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Off-Label Application of Pipeline Embolization Device for Intracranial Aneurysms
Liang Buqing,Lesley Walter S.,Robinson Timothy M.,Chen Wencong,Benardete Ethan A.,Huang Jason H. 대한신경중재치료의학회 2019 Neurointervention Vol.14 No.2
Purpose: The Pipeline embolization device (PED) is approved in the USA for treating giant and large aneurysms arising from the petrous to superior hypophyseal segments of the internal carotid artery in patients older than 21 years of age. This study investigates off-label PED results in a large cohort. Materials and Methods: Retrospective, single-center review of all patients who had off-label PED surgery. Results: Sixty-two aneurysms (48 patients) underwent off-label PED treatment from 2012–2017. There were 44 females and four males (age 21 to 75 years; mean/median, 54.3/55.0 years). The most common presenting symptom was headache (47/62, 75.8%). All aneurysms were in the anterior circulation. Aneurysm size ranged from 1.4 to 25.0 mm (mean/median, 7.6/6.9 mm). Fifty-two aneurysms had post-operative imaging with total/near-complete occlusion of 84.6% (44/52). Aneurysm-based operative near-term complication rate was 9.7% while there were no permanent complications. For aneurysms and headache, 86.7% improved/resolved after embo-surgery, and were four times more likely to have a better clinical outcome (resolved or improved symptoms) after surgery (odds ratio [OR], 4.333; P=0.0325). Left-sided aneurysms had a higher occlusion rate (OR, 20; P=0.0073). Hypertension (OR, 4.2; P=0.0332) and smoking (OR, 7; P=0.0155) were more prone towards aneurysm occlusion. Patients without a family history were 14 times more likely to have favorable imaging outcome (P=0.0405). There is no difference of occlusion rates between untreated and previously treated aneurysms (P=0.6894). Overall, occlusion rate decreased by 14% with an increase of aneurysm size by 1 mm (P=0.0283). Conclusion: For anterior circulation aneurysms, the off-label application of PED is as effective and safe as reported for on-label intracranial aneurysms.
Deregulation of DNA Damage Signal Transduction by Herpesvirus Latency-Associated M2
Liang, Xiaozhen,Pickering, Mary T.,Cho, Nam-Hyuk,Chang, Heesoon,Volkert, Michael R.,Kowalik, Timothy F.,Jung, Jae U. American Society for Microbiology 2006 Journal of virology Vol.80 No.12
<B>ABSTRACT</B><P>Infected cells recognize viral replication as a DNA damage stress and elicit a DNA damage response that ultimately induces apoptosis as part of host immune surveillance. Here, we demonstrate a novel mechanism where the murine gamma herpesvirus 68 (γHV68) latency-associated, anti-interferon M2 protein inhibits DNA damage-induced apoptosis by interacting with the DDB1/COP9/cullin repair complex and the ATM DNA damage signal transducer. M2 expression constitutively induced DDB1 nuclear localization and ATM kinase activation in the absence of DNA damage. Activated ATM subsequently induced Chk activation and p53 phosphorylation and stabilization without eliciting H2AX phosphorylation and MRN recruitment to foci upon DNA damage. Consequently, M2 expression inhibited DNA repair, rendered cells resistant to DNA damage-induced apoptosis, and induced a G1 cell cycle arrest. Our results suggest that γHV68 M2 blocks apoptosis-mediated intracellular innate immunity, which might ultimately contribute to its role in latent infection.</P>