Adverse clinical events after percutaneous coronary intervention in very elderly patients with acute coronary syndrome.

The number of very elderly patients with acute coronary syndrome (ACS) is increasing. Therefore, owing to the need for evidence-based treatment decisions in this population, this study aimed to examine the clinical outcomes during 1 year after percutaneous coronary intervention (PCI) in very elderly patients with ACS. This prospective multicenter observational study comprised 1337 patients with ACS treated with PCI, classified into the following four groups according to age: under 60, <60 years; sexagenarian, ≥60 and <69 years; septuagenarian, ≥70 and <80 years; and very elderly, ≥80 years. The primary endpoint was a composite of the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and bleeding within 1 year after PCI. We used the sexagenarian group as a reference and compared outcomes with those of the other groups. The incidence of the primary endpoint was significantly higher in the very elderly group than in the sexagenarian group (36 [12.7%] vs. 24 [6.9%], respectively; hazard ratio, 1.94; 95% confidence interval: 1.16-3.26; p = 0.012). The higher incidence of the primary endpoint was primarily driven by a higher incidence of all-cause death. When the multivariable analysis was used to adjust for patient characteristics and comorbidities, no difference was observed in the primary endpoint between the very elderly and sexagenarian groups (p = 0.96). The incidence of adverse events after PCI, particularly all-cause death, in very elderly patients with ACS was high. However, if several confounders are adjusted, comparable outcomes may be expected within 1 year after PCI among this population.

Safety and Efficacy of Low-Dose Prasugrel as Part of Triple Therapy With Aspirin and Oral Anticoagulants in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention　- From the TWMU-AF PCI Registry.

BACKGROUND: Using the standard maintenance dose of prasugrel (10 mg/day) as part of triple therapy with aspirin and an oral anticoagulant (OAC) is not recommended in the current guidelines because it increases the risk of bleeding compared with clopidogrel. However, the safety and efficacy of low-dose prasugrel (3.75 mg/day) as part of triple therapy has not been reported. Methods and Results: We registered 816 consecutive patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) from January 2011 to June 2016 at 8 hospitals in Japan. We examined the clinical outcomes of patients who received either low-dose prasugrel (n=57) or clopidogrel (n=451) as part of triple therapy after PCI. The incidences of bleeding (TIMI major and minor) and major adverse cerebrocardiovascular events (MACCE; all-cause death, nonfatal myocardial infarction, stent thrombosis, unplanned revascularization, and stroke) were evaluated. The cumulative 1-year incidence of bleeding was not significantly different (prasugrel 5.6% vs. clopidogrel 8.1%, log-rank P=0.55). In addition, the cumulative 1-year incidence of MACCE was also not significantly different (prasugrel 11.5% vs. clopidogrel 12.3%, log-rank P=0.88). CONCLUSIONS: Low-dose prasugrel, as part of triple therapy, did not increase the risk of bleeding compared with clopidogrel. Therefore, it can be an alternative to clopidogrel for patients with AF undergoing PCI.

Expression profile of mRNAs from rat hippocampus and its application to microarray.

Stress refers to physiological or psychological stimuli that disrupt homeostasis and induce pathophysiological conditions due to maladaptive response, sometimes resulting in mental disorders including depression and post-traumatic stress disorder. Severe stress has been shown to induce neuronal atrophy and apoptosis, especially in the hippocampus, which is thought to be a region of the brain important in stress-related disorders. We have analyzed gene expression in rat hippocampus comprehensively to clarify the molecular mechanism of stress-related disorders. In the present study, we identified and catalogued 13,660 partial complementary DNA sequences (expressed sequence tags (ESTs)) of randomly selected clones from a cDNA library of rat hippocampus. Sequence analysis showed that these clones cluster into 7173 non-redundant sequences comprising 1794 clusters and 5379 singletons. As a result of nucleotide and peptide database search, 2594 were found to represent known rat sequences. Of the remaining 4579 genes, 599 non-redundant ESTs represent rat homologs of genes identified in other species or new members of structurally related families. In addition, we illustrate the use of these clone sets by constructing a cDNA microarray focused on genes categorized into "cell/organism defense". These ESTs and our own microarray thus provide an improved genomic source for molecular studies of animal models of stress-related disorders.

Genetic variations in the WFS1 gene in Japanese with type 2 diabetes and bipolar disorder.

Diabetic and psychiatric symptoms often appear in patients with Wolfram syndrome, and obligate carriers of WFS1 have increased prevalence of type 2 diabetes and are more likely to require hospitalization for psychiatric illness including bipolar disorder. To identify the polymorphisms in Japanese, we examined a region of approximately 50 kb covering the entire WFS1 gene, and evaluated the patterns of linkage disequilibrium. We found a total of 42 variations including 8 novel coding single nucleotide polymorphisms (A6T, A134A, N159N, T170T, E237K, R383C, V412L, and V503G), 14 novel non-coding polymorphisms, and 2 linkage disequilibrium blocks. We also performed association studies in patients with type 2 diabetes mellitus and patients with bipolar disorder. The haplotype comprising R456 and H611 was most associated with type 2 diabetes (p = 0.013) and the haplotype comprising g. -15503C/T and g. 16226G/A was most associated with bipolar disorder (p = 0.006), but neither reached significant difference after multiple adjustment. These genetic variations and linkage disequilibrium patterns in WFS1 in Japanese should be useful in further investigation of genetic diversities of WFS1 and various related disorders.