Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. METHODS: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. RESULTS: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. CONCLUSIONS: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

Prognostic Factors Associated with Poor Treatment Outcomes After Balloon Kyphoplasty in Elderly Patients Aged ≥81 years.

OBJECTIVE: Balloon kyphoplasty (BKP) is an effective procedure for osteoporotic vertebral compression fractures; however, there is limited data regarding its outcomes in patients aged ≥81 years. This study investigated the treatment outcomes and prognostic factors for BKP in this age group. METHODS: A retrospective analysis was conducted on 115 patients with osteoporotic vertebral compression fracture undergoing single-level BKP after failed conservative treatment, classified into the <81 years (n=70) and ≥81 years (n=45) groups. Surgical results were evaluated as good outcomes (independent indoors 1 year postoperatively) and poor outcomes, followed by univariate and multivariate analyses to determine prognostic factors correlating with these outcomes. RESULTS AND CONCLUSION: The majority of patients (<81 years: 85.7%; ≥81 years: 73.3%) had a good degree of independence at 1 year postoperatively, which was comparable in both groups. Further analysis of patients aged ≥81 years showed that longer duration from onset to surgery, more subsequent vertebral fractures, and lower preoperative body mass index were correlated with poorer outcomes postoperatively, and low body mass index, time from onset to surgery, and female sex were independent risk factors for these outcomes (area under the receiver operating characteristics curve: 0.91).

Hemodynamic differences determining rupture and non-rupture in middle cerebral aneurysms after growth.

BACKGROUND AND PURPOSE: Intracranial aneurysm growth is a significant risk factor for rupture; however, a few aneurysms remain unruptured for long periods, even after growth. Here, we identified hemodynamic features associated with aneurysmal rupture after growth. MATERIALS AND METHODS: We analyzed nine middle cerebral artery aneurysms that grew during the follow-up period using computational fluid dynamics analysis. Growth patterns of the middle cerebral artery aneurysms were divided into homothetic growth (Type 1), de novo bleb formation (Type 2), and bleb enlargement (Type 3). Hemodynamic parameters of the four ruptured aneurysms after growth were compared with those of the five unruptured aneurysms. RESULTS: Among nine aneurysms (78%), seven were Type 1, one was Type 2, and one was Type 3. Three (43%) Type 1 aneurysms ruptured after growth. Maximum oscillatory shear index after aneurysmal growth was significantly higher in ruptured Type 1 cases than in unruptured Type 1 cases (ruptured vs. unruptured: 0.455 ± 0.007 vs. 0.319 ± 0.042, p = 0.003). In Type 1 cases, a newly emerged high-oscillatory shear index area was frequently associated with rupture, indicating a rupture point. Aneurysm growth was observed in the direction of the high-pressure difference area before enlargement. In Types 2 and 3 aneurysms, the maximum oscillatory shear index decreased slightly, however, the pressure difference values remain unchanged. In Type 3 aneruysm, the maximum OSI and PD values remained unchanged. CONCLUSIONS: This study suggests that hemodynamic variations and growth pattern changes are crucial in rupture risk determination using computational fluid dynamics analysis. High-pressure difference areas may predict aneurysm enlargement direction. Additionally, high maximum oscillatory shear index values after enlargement in cases with homothetic growth patterns were potential rupture risk factors.

Impact of Morphological Factors on the Future Growth of Unruptured Posterior Communicating Artery Aneurysms.

BACKGROUND: No previous study has established the factors associated with intracranial aneurysm growth using imaging data obtained before the appearance of morphological changes. Therefore, we investigated the factors related to future aneurysm growth in posterior communicating artery (Pcom) aneurysms. METHODS: Using a longitudinal database of intracranial aneurysm cases, we reviewed the findings for consecutive patients with unruptured Pcom aneurysms admitted to our institute from 2012 to 2021. Magnetic resonance images obtained over time were used to evaluate aneurysm growth. Aneurysms showing growth over time (group G) and unchanged aneurysms (group U) were compared in terms of background data and morphological factors. RESULTS: 93 Pcom aneurysms (group G: 25 aneurysms, 25%; group U: 68 aneurysms, 75%) were eligible for the present study. Six aneurysm rupture events occurred in group G (24%). Among morphological factors, Pcom diameter (1.2 ± 0.3 mm vs. 0.8 ± 0.7 mm, P < 0.01), bleb formation (group G: 39% vs. group U: 10%; odds ratio, 5.6; P = 0.01), and the lateral projection of the dome (group G: 52% vs. group U: 13%; odds ratio, 3.2; P = 0.023) were significantly different between the 2 groups. The sensitivity and specificity of a cutoff Pcom diameter of 0.73 mm for predicting enlargement were 96% and 53%, respectively. CONCLUSIONS: Pcom diameter, bleb formation, and lateral dome projection were associated with growth of Pcom aneurysms. Aneurysms with these risk factors require careful follow-up imaging, which may facilitate early detection of aneurysm growth and prevention of rupture through therapeutic interventions.

Effects of acute angle, proximal bending, and distal bending in the deployment vessels on incomplete low-profile visualized intraluminal support (LVIS) expansion: an in vitro study.

BACKGROUND: A low-profile visualized intraluminal support (LVIS) device may incompletely expand during stent deployment in tortuous vessels. However, the cause of incomplete expansion remains uninvestigated. We aimed to examine in vitro the factors causing incomplete expansion in LVIS deployment by using various vessel models. METHODS: A linear model group was created by connecting linear silicone tubes (inner diameter 4 mm) at both sides of the LVIS deployment vessel (inner diameter 4 mm) with different curvature angles of 10-140° at 10° intervals. For comparison, proximal and distal bending model groups were created, both with 90° bending on the proximal/distal larger curvature side of the deployment vessel. A single operator macroscopically deployed an LVIS (4.5×32 mm) four times in each model and 56 times in each group. RESULTS: In each model group the LVIS deployment vessel with a narrow curvature angle incompletely expanded. Incomplete expansion occurred significantly more frequently in the distal bending model group (34%, 19/56) compared with that in the linear model group (14.3%, 8/56; p<0.001), as well as in the proximal bending model group (59%, 33/56) compared with that in the distal bending model group (p<0.05). Compared with the linear model group, the proximal bending model group had a significantly reduced angle between the LVIS and the direction of the LVIS pushing force, but no significant change was found in the distal bending model group compared with that in the linear model group. CONCLUSIONS: Factors such as acute angle, distal bending, and proximal bending of the deployment vessel can cause incomplete LVIS expansion.

Case of a Stuck Coil in the Final Stage of Stent-Assisted Coil Embolization.

Objective: We report a case in which two coils became stuck in a microcatheter at the end of coil embolization for a cerebral aneurysm. Case Presentation: Two coils became stuck in the microcatheter at the final stage of stent-assisted coil embolization for an unruptured anterior communicating artery aneurysm. The rear end of a detached coil was near the tip of the microcatheter. The coil inserted next was pushed out of the microcatheter and pulled back into the microcatheter. Then, the rear end of the detached coil and the retracted coil meshed into the microcatheter, and became immobile. The microcatheter and these two coils were removed simultaneously, and coil embolization was finished. Conclusion: At the end of coil embolization, the filling rate is relatively high. Insertion of another coil and traction may cause the coils to become stuck in the microcatheter.

Transdural reduction of a bone fragment protruding into the spinal canal during surgical treatment of lumbar burst fracture: A case report.

BACKGROUND: There have been many reports on the clinical, radiographic, and surgical management of thoracolumbar burst fractures attributed to high-energy trauma. Interestingly, few reports have described how to extract bone fragments associated with these injuries protruding into the spinal canal contributing to significant neurological deficits. METHODS: An 18-year-old male presented with a severe L3-level paraparesis (i.e., loss of motor/sensory function below L3 lower extremity hyporeflexia, and sphincter dysfunction: American Spinal Injury Association [ASIA] Impairment Scale B) following a high-speed crash. The computed tomography and magnetic resonance studies revealed a L3 burst fracture with bone fragments protruding into the spinal canal causing marked cauda equina compression. Following a L3-L4 laminectomy, and opening of the dorsal dura, the bone fragments were ventrally impacted into the fractured L3 vertebral body a pedicle/screw L1-L5 fusion was then completed. RESULTS: One month later, the patient recovered to an ASIA Scale of C, (i.e., residual proximal 3/5 and distal 2/5 motor deficits, with partial sensory sparing). CONCLUSION: Transdural ventral impaction of protruded bone fragments attributed to high speed lumbar burst fractures contributing to significant cauda equina compression can be safely/effectively accomplished.

Independent Living 1 Year After Balloon Kyphoplasty for Osteoporotic Vertebral Compression Fracture.

BACKGROUND: The prevalence of osteoporotic vertebral compression fracture (OVCF) is increasing. The indications for and efficacy of balloon kyphoplasty (BKP) are controversial. We sought to identify predictors of outcome after BKP in patients with OVCF. METHODS: Between January 2001 and December 2019, 152 patients underwent BKP for painful OVCFs at our institution. This study included 115 patients who were followed for >12 months, and their data were retrospectively analyzed. With regard to the degree of independent living 1 year after BKP, patients were divided into a good outcome group (composed of patients who could independently go indoors) and a poor outcome group. We analyzed factors associated with outcome and subsequent OVCF. RESULTS: Mean age of patients was 77.9 years, 58.2% were female, 81% had a good outcome, and 19% had a poor outcome. Univariable analysis revealed significant differences in age, bone mineral density, preoperative vertebral body decompression rate, body mass index (BMI), preoperative Japanese Orthopaedic Association score, preoperative modified Rankin Scale score, and subsequent OVCF. Multivariable logistic analysis showed that low BMI (odds ratio 1.415, 95% confidence interval 1.06-1.87, P = 0.046) and subsequent OVCF (odds ratio 0.13, 95% confidence interval 0.02-0.69, P = 0.044) were independent risk factors. The incidence of subsequent OVCF was also lower among patients with higher BMI (odds ratio 0.83, 95% confidence interval 0.72-0.95, P = 0.001). CONCLUSIONS: BMI and subsequent OVCF are the most influential predictors of independent living 1 year after BKP for OVCF.

Two Patients Who Underwent Emergency Stenting for Iatrogenic Cervical Internal Carotid Artery Dissection during Thrombectomy.

Objective: Iatrogenic artery dissection during reperfusion therapy is one of the complications causing a poor prognosis. We report two cases of emergent stent placement for iatrogenic cervical carotid artery dissection during reperfusion therapy for acute ischemic stroke. Case Presentation: Two patients, a 77-year-old woman and a 77-year-old man, were diagnosed with acute major cerebral artery occlusion, and underwent reperfusion therapy. The iatrogenic internal carotid artery dissection was caused by derivation of a 6-Fr catheter and 0.014-inch wire in the tortuous cervical internal carotid artery, and emergent stent placement was performed. Recanalization was confirmed and no deterioration caused by the iatrogenic dissection was found. Conclusion: In patients in whom cerebral infarction is localized on MRI, additional stent placement may be effective for preventing adverse events caused by iatrogenic cervical internal carotid artery dissection during reperfusion therapy for intracranial cerebral artery occlusion related to atherosclerotic change.

A Patient with a Large Basilar Artery Aneurysm in Whom Coil Embolization Was Performed by Protruding an LVIS into the Aneurysmal Neck in a Barrel-like Shape and Preserving a Branch Vessel.

Objective: We report a case of a low-profile visualized intraluminal support device (LVIS) being deployed and protruded into an aneurysmal neck in a barrel-like shape to perform dense coil embolization while preserving the branch vessel from the aneurysmal dome in order to prevent aneurysmal enlargement. Case Presentation: A 74-year-old woman had a recurrent large cerebral aneurysm at the bifurcation of the basilar artery and the left superior cerebellar artery (SCA). Therefore, an LVIS was deployed from the left posterior cerebral artery to the basilar artery and protruded into the aneurysmal neck in a barrel-like shape to increase its metal coverage ratio. As the barrel-shaped protruding LVIS served as a scaffold to support the coils, dense coil embolization was performed while preserving the SCA branching from the aneurysmal dome. Images obtained at 6 months and 1 year after the embolization confirmed preservation of the SCA and prevention of aneurysmal enlargement. Conclusion: Protruding the LVIS into an aneurysmal neck in a barrel-like shape is a technique that may help preserve the branch vessel and facilitate dense coil embolization.

A Survived Case of Acute Bilateral Internal Carotid Artery Occlusion Treated by Mechanical Thrombectomy.

Objective: We report a survived case of acute bilateral internal carotid artery occlusion successfully treated by mechanical thrombectomy. Case Presentation: The patient was an 82-year-old right-handed man. Sudden consciousness disturbance and aphasia appeared, and cranial magnetic resonance angiography (MRA) revealed bilateral internal carotid artery occlusion. Cerebral angiography demonstrated occlusion between the cervical and cavernous portions of the bilateral internal carotid artery, and the growth of collateral circulation to the areas where the bilateral internal carotid artery perfused. We performed mechanical thrombectomy first on the left side, which was the main cause of his symptoms and relatively wide ischemic penumbra, and achieved recanalization of the bilateral internal carotid artery and suppressed extensive enlargement of the infarction. Conclusion: Acute bilateral internal carotid artery occlusion requires an optimal treatment strategy based on the clinical symptoms and preoperative imaging.

Dissection of the Vertebral Artery Fenestration Limb Presenting with Occlusion After Rupture.

BACKGROUND: Dissection of a vertebral artery (VA) fenestration is extremely rare. We herein present the first case of a patient who presented with the dissection of a VA fenestration limb accompanied by occlusion after rupture, who was treated with internal trapping of the dissected limb and the parent artery proximal to the fenestration. CASE DESCRIPTION: A 55-year-old man presented with sudden headache and altered consciousness. Computed tomography at admission showed subarachnoid hemorrhage. Angiography showed occlusion of the inner limb of the vertebrobasilar junction fenestration, and the occluded ends had a tapered shape, suggesting the occlusion of the dissection of the inner limb after rupture. Angiography immediately before embolization revealed inner limb recanalization with an irregular string sign; thus only the inner limb was embolized. Angiography after embolization showed near-complete suppression of the blood flow in the inner limb; however, a slight antegrade flow through the coil mass was observed in the late phase. The procedure was finished with the expectation of complete occlusion over time with natural heparin reversal. Angiography 8 days after embolization revealed a significant increase in antegrade blood flow through the coil mass within the inner limb. Therefore additional embolization of the parent artery proximal to the fenestration was performed, which achieved complete occlusion. CONCLUSIONS: The embolization length was limited and the antegrade blood flow through the other limb remained during internal trapping for the dissected VA fenestration limb; therefore careful observation of the blood flow to the dissected segment after embolization is necessary.

Breakage and Retrieval of an Aspiration Catheter Coil with a Stent Retriever During Mechanical Thrombectomy.

BACKGROUND: Some mechanical thrombectomy techniques for acute ischemic stroke use a combination of an aspiration catheter and stent retriever. We experienced a rare case of aspiration catheter coil breakage and subsequent retrieval using a stent retriever. CASE DESCRIPTION: A 79-year-old man suddenly developed somnolence, global aphasia, and right hemiplegia. Magnetic resonance imaging revealed acute infarction of the left frontal lobe and occlusion of the left common carotid artery. Thus, using an aspiration catheter and a stent retriever, mechanical thrombectomy was performed. The stent retriever was deployed from the middle cerebral artery to the internal carotid artery and retracted into the aspiration catheter placed in the internal carotid artery proximal to the thrombus. The catheter was bent during retraction of the stent retriever. After thrombus aspiration, the internal carotid and anterior and middle cerebral arteries were successfully reperfused; however, the stent retriever captured a broken section of the winding coil of the aspiration catheter. We suspected that an X-ray marker on the stent retriever broke the winding coil at the bent segment of the aspiration catheter and the stent captured the broken coil. CONCLUSIONS: The combined use of an aspiration catheter and a stent retriever may cause unexpected device breakage, especially when the catheter is bent.