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204. Change in Transcranial Motor Evoked Potentials in the Porcine Tibialis Anterior Following Continuous Retraction on the L5 Nerve Root
108S
Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S–205S
RESULTS: Twelve (4%) of patients had an immediate post-op Hb level !8 g/dL, 126 (41.3%) O8 and !10 g/dl and 167(54.8%) O10 g/dl. For all investigated outcome measures there were no significant differences between the two groups with higher Hb levels. For the patients with immediate post-op Hb level !8 g/dl there was an increased incidence of surgical site infections (SSI) (18% versus 4%, p5.030). There was a significant increase in use of RBC among those hospitalizations involving SSI (2.79 units versus 1.85 units, p5.049) or deep SSI (3.75 units versus 1.85 units, p5.002). Conversely, hospitalizations involving a clinical SSI reported a decreased use of fresh frozen plasma during surgery (1.50 units versus 2.69 units, p5.042). There was a positive correlation between the use of blood product and length of stay (intensive care unit and ward). CONCLUSIONS: In patients undergoing spine surgery with O 2 liters blood loss, there is no significant difference in morbidity, mortality or length of stay when post-operative Hb levels were in the range of 8 to 10 g/dl or O10 g/dl. In patients who were under resuscitated (Hb !8 g/ dl) there is a significant increased risk of SSI. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
baseline. The NRT following retraction with 2 N increased from .25 mA to 1.8 mA following retraction and correlated with the decrease in tcMEPs (r2 5 0.90, p!0.001). Tonic EMG was elicited in 0/6 nerve roots at 1 N, 2/ 11 nerve roots at 2 N and 9/10 nerve roots at 4 N retraction force. Following ten minute recovery at 1 N, 2 N and 4 N the tcMEPs were 2%, 33% and 48% below baseline, respectively. CONCLUSIONS: Following prolonged retraction of the L5 nerve root a decrease in tcMEPs occurred in the Tibialis Anterior in a curvilinear fashion. The magnitude of the change and slope of the curve was proportional to the force used for retraction and had a high correlation to change in the nerve root threshold measured. Furthermore, the recovery of the tcMEPwas dependent on the force of retraction with the 2 N group recovering more than the 4 N group. The study demonstrates that changes in tcMEPs occurs in a linear fashion rather than in a step-wise fashion. This suggests that frequent tcMEP measurements during spinal manipulation or nerve root retraction can be used to detect subtle neurophysiological changes over time and may help prevent an irreversible injury from occurring. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
doi: 10.1016/j.spinee.2009.08.246 doi: 10.1016/j.spinee.2009.08.247 204. Change in Transcranial Motor Evoked Potentials in the Porcine Tibialis Anterior Following Continuous Retraction on the L5 Nerve Root Shane Burch, MD1, Russel Lyons, MS1, James Mok, MD1, Jeremy Lieberman, MD1; 1University of California, San Francisco, San Francisco, CA, USA
205. CDDO-Me Blocks Constitutively Activated SRC/STAT3 Pathway and Inhibits Growth of Chordoma Cells Cao Yang, MD1, Francis Hornicek2, Kirkham Wood, MD2, Joseph Schwab, MD2, Edwin Choy2, Henry Mankin2, Zhenfeng Duan2; 1Massachusetts General Hospital, Boston, MA, USA; 2Boston, MA, USA
BACKGROUND CONTEXT: The incidence of nerve root injury following correction of spinal deformity has been reported to be as high as 30%. Neurophysicological monitoring in the form of mechanically elicited EMG, evoked EMG and transcranial motor evoked potentials (tcMEPs) has been used to identify nerve root injury but has not been used routinely to predict if an irreversible change is likely to occur. We have previously demonstrated that tcMEPs can accurately detect injury in lumbar nerve roots in a pig model. Although tcMEPs are sensitive to direct nerve root damage, there is limited clinical or animal data describing continuous tcMEP change from injury due to prolonged retraction. An established pig model was used to characterize changes in tcMEPs of the porcine Tibialis Anterior following sustained retraction of the L5 nerve root. PURPOSE: The purpose of this study was to characterize the change in tcMEPs of the tibialis anterior and L5 nerve root thresholds(NRT) following retraction with different forces across the L5 nerve root in an established pig model. The purpose was to determine if changes in tcMEPs occur in a linear versus step-wise fashion and whether the changes corrleated to changes in NRTs. STUDY DESIGN/SETTING: Animal Study. PATIENT SAMPLE: Fifteen female Landrace (48-53 kg) pigs were used in the study. OUTCOME MEASURES: N/A. METHODS: An established porcine model was used. TcMEPs, mechanically elicited EMG and evoked EMG responses (NRT) were recorded from three myotomes before, during and following retraction of the L5 nerve root at 1 N (n56), 2 N (n511), and 4 N (n512) for every minute for ten minutes and then at a ten minute interval following retraction. Retraction was performed with a custom nerve retractor fitted with a tensilometer. Electrophysiological modalities were recorded with a Cadwell system. Changes in tcMEPs were plotted against time and correlated to changes in NRTs. RESULTS: During the ten minute retraction period at 1 N, 2 N and 4 N, the amplitude of the tcMEP for the tibialis anterior muscle progressively decreased in a curvilinear fashion. Following retraction at 1 N, the mean amplitude of tcMEP of the TA muscle dropped 5% down from baseline, at 2 N it dropped 47% from baseline and at 4 N dropped 65% from
BACKGROUND CONTEXT: Chordomas are considered to be refractory to cytotoxic chemotherapy and relatively radiation resistant. The advent of molecularly targeted therapies has raised interest for their use in the treatment of chordomas. Unfortunately, current understanding of molecular marker expression in chordomas is limited. With the introduction of targeted molecular therapeutics into clinical practice, an enhanced understanding of the molecular pathogenesis of chordomas is needed. PURPOSE: To investigate the expression and activation of Src/Stat3 pathway in chordoma cells and to determine the efficiency of inhibit this pathway by CDDO-Me as a potential chemotherapeutic agent for chordoma treatment. STUDY DESIGN/SETTING: An experimental study to investigate the activation of Src/Stat3 pathway in chordomas and blockade of this pathway as a potential strategy for chordoma treatment. PATIENT SAMPLE: Thirteen surgically treated patients diagnosed with chordoma were identified and utilized for the study under an IRB approved protocol. OUTCOME MEASURES: Treatment effects were evaluated using a twosided Student’s t test METHODS: The expression of key components of the Src/Stat3 signaling cascade, including Stat3, pStat3, Src, pSrc, Bcl-XL and MCL-1, was evaluated by Western blot in 13 chordoma tissues and three chordoma cell lines. The effects of CDDO-Me on chordoma cell growth were defined in these chordoma cell lines by MTT assay, The expression of key components of the Src/Stat3 signaling cascade and PARP cleavage in these CDDO-Me treated cells was analyzed by Western blot. Furthermore, the synergistic effect of CDDO-Me on chemotherapy drug cisplatin and doxrorubin induced cell death was evaluated by MTT. Finally, we grow the chordoma cells in 3-D culture and treated with CDDO-Me. The chordoma cell growth and pStat3 expression were determined by cell numeration and immunofluorescence analysis. RESULTS: The key components of the Src/Stat3 signaling cascade, including Stat3, pStat3, Src, pSrc, Bcl-XL and MCL-1, were highly expressed in chordoma tissues and all three chordoma cell lines as compared with normal intervertevbral disk tissue. Expression of pStat3, pSrc, Bcl-XL and MCL-1 was inhibited in all three chordoma cell lines
Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S–205S
RESULTS: Twelve (4%) of patients had an immediate post-op Hb level !8 g/dL, 126 (41.3%) O8 and !10 g/dl and 167(54.8%) O10 g/dl. For all investigated outcome measures there were no significant differences between the two groups with higher Hb levels. For the patients with immediate post-op Hb level !8 g/dl there was an increased incidence of surgical site infections (SSI) (18% versus 4%, p5.030). There was a significant increase in use of RBC among those hospitalizations involving SSI (2.79 units versus 1.85 units, p5.049) or deep SSI (3.75 units versus 1.85 units, p5.002). Conversely, hospitalizations involving a clinical SSI reported a decreased use of fresh frozen plasma during surgery (1.50 units versus 2.69 units, p5.042). There was a positive correlation between the use of blood product and length of stay (intensive care unit and ward). CONCLUSIONS: In patients undergoing spine surgery with O 2 liters blood loss, there is no significant difference in morbidity, mortality or length of stay when post-operative Hb levels were in the range of 8 to 10 g/dl or O10 g/dl. In patients who were under resuscitated (Hb !8 g/ dl) there is a significant increased risk of SSI. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
baseline. The NRT following retraction with 2 N increased from .25 mA to 1.8 mA following retraction and correlated with the decrease in tcMEPs (r2 5 0.90, p!0.001). Tonic EMG was elicited in 0/6 nerve roots at 1 N, 2/ 11 nerve roots at 2 N and 9/10 nerve roots at 4 N retraction force. Following ten minute recovery at 1 N, 2 N and 4 N the tcMEPs were 2%, 33% and 48% below baseline, respectively. CONCLUSIONS: Following prolonged retraction of the L5 nerve root a decrease in tcMEPs occurred in the Tibialis Anterior in a curvilinear fashion. The magnitude of the change and slope of the curve was proportional to the force used for retraction and had a high correlation to change in the nerve root threshold measured. Furthermore, the recovery of the tcMEPwas dependent on the force of retraction with the 2 N group recovering more than the 4 N group. The study demonstrates that changes in tcMEPs occurs in a linear fashion rather than in a step-wise fashion. This suggests that frequent tcMEP measurements during spinal manipulation or nerve root retraction can be used to detect subtle neurophysiological changes over time and may help prevent an irreversible injury from occurring. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
doi: 10.1016/j.spinee.2009.08.246 doi: 10.1016/j.spinee.2009.08.247 204. Change in Transcranial Motor Evoked Potentials in the Porcine Tibialis Anterior Following Continuous Retraction on the L5 Nerve Root Shane Burch, MD1, Russel Lyons, MS1, James Mok, MD1, Jeremy Lieberman, MD1; 1University of California, San Francisco, San Francisco, CA, USA
205. CDDO-Me Blocks Constitutively Activated SRC/STAT3 Pathway and Inhibits Growth of Chordoma Cells Cao Yang, MD1, Francis Hornicek2, Kirkham Wood, MD2, Joseph Schwab, MD2, Edwin Choy2, Henry Mankin2, Zhenfeng Duan2; 1Massachusetts General Hospital, Boston, MA, USA; 2Boston, MA, USA
BACKGROUND CONTEXT: The incidence of nerve root injury following correction of spinal deformity has been reported to be as high as 30%. Neurophysicological monitoring in the form of mechanically elicited EMG, evoked EMG and transcranial motor evoked potentials (tcMEPs) has been used to identify nerve root injury but has not been used routinely to predict if an irreversible change is likely to occur. We have previously demonstrated that tcMEPs can accurately detect injury in lumbar nerve roots in a pig model. Although tcMEPs are sensitive to direct nerve root damage, there is limited clinical or animal data describing continuous tcMEP change from injury due to prolonged retraction. An established pig model was used to characterize changes in tcMEPs of the porcine Tibialis Anterior following sustained retraction of the L5 nerve root. PURPOSE: The purpose of this study was to characterize the change in tcMEPs of the tibialis anterior and L5 nerve root thresholds(NRT) following retraction with different forces across the L5 nerve root in an established pig model. The purpose was to determine if changes in tcMEPs occur in a linear versus step-wise fashion and whether the changes corrleated to changes in NRTs. STUDY DESIGN/SETTING: Animal Study. PATIENT SAMPLE: Fifteen female Landrace (48-53 kg) pigs were used in the study. OUTCOME MEASURES: N/A. METHODS: An established porcine model was used. TcMEPs, mechanically elicited EMG and evoked EMG responses (NRT) were recorded from three myotomes before, during and following retraction of the L5 nerve root at 1 N (n56), 2 N (n511), and 4 N (n512) for every minute for ten minutes and then at a ten minute interval following retraction. Retraction was performed with a custom nerve retractor fitted with a tensilometer. Electrophysiological modalities were recorded with a Cadwell system. Changes in tcMEPs were plotted against time and correlated to changes in NRTs. RESULTS: During the ten minute retraction period at 1 N, 2 N and 4 N, the amplitude of the tcMEP for the tibialis anterior muscle progressively decreased in a curvilinear fashion. Following retraction at 1 N, the mean amplitude of tcMEP of the TA muscle dropped 5% down from baseline, at 2 N it dropped 47% from baseline and at 4 N dropped 65% from
BACKGROUND CONTEXT: Chordomas are considered to be refractory to cytotoxic chemotherapy and relatively radiation resistant. The advent of molecularly targeted therapies has raised interest for their use in the treatment of chordomas. Unfortunately, current understanding of molecular marker expression in chordomas is limited. With the introduction of targeted molecular therapeutics into clinical practice, an enhanced understanding of the molecular pathogenesis of chordomas is needed. PURPOSE: To investigate the expression and activation of Src/Stat3 pathway in chordoma cells and to determine the efficiency of inhibit this pathway by CDDO-Me as a potential chemotherapeutic agent for chordoma treatment. STUDY DESIGN/SETTING: An experimental study to investigate the activation of Src/Stat3 pathway in chordomas and blockade of this pathway as a potential strategy for chordoma treatment. PATIENT SAMPLE: Thirteen surgically treated patients diagnosed with chordoma were identified and utilized for the study under an IRB approved protocol. OUTCOME MEASURES: Treatment effects were evaluated using a twosided Student’s t test METHODS: The expression of key components of the Src/Stat3 signaling cascade, including Stat3, pStat3, Src, pSrc, Bcl-XL and MCL-1, was evaluated by Western blot in 13 chordoma tissues and three chordoma cell lines. The effects of CDDO-Me on chordoma cell growth were defined in these chordoma cell lines by MTT assay, The expression of key components of the Src/Stat3 signaling cascade and PARP cleavage in these CDDO-Me treated cells was analyzed by Western blot. Furthermore, the synergistic effect of CDDO-Me on chemotherapy drug cisplatin and doxrorubin induced cell death was evaluated by MTT. Finally, we grow the chordoma cells in 3-D culture and treated with CDDO-Me. The chordoma cell growth and pStat3 expression were determined by cell numeration and immunofluorescence analysis. RESULTS: The key components of the Src/Stat3 signaling cascade, including Stat3, pStat3, Src, pSrc, Bcl-XL and MCL-1, were highly expressed in chordoma tissues and all three chordoma cell lines as compared with normal intervertevbral disk tissue. Expression of pStat3, pSrc, Bcl-XL and MCL-1 was inhibited in all three chordoma cell lines