BackgroundPreliminary clinical studies on the safety and efficacy of the pipeline embolization device (PED) for the treatment of small/medium aneurysms have demonstrated high occlusion rates with low complications.ObjectiveTo evaluate the safety and effectiveness of the PED for treatment of wide necked small and medium intracranial aneurysms.MethodsPREMIER is a prospective, multicenter, single arm trial. Patients were treated with the PED for unruptured wide necked aneurysms, measuring ≤12 mm along the internal carotid artery or vertebral artery, between July 2014 and November 2015. At 1 year post-procedure, the primary effectiveness endpoint was complete occlusion (Raymond grade 1) without major parent vessel stenosis (≤50%) or retreatment, and the primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death.ResultsA total of 141 patients were treated with PEDs (mean age 54.6±11.3 years, 87.9% (124/141) women). Mean aneurysm size was 5.0±1.92 mm, and 84.4% (119/141) measured <7 mm. PED placement was successful in 99.3% (140/141) of patients. Mean number of PEDs implanted per patient was 1.1±0.26; a single PED was used in 92.9% (131/141) of patients. At 1 year, 97.9% (138/141) of patients underwent follow-up angiography with 76.8% (106/138) of patients having met the study’s primary effectiveness endpoint. The combined major morbidity and mortality rate was 2.1% (3/140).ConclusionsTreatment of wide necked small/medium aneurysms with the PED results in high rates of complete occlusion without significant parent vessel stenosis and low rates of permanent neurologic complications.Trial registrationNCT02186561.

Mutations in MTO1 express a respiratory defect only in the context of a mitochondrial genome with a paromomycin-resistance allele. This phenotype is similar to that described previously for mss1 mutants by Decoster, E., Vassal, A., and Faye, G. (1993) J. Mol. Biol. 232, 79 -88. We present evidence that Mto1p and Mss1p are mitochondrial proteins and that they form a heterodimer complex.In a paromomycin-resistant background, mss1 and mto1 mutants are inefficient in processing the mitochondrial COX1 transcript for subunit 1 of cytochrome oxidase. The mutants also fail to synthesize subunit 1 and show a pleiotropic absence of cytochromes a, a 3 , and b. In vivo pulse labeling of an mto1 mutant, however, indicate increased rates of synthesis of other mitochondrial translation products. The respiratory defective phenotype of mto1 and mss1 mutants is not seen in a paromomycin-sensitive genetic background. The visible absorption spectra of such strains indicate a higher ratio of cytochromes b/a and elevated NADH-and succinate-cytochrome c reductase activities. To explain these phenotypic characteristics, we proposed that the Mto1p⅐Mss1p complex plays a role in optimizing mitochondrial protein synthesis in yeast, possibly by a proofreading mechanism.

Dural arteriovenous fistula (dAVF) accounts for approximately 10% of all intracranial vascular malformations. While they can be benign lesions, the presence of retrograde venous drainage and cortical venous reflux makes the natural course of these lesions aggressive high risk of haemorrhage, neurological injury and mortality. Endovascular treatment is often the first line of treatment for dAVF. Both transarterial and transvenous approaches are used to cure dAVF. The selection of treatment approach depends on the angioarchitecture of the dAVF, the location, the direction of venous flow. Surgery and, to a lesser extent, stereotactic radiosurgery are used when endovascular approaches are impossible or unsuccessful.

OBJECTIVEFlow diversion requires neointimal stent overgrowth to deliver aneurysm occlusion. The existing literature on aneurysm occlusion is limited by heterogeneous follow-up, variable antiplatelet regimens, noninvasive imaging modalities, and nonstandard occlusion assessment. Using a large, single-center cohort with low attrition and standardized antiplatelet tapering, the authors evaluated outcomes after flow diversion of anterior circulation aneurysms to identify predictors of occlusion and aneurysm persistence.METHODSData from a prospective, IRB-approved database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion with the Pipeline embolization device (PED) at the authors’ institution. Follow-up consisted of catheter cerebral angiography at 6 and 12 months postembolization. Clopidogrel was discontinued at 6 months and aspirin was reduced to 81 mg daily at 12 months. Occlusion was graded as complete, trace filling, entry remnant, or aneurysm filling. Multivariate logistic regression was performed to identify predictors of aneurysm persistence.RESULTSFollow-up catheter angiography studies were available for 445 (91%) of 491 PED procedures performed for anterior circulation aneurysms between August 2011 and August 2016. Three hundred eighty-seven patients accounted for these 445 lesions with follow-up angiography. The population was 84% female; mean age was 56 years and mean aneurysm size was 6.6 mm. Aneurysms arose from the internal carotid artery (83%), anterior cerebral artery (13%), and middle cerebral artery (4%). Morphology was saccular in 90% of the lesions, and 18% of the aneurysms has been previously treated. Overall, complete occlusion was achieved in 82% of cases at a mean follow-up of 14 months. Complete occlusion was achieved in 72%, 78%, and 87% at 6, 12, and 24 months, respectively. At 12 months, adjunctive coiling predicted occlusion (OR 0.260, p = 0.036), while male sex (OR 2.923, p = 0.032), aneurysm size (OR 3.584, p = 0.011), and incorporation of a branch vessel (OR 2.206, p = 0.035) predicted persistence. Notable variables that did not predict aneurysm occlusion were prior treatments, vessel of origin, fusiform morphology, and number of devices used.CONCLUSIONSThis is the largest single-institution study showing high rates of anterior circulation aneurysm occlusion after Pipeline embolization. Predictors of persistence after flow diversion included increasing aneurysm size and incorporated branch vessel, whereas adjunctive coiling predicted occlusion.

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