was recently reported by our group for chiral amino acids; however, it lacked sufficient repeatability for several d-amino acids. Thus, the aim of this research was to reduce the experimental variation of chiral amino acid analysis. By installing an automatic switching valve system in LC-MS/MS, it was possible to reduce the relative standard deviations of d-amino acid ratios (d/(d+l)) in rat urine obtained from three technical replicates. The results indicated that the automatic switching valve system was effective in minimizing the variation of d-amino acid ratios, and could be applied for profiling d-amino acids because of its high repeatability.

Mechanistic study on the high-selectivity enantioseparation of amino acids using a chiral crown ether-bonded stationary phase and acidic, highly organic mobile phase by liquid chromatography/time-of-flight mass spectrometry.

The separation mechanism of amino acid enantiomers using a chiral crown ether-bonded stationary phase, CROWNPAK CR-I(+), and acetonitrile (ACN)-rich mobile phases (MPs) was studied. The retention factors of proteinogenic l-amino acids (except proline) formed U-shaped plots against the ACN content in the MP with a sharp increase at a high ACN content, while d-amino acids showed much smaller increases or monotonous decreases in retention within the same range. The use of an acidic, highly organic MP with trifluoroacetic acid (TFA) provided a high enantioselectivity with a short separation time from the contribution of the increased binding of the ammonium group of the analytes to the crown ether functionality of the stationary phase and electrostatic repulsion counteracting the hydrophilic partition mechanism. Optimizing the sample diluent and MP alleviated the peak distortion caused by a moving water band that accompanied the hydrophilic interaction liquid chromatography-like elution conditions. The liquid chromatography/time-of-flight mass spectrometry method with the optimized MP - ACN/ethanol/water/TFA = 80/15/5/0.5 (v/v/v/v) - enabled the determination of eighteen pairs of proteinogenic amino acid enantiomers within 10 min. The conditions also provided the following advantages: (i) fast and highly reproducible separations under isocratic conditions, (ii) high sensitivity and low backpressure using the MP with a high organic content, and (iii) highly reliable peak identification by combining two columns (CR-I(+) and CR-I(-)), reversing the elution orders of the enantiomers.

Investigation of storage time-dependent alterations of enantioselective amino acid profiles in kimchi using liquid chromatography-time of flight mass spectrometry.

Although naturally abundant amino acids are represented mainly by l-enantiomers, fermented foods are known to contain various d-amino acids. Enantiospecific profiles of food products can vary due to fermentation by bacteria, and such alterations may contribute to changes in food properties that would not be dependent exclusively on l-amino acids. Therefore, more attention should be paid to the study of temporal alterations of d-amino acid profiles during fermentation process. However, there have been very few studies reporting time-dependent profiling of d-amino acids because enantioseparation of widely targeted d-amino acids is technically difficult. This study aimed to achieve high throughput profiling of amino acids enantiomers. Enantioselective profiling of amino acids using CROWNPAK CR-I(+) column, liquid chromatography, time of flight mass spectrometry, and principle component analysis was performed to investigate time-dependent alterations in concentrations of free d- and l-amino acids in kimchi stored at 4°C or 25°C. We demonstrated significant changes in d- and l-amino acid profiles in kimchi stored at 25°C. In particular, concentrations of the amino acids d-Ala, d-Ser, d-allo-Ile, d-Leu, d-Asp, d-Glu, and d-Met became higher in kimchi with storage time. This is the first report of time-dependent alterations of d- and l-amino acid contents in kimchi. This study showed that our analytical method of enantioselective detection of amino acids using liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) with CROWNPAK CR-I(+) enables high throughput food screening and can be recommended for advanced studies of the relationship between d-amino acid content and food properties.

Very long-term clinical and angiographic outcomes after sirolimus- and paclitaxel-eluting stent placement for ST-elevation myocardial infarction: a propensity score-matched comparison.

We conducted a retrospective examination of the very long-term outcomes of placing sirolimus (SES) and paclitaxel (PES)-eluting stents in patients with ST-elevation myocardial infarction (STEMI). This was a nonrandomized, retrospective, single-center study that included 872 first STEMI patients who underwent successful placement of either SES (n = 547) or PES from November 2004 to April 2012. The primary end point was the incidence of severe cardiac events comprising cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis (ST). The frequency of target lesion revascularization (TLR) was also compared. A propensity score-matched analysis was used to adjust the 29 baseline variables. In the baseline-adjusted cohorts in 231 STEMI patients in each arm, the frequency of the primary end point in the SES group (5.6 %) during the follow-up duration of 2583 ± 806 days was not significantly different from that in the PES group (6.1 %, follow-up: 1866 ± 699 days). The cumulative primary end point-free ratio in the SES group was not significantly different from that in the PES group (p = 0.503). The frequency of TLR in the SES group (7.5 %) was significantly lower than that in the PES group (16.9 %, p = 0.005), with and the significantly higher cumulative TLR-free ratio in the SES group than that in the PES group (p < 0.001). The very long-term clinical outcomes after SES or PES placement for STEMI patients were statistically equivalent. SES showed the better angiographic outcomes for STEMI compared to PES.

Development of a liquid chromatography-tandem mass spectrometry method for quantitative analysis of trace d-amino acids.

d-Amino acids have recently attracted much attention in various research fields including medical, clinical and food industry due to their important biological functions that differ from l-amino acid. Most chiral amino acid separation techniques require complicated derivatization procedures in order to achieve the desirable chromatographic behavior and detectability. Thus, the aim of this research is to develop a highly sensitive analytical method for the enantioseparation of chiral amino acids without any derivatization process using liquid chromatography-tandem mass spectrometry (LC-MS/MS). By optimizing MS/MS parameters, we established a quantification method that allowed the simultaneous analysis of 18 d-amino acids with high sensitivity and reproducibility. Additionally, we applied the method to food sample (vinegar) for the validation, and successfully quantified trace levels of d-amino acids in samples. These results demonstrated the applicability and feasibility of the LC-MS/MS method as a novel, effective tool for d-amino acid measurement in various biological samples.

In vitro steroid profiling system for the evaluation of endocrine disruptors.

Endocrine disruptors (ED) are chemicals that affect various aspects of the endocrine system, often leading to the inhibition of steroidogenesis. Current chemical safety policies that restrict human exposure to such chemicals describe often time-consuming and costly methods for the evaluation of ED effects. We aimed to develop an effective tool for accurate phenotypic chemical toxicology studies. We developed an in vitro ED evaluation system using gas chromatography/mass spectrometry (GC/MS/MS) methods for metabolomic analysis of multi-marker profiles. Accounting for sample preparation and GC/MS/MS conditions, we established a screening method that allowed the simultaneous analysis of 17 steroids with good reproducibility and a linear calibration curve. Moreover, we applied the developed system to H295R human adrenocortical cells exposed to forskolin and prochloraz in accordance with the Organization for Economic Cooperation and Development (OECD) guidelines and observed dose-dependent variations in steroid profiles. While the OECD guidelines include only testosterone and 17ß-estradiol, our system enabled a comprehensive and highly sensitive analysis of steroid profile alteration due to ED exposure. The application of our ED evaluation screen could be economical and provide novel insights into the hazards of ED exposure to the endocrine system.

Long-term angiographic outcomes of sirolimus- and paclitaxel-eluting stent placement in diabetes, long lesions, and small vessels.

We conducted a lesion-based retrospective sub-analyses of diabetes mellitus (DM), diffuse long lesions (stented segment ≥40 mm; LLs), and small vessels (SVs; reference diameter ≤2.6 mm) in patients who received sirolimus- (SESs) or paclitaxel-eluting stents (PESs) for nonrandom treatment of de novo native coronary stenosis in a clinical practice setting. During the period from May 2007 to February 2009, 490 of 682 PES-treated and 293 of 386 SES-treated lesions were angiographically followed up within 1500 days of PCI, and the retrospective investigation was conducted in April 2013. The frequencies of target lesion revascularization (TLR; any recurrent PCI including both marginal stent restenosis) and binary in-stent restenosis (percentage diameter of in-stent stenosis >50%) upon follow-up angiography, evaluated by adjusting 25 baseline variables using propensity score matching analysis, after placement of SESs and PESs were the following: DM (n = 124 per arm), 14.5 vs. 15.3% (p = 0.842), and 14.5 vs. 16.1% (0.856); LLs (n = 81), 16.0 vs. 21.0% (0.433), and 12.3 vs. 22.2% (0.117); SVs (n = 107), 11.2 vs. 29.9% (<0.001), and 11.2 vs. 30.8% (<0.001), respectively. The p values of log-rank tests for the cumulative TLR-free ratios after SES and PES placement were 0.504 in DM, 0.625 in LLs, and <0.001 in SVs group, respectively. Thus, compared to PES, SES showed the equivalent efficacy for DM, the tendency to be superior for LLs due to approximately 24-45% reductions in TLR and binary restenosis rates, and the promising superiority for SVs on the angiographic outcomes during a long-term observational interval.

Long-term clinical and angiographic outcomes after sirolimus- and paclitaxel-eluting stent placement following rotablation for severely calcified lesions: a retrospective nonrandomized study.

We conducted a retrospective comparison of the long-term clinical and angiographic outcomes of 281 consecutive nonrandomized severely calcified lesions in 221 patients treated with a sirolimus-eluting stent (SES; CYPHER Bx VELOCITY) or a paclitaxel-eluting stent (PES; TAXUS Express) placed after rotablation between August 2004 and February 2009. The clinical safety endpoint, comprising the incidence of cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis, in 164 patients after exclusive SES placement (4.9 % with a mean clinical follow-up period of 1396 ± 763 days) was not significantly different from that after exclusive PES placement in 51 patients (2.0 %, 1011 ± 605 days; p = 0.364 and p < 0.001, respectively). The cumulative clinical safety endpoint-free ratio after exclusive SES placement was not significantly different from that after PES placement (p = 0.61, by log-rank test). The angiographic efficacy endpoint (binary restenosis: diameter stenosis >50 % at follow-up angiography) in the 169 lesions placed using SES (20.1 % with a mean angiographic follow-up period of 669 ± 605 days) was not significantly different from that in the 40 lesions using PES (17.5 %; 498 ± 320 days) (p = 0.707). In univariate analysis, SES use did not relate to the efficacy endpoint (p = 0.707). Thus, our small single-center study showed that the long-term clinical and angiographic outcomes after SES placements for severely calcified lesions after rotablation were not significantly different from those after PES placement.

Midterm outcomes of bare-metal stenting after primary stenting for ST-segment elevated myocardial infarctions in the drug-eluting stent era: a propensity score-matched comparison with sirolimus-eluting stent.

We performed a propensity score-matching comparison of the midterm clinical and angiographic outcomes after primary stenting between using bare-metal stents (BMSs) and sirolimus-eluting stent (SES; Cypher Bx Velocity) for ST-segment elevated myocardial infarction (STEMI), because, in the drug-eluting stent era, the indication of the BMSs when a large balloon diameter is required remained to be controversial. This was a single-center, nonrandomized, retrospective study investigated in October 2013 by enrolling STEMI patients treated with primary stenting using either SES (n = 468) or BMS (n = 171) between September 2004 and December 2011. In 204 patients, the baseline-adjusted values produced similar mean maximum balloon sizes (BMS 3.67 ± 0.47 mm; SES 3.70 ± 0.56 mm; p = 0.477), and the incidence rates of binary in-stent restenosis (% diameter stenosis >50 % on secondary angiography) after SES placement (7.8 %) was significantly lower than that after BMS placement (23.5 %; p = 0.002). In baseline-adjusted 300 patients, the incidence of the clinical endpoints comprising cardiac death, nonfatal recurrent MI, and definite stent thrombosis after SES placement (11.3 %; 1241 ± 786 days; p = 0.557) was not significantly different from after BMS placement (8.7 %; mean follow-up period, 549 ± 486 days; p = 0.557). SES was not significantly related to the clinical endpoint [hazard ratio 2.31; 95 % confidence interval (CI) 0.88-6.08; p = 0.089). BMS did not offset the SES's angiographic efficacy for primary stenting for STEMI patients, despite placed using a large-sized balloon.

Propensity score matched lesion-based comparison of long-term clinical and angiographic outcomes after placement of sirolimus (Cypher Bx Velocity) and paclitaxel (TAXUS Express)-eluting stents for de novo native coronary stenosis.

Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were firstly compared in Japan. During PES-available period from May 2007 to February 2009, 1068 nonrandomized consecutive de novo native coronary lesions treated either with a PES (682 lesions) or SES were enrolled in this study, and a retrospective examination was conducted in April 2013. During that interval, the use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the baselines with a propensity score matching analysis produced 383 lesions in each arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after placement of SES (2.1 %; mean follow-up, 1400 ± 290 days) was not significantly different from that in the PES group (2.6 %; 1394 ± 325 days, p = 0.637). SES did not relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p = 0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in each arm), the incidence of binary restenosis (percent diameter stenosis [%DS] >50 %) in the SES group (12.0 %; mean follow-up, 477 ± 281 days) was not significantly different from that in the PES group (14.5 %; 497 ± 341 days, p = 0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40-1.32; p = 0.295). In conclusion, the present propensity score matched lesion-based analysis firstly showed the statistical equivalent long-term clinical and angiographic outcomes after either SES or PES placement for de novo native coronary lesion in Japanese patients in a daily practice environment.

Propensity score-matched lesion-based comparison of mid-term angiographic outcomes of TAXUS Liberté with Cypher Bx Velocity stents for de novo native coronary stenosis and in patients with diabetes.

OBJECTIVE: We sought to perform a propensity score-matched lesion-based comparison of mid-term angiographic outcomes of sirolimus- (SES, Cypher Bx Velocity) and paclitaxel- (PES, TAXUS Liberté, the 2nd-generation TAXUS) eluting stents to treat de novo coronary stenosis and, particularly, in patients with diabetes mellitus (DM) in a daily practice environment. METHODS: The present study was a non-randomized, retrospective, lesion-based, single center study that included 1,287 de novo native coronary stenosis cases after successful SES or PES placement between February 2007 and April 2011. The primary endpoint was angiographic-based binary in-stent restenosis (% diameter stenosis >50 at secondary angiogram) within 550 days of placement. A propensity score-matched analysis was used to adjust the baselines. RESULTS: Among 360 baseline-adjusted angiographic lesions followed up in each arm, the incidence of the primary endpoint in the PES group (11.7%, follow-up period: 350±76 days) was not significantly different from that in the SES group (10.3%, p=0.645, 354±81 days, p=0.912). PES was not associated with the primary endpoint by logistic regression analysis (odds ratio: 1.15, 95% confidence interval: 0.68-1.93, p=0.605). In the DM specific sub-analysis, the primary endpoint in the PES group (19.6%) was not significantly different from that in the SES group (12.8%, p=0.105) in 148 baseline-adjusted lesions in each arm. CONCLUSION: The mid-term angiographic outcomes after TAXUS Liberté placement for all-comer de novo native coronary stenosis and in patients with DM were not significantly different from those of SES in a Japanese daily practice environment.