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Xiang-Yang Wang, Li-Yang Dai, Hua-Zi Xu and Yong-Long Chi

Object.

Experimental burst fracture models are often developed by using either single or incremental impacts. In both protocols, the weight-drop technique produces the impact. However, to the authors' knowledge in no study have researchers attempted to compare the equivalence of the spine burst fracture produced using the different impact protocols. This study was performed to investigate whether the single and incremental trauma approaches produce equivalent degrees of severity in thoracolumbar burst fractures.

Methods.

Twenty bovine thoracolumbar spines comprising three vertebrae were divided evenly into the single impact and incremental impact groups. The specimens in the incremental impact group were subjected to three axial compressive impacts of increasing energy (78.4, 107.8, and 137.2 J), whereas specimens in the other group were subjected to a single impact (137.2 J). Before and after the final trauma, multidirectional flexibility of each specimen was measured under flexion/extension, right/left lateral bending, and right/left axial rotation, thus quantifying the instability of the fracture. The flexibility parameters were then compared between the two groups.

Results.

A significant increase in flexibility parameters was found after the final trauma in both groups, indicating the instability of the spine (p < 0.01). No significant differences in flexibility parameters were observed in either intact status or injured status between the two groups (p > 0.05).

Conclusions.

In this study the authors have confirmed that the single and incremental impact protocols produced a similar degree of severity in producing an in vitro bovine burst fracture. The results of this study support the use of the incremental impact protocol in future experimental biomechanical studies.

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Xiang-Yang Wang, Li-Yang Dai, Hua-Zi Xu and Yong-Long Chi

Object

Recurrent kyphosis has been commonly seen after posterior short-segment pedicle instrumentation for a thoracolumbar fracture, but studies on this issue are relatively scarce, and the clinical significance of recurrent deformity is uncertain. No study has addressed the associations between the reduction of a burst fracture vertebra and the final recurrent kyphosis after implant removal. The aim of this study was to investigate the recurrent kyphosis after short-segment pedicle screw fixation in thoracolumbar burst fractures and to evaluate the effect of the degree of a vertebral reduction on the recurrent kyphotic deformity after implant removal.

Methods

Twenty-seven patients who had undergone posterior short-segment pedicle screw fixation for thoracolumbar junction burst fractures (T12–L2) were investigated retrospectively. The minimum follow-up period was 2 years (mean 2.7 years). Pain status was evaluated using the Denis pain scale. Changes in the anterior vertebral height ratio, vertebral wedge angle, upper intervertebral angle, lower intervertebral angle, Cobb angle, regional angle, and sagittal index were measured preoperatively, postoperatively, before implant removal, and at final follow-up. The correlation between the reduction of a fractured vertebra and the recurrent kyphotic deformity was also analyzed.

Results

After the initial surgical correction, the reduced vertebral body (VB) height (anterior vertebral height ratio and vertebral wedge angle) remained stable until final follow-up, whereas the intervertebral disc space (the upper and lower intervertebral angles) collapsed, resulting in a progressive kyphotic deformity (Cobb angle, regional angle, and sagittal index). No significant correlation was found between the final kyphosis and pain scale, but the 8 patients with a sagittal index > 15° showed a higher incidence of moderate to severe pain (P3–5 on the Denis pain scale) compared with the remaining 19 patients with a sagittal index < 15°. Significant positive correlation was found between recurrent kyphosis and vertebral wedge angle (r = 0.850, p < 0.001) and the reduced vertebral height (r = −0.727, p < 0.001).

Conclusions

Given that the correction loss occurs primarily through disc space collapse, the amount of the final kyphotic deformity was predictable by the degree of the fractured vertebral reduction as seen on the lateral x-ray study. Surgeons who perform posterior reduction and fixation procedures should pay more attention to reducing the fractured vertebral wedge angle to its intact condition, rather than the segmental angular parameters. If the wedge angle of the fractured VB is unacceptable after reduction, additional reconstruction of the anterior column may be necessary.

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Hao-Li Liu, Hung-Wei Yang, Mu-Yi Hua and Kuo-Chen Wei

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

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Hua Liu, Zhongkun Liu, Yong Liu, Shifeng Kan, Jian Yang and Hongyi Liu

OBJECTIVE

Chronic subdural hematoma (CSDH) is prevalent in the aged population and is commonly treated with bur hole drainage. This treatment, however, can lead to various surgical complications. Atorvastatin may cure CSDH via its antiinflammatory and proangiogenesis effects, but not all patients treated with this medication can avoid surgery. The authors' aim was to investigate the effect of atorvastatin and identify characteristics of patients with CSDH sensitive to atorvastatin therapy.

METHODS

A prospective, placebo-controlled observational study was conducted in 80 patients with evidence of CSDH. The patients were enrolled between February 2012 and August 2014 and were randomly assigned to either atorvastatin treatment (atorvastatin group) or placebo (control group). Patients were followed up for 12 months after initiation of treatment. Clinically relevant data were collected and compared between the 2 groups. The atorvastatin group was subdivided into patients who required surgery and those who did not, and characteristics of these subgroups were also compared. The relationship between atorvastatin treatment and need for surgery was investigated by means of multiple regression analysis using the following variables as predictors: age, sex, admission Markwalder grade, level of dependency in activities of daily living (ADL) as assessed with the modified Barthel Index, presence of hemiparesis, and hematoma volume.

RESULTS

The proportion of patients who required surgical intervention during the follow-up period was significantly lower in the atorvastatin group than in the control group (p = 0.001), and the mean time to surgery was longer in the atorvastatin group (p = 0.018). Within the atorvastatin group, there was a significant difference with respect to Markwalder grades, degree of dependency in ADL, percentage of patients with hemiparesis, and mean hematoma volume between the patients who required surgery during the follow-up period and those who did not (p = 0.002, p = 0.001, p = 0.001, and p = 0.012, respectively). The results of the logistic regression analysis showed that atorvastatin significantly reduced the probability of surgery and that female sex and favorable admission Markwalder grades and favorable dependency status with respect to ADL (independent, slightly dependent, or moderately dependent) were independent predictors of not requiring surgery.

CONCLUSIONS

Atorvastatin administration can promote the resolution of CSDH, especially for women with favorable Markwalder grades and favorable ADL dependency status at admission.

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Jian-Hua Zhong, Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang, Xun Gong, Zhao-Hui Zhang and Zhi-Gang Mei

OBJECTIVE

Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH.

METHODS

ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats’ brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively.

RESULTS

Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH.

CONCLUSIONS

Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.

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Tetsuya Masada, Ya Hua, Guohua Xi, Guo-Yuan Yang, Julian T. Hoff and Richard F. Keep

Object. Adenovirus-mediated overexpression of interleukin-1 receptor antagonist (IL-1ra) attenuates the inflammatory reaction and brain injury that follows focal cerebral ischemia. Recently, an inflammatory reaction after intracerebral hemorrhage (ICH) was identified. In this study the authors examine the hypothesis that overexpression of IL-1ra reduces brain injury (specifically edema formation) after ICH.

Methods. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ, a control protein (Ad.RSVlacZ), or saline were injected into the left lateral cerebral ventricle in rats. On the 5th day after virus injection, 100 µl of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water and ion content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay, as well as histological evaluation. Compared with saline-treated and Ad.RSVlacZ—transduced controls, Ad.RSVIL-1ra-transduced rats had significantly attenuated edema in the ipsilateral basal ganglia 3 days after ICH (81.5 ± 0.3% compared with 83.4 ± 0.4% and 83.3 ± 0.5% in control animals). Thrombin-induced brain edema was also reduced in Ad.RSVIL-1ra—treated rats (81.3 ± 0.4% compared with 83.2 ± 0.4% and 82.5 ± 0.4% in control rats). The reduction in thrombin-induced edema was associated with a reduction in PMNL infiltration into the basal ganglia, as assessed by MPO assay (49% reduction) and histological examination.

Conclusions. Overexpression of IL-1ra by using an adenovirus vector attenuated brain edema formation and thrombin-induced intracerebral inflammation following ICH. The reduction in ICH-induced edema with IL-1ra may result from reduction of thrombin-induced brain inflammation.

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Da Liu, Jun Sheng, Hong-hua Wu, Xia Kang, Qing-yun Xie, Yang Luo, Jiang-jun Zhou and Wei Zheng

OBJECTIVE

The purpose of this study was to compare stability of injectable hollow pedicle screws with different numbers of holes using different volumes of polymethylmethacrylate (PMMA) in severely osteoporotic lumbar vertebrae and analyze the relationship between screw stability and distribution and volume of PMMA.

METHODS

Forty-eight severely osteoporotic cadaveric lumbar vertebrae were randomly divided into 3 groups—groups A, B, and C (16 vertebrae per group). The screws used in group A had 4 holes (2 pairs of holes, with the second hole of each pair placed 180° further along the thread than the first). The screws used in group B had 6 holes (3 pairs of holes, placed with the same 180° difference in position). Unmodified conventional screws were used in group C. Each group was randomly divided into subgroups 0, 1, 2, and 3, with different volumes of PMMA used in each subgroup. Type A and B pedicle screws were directly inserted into the vertebrae in groups A and B, respectively, and then different volumes of PMMA were injected through the screws into the vertebrae in subgroups 0, 1, 2, and 3. The pilot hole was filled with different volumes of PMMA followed by insertion of screws in groups C0, C1, C2, and C3. Distributions of PMMA were evaluated radiographically, and axial pull-out tests were performed to measure the maximum axial pullout strength (Fmax).

RESULTS

Radiographic examination revealed that PMMA surrounded the anterior third of the screws in the vertebral bodies (VBs) in groups A1, A2, and A3; the middle third of screws in the junction area of the vertebral body (VB) and pedicle in groups B1, B2, and B3; and the full length of screws evenly in both VB and pedicle in groups C1, C2, and C3. In addition, in groups A3 and B3, PMMA from each of the screws (left and right) was in contact with PMMA from the other screw and the PMMA was closer to the posterior wall and pedicle than in groups A1, A2, B1, and B2. One instance of PMMA leakage was found (in group B3). Two-way analysis of variance revealed that 2 factors—distribution and volume of PMMA—significantly influenced Fmax (p < 0.05) but that they were not significantly correlated (p = 0.078). The Fmax values in groups in which screws were augmented with PMMA were significantly better than those in groups in which no PMMA was used (p < 0.05).

CONCLUSIONS

PMMA can significantly improve stability of different injectable pedicle screws in severely osteoporotic lumbar vertebrae, and screw stability is significantly correlated with distribution and volume of PMMA. The closer the PMMA is to the pedicle and the greater the quantity of injected PMMA used, the greater the pedicle screw stability is. Injection of 3.0 mL PMMA through screws with 4 holes (2 pair of holes, with the screws in each pair placed on opposite sides of the screw) produces optimal stability in severely osteoporotic lumbar vertebrae.

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Bing Zhao, Hua Yang, Kuang Zheng, Zequn Li, Ye Xiong, Xianxi Tan, Ming Zhong and the AMPAS Study Group

OBJECTIVE

An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have received endovascular treatment. Endovascular treatment of poor-grade aSAH, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade aSAH.

METHODS

A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade aSAH. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mRS) score at 12 months, and poor outcome was defined as an mRS score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model's discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration.

RESULTS

At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mRS score of 4, 6 (4.4%) had an mRS score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI 0.80–0.92, p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI 0.81–0.93, p < 0.001). Both models had good calibration (p = 0.941 and p = 0.653, respectively).

CONCLUSIONS

Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade aSAH. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade aSAH with ruptured wide-neck aneurysms.

▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I.

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Qing Li, Beibei Liu, Yue Zhao, Yumei Liu, Mingjie Gao, Lingyun Jia, Liqun Jiao and Yang Hua

OBJECTIVE

The mechanism of carotid endarterectomy (CEA) restenosis remains unclear. Our research aimed to investigate the relationship between the carotid plaque grayscale median (GSM) value and restenosis after CEA.

METHODS

Between January 2010 and January 2018, 1280 consecutive patients underwent CEA at our institution; 32 patients were diagnosed with restenosis by ultrasound at 1 year after CEA. The correlations between plaque GSM, plaque echogenicity, clinical manifestations, shunting, and restenosis were analyzed.

RESULTS

In total, 829 patients were ultimately enrolled; 32 (4%) presented diagnoses of restenosis (mean age 67.3 ± 8.0 years, 81.2% men). The GSM value was lower in the restenosis group (68.1 ± 19.9 vs 59.9 ± 14.7, p = 0.02). After multiple logistic regression analysis, the GSM value was found to be an independent risk factor for restenosis (OR 0.976, 95% CI 0.957–0.995). Shunting was another significant independent risk factor for restenosis (OR 2.39, 95% CI 1.07–5.34). The GSM cutoff value for predicting restenosis was 75 (sensitivity 0.38, specificity 0.84, area under the curve 0.62). We separated the patients into 2 groups by GSM (GSM ≤ 75 and GSM > 75 subgroups). Comparison of the 2 groups indicated that symptomatic manifestation was related to restenosis in the subgroup with GSM ≤ 75, indicating predominantly echolucent plaques, but not in the subgroup with GSM > 75, indicating predominantly echogenic plaques.

CONCLUSIONS

Predominantly echolucent carotid plaques, as measured by GSM, had a higher restenosis risk at 1 year than echogenic plaques.

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Kuan-Wen Wu, Ming-Hsiao Hu, Shier-Chieg Huang, Ken N. Kuo and Shu-Hua Yang

Although ganglionic cysts located at the hip joint are described infrequently, those found in this region are usually small, deep-seated, and asymptomatic. Occasionally, however, a large ganglionic cyst of the hip area is observed that becomes symptomatic following compression of adjacent neurovascular bundles. In this report, the authors describe a 51-year-old man with symptoms of sciatica caused by a giant ganglionic cyst of the posterior hip joint. Because of its intermuscular location, the cyst was not palpable, and was probably misdiagnosed previously as a herniated disc of the lumbar spine. After resection of the cyst, the patient's symptoms resolved completely. This case highlights the importance of a detailed clinical examination for patients with multiple degenerative joint diseases.