Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for ...glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma.
Background: The role of Trk neurotrophin receptors in glioma is unknown.
Results: TrkB and TrkC are required for survival of brain tumor-initiating cells in the absence of EGF and FGF.
Conclusion: Trk receptors can control the survival of BTICs in the absence of EGF and FGF.
Significance: Trks may be important targets for treatment of malignant gliomas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
To determine if differences in safety or efficacy exist between balloon kyphoplasty (BKP), vertebroplasty (VP) and non-surgical management (NSM) for the treatment of osteoporotic vertebral ...compression fractures (VCFs).
Methods
As of February 1, 2011, a PubMed search (key words: kyphoplasty, vertebroplasty) resulted in 1,587 articles out of which 27 met basic selection criteria (prospective multiple-arm studies with cohorts of ≥20 patients). This systematic review adheres to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
Results
Pain reduction in both BKP (−5.07/10 points,
P
< 0.01) and VP (−4.55/10,
P
< 0.01) was superior to that for NSM (−2.17/10), while no difference was found between BKP/VP (
P
= 0.35). Subsequent fractures occurred more frequently in the NSM group (22 %) compared with VP (11 %,
P
= 0.04) and BKP (11 %,
P
= 0.01). BKP resulted in greater kyphosis reduction than VP (4.8º vs. 1.7°,
P
< 0.01). Quality of life (QOL) improvement showed superiority of BKP over VP (
P
= 0.04), along with a trend for disability improvement (
P
= 0.08). Cement extravasation was less frequent in the BKP (
P
= 0.01). Surgical intervention within the first 7 weeks yielded greater pain reduction than VCFs treated later.
Conclusions
BKP/VP provided greater pain relief and fewer subsequent fractures than NSM in osteoporotic VCFs. BKP is marginally favored over VP in disability improvement, and significantly favored in QOL improvement. BKP had a lower risk of cement extravasation and resulted in greater kyphosis correction. Despite this analysis being restricted to Level I and II studies, significant heterogeneity suggests that the current literature is delivering inconsistent messages and further trials are needed to delineate confounding variables.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The evolution of imaging techniques, along with highly effective radiation options has changed the way metastatic epidural tumors are treated. While high-grade epidural spinal cord compression (ESCC) ...frequently serves as an indication for surgical decompression, no consensus exists in the literature about the precise definition of this term. The advancement of the treatment paradigms in patients with metastatic tumors for the spine requires a clear grading scheme of ESCC. The degree of ESCC often serves as a major determinant in the decision to operate or irradiate. The purpose of this study was to determine the reliability and validity of a 6-point, MR imaging-based grading system for ESCC.
To determine the reliability of the grading scale, a survey was distributed to 7 spine surgeons who participate in the Spine Oncology Study Group. The MR images of 25 cervical or thoracic spinal tumors were distributed consisting of 1 sagittal image and 3 axial images at the identical level including T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images. The survey was administered 3 times at 2-week intervals. The inter- and intrarater reliability was assessed.
The inter- and intrarater reliability ranged from good to excellent when surgeons were asked to rate the degree of spinal cord compression using T2-weighted axial images. The T2-weighted images were superior indicators of ESCC compared with T1-weighted images with and without Gd.
The ESCC scale provides a valid and reliable instrument that may be used to describe the degree of ESCC based on T2-weighted MR images. This scale accounts for recent advances in the treatment of spinal metastases and may be used to provide an ESCC classification scheme for multicenter clinical trial and outcome studies.
Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the ...interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS).
Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable.
The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766).
SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.
Purpose
Various factors have been examined in relation to cage subsidence risk, including cage material, cage geometry, bone mineral density, device type, surgical level, bone graft, and patient age. ...The present study aims to compare and synthesize the literature of both clinical and biomechanical studies to evaluate and present the factors associated with cage subsidence.
Methods
A comprehensive search of the literature from January 2003 to December 2021 was conducted using the PubMed and ScienceDirect databases by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following the screening for inclusion and exclusion criteria, a total of 49 clinical studies were included. Correlations between clinical and biomechanical studies are also discussed.
Results
Patients treated with the cage and plate combination had a lower subsidence rate than patients with the stand-alone cage. Overall, Polyetheretherketone material was shown to have a lower subsidence rate than titanium and other materials. The subsidence rate was also higher when the surgery was performed at levels C5–C7 than at levels C2–C5. No significant correlation was found between age and cage subsidence clinically.
Conclusions
Cage subsidence increases the stress on the anterior fixation system and may cause biomechanical instability. Severe cage subsidence decreases the Cobb angle and intervertebral height, which may cause destabilization of the implant system, such as screw/plate loosening or breakage of the screw/plate. Various factors have been shown to influence the risk of cage subsidence. Examining clinical research alongside biomechanical studies offers a more comprehensive understanding of the subject.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The cervical spine poses many complex challenges that require complex solutions. Anterior cervical discectomy and fusion (ACDF) has been one such technique often employed to address such issues. In ...order to address the problems with ACDF and assess the modifications that have been made to the technique over time, finite element analyses (FEA) have proven to be an effective tool. The variations of cervical spine FEA models that have been produced over the past couple of decades, particularly more recent representations of more complex geometries, have not yet been identified and characterized in any literature. Our objective was to present material property models and cervical spine models for various simulation purposes. The outlining and refinement of the FEA process will yield more reliable outcomes and provide a stable basis for the modeling protocols of the cervical spine.
Cervical degenerative disc diseases such as myelopathy and radiculopathy often require conventional treatments like artificial cervical disc replacement or anterior cervical discectomy and fusion ...(ACDF). When designing a medical device, like the stand-alone cage, there are many design inputs to consider. However, the precise biomechanics of the force between the vertebrae and implanted devices under certain conditions require further investigation. In this study, a new method was developed to evaluate the pressure between the vertebrae and implanted devices by embedding a sensor array into a 3D-printed C2-C3 cervical spine. The 3D-printed cervical spine model was subjected to a range of axial loads while under flexion, extension, bending and compression conditions. Cables were used for the application of a preload and a robotic arm was used to recreate the natural spine motions (flexion, extension, and bending). To verify and predict the total pressure between the vertebrae and the implanted devices, a 3D finite element (FE) numerical mathematical model was developed. A preload was represented by applying 22 N of force on each of the anterior tubercles for the C2 vertebra. The results of this study suggest that the sensor is useful in identifying static pressure. The pressure with the robot arm was verified from the FE results under all conditions. This study indicates that the sensor array has promising potential to reduce the trial and error with implants for various surgical procedures, including multi-level artificial cervical disk replacement and ACDF, which may help clinicians to reduce pain, suffering, and costly follow-up procedures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Anterior cervical discectomy and fusion (ACDF) is widely used to treat patients with spinal disorders, where the cage is a critical component to achieve satisfactory fusion results. However, it is ...still not clear whether a cage with screws or without screws will be the best choice for long-term fusion as the micromotion (sliding distance) and subsidence (penetration) of the cage still take place repeatedly.
This study aims to examine the effect of cage-screws on the biomechanical characteristics of the human spine, implanted cage, and associate hardware by comparing the micromotion and subsidence.
A finite element (FE) analysis study.
A FE model of a C3-C5 cervical spine with ACDF was developed. The spinal segment was modeled with the removal of the anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL), and discectomy was then implanted with a cage-screw system. Three models were analyzed: the first was the original spine (S1 model), the second, S2, was implanted with cages and anterior plating, and the third, S3, was implanted with a cage-screw system in addition to the anterior plate. All investigations were under 1 N•m in flexion, extension, lateral bending, and axial rotation situations.
Finite element analysis (FEA) demonstrated that range of motion (ROM) at C3-C4 in the S2 model was significantly reduced more than that in the S3 model, while the ROM at both C4-C5 in the S3 model was reduced more than that in the S2 model in all simulations. The ROM at C3-C5 in the S1 model was reduced by over 5° in the S2 and S3 models in all loading conditions. The micromotion and subsidence at all contacts of C3-C5 in the S3 model were lower than that in the S2 model in all flexion, extension, bending, and axial simulations. The subsidence and micromotion could be seen in the barrier area of the S2 model, while they occurred near the edge of the screw in the S3 model.
These results showed that the cage-screw and anterior plating combination has promising potential to reduce the risk of micromotion and subsidence of implanted cages in two or more level ACDFs.
The use of double segmental fixation with cage-screw anterior plating combination constructs may increase the stiffness of the construct and reduce the incidence of clinical and radiographic pseudarthrosis following multilevel ACDF, which in turn, could decrease the need for revision surgeries or supplemental posterior fixation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cervical disc implants are conventional surgical treatments for patients with degenerative disc disease, such as cervical myelopathy and radiculopathy. However, the surgeon still must determine the ...candidacy of cervical disc implants mainly from the findings of diagnostic imaging studies, which can sometimes lead to complications and implant failure. To help address these problems, a new approach was developed to enable surgeons to preview the post-operative effects of an artificial disc implant in a patient-specific fashion prior to surgery. To that end, a robotic replica of a person's spine was 3D printed, modified to include an artificial disc implant, and outfitted with a soft magnetic sensor array. The aims of this study are threefold: first, to evaluate the potential of a soft magnetic sensor array to detect the location and amplitude of applied loads; second, to use the soft magnetic sensor array in a 3D printed human spine replica to distinguish between five different robotically actuated postures; and third, to compare the efficacy of four different machine learning algorithms to classify the loads, amplitudes, and postures obtained from the first and second aims. Benchtop experiments showed that the soft magnetic sensor array was capable of precisely detecting the location and amplitude of forces, which were successfully classified by four different machine learning algorithms that were compared for their capabilities: Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Random Forest (RF), and Artificial Neural Network (ANN). In particular, the RF and ANN algorithms were able to classify locations of loads applied 3.25 mm apart with 98.39% ± 1.50% and 98.05% ± 1.56% accuracies, respectively. Furthermore, the ANN had an accuracy of 94.46% ± 2.84% to classify the location that a 10 g load was applied. The artificial disc-implanted spine replica was subjected to flexion and extension by a robotic arm. Five different postures of the spine were successfully classified with 100% ± 0.0% accuracy with the ANN using the soft magnetic sensor array. All results indicated that the magnetic sensor array has promising potential to generate data prior to invasive surgeries that could be utilized to preoperatively assess the suitability of a particular intervention for specific patients and to potentially assist the postoperative care of people with cervical disc implants.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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