Retrospective Evaluation of Changes in Gait Patterns in Children and Adolescents With Cerebral Palsy After Multilevel Surgery

The purpose of this study was to retrospectively investigate changes in gait patterns after single-event multilevel surgery in children and adolescents with bilateral cerebral palsy. Three-dimensional instrumented pre- and postoperative gait data of 12 patients were compared to data of 12 healthy control subjects using principal component analysis to reduce the dimensionality of kinematic and kinetic gait data and detect gait differences. The differences between pre- and postoperative data and between postoperative data and data of control subjects were calculated using a linear mixed model. The results revealed 14 significant effects for pre- and postoperative waveforms and 11 significant effects for postoperative and control waveforms. Patients after single-event multilevel surgery walked with smaller internal foot progression angle throughout the gait cycle, lower knee flexion at initial swing, and earlier knee extension during terminal swing. Retained gait deviations included excessive pelvic tilt and internally rotated and flexed hips over the entire gait cycle. Contrary to our hypothesis, postoperative waveforms in the sagittal plane differed more from control waveforms than from preoperative waveforms. These results emphasize the importance of carefully planning further conservative therapy 2 years after single-event multilevel surgery

Prognostic value and in vitro biological relevance of Neuropilin 1 and Neuropilin 2 in osteosarcoma

Neoadjuvant chemotherapy in osteosarcoma increased the long-term survival of patients with localized disease considerably but metastasizing osteosarcoma remained largely treatment resistant. Neuropilins, transmembrane glycoproteins, are important receptors for VEGF dependent hyper-vascularization in tumor angiogenesis and their aberrant expression promotes tumorigenesis and metastasis in many solid tumors. Our analysis of Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) immunostaining in a tissue microarray of 66 osteosarcoma patients identified NRP2 as an indicator of poor overall, metastasis-free and progression free survival while NRP1 had no predictive value. Patients with tumors that expressed NRP2 in the absence of NRP1 had a significantly worse prognosis than NRP1(-)/NRP2(-), NRP1(+) or NRP1(+)/NRP2(+) tumors. Moreover, patients with overt metastases and with NRP2-positive primary tumors had a significantly shorter survival rate than patients with metastases but NRP2-negative tumors. Furthermore, the expression of both NRP1 and NRP2 in osteosarcoma cell lines correlated to a variable degree with the metastatic potential of the respective cell line. To address the functional relevance of Neuropilins for VEGF signaling we used shRNA mediated down-regulation and blocking antibodies of NRP1 and NRP2 in the metastatic 143B and HuO9-M132 cell lines. In 143B cells, VEGFA signaling monitored by AKT phosphorylation was more inhibited by blocking of NRP1, whereas in HuO9-M132 cells NRP2 blocking was more effective indicating that NRP1 and NRP2 can substitute each other in the functional interaction with VEGFR1. Altogether, these data point to NRP2 as a powerful prognostic marker in osteosarcoma and together with NRP1 as a novel target for tumor-suppressive therapy