Browsing by Author "Chapman, Jens"

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    A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.
    (Journal of neurotrauma, 2011-05) Fehlings, Michael G; Theodore, Nicholas; Harrop, James; Maurais, Gilles; Kuntz, Charles; Shaffrey, Chris I; Kwon, Brian K; Chapman, Jens; Yee, Albert; Tighe, Allyson; McKerracher, Lisa
    Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy.
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    Anterior versus posterior surgical approaches to treat cervical spondylotic myelopathy: outcomes of the prospective multicenter AOSpine North America CSM study in 264 patients.
    (Spine, 2013-12) Fehlings, Michael G; Barry, Sean; Kopjar, Branko; Yoon, Sangwook Tim; Arnold, Paul; Massicotte, Eric M; Vaccaro, Alexander; Brodke, Darrel S; Shaffrey, Christopher; Smith, Justin S; Woodard, Eric; Banco, Robert J; Chapman, Jens; Janssen, Michael; Bono, Christopher; Sasso, Rick; Dekutoski, Mark; Gokaslan, Ziya L

    Study design

    A prospective observational multicenter study.

    Objective

    To help solve the debate regarding whether the anterior or posterior surgical approach is optimal for patients with cervical spondylotic myelopathy (CSM).

    Summary of background data

    The optimal surgical approach to treat CSM remains debated with varying opinions favoring anterior versus posterior surgical approaches. We present an analysis of a prospective observational multicenter study examining outcomes of surgical treatment for CSM.

    Methods

    A total of 278 subjects from 12 sites in North America received anterior/posterior or combined surgery at the discretion of the surgeon. This study focused on subjects who had either anterior or posterior surgery (n = 264, follow-up rate, 87%). Outcome measures included the modified Japanese Orthopedic Assessment scale, the Nurick scale, the Neck Disability Index, and the Short-Form 36 (SF-36) Health Survey version 2 Physical and Mental Component Scores.

    Results

    One hundred and sixty-nine patients were treated anteriorly and 95 underwent posterior surgery. Anterior surgical cases were younger and had less severe myelopathy as assessed by mJOA and Nurick scores. There were no baseline differences in Neck Disability Index or SF-36 between the anterior and posterior cases. Improvement in the mJOA was significantly lower in the anterior group than posterior group (2.47 vs. 3.62, respectively, P < 0.01), although the groups started at different levels of baseline impairment. The extent of improvement in the Nurick Scale, Neck Disability Index, SF-36 version 2 Physical Component Score, and SF-36 version 2 Mental Component Score did not differ between the groups.

    Conclusion

    Patients with CSM show significant improvements in several health-related outcome measures with either anterior or posterior surgery. Importantly, patients treated with anterior techniques were younger, with less severe impairment and more focal pathology. We demonstrate for the first time that, when patient and disease factors are controlled for, anterior and posterior surgical techniques have equivalent efficacy in the treatment of CSM.

    Level of evidence

    3.
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    Assessment of Impact of Long-Cassette Standing X-Rays on Surgical Planning for Cervical Pathology: An International Survey of Spine Surgeons.
    (Neurosurgery, 2016-05) Ramchandran, Subaraman; Smith, Justin S; Ailon, Tamir; Klineberg, Eric; Shaffrey, Christopher; Lafage, Virginie; Schwab, Frank; Bess, Shay; Daniels, Alan; Scheer, Justin K; Protopsaltis, Themi S; Arnold, Paul; Haid, Regis W; Chapman, Jens; Fehlings, Michael G; Ames, Christopher P; AOSpine North America, International Spine Study Group

    Background

    Understanding the role of regional segments of the spine in maintaining global balance has garnered significant attention recently. Long-cassette radiographs (LCR) are necessary to evaluate global spinopelvic alignment. However, it is unclear how LCRs impact operative decision-making for cervical spine pathology.

    Objective

    To evaluate whether the addition of LCRs results in changes to respondents' operative plans compared to standard imaging of the involved cervical spine in an international survey of spine surgeons.

    Methods

    Fifteen cases (5 control cases with normal and 10 test cases with abnormal global alignment) of cervical pathology were presented online with a vignette and cervical imaging. Surgeons were asked to select a surgical plan from 6 options, ranging from the least (1 point) to most (6 points) extensive. Cases were then reordered and presented again with LCRs and the same surgical plan question.

    Results

    One hundred fifty-seven surgeons completed the survey, of which 79% were spine fellowship trained. The mean response scores for surgical plan increased from 3.28 to 4.0 (P = .003) for test cases with the addition of LCRs. However, no significant changes (P = .10) were identified for the control cases. In 4 of the test cases with significant mid thoracic kyphosis, 29% of participants opted for the more extensive surgical options of extension to the mid and lower thoracic spine when they were provided with cervical imaging only, which significantly increased to 58.3% upon addition of LCRs.

    Conclusion

    In planning for cervical spine surgery, surgeons should maintain a low threshold for obtaining LCRs to assess global spinopelvic alignment.
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    Comparing Quality of Life in Cervical Spondylotic Myelopathy with Other Chronic Debilitating Diseases Using the Short Form Survey 36-Health Survey.
    (World neurosurgery, 2017-10) Oh, Taemin; Lafage, Renaud; Lafage, Virginie; Protopsaltis, Themistocles; Challier, Vincent; Shaffrey, Christopher; Kim, Han Jo; Arnold, Paul; Chapman, Jens; Schwab, Frank; Massicotte, Eric; Yoon, Tim; Bess, Shay; Fehlings, Michael; Smith, Justin; Ames, Christopher

    Background

    Although cervical spondylotic myelopathy (CSM) can be devastating, its relative impact on general health remains unclear. Patient responses to the Short Form Survey 36-Health Survey (SF-36) Physical Component Summary (PCS)/Mental Component Summary (MCS) were compared between CSM and other diseases to evaluate their respective impacts on quality of life. The objective of this study was to compare SF-36 PCS/MCS scores in CSM with population and disease-specific norms.

    Methods

    Retrospective analysis of a prospective, multicenter AOSpine North American CSM Study database. Inclusion criteria were symptomatic disease, age older than 18 years, cord compression on magnetic resonance imaging or computed tomography myelography, and baseline SF-36 values. SF-36 PCS/MCS scores in CSM were compared with national normative values and disease-specific norms using Student t test. Analysis of variance was used to assess differences across age groups and offsets from age-matched controls. Threshold for significance was P < 0.05.

    Results

    There were 285 patients who met the inclusion criteria. The mean age was 56.6 ± 12.0 years, with male predominance (60%). SF-36 scores revealed significant baseline disability (PCS: 34.5 ± 9.8; MCS: 41.5 ± 14.4). Although there were no differences across age groups, when compared with age-matched normative data, younger patients had a larger PCS offset than older patients. CSM caused worse physical disability than most diseases except heart failure. Only back pain/sciatica induced worse mental disability.

    Conclusions

    CSM affects quality of life to an extent greater than diabetes or cancer. Although mean impact of CSM does not vary with age, younger patients suffer from greater differences in baseline function. This study highlights the impact of myelopathy on patient function, particularly among younger age groups, and suggests that CSM merits a similar caliber of healthy policy attention as more well-studied diseases.
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    Functional and quality-of-life outcomes in geriatric patients with type-II dens fracture.
    (The Journal of bone and joint surgery. American volume, 2013-04) Vaccaro, Alexander R; Kepler, Christopher K; Kopjar, Branko; Chapman, Jens; Shaffrey, Christopher; Arnold, Paul; Gokaslan, Ziya; Brodke, Darrel; France, John; Dekutoski, Mark; Sasso, Rick; Yoon, S Tim; Bono, Christopher; Harrop, James; Fehlings, Michael G

    Background

    Dens fractures are relatively common in the elderly. The treatment of Type-II dens fractures remains controversial. The aim of this multicenter prospective cohort study was to compare outcomes (assessed with use of validated clinical measures) and complications of nonsurgical and surgical treatment of Type-II dens fractures in patients sixty-five years of age or older.

    Methods

    One hundred and fifty-nine patients with a Type-II dens fracture were enrolled in a multicenter prospective study. Subjects were treated either surgically (n = 101) or nonsurgically (n = 58) as determined by the treatment preferences of the treating physicians and the patients. The subjects were followed at six and twelve months with validated outcome measures, including the Neck Disability Index (NDI) and Short Form-36v2 (SF-36v2). Treatment complications were prospectively recorded. Statistical analysis was performed to compare outcome measures before and after adjustment for confounding variables.

    Results

    The two groups were similar with regard to baseline characteristics. The most common surgical treatment was posterior C1-C2 arthrodesis (eighty of 101, or 79%) while the most common nonsurgical treatment was immobilization with use of a hard collar (forty-seven of fifty-eight, or 81%). The overall mortality rate was 18% over the twelve-month follow-up period. At twelve months, the NDI had increased (worsened) by 14.7 points in the nonsurgical cohort (p < 0.0001) compared with a nonsignificant increase (worsening) of 5.7 points in the surgical group (p = 0.0555). The surgical group had significantly better outcomes as measured by the NDI and SF-36v2 Bodily Pain dimension compared with the nonsurgical group, and these differences persisted after adjustment. There was no difference in the overall rate of complications, but the surgical group had a significantly lower rate of nonunion (5% versus 21% in the nonsurgical group; p = 0.0033). Mortality was higher in the nonsurgical group compared with the surgical group (annual mortality rates of 26% and 14%, respectively; p = 0.059).

    Conclusions

    We demonstrated a significant benefit with surgical treatment of dens fractures as measured by the NDI, a disease-specific functional outcome measure. As a result of the nonrandomized nature of the study, the results are vulnerable to the effects of possible residual confounding. We recommend that elderly patients with a Type-II dens fracture who are healthy enough for general anesthesia be considered for surgical stabilization to improve functional outcome as well as the union and fusion rates.
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    In response.
    (Spine, 2014-07) Fehlings, Michael G; Barry, Sean; Kopjar, Branko; Yoon, Sangwook Tim; Arnold, Paul; Massicotte, Eric M; Vaccaro, Alexander; Brodke, Darrel S; Shaffrey, Christopher; Smith, Justin S; Woodard, Eric; Banco, Robert J; Chapman, Jens; Janssen, Michael; Bono, Christopher; Sasso, Rick; Dekutoski, Mark; Gokaslan, Ziya L
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    The AOSpine North America Geriatric Odontoid Fracture Mortality Study: a retrospective review of mortality outcomes for operative versus nonoperative treatment of 322 patients with long-term follow-up.
    (Spine, 2013-06) Chapman, Jens; Smith, Justin S; Kopjar, Branko; Vaccaro, Alexander R; Arnold, Paul; Shaffrey, Christopher I; Fehlings, Michael G
    STUDY DESIGN: Retrospective, multicenter cohort study. OBJECTIVE: Assess for differences in short- and long-term mortality between operative and nonoperative treatment for elderly patients with type II odontoid fractures. SUMMARY OF BACKGROUND DATA: There is controversy regarding whether operative or nonoperative management is the best treatment for elderly patients with type II odontoid fractures. METHODS: This is a retrospective study of consecutive patients aged 65 years or older with type II odontoid fracture from 3 level I trauma centers from 2003-2009. Demographics, comorbidities, and treatment were abstracted from medical records. Mortality outcomes were obtained from medical records and a public database. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 322 patients were included (mean age, 81.8 yr; range, 65.0-101.5 yr). Compared with patients treated nonoperatively (n = 157), patients treated operatively (n = 165) were slightly younger (80.4 vs. 83.2 yr, P = 0.0014), had a longer hospital (15.0 vs. 7.4 d, P < 0.001) and intensive care unit (1.5 vs. 1.1 d, P = 0.008) stay, and were more likely to receive a feeding tube (18% vs. 5%, P = 0.0003). Operative and nonoperative treatment groups had similar sex distribution (P = 0.94) and Charlson comorbidity index (P = 0.11). Within 30 days of presentation, 14% of patients died, and at maximal follow-up (average = 2.05 yr; range = 0 d-7.02 yr), 44% had died. On multivariate analysis, nonoperative treatment was associated with higher 30-day mortality (HR = 3.00, 95% CI = 1.51-5.94, P = 0.0017), after adjusting for age (HR = 1.10, 95% CI = 1.05-1.14; P < 0.0001), male sex (P = 0.69), and Charlson comorbidity index (P = 0.16). At maximal follow-up, there was a trend toward higher mortality associated with nonoperative treatment (HR = 1.35, 95% CI = 0.97-1.89, P = 0.079), after adjusting for age (HR = 1.07, 95% CI = 1.05-1.10; P < 0.0001), male sex (HR = 1.55, 95% CI = 1.10-2.16; P = 0.012), and Charlson comorbidity index (HR = 1.28, 95% CI = 1.16-1.40; P < 0.0001). CONCLUSION: Surgical treatment of type II odontoid fracture in this elderly population did not negatively impact survival, even after adjusting for age, sex, and comorbidities. The data suggest a significant 30-day survival advantage and a trend toward improved longer-term survival for operatively treated over nonoperatively treated patients. LEVEL OF EVIDENCE: 4.