Radiomics and visual analysis for predicting success of transplantation of heterotopic glioblastoma in mice with MRI.

BACKGROUND: Quantifying tumor growth and treatment response noninvasively poses a challenge to all experimental tumor models. The aim of our study was, to assess the value of quantitative and visual examination and radiomic feature analysis of high-resolution MR images of heterotopic glioblastoma xenografts in mice to determine tumor cell proliferation (TCP). METHODS: Human glioblastoma cells were injected subcutaneously into both flanks of immunodeficient mice and followed up on a 3 T MR scanner. Volumes and signal intensities were calculated. Visual assessment of the internal tumor structure was based on a scoring system. Radiomic feature analysis was performed using MaZda software. The results were correlated with histopathology and immunochemistry. RESULTS: 21 tumors in 14 animals were analyzed. The volumes of xenografts with high TCP (H-TCP) increased, whereas those with low TCP (L-TCP) or no TCP (N-TCP) continued to decrease over time (p < 0.05). A low intensity rim (rim sign) on unenhanced T1-weighted images provided the highest diagnostic accuracy at visual analysis for assessing H-TCP (p < 0.05). Applying radiomic feature analysis, wavelet transform parameters were best for distinguishing between H-TCP and L-TCP / N-TCP (p < 0.05). CONCLUSION: Visual and radiomic feature analysis of the internal structure of heterotopically implanted glioblastomas provide reproducible and quantifiable results to predict the success of transplantation.

Propentdyopents as Heme Degradation Intermediates Constrict Mouse Cerebral Arterioles and Are Present in the Cerebrospinal Fluid of Patients With Subarachnoid Hemorrhage.

RATIONALE: Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. OBJECTIVE: To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. METHODS AND RESULTS: Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. CONCLUSIONS: For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.

Prospective randomized comparison of early versus newer-generation vertebral access devices for kyphoplasty.

INTRODUCTION: Kyphoplasty is an established method of treating osteoporotic vertebral body compression fractures. In recent years, several techniques to enhance the efficiency and outcomes of this surgery have been developed and implemented in clinical practice. In the present study, we assess the impact of two new access instruments on overall operation time and the administered dose area product in comparison with the standard access instrument used in our clinical practice. The two newer comparator devices have been designed with the intention of streamlining intraoperative workflow by omitting several procedural steps. MATERIALS AND METHODS: This was a single-center prospective randomized trial investigating three distinct access instruments compatible with the Joline Allevo balloon catheter system. Specifically, two newer access devices marketed as being able to enhance surgical workflow (Joline RapidIntro Vertebra Access Device with a trocar tip and Joline SpeedTrack Vertebra Introducer Device with a short, tapered tip) were compared with the older, established Joline Vertebra Access Device from the same firm. Consecutive eligible and consenting patients scheduled to undergo kyphoplasty for osteoporotic vertebral compression fracture refractory to conservative, medical treatment during the period May 2012-August 2015 were randomized to receive surgery using one of the three devices. Besides the use of the trial instruments, all other preoperative, intraoperative and postoperative care was delivered according to standard practice. RESULTS: 91 kyphoplasties were performed on 65 unique patients during the study period. The median operation time across the three groups was 29 min (IQR 22.5-35.5) with a median irradiation time of 2.3 min (IQR 1.2-3.4). The median patient age was 74 years (IQR 66-80). The groups did not significantly differ in terms of age (p = 0.878), sex (p = 0.37), T score (p = 0.718), BMI (p = 0.285) or the applied volume of cement (p = 0.792). There was no significant difference between the treatment groups with respect to surgical duration (p = 0.157) or dose area product (p = 0.913). CONCLUSIONS: Although use of the two newer-generation access instruments were designed to involve fewer unique steps per operation, their use was not associated with reduction in surgical duration, irradiation time or dose area product administered compared with the older, established vertebral access device. Care should be taken to evaluate the impact of new instruments on key surgery-related parameters such as surgical duration and radiation exposure and claims made about new instruments should be assessed a structured fashion.

Achievable Central Nervous System Concentrations of the Green Tea Catechin EGCG Induce Stress in Glioblastoma Cells in Vitro.

The polyphenolic compounds present in green tea are preventative against cancer in several animal tumor models. However, direct cytotoxic effects on cancer cells have also been reported. In order to determine whether drinking of green tea has chemopreventive or cytotoxic effects on brain cancer cells, we investigated the effect of the major green tea polyphenol EGCG as a pure substance and as tea extract dietary supplement on primary human glioblastoma cell cultures at the CNS-achievable concentration of 100 nM reported in the literature. We compared this with the effect of the cytotoxic concentration of 500 µM determined to be specific for the investigated primary glioblastoma cultures. After treatment with 500 µM EGCG, strong induction of autophagy and apoptosis was observed. Under treatment with 100 nM EGCG, glioblastoma cells proliferated over the entire observation period of 6 days without any detectable signs of cell death. Only within the first 12 h of treatment was increased accumulation of autophagic vacuoles and increased reactive oxygen species production as a stress response demonstrated. Mild forms of stress, such as treatment with 100 nM EGCG, activate different endogenous repair mechanisms to protect cells. Our data imply that drinking of green tea may have chemopreventive effects, but no direct cytotoxic properties.

NANOG overexpression and its correlation with stem cell and differentiation markers in meningiomas of different WHO grades.

NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize NANOG and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53, and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in high-grade (WHO grade II/III) meningiomas with dural tissue as reference. Immunofluorescence co-localization analysis following confocal fluorescence microscopy for NANOG, OCT4, SOX2, Nestin, KI-67, and CD44 was also performed. There was a significant overexpression of NANOG, MSI1, and EPAS1 and a downregulation of NES in all examined tumors. Subgroup analysis (WHO grade I versus grade II/III) revealed differences in the expression of NANOG, CD44, and MSI1. We found 1% NANOG-positive (NANOG+) cells in low-grade and 2% in grade II/III meningiomas co-expressing the other mentioned markers in various compositions. In particular, NANOG+ cells expressing SOX2 and OCT4 were successfully identified (26% low-grade versus 20% high-grade). Our data reveal an overexpression of NANOG and other markers of pluripotency and stemness in meningiomas. Such potentially pluripotent "stem cell-like" cells may have an impact on tumorigenesis and progression in human meningiomas.

Selection of suitable reference genes for expression analysis in human glioma using RT-qPCR.

In human glioma research, quantitative real-time reverse-transcription PCR is a frequently used tool. Considering the broad variation in the expression of candidate reference genes among tumor stages and normal brain, studies using quantitative RT-PCR require strict definition of adequate endogenous controls. This study aimed at testing a panel of nine reference genes [beta-2-microglobulin, cytochrome c-1 (CYC1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hydroxymethylbilane synthase, hypoxanthine guanine phosphoribosyl transferase 1, ribosomal protein L13a (RPL13A), succinate dehydrogenase, TATA-box binding protein and 14-3-3 protein zeta] to identify and validate the most suitable reference genes for expression studies in human glioma of different grades (World Health Organization grades II-IV). After analysis of the stability values calculated using geNorm, NormFinder, and BestKeeper algorithms, GAPDH, RPL13A, and CYC1 can be indicated as reference genes applicable for accurate normalization of gene expression in glioma compared with normal brain and anaplastic astrocytoma or glioblastoma alone within this experimental setting. Generally, there are no differences in expression levels and variability of candidate genes in glioma tissue compared to normal brain. But stability analyses revealed just a small number of genes suitable for normalization in each of the tumor subgroups and across these groups. Nevertheless, our data show the importance of validation of adequate reference genes prior to every study.

Cement augmented anterior odontoid screw fixation is biomechanically advantageous in osteoporotic patients with Anderson Type II fractures.

STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: The authors tested a cannulated and perforated lag screw and compared in situ polymethylmethacrylate (PMMA) augmentation against nonaugmentation for fixation of osteoporotic type II odontoid fractures. SUMMARY OF BACKGROUND DATA: Osteoporosis has been identified as a strong predictor for pseudarthrosis after screw fixation of type II odontoid fractures with cut-out through the anterior wall of C2 as the most frequent mode of implant failure. The concept of PMMA augmentation of the proximal screw shank could serve as a useful supplement in this context. METHODS: A total of 18 fresh-frozen human cadaveric C2 vertebrae were harvested (median 86.5 y; range, 69-98 y). Reduced bone quality was verified by quantitative computed tomography. Type II odontoid fractures were created and repaired with a cannulated lag screw, which has perforations in the proximal screw shank. Additional PMMA augmentation was carried out for 9 specimens. The position of the screw and cement distribution were evaluated by computed tomography. Values for maximum force to failure, energy to failure, and stiffness were statistically compared between cement augmented and nonaugmented screws. RESULTS: Cement distribution in the C2 vertebral body was circumferential around the screw shank without leakage into the spinal canal or into the fracture gap in all 9 specimens. The cement augmented screws showed a 2.4 times higher maximum force to failure (363±94 N, P<0.001), a 2.7 times higher energy to failure (1300±698 mJ, P<0.001), and a 1.76 times higher stiffness (90±35 N/mm, P=0.031) in comparison with the nonaugmented screws. CONCLUSIONS: Cement augmentation for fixation of osteoporotic type II odontoid fractures showed biomechanical advantages. It was also shown that cement augmentation of the newly developed screw is technically easy and safe under in vitro conditions. The technique might be useful with regard to the surgical treatment of elderly patients with osteoporotic odontoid fractures.

Methylation-specific multiplex ligation-dependent probe amplification and its impact on clinical findings in medulloblastoma.

Gain of (proto-)oncogenes and loss or promoter hypermethylation of tumor suppressor genes (TSGs) play essential roles in tumorigenesis. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) allows simultaneous detection of both these alterations. MS-MLPA was performed on 20 medulloblastoma samples (n = 12 cryoconserved; n = 8 formalin-fixed paraffin-embedded, FFPE) in order to screen for copy number changes in 77 unselected TSGs and (proto-)oncogenes as well as for promoter hypermethylation in a subset of 33 TSGs. In all specimens, determination of promoter methylation status was possible, whereas robust data concerning copy number changes could be obtained on cryopreserved material only. We found a median of 1.5 deletions and 6.5 amplifications in the 12 cryopreserved medulloblastoma and a median of 5 promoter hypermethylation per tumor. Frequent copy number changes included amplification of ASC on 16p12 (5/12) and amplification of several adjacent genes on 17q (3/12) including IGFBP4. Hypermethylation of MSH6 on 2p16 was found in 16 samples. MS-MLPA findings were also correlated with clinical and histological characteristics. The number of promoter hypermethylation was significantly associated with presence of necrosis (p = 0.004). Tumors which recurred within 1 year were more likely to show amplification of the GATA5 gene (p = 0.038), while hypermethylation of CASP8 was associated with a lower tumor recurrence rate (p = 0.036). There was also a trend towards a correlation between total number of aberrations and CSF dissemination (p = 0.055). Our findings confirm frequent presence of certain aberrations and reveal novel candidates for improving prognosis based on genetic and epigenetic tumor features. A medulloblastoma-specific MS-MLPA probe set seems a potentially valuable tool for further investigations on larger sample series.

Overexpression of fatty acid synthase in human gliomas correlates with the WHO tumor grade and inhibition with Orlistat reduces cell viability and triggers apoptosis.

Fatty acid synthase (FASN), catalyzing the de novo synthesis of fatty acids, is known to be deregulated in several cancers. Inhibition of this enzyme reduces tumor cell proliferation. Unfortunately, adverse effects and chemical instability prevent the in vivo use of the best-known inhibitors, Cerulenin and C75. Orlistat, a drug used for obesity treatment, is also considered as a potential FASN inhibitor, but its impact on glioma cell biology has not yet been described. In this study, we analyzed FASN expression in human glioma samples and primary glioblastoma cell cultures and the effects of FASN inhibition with Orlistat, Cerulenin and C75. Immunohistochemistry followed by densitometric analysis of 20 glioma samples revealed overexpression of FASN that correlated with the WHO tumor grade. Treatment of glioblastoma cells with these inhibitors resulted in a significant, dose-dependent reduction in tumor cell viability and fatty acid synthesis. Compared to Cerulenin and C75, Orlistat was a more potent inhibitor in cell cultures and cell lines. In LN229, cell-growth was reduced by 63.9 ± 8.7 % after 48 h and 200 µM Orlistat compared to controls; in LT68, the reduction in cell growth was 76.3 ± 23.7 %. Nuclear fragmentation assay and Western blotting analysis after targeting FASN with Orlistat demonstrated autophagy and apoptosis. Organotypic slice cultures treated with Orlistat showed reduced proliferation after Ki67 staining and increased caspase-3 cleavage. Our results suggest that FASN may be a therapeutic target in malignant gliomas and identify Orlistat as a possible anti-tumor drug in this setting.

Denervation and atrophy of paraspinal muscles after open lumbar interbody fusion is associated with clinical outcome--electromyographic and CT-volumetric investigation of 30 patients.

BACKGROUND: Different studies have shown that atrophy of paraspinal muscles arises after open dorsal lumbar fusion, and the reasons for this atrophy are still not yet fully clarified. This prospective study investigates the extent of atrophy of the lumbar paraspinal muscles after open lumbar interbody fusion, its possible causes, and their association with clinical outcome measures. METHODS: Thirty consecutive patients were prospectively included (13 male, 17 female, median age 60.5 years, range 33-80 years). Mono or bisegmental, posterior lumbar interbody fusion and instrumentation was performed applying a conventional, open lumbar midline approach. Clinical outcome was assessed by the Short Form (36) Health Survey (SF-36) questionnaire and visual analogue scale. Needle electromyography of paraspinal muscles was performed preoperatively, at 6 and 12 months. Serum values of creatine kinase, lactate dehydrogenase and myoglobin were determined preoperatively, at day 2 after surgery and at discharge. Paraspinal muscle volume was determined by volumetric analysis of thin-slice computed tomography scans preoperatively and 1 year after surgery. RESULTS: There was a significant increase of electromyographic denervation activity (p =0.024) and reduced recruitment of motor units (p = 0.001) after 1 year. Laboratory studies showed a significant increase of CK (p < 0.001) and myoglobin (p < 0.001) serum levels at day 2 after surgery. The paraspinal muscle volume decreased from 67.8 to 60.4 % (p < 0.001) after 1 year. Correlation analyses revealed a significant negative correlation between denervation and muscle volume (K = -0.219, p = 0.002). Paraspinal muscle volume is significantly correlated with physical outcome (K = 0.169, p = 0.020), mental outcome (K = 0.214, p = 0.003), and pain (K = 0.382, p < 0.001) after 1 year. CONCLUSIONS: Atrophy of paraspinal muscles after open, posterior lumbar interbody fusion seems to be associated with denervation, as well as direct muscle trauma during surgery. While muscle atrophy is also correlated with a worse clinical outcome, it seems to be a determining factor for successful lumbar spine surgery.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Bone flap necrosis after decompressive hemicraniectomy for malignant middle cerebral artery infarction.

BACKGROUND: Autologous bone flap reinsertion follows as a second surgical intervention after decompressive craniectomy in patients with malignant middle cerebral artery (MCA) infarction. In addition to surgery-related short-term complications, aseptic resorption of the reimplanted bone flap is a possible long-term problem which has not yet been sufficiently elucidated in these patients. METHODS: A total of 109 patients who had undergone decompressive hemicraniectomy for malignant MCA infarction in our institution between September 1994 and December 2011 were included in the study. Clinical and radiological findings were retrieved retrospectively. Aseptic bone necrosis was classified into two categories based on computer tomographic features. RESULTS: A total of 76 patients received their own cryoconserved bone flap (mean age 54.34 ± 10.73 years; 49 males). The overall short-term complication rate was 9.2 %. Bone flap necrosis occurred in 26 patients (22.8 %) with 7 flaps showing signs of surgically relevant type II necrosis after a median time of 14 months (interquartile range [IQR] 4-22). CONCLUSIONS: There is a noticeable complication rate in patients undergoing bone flap reinsertion after hemicraniectomy due to malignant MCA infarction. Aseptic bone necrosis represents a significant complication during long-term follow-up. The pathophysiological mechanisms remain unclear and more efforts should be undertaken to understand and possibly prevent this complication in these patients.

Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings-A Pilot Study.

BACKGROUND: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. METHODS: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm3, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. RESULTS: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. CONCLUSIONS: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis.

Fluctuations in serum sodium level are associated with an increased risk of death in surgical ICU patients.

OBJECTIVE: Dysnatremia may have an impact on outcomes in critically ill patients, but this has not been widely investigated in surgical ICU patients. We investigated the epidemiology of dysnatremia in a large cohort of surgical ICU patients and evaluated the possible influence of the time of acquisition of dysnatremia and fluctuations in serum sodium concentrations on hospital mortality in these patients. DESIGN: Retrospective analysis. SETTING: Fifty-bed surgical ICU. PATIENTS: All patients admitted to the ICU between January 2004 and January 2009. MEASUREMENTS AND MAIN RESULTS: Hyponatremia was defined as a serum sodium concentration <135 mmol/L and hypernatremia as a serum sodium concentration >145 mmol/L. Of the 10,923 surgical ICU patients included in the study, 1,215 (11.2%) had hyponatremia and 277 (2.5%) had hypernatremia at admission to the ICU. Among patients with normonatremia at admission to the ICU (n = 9431), the prevalence of ICU-acquired dysnatremia was 31.3%. Dysnatremia present at ICU admission (odds ratio 2.53; 95% confidence interval 2.06-3.12; p < .001) and ICU-acquired dysnatremia (odds ratio 2.06; 95% confidence interval 1.71-2.48; p < 0.001) were independently associated with an increased risk of in-hospital death compared to normonatremia. Dysnatremia at ICU admission (odds ratio 1.23; 95% confidence interval 1.01-1.50) was associated with a higher risk of in-hospital death, compared with ICU-acquired dysnatremia. Fluctuation in serum sodium concentration was also independently associated with an increased risk of in-hospital mortality, in patients who remained normonatremic (>6 mmol/L/ICU stay) and in those with dysnatremia (>12 mmol/L/24 hrs or >12 mmol/L/ICU stay). CONCLUSIONS: Dysnatremia was common in surgical ICU patients and was independently associated with an increased risk of in-hospital death in these patients. Dysnatremia at ICU admission was associated with a higher risk of death compared with ICU-acquired dysnatremia. Fluctuations in serum sodium concentrations were independently associated with an increased risk of in-hospital death, even in patients who remained normonatremic during the ICU stay.

CT-navigation versus fluoroscopy-guided placement of pedicle screws at the thoracolumbar spine: single center experience of 4,500 screws.

PURPOSE: Single center evaluation of the placement accuracy of thoracolumbar pedicle screws implanted either with fluoroscopy or under CT-navigation using 3D-reconstruction and intraoperative computed tomography control of the screw position. There is in fact a huge variation in the reported placement accuracy of pedicle screws, especially concerning the screw placement under conventional fluoroscopy most notably due to the lack of the definition of screw misplacement, combined with a potpourri of postinstrumentation evaluation methods. METHODS: The operation data of 1,006 patients operated on in our clinic between 1995 and 2005 is analyzed retrospectively. There were 2,422 screws placed with the help of CT-navigation compared to 2,002 screws placed under fluoroscopy. The postoperative computed tomography images were reviewed by a radiologist and an independent spine surgeon. RESULTS: In the lumbar spine, the placement accuracy was 96.4 % for CT-navigated screws and 93.9 % for pedicle screws placed under fluoroscopy, respectively. This difference in accuracy was statistically significant (Fishers Exact Test, p = 0.001). The difference in accuracy became more impressing in the thoracic spine, with a placement accuracy of 95.5 % in the CT-navigation group, compared to 79.0 % accuracy in the fluoroscopy group (p < 0.001). CONCLUSION: This study underlines the relevance of CT-navigation-guided pedicle screw placement, especially when instrumentation of the middle and upper thoracic spine is carried out.

Expandable titanium cages for anterior column cervical reconstruction and their effect on sagittal profile: a review of 48 cases.

BACKGROUND: Expandable cervical cages have been utilised successfully to reconstruct the cervical spine for various conditions. However, to date there are only limited data on their influence on cervical sagittal profile. In this retrospective study, we present our experience with performing anterior cervical corpectomy in one or two levels using expandable titanium cages in order to achieve stable reconstruction and restoration of cervical lordosis. METHODS: A case series of data from 48 consecutive patients (20 men, 28 women; mean age 61 years) operated upon in a 5-year-period is retrospectively reviewed. Standard anterior single- or two-level cervical corpectomy, fusion and spinal reconstruction were performed, including placement of an expandable titanium cage and an anterior cervical plate. The mean follow-up was 23 months (range, 8-42 months). Outcome was measured by clinical examinations and visual analogue scale (VAS) scale; myelopathy was classified according the Nurick grading system. Radiographic analysis comprised several parameters, including segmental Cobb angle, cervical lordosis, subsidence ratio and sagittal cage angle. Computed tomography was done 1 and 2 years after surgery; cervical spine radiographs were obtained 3, 6, 12 and 24 months after surgery. RESULTS: In 38 patients (79 %) osseous fusion or stability of construct could be demonstrated in the 2-year follow up examination. The mean restoration of segmental Cobb angle as well as cervical lordosis amounted to 7.6° and 5.4° respectively, both being statistically significant. Furthermore, a profound correction (10° or more) of the sagittal cervical curve was shown in 15 patients. CONCLUSION: Regarding the restoration of the physiological sagittal cervical profile, expandable cervical cages seem to be efficient and easy to use for cervical spine reconstruction after anterior corpectomy. Donor-site-related complications are avoided, fast and strong reconstruction of the anterior column is provided, resulting in satisfactory fusion rates after 2 years.

Anterior cervical intercorporal fusion in patients with osteoporotic or tumorous fractures using a cement augmented cervical plate system: first results of a prospective single-center study.

STUDY DESIGN: Prospective observational clinical study. OBJECTIVE: The aim of this study is to evaluate the technical feasibility and the safety of additional cement augmentation of anterior cervical implants in patients with poor bone quality because of osteoporosis or tumor infiltration. SUMMARY OF BACKGROUND DATA: With an increasing number of elderly patients in spinal surgery the problem of implant dislocation after cervical instrumentation will become a more and more important problem. Whereas in the thoracolumbar area cement augmented screws have become widely accepted to ensure a rigid fixation in patients with reduced bone quality there are no data concerning an additional intravertebral cement augmentation after cervical plating. METHODS: Nine patients (4 males, 5 females, mean age 62.8 y) with newly diagnosed fractures of 1 or 2 cervical vertebrae because of tumor infiltration (6 cases) or osteoporosis (3 cases) were included in our study. A standard 1-level or 2-level cervical corpectomy with vertebral body replacement by an in situ expandable titanium cage and additional anterior plating was carried out. After this, additional cement augmentation was performed as a vertebroplasty of the anterior two thirds of the cranial and caudal adjacent vertebra by a new anterior hole. The cement should enclose the screws and stabilize the endplates of the adjacent vertebrae. Follow-up comprised clinical examinations, SF-36 questionnaire and visual analog scale 3, 6, and 12 months after surgery. Cervical spine radiographs were obtained 3 and 6 months after surgery and computed tomography scans 6 and 12 months after surgery. RESULTS: The median follow-up was 10 months with a range of 4-18 months. There was no intraoperative cement leakage into the spinal canal. The visual analog scale decreased from 8.2 to 4.2 at 6 months, physical and mental component summaries of SF-36 increased significantly from 27.7 to 36.1 and 31.5 to 48.6 at 6 months, respectively. Loosening of screws or plates was not detected throughout the whole observation period. There was 1 subsidence of a titanium cage into an adjacent vertebra without any clinical consequences. There was no adjacent fracture during the follow-up period and other surgical interventions or revisions were not necessary in any patient. CONCLUSIONS: In patients with severe osteoporosis or in patients with advanced tumor disease, excellent surgical, clinical, and radiologic results are possible following our method. In our opinion, a second-step posterior approach can be avoided by this technique.

Cement leakage as a possible complication of balloon kyphoplasty--is there a difference between osteoporotic compression fractures (AO type A1) and incomplete burst fractures (AO type A3.1)?

BACKGROUND: Besides the treatment of osteoporotic vertebral compression fractures of AO type A1, balloon kyphoplasty (BKP) is seen as a therapeutic option even in the treatment of incomplete osteoporotic burst fractures (AO type A3.1). However, due to involvement of the posterior vertebral body wall, the risk of cement leakages is considered to be higher. This study focuses on the frequency and pattern of cement leakages in AO type A3.1 fractures compared with osteoporotic compression fractures (AO type A1). PATIENTS AND METHODS: Retrospective cohort analysis was done of all patients (n = 138) treated by BKP for osteoporotic vertebral fractures (n = 173) between January 2007 and December 2010 in our department. Cement extravasations into three pre-defined anatomical compartments were evaluated on postoperative CT scans of the augmented vertebral bodies, with even minor cement detections beyond the vertebral body's wall being strictly inidicated as leakages. The frequency of cement leakages in relation to the fracture type was statistically analyzed using Pearson's chi-square test. Clinical and radiological follow-up was done 6 weeks, 3 and 6 months postoperatively. RESULTS: The overall cement leakage rate of BKP in 173 treated osteoporotic vertebral fractures was 30.6%. Cement extravasations were detected in 20.3% of A1.1, 30.5% of A1.2, 37.8% of A1.3, and 39.0% of A3.1 fractures, respectively. There was no statistically significant difference in the leakage rate between A3.1 and all A1 fractures (28.0%; p > 0.05), but between A3.1 and A1.1 fractures (p < 0.05). Intraspinal cement extravasations, being the most dangerous, were seen in 25.5% of all leakages (n = 53), whereas in relation to the total number of treated fracture types, there were only 5.1% intraspinal leakages in A1.1, 5.6% in A1.2, 10.9% in A1.3, and 9.8% in A3.1 fractures. Two of 13 patients with intraspinal leakages and 1 patient with a paraaortal anterolateral cement extravasation needed surgical revisions. Two pulmonary PMMA cement embolisms were detected, but without any clinical consequences. None of the patients with cement leakages during BKP suffered from new neurological deficits. CONCLUSIONS: Cement leakages remain a problem in BKP. Although there was no significant difference between AO type A3.1 and all A1 fractures, subgroup analysis revealed a statistically significant higher risk of cement extrusions in A3.1 compared to A1.1 fractures. None of the affected patients showed new neurological deficits due to cement extravasations. Still, balloon kyphoplasty can be considered a safe procedure, even in the treatment of painful osteoporotic vertebral fractures of AO type A3.1.

Scalp defect repair: a comparative analysis of different surgical techniques.

Scalp defects often arise in multimorbid patients. This study aimed at establishing an algorithm of defect repair with particular focus on new regenerative options.All patients, who consulted to the Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Jena between April 2005 and March 2010 were reviewed. Different reconstructive options were compared with regard to duration of hospital stay as well as rate of reoperations needed to achieve full closure.Sixty-eight patients were identified. Local flaps were more effective than skin grafts (P = 0.038) and microvascular free flaps (P = 0.037) in case of skin-galea-periosteal-defects. However, no differences were found between skin grafting in combination with wound bed preconditioning using a dermal regeneration template and microvascular free flap transfer. Scalp defects should be repaired based on careful evaluation of defect anatomy as well as patient's general health. Application of dermal regeneration templates allows for an increase of the indication spectrum of free skin grafts.

A new amplicon-based gene panel for next generation sequencing characterization of meningiomas.

Meningiomas are the most frequent primary intracranial tumors. The considerable variety of histological subtypes has been expanded by the definition of molecular alterations, which can improve both diagnostic accuracy and determination of individual patient's outcome. According to the upcoming WHO classification of brain tumors, the in-time analysis of frequent molecular events in meningiomas may become mandatory to define meningioma subtypes. We have compiled a custom-made amplicon-based next generation sequencing (NGS) meningioma panel covering the most frequent known recurrent mutations in 15 different genes. In an unselected consecutive meningioma cohort (109 patients) analyzed over a period of 12 months, we detected mutations in 11 different genes, with most frequent alterations in NF2 (43%), AKT1E17K (15%), and TRAF7 (13%). In 39 tumors (36%), two different mutations were detected, with NF2 and SUFU (n = 5) and KLF4 and TRAF7 (n = 5) being the most frequent combinations. No alterations were found in POLR2A, CDKN2A, CDKN2B, and BAP1, and no homozygous CDKN2A/B deletion was detected. NF2 mutations were found in tumors of all WHO grades, whereas mutations in KLF4, TRAF7, and SMO were restricted to WHO grade I meningiomas. In contrast, SMARCE1 and TERT mutations were associated with WHO grade II meningiomas (according to the WHO classification 2016). The distribution of mutations across histological subtypes or tumor localization was in line with the existing literature, with typical combinations like KLF4K409Q /TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1E17K mutations. Thus, we present a custom-made NGS meningioma panel providing a time and cost-efficient reliable detection of relevant somatic molecular alterations in meningiomas suitable for daily routine.