Extended monitoring of re-coiled cerebral aneurysms after initial postcoiling recanalization: Safety and durability of repeat coil embolization.

PURPOSE: In the endovascular era, postcoiling recanalization of cerebral aneurysms is occurring with greater frequency. Repeat coiling is usually done to prevent rebleeding, although long-term outcomes of re-embolization have yet to be adequately investigated. The present study was undertaken to assess clinical and radiographic outcomes of re-embolization in recanalized aneurysms, focusing on procedural safety, efficacy, and durability. METHOD: In this retrospective review, we examined 308 patients with 310 recurrent aneurysms. All lesions were re-coiled, once major recanalization (after initial coil embolization) was established. Medical records and radiologic data amassed during extended follow-up were then subject to review. Cox proportional hazards regression analysis was undertaken to identify risk factors for subsequent recurrence. RESULT: During a lengthy follow-up (mean, 40.2 ± 33.0 months), major recanalization developed again in 87 aneurysms (28.1%). Multivariable Cox regression analysis linked re-recanalization to initial saccular neck width (p=.003) and autosomal dominant polycystic kidney disease (ADPKD; p<.001). Stent implantation (p=.038) and successful occlusion at second coiling (p=.012) were protective against later recanalization in this setting. The more recent the second embolization was performed, the lower the risk of further recurrence (p=.023). Procedure-related complications included asymptomatic thromboembolism (n = 9), transient ischemic neurologic deficits (n = 2), procedural bleeding (n = 1), and coil migration (n = 1), but there were no residual effects or deaths. CONCLUSION: Repeat coil embolization is a safe therapeutic option for recanalized cerebral aneurysms. Wide-necked status and ADPKD emerged as risks for subsequent recanalization, whereas successful occlusion and stent implantation seemed to reduce the likelihood of recurrence after re-embolization procedures.

Endovascular Treatment in Precommunicating Segment Aneurysms of Posterior Cerebral Artery.

BACKGROUND: Precommunicating (P1) segment aneurysms of the posterior cerebral artery are rare, with few studies reported to date. Herein, we address the clinical and radiologic outcomes of their endovascular treatment. METHODS: For this study, we retrieved prospectively collected data on 35 consecutive patients with 37 P1 aneurysms, analyzing the clinical ramifications and morphologic outcomes of treatment. All subjects received endovascular interventions between January 2001 and October 2021. RESULTS: There were 16 aneurysms (43.2%) of P1 segment sidewalls and 21 (56.8%) at P1/posterior communicating artery junctions. Five (13.5%) were fusiform, and 14 (37.8%) were ruptured. In 14 patients (40%), 16 aneurysms (43%) were associated with intracranial arterial occlusive disease of the anterior circulation. Selective coiling was undertaken in 34 aneurysms (91.9%), using single (n = 24) or double (n = 4) microcatheters, microcatheter protection (n = 2), or stents (n = 4); and trapping was done in 3 (8.1%). No procedure-related morbidity or mortality resulted. Excluding the trapped lesions, angiographic follow-up of 29 aneurysms obtained >6 months after embolization (mean, 12.4 month) revealed stable occlusion in 21 (72.4%), with some recanalization in the other 8 (minor: 3/29, 10.4%; major: 5/29, 17.2%). CONCLUSIONS: Aneurysms of P1 segment (vs. other locations) are strongly associated with intracranial arterial occlusive disease of the anterior circulation and thus are likely flow related. Endovascular treatment of such lesions seems safe and efficacious, despite the array of technical strategies that their distinctive anatomic configurations impose.

Stent-Assisted Coil Embolization Versus Flow-Diverting Stent in Unruptured Vertebral Artery Dissecting Aneurysms: Efficacy and Safety Comparison.

BACKGROUND: Reconstructive strategies for unruptured vertebral artery dissecting aneurysms (VADAs) have increasingly relied on newly developed endovascular devices. However, their clinical performance metrics are seldom reported. OBJECTIVE: To compare stent-assisted coil embolization (SACE) and flow-diverting stent (FDS) deployment as treatments for unruptured VADAs, focusing on efficacy and safety. METHODS: A total of 72 VADAs were submitted to SACE (n = 48) or FDS (n = 24) between April 2009 and September 2021. We reviewed medical records and radiological data to assess efficacy and safety outcomes by method, building an inverse probability of treatment-weighted (IPTW) logistic regression model and conducting survival analyses. RESULTS: Ultimately, 24 aneurysms (33.3%) showed signs of recanalization (major, 14; minor, 10) at 6-month follow-up. Initially determined 6-month rates of overall (SACE, 31.2%; FDS, 41.7%) and major (SACE, 20.8%; FDS, 16.7%) recanalization did not differ significantly by modality; but in the IPTW logistic regression model, adjusted for aneurysm morphology, major recanalization at 6 months was lower for the FDS (vs SACE) subset (odds ratio = 0.196; P = .027). Likewise, the cumulative rate of major recanalization was more favorable for the FDS (vs SACE) subset (hazard ratio = 0.291; P = .048) in IPTW Cox proportional hazards model adjusted for aneurysm morphology. Modality-based assessments of procedural and delayed complications were similar. CONCLUSION: Both reconstructive VADA interventions are safe and effective by adjusting treatment modality depending on the angioanatomic configuration. However, follow-up data after treatment proved more favorable for FDS deployment than for SACE in limiting major recanalization. Case-controlled studies of more sizeable cohorts are needed for corroboration.

Endovascular Treatment of Intracranial Aneurysms Using a Microcatheter Protection.

PURPOSE: Stent protective or balloon remodeling techniques have enabled coil embolization of complexly configured aneurysms. Still, the utility of such methods may be limited in some small-caliber and/or inherently tortuous lesions. The present study was conducted to examine the efficacy of microcatheter protection (MCP) when applied in these circumstances. METHODS: This retrospective review included 432 patients with 452 intracranial aneurysms subjected to MCP between April 2001 and January 2021. All available medical records and radiologic data were analyzed, focusing on strategic, safety, and efficacy aspects of the procedures. RESULTS: In a majority (255/452, 56.4%) of cases, MCP was applied throughout entire coiling procedures, as opposed to coil framing (137/452, 30.3%) or filling/finishing (60/452, 13.3%) only. Lesions of the middle cerebral artery (54.9%) predominated, followed by anterior (12.4%) and posterior (11.1%) communicating artery aneurysms. Stent protection was also used occasionally (46/452, 10.2%). Procedural morbidity was low (3/432, 0.7%), limited to symptomatic thromboembolism and procedural leakage, and there were no deaths. Occlusion was successfully achieved by MCP in 424 aneurysms (93.8%). During the follow-up period (mean, 43.4 ± 30.4 months), satisfactory occlusion was documented in 406 of 440 (92.3%) aneurysms. CONCLUSION: MCP is feasible and safe for coil embolization of intracranial aneurysms, in conjunction with multicatheter, balloon, or stenting techniques. MCP may have merit in small-sized or tortuous lesions not amenable to balloon or stent usage, often eliminating the need for stenting altogether.

Flow Diverter in Unruptured Intracranial Vertebral Artery Dissecting Aneurysm.

Objective: Intracranial vertebral artery dissecting aneurysm (VADA) may present as aneurysmal dilation alone, dilation with coexisting stenosis, or, in some cases, as a recurrent aneurysm after previous reconstructive treatment. To date, the clinical utility of flow diverters in VADA has not been examined according to these various circumstances. This study aims to report the safety and efficacy of flow diverters in the treatment of various manifestations of intracranial VADA. Methods: A total of 26 patients and 27 VADAs treated with flow diverting stents from November 2014 to September 2021 were included. Medical records and radiologic data were analyzed to assess the safety and efficacy of flow diverting stents. Results: The results showed that 12 cases (44.4%) presented with aneurysmal dilation only, 7 (26.0%) with aneurysmal dilation and one or more associated stenotic lesions, and 8 (29.6%) as recurrence after previous treatment, including stent-assisted coil embolization (n = 5), single stent only (n = 1), and coil embolization without stent (n = 2). Among 27 lesions, 25 were treated with single flow diverters; additional flow diverting stents were required in 2 cases because of incomplete coverage of the aneurysm neck. There was one instance of incomplete expansion of the flow diverter. All cases showed contrast stagnation in the aneurysmal sac immediately after deployment of the flow diverting stent, and during a mean follow-up period of 18.6 months (range 6 to 60), the overall complete occlusion rate was 55.6%, with complete occlusion of 83.3% of aneurysmal dilation only lesions, 42.9% of aneurysms with stenosis, and 25% of the recurrent aneurysm. Only two patients (7.7%) had delayed ischemic complications. Conclusion: Flow diverters have proven safe and effective in unruptured VADA. However, the complete occlusion rate with the flow diverter is relatively lower in VADA with stenosis or with previous stent placement than in dilation-only lesions. Further study with a larger cohort would be needed to confirm these results.

Stretchable Inorganic LED Displays with Double-Layer Modular Design for High Fill Factor.

The recent commercial success of flexible and foldable displays has resulted in growing interest in stretchable electronics which are considered to be the next generation of the optoelectronic technology. Stretchable display technologies are being intensively studied for versatile applications including wearable, attachable, and shape changeable electronics. In this paper, we present high fill factor, stretchable inorganic light-emitting diode (LED) displays fabricated by connecting mini-LEDs and stretchable interconnects in a double-layer modular design. The double-layer modular design enables an increased areal coverage of LEDs and stretchable interconnectors with both electrical and mechanical stability. The main features of the double-layer modular design, fabrication processes, and device characteristics for the high fill factor, stretchable inorganic LED display are discussed, with experimental and computational results. Demonstrations of a passive matrix LED display confirm the potential value of the multi-layer structured, stretchable electronics in a wide range of applications that need high fill factor with high stretchability.

Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo.

In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit(®)) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric-coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8.

Synergistic anticancer effects of lectin and doxorubicin in breast cancer cells.

We studied the effects, either combined or alone, of lectin from Korean mistletoe (Viscum album var. coloratum agglutinin, VCA) and doxorubicin (DOX) in MCF-7 (estrogen receptor-positive) and MDA-MB231 (estrogen receptor-negative) human breast cancer cells. When VCA and DOX were combined, a strong synergistic effect was shown in cell growth inhibition, compared to VCA or DOX treatment alone. In quantitative apoptosis studies analyzed by flow cytometry, a combination of two agents showed an increase in apoptosis in both cells, compared to agents alone. Also, pro-apoptotic proteins including Bax, Bik, and Puma were increased in both cells, and the survival factor Bcl-2 was inhibited in MCF-7 cells when drugs were combined. Furthermore, VCA combined with DOX mediated S phase arrest, accompanied with a decrease of cell number at G0/G1 phase. This suggests that VCA and DOX combination may possibly lead to a novel strategy for the treatment of breast cancer.

Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity.

Fatty acid synthase (FAS) has been proposed to be a new drug target for the development of anticancer agents because of the significant difference in expression of FAS between normal and tumour cells. Since a n-hexane-soluble extract from Ginkgo biloba was demonstrated to inhibit FAS activity in our preliminary test, we isolated active compounds from the n-hexane-soluble extract and evaluated their cytotoxic activity in human cancer cells. Three ginkgolic acids 1-3 isolated from the n-hexane-soluble extract inhibited the enzyme with IC(50) values 17.1, 9.2 and 10.5 µM, respectively, and they showed cytotoxic activity against MCF-7 (human breast adenocarcinoma), A549 (human lung adenocarcinoma) and HL-60 (human leukaemia) cells. Our findings suggest that alkylphenol derivatives might be a new type of FAS inhibitor with cytotoxic activity.

Evaluation of the Mutagenic Properties of Two Lignans from Acanthopanax koreanum Nakai.

Acanthopanax koreanum Nakai, a well known traditional herb grown in Jeju Island, South of Korea, has been used as a tonic and sedative agent, as well as in the treatment of diabetes and immune diseases. Mutagenicity of two lignans, syringaresinol and tortoside A isolated from A. koreanum, was assessed using Salmonella/microsome (Ames) test. Tester strains used were Salmonella typhimurium TA98, TA100, TA1535, and Escherichia coli WP2uvrA. The mutagenic activity was determined both in the absence or presence of S9 mixture. As a result, tortoside A did not cause any increase in the number of his(+) revertants in S. typhimurium and E. coli WP2uvrA strains in the presence or absence of S9 mix, compared to the controls. Similarly, low concentrations of syringaresinol (750 and 1,500 µg/plate) did not show any mutagenic properties in all bacterial strains, in the presence or absence of S9 mixture. However, in the high concentration of syringaresinol (3,000 µg/plate), the number of revertants were increased in TA1535 strains, in the absence of S9 metabolic activation. Therefore, in vivo experiments such as comet assay are needed to further determine the genotoxic/carciogenic potential of syringaresinol isolated from A. koreanum.

The antimutagenic effect of mistletoe lectin (Viscum album L. var. coloratum agglutinin).

A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anticancer activity, was isolated from mistletoe. In this study, we investigated the antimutagenic potentials of VCA by using the pre-incubation method of the Ames test (Salmonella typhimurium TA98 and TA100) in the presence or absence of S9 mixture. Viscum album L. var. coloratum agglutinin was assessed for its antimutagenic properties against the mutagens 2-aminoanthracene (2AA) and furylfuramide (AF-2) for strain TA98, and sodium azide (NaN(3) ) and 2-aminoanthracene (2AA) for strain TA100. The concentrations used for this test compound were 100, 200 and 400 µg per plate. Viscum album L. var. coloratum agglutinin showed moderate, but not negligible, protective effects regarding the antimutagenic properties against the direct-acting mutagens NaN(3) and AF-2. Furthermore, VCA was more effective in preventing the mutagenicity of the indirect-acting mutagen 2-AA (in the presence of S9) when tested with both TA98 and TA100. In conclusion, this report has shown broad ranging antimutagenic effects of VCA to numerous mutagens in TA98 and TA100 Salmonella typhimurium strains. Although the data presented here cannot be applied in vivo, they can support other antimutagenic and anticarcinogenic findings for VCA.

Mutagenicity and anti-mutagenicity of Acanthopanax divaricatus var. albeofructus.

The beneficial effects of Acanthopanax divaricatus var. albeofructus (ADA) extracts have been assessed by mutagenic and anti-mutagenic activities by Ames test. Mutation of Salmonella typhimurium strains TA 98, TA 100, TA1535, TA1537, and Escherichia coli WP2 uvr A was assayed in duplicates by the procedure of Maron and Ames in the presence or absence of S9 mix. As a result, ADA extracts were not mutagenic for S. typhimurium strains TA 98, TA 100, TA1535, TA1537, and E. coli by the Ames assay. Anti-mutagenic activity was assayed by the Ames mutagenicity assay using histidine mutant of S. typhimurium strains TA 98 and TA 100, using the plate-incorporation method. 2-Aminoanthrancene (2-AA), 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2), and sodium azide (NaN(3)) were used as the mutagens. ADA extracts showed a strong anti-mutagenic activity against 2-AA-induced mutagenesis which requires liver-metabolizing enzymes, and the same extract exhibited inhibitory effects on AF-2 and NaN(3)-induced mutagenesis in the absence of liver-metabolizing enzymes. The data indicate that ADA extracts contain anti-mutagenic activities against typical mutagens. The anti-mutagenic property of ADA provides additional health supplemental value to the other claimed therapeutic properties of the plant.

Anti-inflammatory and Anti-oxidative Effects of Korean Red Ginseng Extract in Human Keratinocytes.

BACKGROUND: In this study, we have investigated the effect of Korean red ginseng (KRG) extracts on the production of TNF-α and IL-8 in human keratinocytes. Also, to examine the antioxidative effect of red ginseng extracts, free radical scavenging activity and superoxide dismutase (SOD) activity in human dermal fibroblasts was measured. METHODS: To investigate the effect of KRG in atopic dermatitis, we measured the level of TNF-α and IL-8 secretion in LPS-stimulated human keratinocytes after the treatment of KRG extracts using enzyme-linked immunosorbent assay. Anti-oxidative activity was investigated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and SOD activity. RESULTS: The stimulation of human keratinocytes with KRG extracts shifted the LPS-induced cytokine secretion toward a more immunosuppressive response. KRG dose-dependently decreased TNF-α and IL-8 production in HaCaT cells and a significant inhibition of TNF-α was shown when cells were treated with 500 and 1,000 µg/ml of KRG extracts. Additionally, KRG extracts showed DPPH radical scavenging and SOD activity in a dose-dependent manner. Particularly, SOD activities of concentrations higher than 60 µg/ml of KRG extracts were significantly different in human dermal fibroblast cells. CONCLUSION: Based on this study, KRG extracts may be a useful immunosuppressive agent in the treatment of atopic dermatitis.

Genotoxicity detection of five medicinal plants in Nigeria.

This study was performed to investigate the safety of Alchornea cordifolia, Cnestis ferruginea, Lonchocarpus sericeus, Trema orientalis, and Senna alata in respect to genotoxicity. These five medicinal plants are widely distributed in Africa. They are used as a traditional medicine in many African counties for the treatment of microbial, inflammatory, and stress-related diseases. To evaluate the bacterial reverse mutation of these five medicinal plants, the in vitro Ames test using Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2uvrA, with or without the addition of S9 mixture was performed. Concentrations used for this test were 625, 2,500, and 5,000 µg per plate. A. cordifolia, C. ferruginea, L. sericeus, and T. orientalis showed negative results in the bacterial reverse mutation test, suggesting that it is potentially safe for these plants to be used in medicinal plants supplements at high doses. However, our experiments suggest that S. alata is a potent mutagen. Therefore, further studies are needed to evaluate the carcinogenicity of S. alata in order to adequately assess the risks for human health.