IMPORTANCE Thromboembolism is the most common complication in coiling for an unruptured aneurysm and is frequent in patients with high on-treatment platelet reactivity (HTPR) who are prescribed a standard antiplatelet preparation for its prevention.OBJECTIVE To evaluate the effect of a modified antiplatelet preparation compared with a standard preparation in patients with HTPR undergoing coiling. DESIGN, SETTING, AND PARTICIPANTSA prospective randomized open-label active-control trial with blinded outcome assessment at the Seoul National University Bundang Hospital from May 27, 2013, to April 7, 2014. Patients with HTPR were randomly assigned (1 to 1) to the standard or modified preparation group. Patients without HTPR were assigned to the non-HTPR group. A total of 228 patients undergoing coiling for unruptured aneurysms were enrolled and allocated to the study, 126 in the HTPR group (63 to the standard preparation group and 63 to the modified preparation group) and 102 to the non-HTPR group. Intent-to-treat analysis was performed. INTERVENTIONSThe modified preparation (HTPR to aspirin, 300 mg of aspirin and 75 mg of clopidogrel bisulfate; and HTPR to clopidogrel, 200 mg of cilostazol added to the standard regimen) was performed before coiling in the modified preparation group. Standard preparation (100 mg of aspirin and 75 mg of clopidogrel) was maintained in the standard preparation and non-HTPR groups. MAIN OUTCOMES AND MEASURESThe primary outcome was a thromboembolic event defined as thromboembolism during coiling and a transient ischemic attack or ischemic stroke within 7 days after coiling. The principal secondary outcome was a bleeding complication according to Thrombolysis in Myocardial Infarction bleeding criteria within 30 days after coil embolization. RESULTSThe thromboembolic event rate was low in the modified preparation group (1 of 63 [1.6%]) compared with the standard preparation group (7 of 63 [11.1%]; adjusted risk difference, −11.7% [95% CI, −21.3% to −2.0%]; P = .02), which had a higher thromboembolic risk than the non-HTPR group (1 of 102 [1.0%]; adjusted risk difference, 8.6% [95% CI, 1.0% to 16.3%]; P = .03). All bleeding complications were of minimal grade according to Thrombolysis in Myocardial Infarction bleeding criteria. The bleeding rate was not different between the modified (6 of 63 [9.5%]) and standard (4 of 63 [6.3%]) preparation groups (adjusted risk difference, 5.6% [95% CI, −4.2% to 15.4%]; P = .26). CONCLUSIONS AND RELEVANCEModified antiplatelet preparation for patients with HTPR compared with standard antiplatelet preparation reduced the thromboembolic event rate in coiling for an unruptured aneurysm without increasing bleeding.TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0000804.

Although incidental small paraclinoid UIAs have a relatively lower rupture and growth risk, patients with high-risk factors, including aneurysm ≥4 mm, HTN, arterial branch-related aneurysms, and multiple aneurysms must be monitored closely. The limitation of the retrospective nature of this study should be taken into consideration.

Cell metastasis is a major cause of death from cancer and can arise from excessive levels of oxidative stress. The objective of this study was to investigate whether the natural flavonoid quercetin can inhibit matrix metalloproteinase (MMP)-2 and -9 activities through the attenuation of reactive oxygen species (ROS) formation, an event expected to lead to the inhibition of cell motility. To induce sustained ROS formation, cells were treated with phenazine methosulfate (PMS; 1 μM). Noncytotoxic concentrations of quercetin inhibited PMS-induced increases in cell motility in HT1080 human fibrosarcoma (HT1080) cells. While nearly 100% of cells were observed to migrate after 24 h of PMS treatment, quercetin significantly (P < 0.01) suppressed this effect. We also found that quercetin, up to 10 μg/mL, attenuated PMS-induced MMP-2 activation. We then investigated whether the decreased levels of MMP-2 activation could be attributable to lower levels of ROS formation by quercetin. We found that quercetin treatments significantly attenuated PMS-induced ROS formation (P < 0.01) and resulted in decreased cell motility associated with a reduction in MMP-2 and -9 activitiy in HT1080 cells, even in the absence of PMS treatment. Collectively, these results suggest that quercetin inhibits cell motility via the inhibition of MMP activation in HT1080 cells in the presence and absence of PMS. This is likely to be a result of the suppression of intracellular ROS formation by quercetin.

ObjectiveWe conducted a retrospective cohort study to elucidate the natural course of unruptured intracranial aneurysms (UIAs) at a single institution.MethodsData from patients diagnosed with UIA from March 2000 to May 2008 at our hospital were subjected to a retrospective analysis. The cumulative and annual aneurysm rupture rates were calculated. Additionally, risk factors associated with aneurysmal rupture were identified.ResultsA total of 1339 aneurysms in 1006 patients met the inclusion criteria. During the follow-up period, 685 aneurysms were treated before rupture via either an open surgical or endovascular procedure. Six hundred fifty-four UIAs were identified and not repaired during the follow-up period. The mean UIA size was 4.5±3.2 mm, and 86.5% of the total UIAs had a largest dimension <7 mm. Among these UIAs, 18 ruptured at a median of 1.6 years (range : 27 days to 9.8 years) after day 0. The annual rupture risk during a 9-year follow-up was 1.00%. A multivariate Cox proportional hazards analysis revealed that the aneurysm size and a history of subarachnoid hemorrhage (SAH) were statistically significant risk factors for rupture. For an aneurysms smaller than 7 mm in the absence of a history of SAH, the annual rupture risk was 0.79%.ConclusionIn our study, the annual rupture risk for UIAs smaller than 7 mm in the absence of a history of SAH was higher than that of Western populations but similar to that of the Japanese population.

Japanese red pine (Pinus densiflora) is widely present in China, Japan, and Korea. Its green pine leaves have traditionally been used as a food as well as a coloring agent. After being shed, pine leaves change their color from green to brown within two years, and although the brown pine leaves are abundantly available, their value has not been closely assessed. In this study, we investigated the potential anti-photoaging properties of brown pine leaves for skin. Brown pine leaf extract (BPLE) inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) expression to a greater extent than pine leaf extract (PLE) in human keratinocytes and a human skin equivalent model. HPLC analysis revealed that the quantity of trans-communic acid (TCA) and dehydroabietic acid (DAA) significantly increases when the pine leaf color changes from green to brown. BPLE and TCA elicited reductions in UVB-induced MMP-1 mRNA expression and activator protein-1 (AP-1) transactivation by reducing DNA binding activity of phospho-c-Jun, c-fos and Fra-1. BPLE and TCA also inhibited UVB-induced Akt phosphorylation, but not mitogen activated protein kinase (MAPK), known regulators of AP-1 transactivation. We additionally found that BPLE and TCA inhibited phosphoinositide 3-kinase (PI3K), the upstream kinase of Akt, in vitro. In summary, both BPLE and its active component TCA exhibit protective effects against UVB-induced skin aging. Taken together, these findings underline the potential for BPLE and TCA to be utilized as anti-wrinkling agents and cosmetic ingredients, as they suppress UVB-induced MMP-1 expression.