Photochemical versus Thermal Synthesis of Cobalt Oxyhydroxide Nanocrystals

Photochemical methods facilitate the generation, isolation, and study of metastable nanomaterials having unusual size, composition, and morphology. These harder-to-isolate and highly reactive phases, inaccessible using conventional high-temperature pyrolysis, are likely to possess enhanced and unprecedented chemical, electromagnetic, and catalytic properties. We report a fast, low-temperature and scalable photochemical route to synthesize very small (~3 nm) monodisperse cobalt oxyhydroxide (Co(O)OH) nanocrystals. This method uses readily and commercially available pentaamminechlorocobalt(III) chloride, [Co(NH3) 5Cl]Cl2, under acidic or neutral pH and proceeds under either near-UV (350 nm) or Vis (575 nm) illumination. Control experiments showed that the reaction proceeds at competent rates only in the presence of light, does not involve a free radical mechanism, is insensitive to O 2, and proceeds in two steps: (1) Aquation of [Co(NH3) 5Cl] 2+ to yield [Co(NH3) 5(H2O)] 3+, followed by (2) slow photoinduced release of NH3 from the aqua complex. This reaction is slow enough for Co(O)OH to form but fast enough so that nanocrystals are small (ca. 3 nm). The alternative dark thermal reaction proceeds much more slowly and produces much larger (~250 nm) polydisperse Co(O)OH aggregates. UV-Vis absorption measurements and ab initio calculations yield a Co(O)OH band gap of 1.7 eV. Fast thermal annealing of Co(O)OH nanocrystals leads to Co3O4 nanocrystals with overall retention of nanoparticle size and morphology. Thermogravimetric analysis shows that oxyhydroxide to mixed-oxide phase transition occurs at significantly lower temperatures (up to T = 64 degrees C) for small nanocrystals compared with the bulk

P-047 Multimodal endovascular treatment of wide-necked aneurysms: safety and occlusion outcomes from the sterling registry

PurposeWe present core-lab adjudicated immediate post-procedural angiographic outcomes following endovascular treatment of side wall and bifurcation wide-necked aneurysms using MICRUSFRAME and GALAXY coils and various adjunctive devices within the STERLING registry.MethodsSTERLING is an ongoing single-arm prospective post-market surveillance registry evaluating ruptured/unruptured aneurysms treated with MICRUSFRAME and GALAXY coils (Cerenovus, Irvine, CA). All cases of wide-neck aneurysm treatment (neck > 4 mm or dome-to-neck ratio 5mm and 13 mm. The average procedure time was 1.74 hours (SD 0.99) and the average fluoroscopy time was 49.7 minutes (SD 29.6).Aneurysms were treated using the following modalities: coiling alone (58.3%), stent-assisted coiling (24.4%), coiling plus flow diversion (8.3%), Pulserider-assisted coiling (4.2%), balloon-assisted coiling (1.2%), other adjunctive devices (1.8%), and multiple adjunctive devices (1.8%). Across the entire cohort, 82.1% of patients achieved adequate occlusion, defined as mRR class I or II. Angiographic outcomes according to treatment modality are summarized in table 1.Abstract P-047 Table 1Core-lab adjudicated immediate post-procedural occlusion scores Modified Raymond-Roy Outcome Coils Only (N=98) Stent-Assisted Coiling (N=41) Coils + Flow Diverter (N=14) Pulserider (N=7) Balloon Assisted Coiling (N=2) Other Adjunctive Devices (N=3) Multiple Adjunctive Devices (N=3) Total (N=168) Class I 50/98 (51.0%) 23/41 (56.1%) 1/14 (7.1%) 3/7 (42.9%) 2/2 (100.0%) 0 2/3 (66.7%) 81/168 (48.2%) Class II 42/98 (42.9%) 11/41 (26.8%) 1/14 (7.1%) 2/7 (28.6%) 0 0 1/3 (33.3%) 57/168 (33.9%) Class III 6/98 (6.1%) 7/41 (17.1%) 12/14 (85.7%) 2/7 (28.6%) 0 3/3 (100.0%) 0 30/168 (17.9%) IIIa 0 1/7 (2.5%) 0 0 0 0 0 1/168 (0.6%) IIIb 6/98 (6.1%) 6/7 (14.6%) 12/14 (85.7%) 2/7 (28.6%) 0 3/3 (100.0%) 0 29/168 (17.3%) Adequate occlusion (I or II ) 92/98 (93.9%) 34/41 (82.9%) 2/14 (14.3%) 5/7 (71.4%) 2/2 (100.0%) 0 3/3 (100.0%) 138/168 (82.1%) Procedure-related adverse events occurred in 7 cases (4.2%). These included 3 intraprocedural ruptures (1 ruptured, 2 unruptured at baseline), 1 cerebrovascular accident, and 3 asymptomatic thromboembolic events. There were no deaths.ConclusionEndovascular treatment of wide-neck aneurysms using MICRUSFRAME and GALAXY coils is safe and effective when used alone or in conjunction with currently available adjunctive devices.Disclosures R. De Leacy: 6; C; Non-financial support from Penumbra, Cerenovus, and Siemens. A. Puri: 1; C; Received research grants from Medtronic Neurovascular and Stryker Neurovascular. 2; C; Serves as consultant for Medtronic Neurovascular and Stryker Neurovascular. R. Starke: 2; C; Serves as consultant for Medtronic Neurovascular, Penumbra, Cerenovus, and Abbott. B. Jankowitz: 2; C; Serves as consultant for Medtronic and Stryker. A. Yoo: 1; C; Receives research grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. 2; C; Serves as consultant for Cerenovus, Penumbra, and Zoll. 4; C; Has equity interest in Insera Therapeutics.. G. Pero: None. C. Chivot: None. T. Yao: 2; C; Serves as consultant/proctor for Medtronic. O. Zaidat: 2; C; Serves as a consultant for Neuravi, Stryker, Penumbra, and Medtronic

E-125 Impact of COVID related restrictions on clinical trials – Insights from the sterling registry

IntroductionThe STERLING registry is a prospective collection of aneurysms treated with endovascular techniques. The primary intention is to assess the efficacy and safety of Galaxy and MicrusFrame coils (Cerenovus, Irvine, CA). The Covid pandemic has the potential to alter the delivery of medical care or trial enrollment. Changes to regional or hospital specific research infrastructure will likely affect trials for the worse.MethodsA retrospective review of STERLING sites and patients was undertaken to better understand regional variation in adapting to the pandemic and how enrollment was affected.Results45 global sites currently take part in the STERLING registry. 28 sites began enrolling pre-Covid. 34% of U.S. sites were required to halt research, enrollment or elective surgery, whereas only 8% of EU and none of the Japanese sites were required to significantly change their research protocols respectively. At the 10 (9 US, 1 EU) sites required to put a hold on research, rates of enrollment dropped from an average of 0.6 subjects/month in the US (0.5 in EU) to 0 in the first month and 0.1 subjects/month in the second month of Covid-related restrictions. At the time of this analysis (1/2021), the average rate of enrollment across those sites partially recovered to 0.2 subjects/month in the US and 0.2 in EU, although 5 of the 10 sites (all US) had not enrolled any subjects post Covid. Overall, mean actual vs. projected enrollment rates decreased more in the U.S. than in the EU and Japan. The percent of ruptured aneurysms in the per-protocol analysis increased from 23% to 40%, while the percent of unruptured aneurysms decreased from 76% to 60%. There were no significant changes to occlusion rates or adverse events pre/post Covid.Abstract E-125 Table 1Post-COVID differences in actual vs. projected monthly enrollment rates by region Region Actual (mean ± SD) Projected(mean ± SD) Mean Diff. 95% CI US 5.92 ± 3.53 9.58 ± 0.51 3.67 1.53; 5.80 EU 3.83 ± 2.04 5.83 ± 1.34 2.00 0.54; 3.46 Japan 1.25 ± 1.60 2.17 ± 0.39 0.92 -0.07; 1.90 Global 3.67 ± 1.61 5.86 ± 0.67 2.19 1.15; 3.24 ConclusionThe Covid pandemic has the potential to dramatically alter how research is conducted worldwide. U.S. sites faced tougher restrictions than their EU and Japan counterparts. Particularly within the U.S., moratoriums on research and elective surgery may be the driving factor in reducing overall enrollment and increasing the percentage of ruptured aneurysm enrollment. Fortunately, these changes did not appear to negatively affect occlusion rates or adverse events.Disclosures R. De Leacy: 6; C; Reports other and non-financial support from Penumbra; and non-financial support from Cerenovus and Siemens. A. Puri: 1; C; Has received research grants from Medtronic Neurovascular and Stryker Neurovascular.. 2; C; Serves as a consultant for Medtronic Neurovascular Stryker Neurovascular. R. Starke: 2; C; Serves as a consultant for for Medtronic Neurovascular, Penumbra, Cerenovus, and Abbott. B. Jankowitz: 2; C; Serves as a consultant for Medtronic and Stryker. A. Yoo: 1; C; Receives research grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. 2; C; Serves as a consultant for Cerenovus, Penumbra, and Zoll.. 4; C; Has equity interest in Insera Therapeutics.. G. Pero: None. C. Chivot: None. T. Yao: 2; C; Serves as a consultant/proctor for Medtronic. O. Zaidat: 2; C; Serves as a consultant for Neuravi, Stryker, Penumbra, and Medtronic

E-065 Interim safety and occlusion outcomes of endovascular treatment of large intracranial aneurysms in the sterling registry

Introduction Endovascular treatment for intracranial aneurysms has been evolving. Since the results of the ISAT and BRAT trial were published, multiple advancement of endovascular devices and procedures have occurred. The aim of this study is to share interim results for large aneurysms (> 10 mm) treated within the STERLING registry. Methods The STERLING registry (NCT03642639) is a Prospective, Multi-center, Single Arm Study to Obtain ’Real World’ Clinical Data and Characterize the Acute and Long-term Performance of the MICRUSFRAME and GALAXY Coils including the PulseRider Aneurysm Neck Reconstruction Device for the Endovascular Treatment of Intracranial Aneurysms (Cerenovus, Irvine, CA). The primary endpoint was adequate occlusion rate without retreatment at 12 months measured by Independent Core Lab. Secondary outcome measures were packing density, good functional outcome (mRS 0-2), as well as device-related serious events and retreatment rate within 1-year. Results Among the 450 subjects in the STERLING interim analysis, 44 patients had large aneurysms. Mean (Standard Deviation [SD]) age was 60.6(11.35), and most patients were females (77.3%). Hypertension was prevalent in (59.1%) of the cohort, while half of the cohort were smokers and (13.6%) had a history of SAH. Baseline mRS score was 0 and 1 in 61.4% and 27.3%, respectively. Mean (SD) aneurysm height and width were 11.06 mm (3.78) and 10.67 mm (3.44), respectively. Most aneurysms were in the anterior circulation (84.1%) and (61.9%) were sidewall. Median (IQR) dome to neck ratio was 2.0 (1.70-2.65) and 35 (79.5%) aneurysms had a wide neck. Saccular aneurysm was the most common morphology (86.4%) and (27.3%) were ruptured aneurysms. Most common method of treatment was primary coiling (n=16) followed by coiling+flow diversion (n=12). Mean (SD) packing density was 16.8(8.88). Adequate occlusion on 1-year follow-up was achieved in 86.7% (13/15) and four patients required retreatment within 1-year, resulting in 66.7% (10/15) patients with adequate occlusion without retreatment. There was no occurrence of intraprocedural rupture nor symptomatic intraprocedural thromboembolic events. Clinical outcome was available for unruptured aneurysms for 1 year follow-up and good functional outcome was achieved in 85.7% (12/14). Device related significant adverse events occurred in 1 patient only (2.3%). Conclusion Early results from the STERLING registry for large aneurysms are promising. Adequate occlusion per Independent Core Lab was achieved in 86.7% and retreatment rates were relatively low over 1-year follow-up. A good functional outcome was achieved in 85.7% of patients Disclosures O. Zaidat: 1; C; Stryker, Medtronic, Cerenovus, Penumbra, and Genentech. 2; C; Stryker, Medtronic, Cerenovus, Penumbra, and Neuravi. 4; C; ownership interest in Galaxy Therapeutics LLC;. 6; C; honoraria from Codman,Stryker,Penumbra, Medtronic. serves on the endovascular committee as co-chair for NIH StrokeNet Consortium; has served as an expert witness; had a patent for Ischemic stroke.. Y. Ashouri: None. R. Starke: 2; C; Medtronic Neurovascular, Penumbra, Cerenovus, Abbott.,. A. Puri: 1; C; Stryker Neurovascular, Medtronic, Cerenovus. He has received NIH grants. 2; C; tryker Neurovascular, Medtronic, Cerenovus, Microvention, QApel, Perfuze Medical, Arsenal Medical, Merit Medical Agile, Corindus, Imperative Care. 4; C; InNeuroCo Inc, Galaxy therapeutics, Agile Medical, Perfuze medical and Neurotechnology Investors. B. Jankowitz: None. A. Yoo: 1; C; Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. 2; C; Cerenovus, Penumbra, and Zoll. 6; C; Equity interest in Insera Therapeutics. G. Marnat: None. Z. Kulcsar: None. K. Sugiu: None. S. Jahshan: None. P. Machi: None. G. Pero: None. S. Castro: None. J. Howington,: None. C. Schirmer: None. C. Kilburg: None. C. Chivot: None. F. Al-Mufti: None. V. Da Ros: None. B. Gory: None. T. Yao: 2; C; Medtronic. A. Polifka: None. O. Francois,: None. A. Evans: None. J. Machaj: None. R. De Leacy: 2; C; Imperative Care, Cerenovus, Siemens Healthineers, Penumbra. 6; C; equity in Synchron, Endostream, Q’Apel Medical, Spartan Micro, Vastrax