Markus Schultheiss

Is it possible to simulate physiologic loading conditions by applying pure moments? A comparison of in vivo and in vitro load components in an internal fixator.

Study Design. Loads acting in an internal fixator measured in vitro under the application of pure moments such as those commonly used for implant testing and basic research were compared with loads measured in 10 patients in vivo. Objectives. To investigate whether these recommended loading conditions are valid by comparing in vivo measurements and those obtained in an in vitro experiment. Summary of Background Data. Pure bending moments are often preferred as loading conditions for spinal in vitro testing, either for implant testing or basic research. The advantage of this loading pattern is that the bending moment is uniform along the multisegmental specimen. However, functional loading of the spine by muscles or external loads subjects the spine to a combination of forces and moments. Methods. In an in vivo experiment, loads acting on an internal spinal fixator in 10 patients were determined before and after anterior interbody fusion during flexion, extension, left and right lateral bending, and left and right axial twisting of the upper body with the patient standing. For comparison, an equivalent in vitro data set was created with 7 human lumbar specimens in which the same type of fixator was used. All specimens were tested under the application of pure bending moments in the three main motion planes in the intact state with fixator, after corpectomy, and with bone graft. Results. Consistent qualitative agreement between in vivo and in vitro measurements for the loads acting in the internal spinal fixator were found for axial rotation and lateral bending. For flexion and extension, reasonable agreement was found only for the intact spines with fixators. After corpectomy and after inserting a bone graft, the median values for axial force and bending moment in the sagittal plane in vitro did not agree with in vivo measurements. An axial preload in the in vitro experiment slightly increased the axial compression force and flexion bending moment in the fixators. Conclusions. The application of pure moments to intact lumbar spinal specimens in vitro produces forces andmoments in implants comparable with loads observed in vivo. During basic research on intact specimens or implant testing involving a removed disc or corpectomy, muscle forces are necessary to simulate realistic conditions.

Minimally invasive ventral spondylodesis for thoracolumbar fracture treatment: surgical technique and first clinical outcome

A new instrumentation system for ventral stabilization of the spine that can be used for an endoscopic and minimally invasive approach was developed. We describe the implantation technique and report on the first clinical results. This prospective study covers the first 45 patients to undergo this new technique since it was introduced in 1999. In all patients the operation was successfully performed in a completely minimally invasive procedure. Mono- and bisegmental stabilization was performed mainly at the thoracolumbar junction after initial posterior instrumentation in most cases. Lesions varied from fresh/old fractures to metastases (T5–L3). Pre- and postoperative follow-up included clinical examination and radiological visualization via X-ray and computed tomographic scan. Our experience with this minimally invasive procedure demonstrated the feasibility of the method.

Vertebral body replacement with a bioglass-polyurethane composite in spine metastases – clinical, radiological and biomechanical results

Abstract Metastatic spine lesions frequently require corpectomy in order to achieve decompression of the spinal cord and restoration of spinal stability. A variety of systems have been developed for vertebral body replacement. In patients with prolonged life expectancy due to an improvement of both systemic and local therapy, treatment results can be impaired by a loosening at the implant-bone interface or mechanical failure. Furthermore, early detection of a metastatic recurrence using sensitive imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) is possible in these patients without artefact interference. The aim of our pilot study was to evaluate the clinical applicability and results of a new radiolucent system for vertebral body replacement in the lumbar spine. The system consists of bone-integrating biocompatible materials – a polyetherurethane/bioglass composite (PU-C) replacement body and an integrated plate of carbon-fibre reinforced polyetheretherketone (CF-PEEK) – and provides high primary stability with anterior instrumentation alone. In a current prospective study, five patients with metastatic lesions of the lumbar spine were treated by corpectomy and reconstruction using this new system. Good primary stability was achieved in all cases. Follow-up (median ¶15 months) using CT and MRI revealed progressive osseous integration of the PU-C spacer in four patients surviving more than 6 months. Results obtained from imaging methods were confirmed following autopsy by biomechanical investigation of an explanted device. From these data, it can be concluded that implantation of the new radiolucent system provides sufficient long-term stability for the requirements of selected tumour patients with improved prognosis.

Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway

Chordomas are tumors that arise at vertebral bodies and the base of the skull. Although rare in incidence, they are deadly owing to slow growth and a lack of effective therapeutic options. In this study, we addressed the need for chordoma cell systems that can be used to identify therapeutic targets and empower testing of candidate pharmacologic drugs. Eight human chordoma cell lines that we established exhibited cytology, genomics, mRNA, and protein profiles that were characteristic of primary chordomas. Candidate responder profiles were identified through an immunohistochemical analysis of a chordoma tissue bank of 43 patients. Genomic, mRNA, and protein expression analyses confirmed that the new cell systems were highly representative of chordoma tissues. Notably, all cells exhibited a loss of CDKN2A and p16, resulting in universal activation of the CDK4/6 and Rb pathways. Therefore, we investigated the CDK4/6 pathway and responses to the CDK4/6-specific inhibitor palbociclib. In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder versus nonresponder molecular signature was defined on the basis of immunohistochemical expression of CDK4/6/pRb (S780). Overall, our work offers a valuable new tool for chordoma studies including the development of novel biomarkers and molecular targeting strategies.

Thoracolumbar fracture stabilization: comparative biomechanical evaluation of a new video-assisted implantable system

Minimally invasive techniques for spinal surgery are becoming more widespread as improved technologies are developed. Stabilization plays an important role in fracture treatment, but appropriate instrumentation systems for endoscopic circumstances are lacking. Therefore a new thoracoscopically implantable stabilization system for thoracolumbar fracture treatment was developed and its biomechanical in vitro properties were compared. In a biomechanical in vitro study, burst fracture stabilization was simulated and anterior short fixation devices were tested under load with pure moments to evaluate the biomechanical stabilizing characteristics of the new system in comparison with a currently available system. With interbody graft and fixation the new system demonstrated higher stabilizing effects in flexion/extension and lateral bending and restored axial stability beyond the intact spine, as well as having comparable or improved effects compared with the current system. Because of this biomechanical characterization a clinical trial is warranted; the usefulness of the new system has already been demonstrated in 45 patients in our department and more than 300 cases in a multicenter study which is currently under way.

A new radiolucent system for vertebral body replacement: Its stability in comparison to other systems

Anterior intervention of metastatic lesions of the spine can accomplish relief of pain, spinal decompression, and restoration of spinal stability. Ventral vertebral body replacements have been developed to provide these conditions but there have been problems with loosening at the implant-bone interface, mechanical failure, and X-ray artifacts from the metal. Intraoperative stability of the vertebral body replacement is especially critical to avoid loosening of the implant and to achieve long-term bony incorporation. This study compared the biomechanical performance in vitro of a new radiolucent system for vertebral body replacement to three currently marketed systems. The new system features a composite bioglass-polyurethane body and a new configuration of polymeric fastening hardware. Range of motion, neutral zone, and several interfacial motion parameters were measured under pure moments of 3.75 Nm in the three anatomical directions. The new system provided the significantly highest restraint of motion for all parameters. Mechanically, the new system is preferable at least initially to a sampling of systems representative of those currently used.

H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant

Giant cell tumour of the bone (GCTB) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumours giant cell‐rich morphology, which overlaps with other giant cell‐containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell‐containing lesions.

Integrated FDG-PET-CT: its role in the assessment of bone and soft tissue tumors

PurposeThe purpose of this study was to evaluate prospectively, whether integrated 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography (FDG-PET-CT) is more accurate for determination musculoskeletal tumors compared with separate interpretation of CT and FDG-PET, because most of the current clinical data come from patients studied with PET.MethodsEighty patients with newly diagnosed musculoskeletal tumors underwent FDG-PET-CT. CT, FDG-PET, and FDG-PET-CT were interpreted separately to determine the performance of each imaging modality.ResultsAssuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity and accuracy for CT alone was 81, 84, 83%, for PET 71, 82, 76, and for PET-CT 80, 83 and 86%. Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 61, 100, 70%, for PET 69, 100, 79, and for PET-CT 69, 100 and 79%.ConclusionsCombined FDG-PET-CT reliably differentiates soft tissue and bone tumors from benign lesions. The value of the information provided by FDG-PET-CT for planning surgical procedures must be evaluated in further studies.

Influence of screw-cement enhancement on the stability of anterior thoracolumbar fracture stabilization with circumferential instability

The influence of additional dorsal structure damage on anterior stabilization of a thoracolumbar fracture is still unknown. Screw-cement enhancement can be used to reinforce the stability of anterior instrumentation. We have developed a new anchorage system for fixation of anterior stabilization devices, adapted through geometric optimization and the additional option of cementation after screw insertion. This study examines the question of whether this enhancement is strong enough to enable a single anterior procedure and still compensate for dorsal instability. Various spinal reconstruction procedures were evaluated biomechanically in an increasing ventrodorsal instability model for thoracolumbar fracture stabilization. A biomechanical in vitro study, simulating stabilized defect situations (corporectomy/vertebrectomy) with strut grafting and overbridging instrumentation, was performed on six human T10–L2 cadaveric specimens. The primary stability parameters, range of motion and neutral zone, were evaluated with or without anterior screw-cement enhancement. This was compared with a single conventional anterior stabilization without a dorsal defect (corporectomy). It was also compared with a single anterior, posterior or combined procedure in the presence of additional dorsal structure damage (vertebrectomy). The use of an additional cementable screw dowel enhanced the primary stability of the anterior instrumentation, compensating for dorsal instability. These results are warranted for the clinical use of minimally open or endoscopic techniques, creating the highest possible primary stability while performing a single anterior enhanced instrumentation with a tissue-preserving approach.

Axial compression force measurement acting across the strut graft in thoracolumbar instrumentation testing

OBJECTIVE Current recommendations for spinal implant testing do not consider the determination of axial compression forces of the overbridging implant on the strut graft. No direct data exist on the influence of load transfer through the strut graft and of the kind of instrumentation, especially in thoracolumbar corpectomy models. DESIGN Therefore in this biomechanical in vitro study a method for measurement of the axial compression force acting across the strut graft in different thoracolumbar instrumentations was developed. METHODS In this in vitro study, a corpectomy model was simulated and anterior, posterior and combined short fixation devices currently available were tested under pure moments to evaluate their biomechanical stabilizing characteristics. Range of motion, neutral zone and the axial compressive force acting on the strut graft were measured continuously in the three primary directions. RESULTS Without loads, the combined stabilization and followed by anterior instrumentation created a higher axial compression force than the dorsal instrumentation on the strut graft. Especially during maximal extension there was no axial compression of the dorsal instrumentation on the strut graft, which resulted in an increase of the range of motion. CONCLUSION The feasibility of the new method was demonstrated in this study. For the purpose of standardization and comparison it should be considered in spinal implant testing.