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Introduction: Percutaneous vertebral augmentation is a common therapeutic approach for osteoporotic or osteolytic vertebral fractures. Due to the variable pedicle anatomy two different approaches, the transpedicular and the extrapedicular approach have been established. In particular, in the middle and upper thoracic spine, percutaneous procedures are challenging because of difficult visualisation of anatomical landmarks and a more unfavourable anatomy with smaller and differently orientated pedicles. Material and methods: In our cadaveric study we compared the transpedicular and the extrapedicular approach to the thoracic spine. In 26 cadaveric spine specimes, embalmed using Thiel's method, we placed a total of 486 trans-and extrapedicular K-wires through Jamshidi needles in the vertebral bodies T4-T12 under fluoroscopy. A CT scan was then performed to verify the actual position of the K-wire. Malpositioning was defined as deviation from the planned approach or placement of the K-wire in the spinal canal or outside the vertebral body. Number and direction of malpositionings was recorded. Results: Malpositioning occurred in 68 of 468 K-wires. It was more frequent in the transpedicular (54) than in the extrapedicular (14) approach. Intraspinal malposition was seen more often in the transpedicular approach (n = 36) especially in the upper and middle thoracic spine. Conclusion: In summary both approaches are relatively safe but in the upper and middle thoracic spine the risk of intraspinal malpositioning seems to be lower when using the extrapedicular approach.

Background and Objectives Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF- β signaling is altered in pro-hypertrophic conditions. Methods and Results Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF- β and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF- β and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGF β -type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGF β -type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF- β -1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4. Conclusions Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGF β signaling.

BackgroundCASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid.MethodsWe retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-α and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets.ResultsDiagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-α gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene.ConclusionsAll tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-α gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1658499296115016

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Background: The heterogeneity of patients with osteoporotic vertebral compression fractures (VCF) necessitates a tailored approach of balancing the benefits and limitations of available treatments. Current guidelines are divergent, sometimes contradictory, and often insufficiently detailed to guide practice decisions. Objectives: This study aimed at establishing treatment recommendations at the patientspecific level. Study Design: Using the RAND/UCLA Appropriateness Method (RAM), the appropriateness of different treatment options for osteoporotic VCFs was assessed. Setting: The assessment was conducted by a European multidisciplinary panel of 12 experts. Methods: The appropriateness of non-surgical management (NSM), vertebroplasty (VP), and balloon kyphoplasty (BKP) was determined for 128 hypothetical patient profiles. These were unique combinations of clinical factors considered relevant to treatment choice (time since fracture, MRI findings, impact and evolution of symptoms, spinal deformity, ongoing fracture process, and pulmonary dysfunction). After 2 individual rating rounds and plenary meetings, appropriateness statements (appropriate, inappropriate, and uncertain) were calculated for all clinical scenarios. Results: Disagreement dropped from 31% in the first round to 7% in the second round. Appropriateness outcomes showed specific patterns for the 3 treatments. For three-quarters of the profiles, only one treatment was considered appropriate: NSM 25%, VP 6%, and BKP 45%. NSM was usually appropriate in patients with a negative MRI or a positive MRI without other unfavorable conditions (poor outcomes for the other variables). VP was usually appropriate in patients with a positive MRI, time since fracture ≥ 6 weeks, and no spinal deformity. BKP was recommended for all patients with an ongoing fracture process, and also in most patients with a positive MRI and ≥ 1 other unfavorable factor. Limitations: The prevalence of the patient profiles in daily practice is yet unknown. Conclusion: The panel results may help to support treatment choice in the heterogeneous population of patients with osteoporotic VCF. Key words: Appropriateness criteria, balloon kyphoplasty, non-surgical management, osteoporosis, RAND/UCLA Appropriateness Method, treatment choice, vertebral compression fractures, vertebroplasty:

The health target of eliminating measles will not likely be reached. STIKO's recommendations as well as periodically vocational training courses, should be more compulsory to physicians. Self-responsibility of patients and parents should be raised by financial incentives on sick funds premiums.

clinically confirmed [1]. Patients may experience prolonged pain and increasing kyphosis due to changes to the structure of the spine. This can result in a higher risk of additional adjacent fractures and impaired lung function. For many individuals affected, the lasting, gruelling pain symptoms and resultant