This study investigated ovarian expressions of bone morphogenetic protein 15 (BMP15), growth differentiation factor 9 (GDF9), and C-KIT according to age in female mice to determine whether these factors can be served as new potential biomarkers of ovarian aging. Ovaries were collected from mice aged 10, 20, 30, and 40 weeks, and ovarian expressions of BMP15, GDF9, and C-KIT were examined by real-time PCR, Western blot, and immunohistochemistry. Follicle counts were measured on histological hematoxylin and eosin staining. In the second experiment to evaluate ovarian function, after superovulation with PMSG and hCG, the numbers of zygotes retrieved and embryo development rate were examined. Ovarian expressions of BMP15, GDF9, and C-KIT decreased with age. Follicle counts, numbers of retrieved zygotes, and embryo development rate were also significantly reduced in old mice over 30 weeks compared with young mice. These results indicate that these factors could be served as new potential biomarkers of ovarian aging. Impact statement Ovarian aging is becoming a more important issue in terms of fertility preservation and infertility treatment. Serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC) are being practically used as markers of ovarian aging as well as ovarian reserve in human. However, these factors have some drawbacks in assessing ovarian aging and reserve. Therefore, the identification of ovarian expressions of BMP15, GDF9, and C-KIT according to female could be applied as a potent predictor of ovarian aging. This work provides new information on the development of diagnosis and treatment strategy of age-related fertility decline and premature ovarian insufficiency.

Hypothetically, diminished platelet reactivity (PR) during dual antiplatelet therapy (DAPT) should cause extra major bleeding events (MBE), although definite evidence is lacking. Multiple scores have been proposed to stratify bleeding risk, but their predictive value during DAPT is unclear. We compared the performance of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) with PR testing to predict MBE in Korean patients with acute coronary syndrome. We screened 1105, and included 903 consecutive patients who underwent coronary interventions. All patients received DAPT, while MBE were assessed by BARC scale. Admission platelet reactivity was assessed with VerifyNow Analyzer simultaneously with CRUSADE score, and MBE were collected at 1 month and at 1 year post stenting. There were a total of 113 (11%) MBE at 1 month, and extra 41(5%) MBE at 1 year. At 1 month MBE prediction was superior by CRUSADE score (AUC: 0.816, 95% CI: 0.79 0.84, p < 0.0001), compared to PR (AUC: 0.605, 95% CI: 0.572–0.637, p = 0.0007). Moreover, CRUSADE score remains the independent predictor of MBE by multivariate analyses (OR = 2.94, 95% CI: 2.18–3.96, p < 0.0001). At 1 year MBE also correlated, but were not significantly different between admission CRUSADE score (AUC: 0.62, 95% CI: 0.58 0.66, p = 0.0183) and PR (AUC: 0.674, 95% CI: 0.63–0.71, p = 0.002). We conclude that MBE are more common in real life than reported in clinical trials. CRUSADE score was superior to PR testing for predicting short-term, but not 1 year MBE in Korean patients undergoing percutaneous coronary intervention and treated with DAPT.

Background: The optimal dosing of novel oral P2Y₁₂ receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y₁₂ flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y₁₂ receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

This small study showed that our technique is technically feasible and may be safely performed to the selective patients. The LITA auto Y graft might be an additional surgical option, in terms of not only preserving the other grafts and maintaining patency in the LAD area bypass, but also preventing the need for sequential anastomoses.

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