BackgroundThe Pipeline Embolisation Device with Shield technology (PED-Shield) is suggested to have reduced thrombogenicity. This reduced thrombogenicity may make it possible to use safely in the acute treatment of aneurysmal subarachnoid haemorrhage (aSAH) on single antiplatelet therapy (SAPT).ObjectiveTo evaluate the safety and efficacy of the off-label use of PED-Shield with SAPT for the acute treatment of aSAH.MethodsPatients who underwent acute treatment of ruptured intracranial aneurysms with the PED-Shield with SAPT were retrospectively identified from prospectively maintained databases at three Australian neurointerventional centres. Patient demographics, aneurysm characteristics, clinical and imaging outcomes were reviewed.ResultsFourteen patients were identified (12 women), median age 64 (IQR 21.5) years. Aneurysm morphology was saccular in seven, fusiform in five, and blister in two. Aneurysms arose from the anterior circulation in eight patients (57.1%). Six (42.9%) patients were poor grade (World Federation of Neurological Societies grade ≥IV) SAH. Median time to treatment was 1 (IQR 0.5) day. Complete or near complete aneurysm occlusion (Raymond-Roy <3) was achieved in 12 (85.7%) patients at the end of early-acute follow-up (median day 7 after SAH). Permanent, treatment-related morbidity occurred in one (7.1%) patient and one (7.1%) treatment-related death occurred. The use of a postoperative heparin infusion (n=5) was associated with a higher rate of all complications (80.0% vs 11.1%, p=0.023) and symptomatic complications (60% vs 0.0%, p=0.028). No symptomatic ischaemic or haemorrhagic complications were observed in the patients who did not receive a post-operative heparin infusion. Nine (64.3%) patients were functionally independent on discharge from the treatment centre.ConclusionThe PED-Shield may be safe to use in the acute treatment of ruptured intracranial aneurysms with SAPT. Further investigation with a formal treatment registry is needed.
BRCA1 is a tumor suppressor that functions in controlling cell growth and maintaining genomic stability. BRCA1 has also been implicated in telomere maintenance through its ability to regulate the transcription of hTERT, the catalytic subunit of telomerase, resulting in telomere shortening, and to colocalize with the telomere-binding protein TRF1. The high incidence of nonreciprocal translocations in tumors arising from BRCA1 mutation carriers and Brca1-null mice also raises the possibility that BRCA1 plays a role in telomere protection. To date, however, the consequences for telomere status of disrupting BRCA1 have not been reported. To examine the role of BRCA1 in telomere regulation, we have expressed a dominant-negative mutant of BRCA1 (trBRCA1), known to disrupt multiple functions of BRCA1, in telomerase-positive mammary epithelial cells (SVCT) and telomerase-negative ALT cells (GM847). In SVCT cells, expression of trBRCA1 resulted in an increased incidence of anaphase bridges and in an increase in telomere length, but no change in telomerase activity. In GM847 cells, trBRCA1 also increased anaphase bridge formation but did not induce any change in telomere length. BRCA1 colocalized with TRF2 in telomerase-positive cells and with a small subset of ALT-associated PML bodies (APBs) in ALT cells. Together, these results raise the possibility that BRCA1 could play a role in telomere protection and suggest a potential mechanism for one of the phenotypes of BRCA1-deficient cells.
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