Transvenous Onyx Embolization of a Type D Carotid-Cavernous-Fistula: Operative Video.

Carotid-cavernous fistulas (CCFs) are acquired pathologic shunts between the carotid circulation and the cavernous sinus that result in venous congestion.1 They often present with ocular symptoms, such as chemosis, proptosis, and blurry vision. Cranial nerve deficits and increased intraocular pressure are often seen on the neuro-ophthalmologic examination.2 If left untreated, they can lead to cortical venous reflux and intracranial hemorrhage. A cerebral angiogram is the gold standard to diagnose these lesions. The hallmark of dural CCF is opacification of venous structures in the arterial phase of the angiogram. Dependent on carotid branches contributing to the fistula, 4 types are classically defined by Barrow et al.3 When the fistula is indirect (types B-D), the goal of treatment is obliteration via the transvenous route.4 We present the case of a patient who had chemosis and proptosis of the left eye with imaging findings concerning for dural CCF (Video 1). An informed consent was obtained and the patient underwent a cerebral angiogram and treatment of the CCF. In the operative video, we showcase the treatment of a type D CCF using transvenous embolization with Onyx (Covidien, Irvine, CA) and achieve angiographic cure of the fistula. We were able to use Onyx for embolization since the superselective injection did not show cortical venous drainage. This is important as obliteration of cortical veins with liquid embolisate could cause venous infarcts. To our knowledge, this is the first video article that illustrates the endovascular embolization of a CCF and highlights the angiographic findings pre- and post-embolization.

Combination of Phospholipid Complex and Matrix Dispersion.

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)-loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

Systematic review of embolization of type I endoleaks using liquid embolic agents.

OBJECTIVE: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. METHODS: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. RESULTS: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. CONCLUSIONS: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.

Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol.

Resveratrol is a very promising anti-oxidant drug candidate with low oral bioavailability due to its intrinsic poor water solubility, intestinal efflux and metabolization mechanisms. Resveratrol solubility high-throughput screening with different carriers was performed showing an enhancement above 2000-fold with Soluplus® and Tween® 80. The former was selected as a carrier at the ratio of resveratrol: Soluplus® (1:2). Then, third-generation solid dispersions were developed with Gelucire® and poloxamer 407 at 5 and 15% to resveratrol: Soluplus® (1:2). All formulations enhanced solubility around 2-fold when compared to resveratrol: Soluplus® (1:2) solid dispersion. Caco-2 cells permeability studies showed that both surfactants increased drug permeability and the fraction recovered (2-fold) suggesting that these could reduce efflux mechanism and metabolism. Formulation with 15% poloxamer 407 demonstrated most promising results and was selected for further studies. In in vivo studies, resveratrol:Soluplus®: poloxamer 407 (1:2-15%) third generation solid dispersion presented an AUCo-t of 279 ± 54 ng.h/mL and a Cmax of 134 ± 78 ng/mL, 2.5 fold higher than solid dispersion without poloxamer 407. This work reports the development of third-generation solid dispersion that significantly improved resveratrol bioavailability. This was accomplished by an increased solubility and most probably by reducing intestinal efflux and metabolism mechanisms.

Middle meningeal artery embolization for chronic subdural hematoma: an institutional technical analysis.

BACKGROUND: Recently, middle meningeal artery (MMA) embolization has emerged as a potentially safe and effective method of treating chronic subdural hematoma (cSDH). OBJECTIVE: To report a single-center experience with MMA embolization and examines the type of embolic material used, the extent of penetration, and the number of MMA branches embolized. METHODS: A retrospective analysis of all patients with MMA embolization from 2018 through 2019 was performed. A failed outcome was defined as either surgical rescue and/or greater than 10 mm of hematoma residual or reaccumulation following embolization. RESULTS: Of 35 patients, surgery had failed for 9 (26%) and initial conservative treatment had failed for 6 (17%). Of 41 MMA embolizations, including those in six patients with bilateral cSDH who underwent bilateral MMA embolization, 29 (72%) were performed using ethylene vinyl alcohol copolymer (Onyx), 7 (17%) using particles, and 5 (12%) using n-butyl cyanoacrylate. Both the anterior and posterior MMA divisions were embolized in 29 cases (71%); distal penetration of these branches was achieved in 25 embolizations (61%). Twenty-six (63%) cSDHs completely resolved. Complete resolution was seen in 22 of 29 hematomas (76%) in which both anterior and posterior MMA branches were occluded versus 4 of 12 (33%) following single-branch embolization (p=0.014). Embolization of one cSDH (2%) failed. CONCLUSION: MMA embolization of cSDHs appears to be both safe and efficacious. Furthermore, embolization of both the anterior and posterior MMA branches may be associated with increased odds of complete resolution.

Outcomes of Type II Endoleak Treatment Using Ethylene Vinyl Alcohol Copolymer (OnyxTM).

INTRODUCTION: This study reports our experience with the use of an ethylene vinyl alcohol copolymer (Onyx™) for the treatment of type II endoleak after endovascular repair of abdominal aortic aneurysms (EVAR) in comparison to coils and cyanoacrylate glue. METHODS: Clinical data of all patients treated for type II endoleak following EVAR between 2009 and 2017 were retrospectively analyzed. Abdominal aortic aneurysm (AAA) diameter and AAA sac volume during follow-up were measured using computed tomography angiography (CTA). Treatment failure variables were created for the change in sac diameter and volume. An increase in sac diameter ≥ 5 mm was considered a failure, as was an increase ≥ 10% in AAA sac volume. RESULTS: 35 patients underwent treatment for a persistent type II endoleak following EVAR. Of these patients, 18 (51.4%) were treated with Onyx and 17 (48.6%) were treated with coils ± cyanoacrylate glue embolization. There were no significant differences between the 2 groups with regard to demographics. The average volume of Onyx used per treatment was 13.4 ml (range 4.5 ml- 39 ml). There was no difference in efficacy between the Onyx and non-Onyx group. Complications were limited to 1 non-target embolization without significant clinical sequelae. CONCLUSIONS: Ethylene vinyl alcohol copolymer (Onyx™) embolization is similarly effective compared to traditional cyanoacrylate glue or coil embolization in the treatment of type II endoleak after EVAR.

Management of distal aneurysm of the superior mesenteric artery by percutaneous ultrasound-guided Onyx injection: A case report.

OBJECTIVES: The aim of this article is to report an alternative approach for the management of a distal aneurysm of superior mesenteric artery using direct percutaneous ultrasound-guided Onyx injection. METHODS: We report a rare case of symptomatic superior mesenteric artery aneurysm. A 78-year-old man presents with pain and pulsating mass in the right umbilical region of the abdomen. The patient was treated by percutaneous ultrasound-guided Onyx injection after several failing transarterial embolization attempts. RESULTS: The procedure was successful without any complication, and the patient wasdischarged to home the day after procedure. Follow-up at 60 months confirmed the complete thrombosis of the aneurysm sac. Ultrasound-guided Onyx injection for distal superior mesenteric artery aneurysm could provide an alternative to transcatheter arterial embolization or open surgery. Anatomical assessment of collaterals and knowledge of abdomen anatomy could play important roles in preventing bowel ischemia and minimizing the risk of procedural complication. CONCLUSION: Ultrasound-guided Onyx injection of superior mesenteric artery aneurysm is a feasible, effective, and cost-saving technique that can be used when endovascular approach is not possible or has failed.

First clinical multicenter experience with the new Scepter Mini microballoon catheter.

BACKGROUND: Balloon-assisted techniques can improve the endovascular treatment of cerebrospinal vascular malformations. The aim of this study was to report the first clinical multicenter experience with the new Scepter Mini dual-lumen microballoon catheter. METHODS: Patients with cerebral or spinal vascular malformations treated with the Scepter Mini at seven European neurovascular centers were retrospectively reviewed. Clinical data, angiographic features of the vascular malformations, procedural parameters including the type of application, navigability, technical failures, complications and embolization success were assessed. RESULTS: The usage of 34 Scepter Mini microballoon catheters in 20 patients was analyzed. Most treated malformations (80.0%) were cerebral arteriovenous malformations. Four different applications were reported: embolization via Scepter Mini (n=23, 67.6%), balloon-occlusion with simultaneous embolization via a second microcatheter (n=3, 8.8%), diagnostic angiography with simultaneous balloon-inflation for flow arrest (n=4, 11.8%), and navigation support (n=4, 11.8%). The mean diameter of the blood vessels in which the Scepter Mini was inflated was 1.9±0.5 mm. The navigability of the Scepter Mini was rated as 'easy' or 'very easy' in 88.2% of cases. Complete occlusion of the malformation was achieved in 60.9% of cases. Technical failures occurred in 4/23 embolization procedures, and all were related to insufficient stability of the balloon within the vessel. No complications related to the Scepter Mini were observed, while unrelated complications occurred in three patients (15.0%). CONCLUSIONS: The Scepter Mini is a promising new device for balloon-assisted embolization of cerebrospinal vascular malformations via small feeders. Beyond embolization, the Scepter Mini can also be used for other applications, such as superselective flow arrest and navigation support.

Embolization of peripheral arteriovenous malformations and fistulas with precipitating hydrophobic injectable liquid (PHIL®).

PURPOSE: This paper reports on the preliminary experience of a single center in the embolization of peripheral AVMs and fistulas with precipitating hydrophobic injectable liquid (PHIL®), focusing on technical aspects and short-term clinical outcomes. MATERIALS AND METHODS: Seven males and five females were included in this study, mean age 42.16 years. For ten of them, it was the first embolization treatment; two had been previously treated with Onyx® embolization. PHIL® was injected with a transarterial approach without other embolics during the same procedure. Lesions were localized in small bowel (1), colon (1), head face (5), forefoot (1), uterus (1) and thorax (3); all were symptomatic. After 30-day clinical follow-up, a contrast-enhanced CT or MR was acquired at 3 months from intervention to detect eventual lesion residual. RESULTS: After a single embolization procedure, complete technical success was obtained in 50%, while clinical improvement without additional therapies was appreciable in all patients. No technical failure occurred; in two cases, a small amount of PHIL® proximally refluxed in nontarget vessels without clinical effects. No tattooing effects of superficial lesions neither artifacts at CT and cone-beam CT controls were evident. CONCLUSIONS: PHIL® seems to be a safe and effective liquid embolic agent for the treatment of peripheral AVMs and fistulas; although a direct comparison between PHIL and Onyx was not performed, PHIL might present the advantages of reduced artifacts at postprocedural CT scan and no need for shaking time preparation, but it is more expensive due to lower volume of product for each package and slightly less radiopaque at fluoroscopy.

Onyx versus coil embolization for the treatment of type II endoleaks.

OBJECTIVE: Little evidence is available supporting the optimal treatment of type II endoleaks associated with aortic sac growth. Previous studies have lacked comparisons between treatment methods and long-term follow-up. The purpose of the present study was to review our center's experience with the treatment of type II endoleaks comparing Onyx (a liquid embolization agent consisting of ethylene vinyl alcohol; Medtronic, Minneapolis, Minn) embolization and coil embolization. METHODS: A retrospective review of prospectively collected data from a vascular surgery database was performed to identify all patients who had undergone embolization of a type II endoleak for aortic sac growth after endovascular aneurysm repair from 2005 to 2018. The Onyx and coil embolization groups were compared using univariate statistics. RESULTS: A total of 58 patients had undergone 77 embolization procedures for type II endoleaks with either Onyx (27 patients; 37 procedures) or coils (31 patients; 40 procedures). The average aneurysm size at embolization was larger in the Onyx group (77.9 ± 15.1 mm) compared with coil embolization (73.4 ± 11.9 mm). The mean follow-up was 57 months for the Onyx group and 74 months for the coil embolization group. Of the 27 patients who had undergone Onyx embolization, 2 (7.4%) had required graft explantation compared with 5 of the 31 patients (16.1%) who had undergone coil embolization (P = .33). The results of the per-patient analysis showed that the coil embolization group had a significantly greater rate of the need for further reintervention compared with the Onyx group (55% vs 19%; P < .01). Clinical success was observed in 13 patients (48%) in the Onyx embolization group compared with 10 patients (32%) in the coil embolization group (P = .04). Two patients in each group had presented with secondary rupture of the aneurysm sac after attempted embolization. CONCLUSIONS: Type II endoleaks associated with sac growth treated with Onyx were less likely to require further reinterventions than were those treated with coil embolization. A trend was found toward a greater need for endovascular aneurysm repair explant after coil embolization. With a high rate of further reintervention and potential for sac rupture, diligent follow-up is required after attempted type II embolization, regardless of the technique used.

Long-term follow-up of transarterial balloon-assisted Onyx embolization for endovascular treatment of dural arteriovenous fistulas: A single-institution case series and literature review.

OBJECTIVE: Dural arteriovenous fistulas (DAVFs)-specifically, symptomatic DAVFs with cortical venous reflux-are aggressive lesions with a poor prognosis. Intra-arterial endovascular closure is considered the optional treatment for DAVFs and is currently performed at several international centers. However, long-term outcomes remain unknown. This study investigated the long-term efficacy and safety of transarterial balloon-assisted Onyx embolization in the treatment of DAVFs. METHODS: A total of 14 consecutive patients who underwent endovascular treatment for DAVFs were treated by balloon-assisted Onyx embolization. Additionally, we retrospectively reviewed all cases reported in the literature and compared the outcomes of patients treated with single- vs dual-lumen microcatheters. RESULTS: The patients at our institution were followed-up for 114.57 ± 33.52 months. Embolization was performed by balloon-assisted Onyx injection via a single feeding artery. Complete occlusion was achieved in 13 cases and partial occlusion in 1 case. At the final follow-up, all patients were functionally independent (Modified Rankin Scale score of 0-2), with no recurrence. In our review of 70 published cases of DAVFs that underwent endovascular treatment by balloon-assisted Onyx embolization, single- and dual-lumen balloon catheters were used in 33 and 37 patients, respectively. In the former group, there was complete or near-complete occlusion in 32 cases and partial occlusion in 1 case; and in the latter, there was complete or near-complete occlusion in 35 cases and partial occlusion in 2 cases. There were no deaths following endovascular treatment. CONCLUSION: Measurable and durable outcomes can be achieved by endovascular treatment of DAVFs with the transarterial balloon-assisted Onyx embolization technique, especially in cases with small, distal, and circuitous feeding arteries.

Optimization, characterization and evaluation of ZnO/polyvinylidene fluoride nanocomposites for orthopedic applications: improved antibacterial ability and promoted osteoblast growth.

Herein, electrospun zinc oxide nanoparticle/poly (vinylidene fluoride) (ZnONP/PVDF) composite fiber membranes were designed, fabricated, and tested for improved orthopedic applications. A single factor screening study was conducted to determine the optimal ZnONP/PVDF formulation based on osteoblast (bone forming cells) proliferation and antibacterial properties. Further, ZnONP/PVDF materials were characterized for their morphology, crystallinity, roughness, piezoelectric properties, and chemistry to understand such cell results. The optimal concentration of high molecular weight PVDF (18%, w/v) and a low concentration of ZnONPs (1 mg/ml) were identified for electrospinning at room temperature in order to inhibit bacterial colonization (without resorting to antibiotic use) and promote osteoblast proliferation. Compared to no ZnO/PVDF scaffold without Piezo-excited group,the study showed that on the 1 mg/ml ZnO/PVDF scaffolds with piezo-excitation, the density of SA and E.coli decreased by 68% and 56%.The density of osteoblasts doubled within three days(compared to the control). In summary, ZnONP/PVDF composite fiber membranes were formulated by electrospinning showing an exceptional ability to eliminate bacteria colonization while at the same time promote osteoblast functions and, thus, they should be further studied for a wide range of orthopedic applications.

Direct transcranial coil and Onyx embolization of a dural arteriovenous fistula: Technical note and brief literature review.

Intracranial high-grade dural arteriovenous fistulas (DAVFs) have higher bleeding rates compared to other intracranial vascular malformations. Endovascular treatment is usually recommended for high-grade lesions, aiming at a complete fistula obliteration. However, some patients have vascular abnormalities that limit endovascular access to the precise location of the shunt. Alternative techniques may be considered in this scenario. A middle-aged man presented with intracranial hypertension secondary to a high-grade DAVF. Because of vascular abnormalities precluding transvenous access to the intracranial venous circulation, the patient required treatment by a direct transcranial coil and Onyx embolization of the shunt. Direct transcranial cannulation of a dural sinus is an alternative and effective route for transvenous embolization of DAVFs, especially if abnormal venous anatomy precluding venous access to the required cranial venous system is identified.

Complete Obliteration of a Foramen Magnum Dural Arteriovenous Fistula by Microsurgery After Failed Endovascular Treatment Using Onyx: Case Report and Literature Review.

BACKGROUND: Foramen magnum dural arteriovenous fistula (DAVF) is a rare disease, with some reported cases of successful treatment. We achieved complete obliteration of the foramen magnum DAVF through microsurgery after complications of endovascular embolization. We reviewed the treatment modalities and outcomes, focusing on pathologic and anatomic features from the literature. CASE DESCRIPTION: A 65-year-old man was admitted to our hospital with sudden diplopia. Magnetic resonance imaging revealed a subarachnoid hemorrhage around the right side of the prepontine cistern, and a foramen magnum DAVF was diagnosed by angiography. Subsequent angiography revealed that the fistula was supplied by the right neuromeningeal trunk of the ascending pharyngeal artery and the right posterior meningeal artery of the vertebral artery (VA), and the veins of the pouch via the fistula were retrogradely draining into the intracranial veins. We aimed to treat complete occlusion endovascularly with balloon-augmented transarterial Onyx injection via the posterior meningeal artery, but Onyx was refluxed to the VA through the anastomosis between the VA and posterior meningeal artery. Onyx subsequently migrated to the top of the basilar artery, causing occlusion, so we urgently removed the Onyx with a stent retriever (Trevo). Several weeks later, we performed complete obliteration of the foramen magnum DAVF via a lateral suboccipital approach with a C1 laminectomy. CONCLUSIONS: Most foramen magnum DAVFs were obliterated completely with only endovascular treatment. Microsurgery is an effective and reliable treatment for incomplete occlusion and complications.

Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability.

BACKGROUND AND PURPOSE: The traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability. METHODS: The crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated. RESULTS: Soluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months. CONCLUSION: These results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.