Two years of neurosurgical intraoperative MRI in Sweden - evaluation of use and costs.

BACKGROUND: The current shortage of radiology staff in healthcare provides a challenge for departments all over the world. This leads to more evaluation of how the radiology resources are used and a demand to use them in the most efficient way. Intraoperative MRI is one of many recent advancements in radiological practice. If radiology staff is performing intraoperative MRI at the operation ward, they may be impeded from performing other examinations at the radiology department, creating costs in terms of exams not being performed. Since this is a kind of cost whose importance is likely to increase, we have studied the practice of intraoperative MRI in Sweden. METHODS: The study includes data from the first four hospitals in Sweden that installed MRI scanners adjacent to the operating theaters. In addition, we included data from Karolinska University Hospital in Solna where intraoperative MRI is carried out at the radiology department. RESULTS: Scanners that were moved into the operation theater and doing no or few other scans were used 11-12% of the days. Stationary scanners adjacent to the operation room were used 35-41% of the days. For scanners situated at the radiology department doing intraoperative scans interspersed among all other scans, the proportion was 92%. CONCLUSION: Our study suggests that performing exams at the radiology department rather than at several locations throughout the hospital may be an efficient approach to tackle the simultaneous trends of increasing demands for imaging and increasing staff shortages at radiology departments.

Standardized reporting of adverse events and functional status from the first 5 years of awake surgery for gliomas: a population-based single-institution consecutive series.

OBJECTIVE: To report our experience and investigate frequencies of adverse events and functional status from the first 5 years of performing awake surgery for gliomas in a single-center population-based setting. METHODS: We conducted a review of all patients with a glioma treated with awake surgery during the first 5 years following introduction of awake surgery at our center (February 2015 to February 2020). We assessed functional and radiological outcome, with adverse events classified according to the Landriel-Ibanez classification for neurosurgical complications, while neurological deficits were further subdivided into transient vs permanent. We sought to analyze our initial results and learning curve, as well as compare our results with literature. RESULTS: Forty-two patients were included. The median age was 38 years (range 18-66) and 13 (31%) were female. The indication for awake surgery was a presumed glioma in or near an eloquent area. The overall 30-day complication rate was 25 (59%), with 19 (45%) grade I complications, 3 (7%) grade II complications, and 3 (7%) grade III complications. Fifteen patients (36%) experienced transient neurological deficits, and 11 (26%) permanent neurological deficits. At 3-month follow-up, the Karnofsky Performance Score was 80 or higher for the entire cohort. The median extent of resection was 87%, with GTR achieved in 11 (26%). In search of potential learning curve difficulties, patients were divided into the 21 patients treated first (Early Group) versus the remaining 21 patients treated later (Late Group); no statistically significant difference in operating time, amount of tumor removed, or incidence of long-term postoperative neurological deficit was identified between groups. No awake surgery was aborted due to seizures. Comparison to the literature was limited by the diverse and unsystematic way in which previous studies have reported adverse events after awake craniotomy for gliomas. CONCLUSION: We provide a standardized report of adverse events and functional status following awake surgery for glioma during a single-center 5-year learning period, with similar rates of severe adverse events and functional outcome compared to literature without concerns of substantial learning curve difficulties. However, this comparison was flawed by non-standardized reporting of complications, highlighting a demand for more standardized reporting of adverse events after awake craniotomies.

Feasibility and Accuracy of Thoracolumbar Pedicle Screw Placement Using an Augmented Reality Head Mounted Device.

BACKGROUND: To investigate the accuracy of augmented reality (AR) navigation using the Magic Leap head mounted device (HMD), pedicle screws were minimally invasively placed in four spine phantoms. METHODS: AR navigation provided by a combination of a conventional navigation system integrated with the Magic Leap head mounted device (AR-HMD) was used. Forty-eight screws were planned and inserted into Th11-L4 of the phantoms using the AR-HMD and navigated instruments. Postprocedural CT scans were used to grade the technical (deviation from the plan) and clinical (Gertzbein grade) accuracy of the screws. The time for each screw placement was recorded. RESULTS: The mean deviation between navigation plan and screw position was 1.9 ± 0.7 mm (1.9 [0.3-4.1] mm) at the entry point and 1.4 ± 0.8 mm (1.2 [0.1-3.9] mm) at the screw tip. The angular deviation was 3.0 ± 1.4° (2.7 [0.4-6.2]°) and the mean time for screw placement was 130 ± 55 s (108 [58-437] s). The clinical accuracy was 94% according to the Gertzbein grading scale. CONCLUSION: The combination of an AR-HMD with a conventional navigation system for accurate minimally invasive screw placement is feasible and can exploit the benefits of AR in the perspective of the surgeon with the reliability of a conventional navigation system.

Fluoroscopy-Assisted C1-C2 Posterior Fixation for Atlantoaxial Instability: A Single-Center Case Series of 78 Patients.

Background and Objectives: Posterior C1-C2 fixation, with trans-articular screws (TAS) or screw-rod-construct (SRC), is the main surgical technique for atlantoaxial instability, and can be performed with a fluoroscopy-assisted free-handed technique or 3D navigation. This study aimed to evaluate complications, radiological and functional outcome in patients treated with a fluoroscopy-assisted technique. Materials and Methods: A single-center consecutive cohort study was conducted of all adult patients who underwent posterior C1-C2 fixation, using TAS or CRS, between 2005-2019. Results: Seventy-eight patients were included, with a median follow-up time of 6.8 years. Trauma was the most common injury mechanism (64%), and cervicalgia the predominant preoperative symptom (88%). TAS was used in 33%, and SRC in 67% of cases. Surgery was associated with a significant reduction in cervicalgia (from 88% to 26%, p < 0.001). The most common complications were vertebral artery injury (n = 2, 2.6%), and screw malposition (n = 5, 6.7%, of which 2 were TAS and 3 were SRC). No patients deteriorated in their functional status following surgery. Conclusions: Fluoroscopy-assisted C1-C2 fixation with TAS or SRC is a safe and effective treatment for atlantoaxial instability, with a low complication rate, few surgical revisions, and pain relief in the majority of the cases.

Augmented reality navigation for cranial biopsy and external ventricular drain insertion.

OBJECTIVE: The aim of this study was to evaluate the accuracy (deviation from the target or intended path) and efficacy (insertion time) of an augmented reality surgical navigation (ARSN) system for insertion of biopsy needles and external ventricular drains (EVDs), two common neurosurgical procedures that require high precision. METHODS: The hybrid operating room-based ARSN system, comprising a robotic C-arm with intraoperative cone-beam CT (CBCT) and integrated video tracking of the patient and instruments using nonobtrusive adhesive optical markers, was used. A 3D-printed skull phantom with a realistic gelatinous brain model containing air-filled ventricles and 2-mm spherical biopsy targets was obtained. After initial CBCT acquisition for target registration and planning, ARSN was used for 30 cranial biopsies and 10 EVD insertions. Needle positions were verified by CBCT. RESULTS: The mean accuracy of the biopsy needle insertions (n = 30) was 0.8 mm ± 0.43 mm. The median path length was 39 mm (range 16-104 mm) and did not correlate to accuracy (p = 0.15). The median device insertion time was 149 seconds (range 87-233 seconds). The mean accuracy for the EVD insertions (n = 10) was 2.9 mm ± 0.8 mm at the tip with a 0.7° ± 0.5° angular deviation compared with the planned path, and the median insertion time was 188 seconds (range 135-400 seconds). CONCLUSIONS: This study demonstrated that ARSN can be used for navigation of percutaneous cranial biopsies and EVDs with high accuracy and efficacy.

Augmented reality navigation in spine surgery: a systematic review.

BACKGROUND: Conventional spinal navigation solutions have been criticized for having a negative impact on time in the operating room and workflow. AR navigation could potentially alleviate some of these concerns while retaining the benefits of navigated spine surgery. The objective of this study is to summarize the current evidence for using augmented reality (AR) navigation in spine surgery. METHODS: We performed a systematic review to explore the current evidence for using AR navigation in spine surgery. PubMed and Web of Science were searched from database inception to November 27, 2020, for data on the AR navigation solutions; the reported efficacy of the systems; and their impact on workflow, radiation, and cost-benefit relationships. RESULTS: In this systematic review, 28 studies were included in the final analysis. The main findings were superior workflow and non-inferior accuracy when comparing AR to free-hand (FH) or conventional surgical navigation techniques. A limited number of studies indicated decreased use of radiation. There were no studies reporting mortality, morbidity, or cost-benefit relationships. CONCLUSIONS: AR provides a meaningful addition to FH surgery and traditional navigation methods for spine surgery. However, the current evidence base is limited and prospective studies on clinical outcomes and cost-benefit relationships are needed.

Incidence and predictors of kyphotic deformity following resection of cervical intradural tumors in adults: a population-based cohort study.

BACKGROUND: The first line of treatment for most cervical intradural tumors is surgical resection through laminotomy or laminectomy. This may cause a loss of posterior pulling force leading to kyphosis, which is associated with decreased functional outcome. However, the incidence and predictors of kyphosis in these patients are poorly understood. OBJECT: To assess the incidence of posterior fixation (PF), as well as predictors of radiological kyphosis, following resection of cervical intradural tumors in adults. METHODS: A population-based cohort study was conducted on adult patients who underwent intradural tumor resection via cervical laminectomy with or without laminoplasty between 2005 and 2017. Primary outcome was kyphosis requiring PF. Secondary outcome was radiological kyphotic increase, measured by the change in the C2-C7 Cobb angle between pre- and postoperative magnetic resonance images. RESULTS: Eighty-four patients were included. Twenty-four percent of the tumors were intramedullary, and the most common diagnosis was meningioma. The mean laminectomy range was 2.4 levels, and laminoplasty was performed in 40% of cases. No prophylactic PF was performed. During a mean follow-up of 4.4 years, two patients (2.4%) required delayed PF. The mean radiological kyphotic increase after surgery was 3.0°, which was significantly associated with laminectomy of C2 and C3. Of these, C3 laminectomy demonstrated independent risk association. CONCLUSIONS: There was a low incidence of delayed PF following cervical intradural tumor resection, supporting the practice of not performing prophylactic PF. Kyphotic increase was associated with C2 and C3 laminectomy, which could help identify at-risk patients were targeted follow-up is indicated.

Towards Optical Imaging for Spine Tracking without Markers in Navigated Spine Surgery.

Surgical navigation systems are increasingly used for complex spine procedures to avoid neurovascular injuries and minimize the risk for reoperations. Accurate patient tracking is one of the prerequisites for optimal motion compensation and navigation. Most current optical tracking systems use dynamic reference frames (DRFs) attached to the spine, for patient movement tracking. However, the spine itself is subject to intrinsic movements which can impact the accuracy of the navigation system. In this study, we aimed to detect the actual patient spine features in different image views captured by optical cameras, in an augmented reality surgical navigation (ARSN) system. Using optical images from open spinal surgery cases, acquired by two gray-scale cameras, spinal landmarks were identified and matched in different camera views. A computer vision framework was created for preprocessing of the spine images, detecting and matching local invariant image regions. We compared four feature detection algorithms, Speeded Up Robust Feature (SURF), Maximal Stable Extremal Region (MSER), Features from Accelerated Segment Test (FAST), and Oriented FAST and Rotated BRIEF (ORB) to elucidate the best approach. The framework was validated in 23 patients and the 3D triangulation error of the matched features was < 0 . 5 mm. Thus, the findings indicate that spine feature detection can be used for accurate tracking in navigated surgery.

Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G.

Objective- Coronary artery thrombosis can occur in the absence of plaque rupture because of superficial erosion. Erosion-prone atheromata associate with more neutrophil extracellular traps (NETs) than lesions with stable or rupture-prone characteristics. The effects of NETs on endothelial cell (EC) inflammatory and thrombogenic properties remain unknown. We hypothesized that NETs alter EC functions related to erosion-associated thrombosis. Approach and Results- Exposure of human ECs to NETs increased VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA and protein expression in a time- and concentration-dependent manner. THP-1 monocytoid cells and primary human monocytes bound more avidly to NET-treated human umbilical vein ECs than to unstimulated cells under flow. Treatment of human ECs with NETs augmented the expression of TF (tissue factor) mRNA, increased EC TF activity, and hastened clotting of recalcified plasma. Anti-TF-neutralizing antibody blocked NET-induced acceleration of clotting by ECs. NETs alone did not exhibit TF activity or acceleration of clotting in cell-free assays. Pretreatment of NETs with anti-interleukin (IL)-1α-neutralizing antibody or IL-1Ra (IL-1 receptor antagonist)-but not with anti-IL-1ß-neutralizing antibody or control IgG-blocked NET-induced VCAM-1, ICAM-1, and TF expression. Inhibition of cathepsin G, a serine protease abundant in NETs, also limited the effect of NETs on EC activation. Cathepsin G potentiated the effect of IL-1α on ECs by cleaving the pro-IL-1α precursor and releasing the more potent mature IL-1α form. Conclusions- NETs promote EC activation and increased thrombogenicity through concerted action of IL-1α and cathepsin G. Thus, NETs may amplify and propagate EC dysfunction related to thrombosis because of superficial erosion.

Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells.

Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.

NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma.

The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1 protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and 9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could detect antigen-specific IFN-γ responses in 25% blood samples for NY-ESO-1 and 30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable targets for anticancer-directed T-cells for the biological therapy of patients with glioma.

Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in vestibular schwannoma patients: a systematic review.

OBJECTIVE: Repeated controlled studies have revealed that stereotactic radiosurgery is better than microsurgery for patients with vestibular schwannoma (VS) <3 cm in need of intervention. In this systematic review we aimed to compare results from single-fraction stereotactic radiosurgery (SRS) to fractionated stereotactic radiotherapy (FSRT) for patients with VS. DATA SOURCES AND ELIGIBILITY CRITERIA: We systematically searched MEDLINE, Web of Science, Embase and Cochrane and screened relevant articles for references. Publications from 1995 through 2014 with a minimum of 50 adult (>18 years) patients with unilateral VS, followed for a median of >5 years, were eligible for inclusion. After screening titles and abstracts of the 1094 identified articles and systematically reviewing 98 of these articles, 19 were included. INTERVENTION: Patients with unilateral VS treated with radiosurgery were compared to patients treated with fractionated stereotactic radiotherapy. RESULTS: No randomized controlled trial (RCT) was identified. None of the identified controlled studies comparing SRS with FSRT were eligible according to the inclusion criteria. Nineteen case series on SRS (n = 17) and FSRT (n = 2) were included in the systematic review. Loss of tumor control necessitating a new VS-targeted intervention was found in an average of 5.0% of the patients treated with SRS and in 4.8% treated with FSRT. Mean deterioration ratio for patients with serviceable hearing before treatment was 49% for SRS and 45% for FSRT, respectively. The risk for facial nerve deterioration was 3.6% for SRS and 11.2% for FSRT and for trigeminal nerve deterioration 6.0% for SRS and 8.4% for FSRT. Since these results were obtained from case series, a regular meta-analysis was not attempted. CONCLUSION: SRS and FSRT are both noninvasive treatment alternatives for patients with VS with low rates of treatment failure in need of rescue therapy. In this selection of patients, the progression-free survival rates were on the order of 92-100% for both treatment options. There is a lack of high-quality studies comparing radiation therapy alternatives for patients with VS. Finally, 19 articles reported long-term tumor control after SRS, while only 2 articles reported long-term FSRT results, making effect estimates more uncertain for FSRT.

Automatic image registration on intraoperative CBCT compared to Surface Matching registration on preoperative CT for spinal navigation: accuracy and workflow.

INTRODUCTION: Spinal navigation solutions have been slower to develop compared to cranial ones. To facilitate greater adoption and use of spinal navigation, the relatively cumbersome registration processes need to be improved upon. This study aims to validate a new solution for automatic image registration and compare it to a traditional Surface Matching method. METHOD: Adult patients undergoing spinal surgery requiring navigation were enrolled after providing consent. A registration matrix-Universal AIR (= Automatic Image Registration)-was placed in the surgical field and used for automatic registration based on intraoperative 3D imaging. A standard Surface Matching method was used for comparison. Accuracy measurements were obtained by comparing planned and acquired coordinates on the vertebrae. RESULTS: Thirty-nine patients with 42 datasets were included. The mean accuracy of Universal AIR registration was 1.20 ± 0.42 mm, while the mean accuracy of Surface Matching registration was 1.94 ± 0.64 mm. Universal AIR registration was non-inferior to Surface Matching registration. Post hoc analysis showed a significantly greater accuracy for Universal AIR registration. In Surface Matching, but not automatic registration, user-related errors such as incorrect identification of the vertebral level were seen. CONCLUSION: Automatic image registration for spinal navigation using Universal AIR and intraoperative 3D imaging provided improved accuracy compared to Surface Matching registration. In addition, it minimizes user errors and offers a standardized workflow, making it a reliable registration method for navigated spinal procedures.

Diffuse reflectance spectroscopy sensor to differentiate between glial tumor and healthy brain tissue: a proof-of-concept study.

Glial tumors grow diffusely in the brain. Survival is correlated to the extent of tumor removal, but tumor borders are often invisible. Resection beyond the borders as defined by conventional methods may further improve prognosis. In this proof-of-concept study, we evaluate diffuse reflectance spectroscopy (DRS) for discrimination between glial tumors and normal brain ex vivo. DRS spectra and histology were acquired from 22 tumor samples and nine brain tissue samples retrieved from 30 patients. The content of biological chromophores and scattering features were estimated by fitting a model derived from diffusion theory to the DRS spectra. DRS parameters differed significantly between tumor and normal brain tissue. Classification using random forest yielded a sensitivity and specificity for the detection of low-grade gliomas of 82.0% and 82.7%, respectively, and the area under curve (AUC) was 0.91. Applied in a hand-held probe or biopsy needle, DRS has the potential to provide intra-operative tissue analysis.

Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages.

Glioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA-sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells of 100 patients to determine the relation of glioblastoma cells to normal brain cell types. A novel neural network-based projection of the developmental trajectory of normal brain cells uncovered two principal cell-lineage features of glioblastoma, neural crest perivascular and radial glia, carrying defining methylation patterns and survival differences. Consistently, introducing tumorigenic alterations in naïve human brain perivascular cells resulted in brain tumors. Thus, our results suggest that glioblastoma can arise from the brains' vasculature, and patients with such glioblastoma have a significantly poorer outcome.

Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas.

Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1-2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.

Long-Term Follow-Up and Predictors of Functional Outcome after Surgery for Spinal Meningiomas: A Population-Based Cohort Study.

Spinal meningiomas are the most common adult primary spinal tumor, constituting 24-45% of spinal intradural tumors and 2% of all meningiomas. The aim of this study was to assess postoperative complications, long-term outcomes, predictors of functional improvement and differences between elderly (≥70 years) and non-elderly (18-69 years) patients surgically treated for spinal meningiomas. Variables were retrospectively collected from patient charts and magnetic resonance images. Baseline comparisons, paired testing and regression analyses were used. In conclusion, 129 patients were included, with a median follow-up time of 8.2 years. Motor deficit was the most common presenting symptom (66%). The median time between diagnosis and surgery was 1.3 months. A postoperative complication occurred in 10 (7.8%) and tumor growth or recurrence in 6 (4.7%) patients. Surgery was associated with significant improvement of motor and sensory deficit, gait disturbance, bladder dysfunction and pain. Time to surgery, tumor area and the degree of spinal cord compression significantly predicted postoperative improvement in a modified McCormick scale (mMCs) in the univariable regression analysis, and spinal cord compression showed independent risk association in multivariable analysis. There was no difference in improvement, complications or tumor control between elderly and non-elderly patients. We concluded that surgery of spinal meningiomas was associated with significant long-term neurological improvement, which could be predicted by time to surgery, tumor size and spinal cord compression.

Distribution, cellular localization, and therapeutic potential of the tumor-associated antigen Ku70/80 in glioblastoma multiforme.

Antibodies specifically targeting tumor-associated antigens have proved to be important tools in the treatment of human cancer. A desirable target antigen should be unique to tumor cells, abundantly expressed, and readily available for antibody binding. The Ku70/80 DNA-repair protein is expressed in the nucleus of most cells; it is, however, also present on the cell surface of tumor cell lines, and antibodies binding Ku70/80 at the cell surface were recently shown to internalize into tumor cells. To evaluate the potential of Ku70/80-antigen as a therapeutic target for immunotoxins in glioblastoma multiforme, we investigated binding and localization of Ku70/80-specific antibodies in tissue samples from glioblastomas and normal human brains, and in glioma cell cultures. Furthermore, the internalization and drug-delivery capacity were evaluated by use of immunotoxicity studies. We demonstrate that Ku70/80 is localized on the cell plasma membrane of glioma cell lines, and is specifically present in human glioblastoma tissue. Antibodies bound to the Ku70/80 antigen on the cell surface of glioma cells were found to internalize via endocytosis, and shown to efficiently deliver toxins into glioblastoma cells. The data further imply that different antibodies directed against Ku70/80 possess different abilities to target the antigen, in relation to its presentation on the cell surface or intracellular localization. We conclude that Ku70/80 antigen is uniquely presented on the plasma membrane in glioblastomas, and that antibodies specific against the antigen have the capacity to selectively bind, internalize, and deliver toxins into tumor cells. These results imply that Ku70/80 is a potential target for immunotherapy of glioblastoma multiforme.

Anterior Cervical Corpectomy and Fusion for Degenerative and Traumatic Spine Disorders, Single-Center Experience of a Case Series of 119 Patients.

BACKGROUND: Anterior cervical corpectomy and fusion (ACCF) is a treatment option for several cervical pathologies. Various graft materials such as autografts, titanium mesh cages (TMC), or poly-ether-ether-ketone (PEEK) cages are used. Additional posterior fixation (PF) to provide extra support and improve stability is sometimes performed initially, or later as supplementary treatment. OBJECTIVE: To describe our retrospective study of 119 consecutive cases of ACCF with synthetic grafts, in 3 cohorts of cervical spondylotic myelopathy (CSM), infectious and neoplastic processes, and trauma, with special focus on need for supplementary PF. METHODS: A total of 135 adult patients treated with ACCF between January 2005 and January 2018 were identified. Patients lost to follow-up were excluded, and 119 remaining patients were included for retrospective clinical and radiological assessment. RESULTS: Synthetic grafts were used in 116 (97%) cases. Only 9 (8%) ACCF cases required later supplementary PF, where 7 (78%) cases were multilevel. There was a statistically significant difference in revision rate with PF for single-level compared to multilevel ACCFs (P = .001). Revision rates with PF were 2%, 29%, and 7% in CSM, infectious and neoplastic processes, and trauma cohorts, respectively. CONCLUSION: The results indicate that ACCF is a safe and effective treatment for degenerative and traumatic cervical spine disorders, with low complication and revision rates. Single-level ACCF can be performed without additional PF. Multilevel ACCF (n > 2) and pathologies affecting bone quality seem to be risk factors for material subsidence and instability. In these cases, additional PF should be considered.

Frameless Patient Tracking With Adhesive Optical Skin Markers for Augmented Reality Surgical Navigation in Spine Surgery.

STUDY DESIGN: Observational study. OBJECTIVE: The aim of this study was to evaluate the accuracy of a new frameless reference marker system for patient tracking by analyzing the effect of vertebral position within the surgical field. SUMMARY OF BACKGROUND DATA: Most modern navigation systems for spine surgery rely on a dynamic reference frame attached to a vertebra for tracking the patient. This solution has the drawback of being bulky and obstructing the surgical field, while requiring that the dynamic reference frame is moved between vertebras to maintain accuracy. METHODS: An augmented reality surgical navigation (ARSN) system with intraoperative cone beam computed tomography (CBCT) capability was installed in a hybrid operating room. The ARSN system used input from four video cameras for tracking adhesive skin markers placed around the surgical field. The frameless reference marker system was evaluated first in four human cadavers, and then in 20 patients undergoing navigated spine surgery. In each CBCT, the impact of vertebral position in the surgical field on technical accuracy was analyzed. The technical accuracy of the inserted pedicle devices was determined by measuring the distance between the planned position and the placed pedicle device, at the bone entry point. RESULTS: The overall mean technical accuracy was 1.65 ±â€Š1.24 mm at the bone entry point (n = 366). There was no statistically significant difference in technical accuracy between levels within CBCTs (P ≥ 0.12 for all comparisons). Linear regressions showed that null- to negligible parts of the effect on technical accuracy could be explained by the number of absolute levels away from the index vertebrae (r ≤ 0.007 for all, ß ≤ 0.071 for all). CONCLUSION: The frameless reference marker system based on adhesive skin markers is unobtrusive and affords the ARSN system a high accuracy throughout the navigated surgical field, independent of vertebral position. LEVEL OF EVIDENCE: 3.