The total disc replacement (TDR) devices are gaining popularity because of their capability of allowing joint motion at the index level. Studies have shown that motion preservation can reduce the likelihood of further degeneration at the adjacent level with better surgical outcome. Current lumbar TDR devices require an anterior approach for implantation. However, it is known that its clinical outcome may depend on implant insertion and placement during surgery. Only limited number of biomechanical studies regarding the effect of placement orientation on the clinical outcome is currently available. The purpose of this study was to investigate effects of various surgical placement of a lumbar TDR on the kinematics and load-sharing characteristics using finite element method (FEM).

A previously-validated 3-D nonlinear FE model of the intact lumbar motion segment (L3-S1) based on computer tomography (CT) images of a cadaveric specimen (male, age 56, no pathologies) was used as the baseline FE model. Then, implantation of ProDisc-L (Spine Solutions, Inc., Synthes, Paoli, PA, USA) was simulated into the L4–L5 disc space through anterior approach with removal of the nucleus, anterior longitudinal ligament, and the anterior part of the annulus. The location of lumbar TDR was varied in the sagittal and the coronal planes. In the sagittal plane, the implants were placed anteriorly at 3-mm (S-3), 5-mm (S-5), and 7-mm (S-7) offset from the posterior margin of the endplate. In the coronal plane, the devices were shifted from the baseline position laterally to the right by 1-mm (C-1), 2-mm (C-2), and 3-mm (C-3) from the mid-sagittal line along the lower endplate. All of the models were subject to 150N compressive pre-load and flexion/extension moments of 10Nm at the superior endplate L4, while the inferior endplate of L5 was fully constrained. Changes in motion (ROM) and facet loads at the index and adjacent levels were assessed at different implant position.

Results showed that deviation from the central placement (from S-3 to S-7 and from C-1 to C-3) decreases ROM while increasing facet load at the index level. The effect was more pronounced in the sagittal plane than in the coronal plane:10% decrease in ROM and 1% increase in facet load in the sagittal plane vs. no significant change in the coronal plane. As expected, changes were more evident during extension than in flexion. While the kinematics of the spine was restored to the pre-operative stage at the index level (L4-5), the ROM decreased at the adjacent level (L5-S1) in a compensating manner. The overloading of the facet seemed to indicate mal-alignment of the implant can further trigger facet degeneration, which may require unwanted revision or additional surgical treatment.

Purpose: Thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), are a serious risk after major orthopaedic surgery. BAY 59-7939 is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. The efficacy and safety of BAY 59-7939 for thromboprophylaxis have been determined relative to enoxaparin in two clinical trials, one after elective total hip replacement surgery, and one after elective total knee replacement surgery. This pre-specified analysis combines data from two multicenter, multinational, double-blind, dose-ranging studies; the hip surgery trial was performed in Europe, and the knee surgery trial in North America.

Methods: Patients (N=1343) were randomized to oral BAY 59-7939 at 2.5, 5, 10, 20, or 30 mg twice daily (bid), or subcutaneous enoxaparin (40 mg once daily starting 12 hours before hip surgery, or 30 mg bid starting 12 hours after knee surgery), continuing until mandatory bilateral venography was performed 5–9 days after surgery. The primary efficacy endpoint was a composite of DVT, PE, and all-cause mortality. The primary safety endpoint was major, post-operative bleeding.

Results: The primary efficacy endpoint occurred in 21.6%, 22.9%, 16.1%, 24.4%, and 19.3% of patients receiving BAY 59-7939 2.5, 5, 10, 20, and 30 mg bid, respectively, and 27.8% receiving enoxaparin (n=914). No significant dose–response relationship for efficacy was observed with BAY 59-7939 (P=0.39); this was potentially due to the efficacy achieved with the lower BAY 59-7939 doses. A significant dose–response relationship was observed for major, post-operative bleeding with BAY 59-7939 (P< 0.001), which occurred in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving BAY 59-7939 2.5, 5, 10, 20, and 30 mg bid, respectively, and 1.7% of patients receiving enoxaparin (n=1317).

Conclusions: This analysis showed that BAY 59-7939 has a wide therapeutic window for the prevention of VTE following major orthopaedic surgery, and, at doses of 2.5–10 mg bid, has similar efficacy and safety to the enoxaparin regimens.

Funding : Commerical funding

Funding Parties : This study was sponsored by Bayer HealthCare AG