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Keun Su Kim, S. Tim Yoon, Jin Soo Park, Jun Li, Moon Soo Park and William C. Hutton

Object. Systemic nicotine has been hypothesized to cause degeneration of the intervertebral disc which in turn decreases vascular supply to the disc through a cholinergic receptor—mediated process. Another possible mechanism may be through direct regulatory effects on disc cells. In this study, the authors tested the hypothesis that nicotine adversely affects nucleus pulposus cells by directly inhibiting proteoglycan synthesis and gene expression of type II collagen (Phase I study). They also assessed the hypothesis that nicotine inhibits the bone morphogenetic protein (BMP)—2-induced upregulation of extracellular matrix (Phase II study).

Methods. Cells were isolated from nucleus pulposus obtained in rat lumbar discs and cultured on a monolayer. Media were treated with nicotine and/or recombinant human (rh)BMP-2 for 7 days. Sulfated glycosaminoglycan (SO4-GAG) in media was quantified using 1,9-dimethylmethylene blue (DMMB) assay. Gene assay of types I and II collagen, Sox9, and glyceraldehyde-3-phosphate dehydrogenase were quantified using reverse transcriptase—polymerase chain reaction (RT-PCR) and real time PCR. In the Phase I study, nicotine-treated (100 µg/ml) and nontreated cells were compared. The s-GAG production and messenger RNA (mRNA) of type II collagen and Sox9 decreased significantly in the nicotine-treated group. In the Phase II study, five groups were compared: 1) nontreatment; 2) rhBMP-2 only (100 ng/ml); and 3–5) with rhBMP-2 (100 ng/ml) and increasing doses of nicotine (1 [third group], 10, [fourth group], 100 [fifth group] µg/ml). The SO4-GAG production and mRNA of type II collagen and Sox9 decreased significantly in the groups treated with rhBMP-2 combined with 10 and 100 µg/ml of nicotine compared with the group treated with rhBMP-2.

Conclusions. The results of this study raise the possibility that nicotine may contribute to the process of disc degeneration by a direct effect on the nucleus pulposus cells, possibly by antagonizing the effect of BMP-2.

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Zorica Buser, Darrel S. Brodke, Jim A. Youssef, Hans-Joerg Meisel, Sue Lynn Myhre, Robin Hashimoto, Jong-Beom Park, S. Tim Yoon and Jeffrey C. Wang

The purpose of this review was to compare the efficacy and safety of synthetic bone graft substitutes versus autograft or allograft for the treatment of lumbar and cervical spinal degenerative diseases. Multiple major medical reference databases were searched for studies that evaluated spinal fusion using synthetic bone graft substitutes (either alone or with an autograft or allograft) compared with autograft and allograft. Randomized controlled trials (RCT) and cohort studies with more than 10 patients were included. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest.

The search yielded 214 citations with 27 studies that met the inclusion criteria. For the patients with lumbar spinal degenerative disease, data from 19 comparative studies were included: 3 RCTs, 12 prospective, and 4 retrospective studies. Hydroxyapatite (HA), HA+collagen, β-tricalcium phosphate (β-TCP), calcium sulfate, or polymethylmethacrylate (PMMA) were used. Overall, there were no differences between the treatment groups in terms of fusion, functional outcomes, or complications, except in 1 study that found higher rates of HA graft absorption.

For the patients with cervical degenerative conditions, data from 8 comparative studies were included: 4 RCTs and 4 cohort studies (1 prospective and 3 retrospective studies). Synthetic grafts included HA, β-TCP/HA, PMMA, and biocompatible osteoconductive polymer (BOP). The PMMA and BOP grafts led to lower fusion rates, and PMMA, HA, and BOP had greater risks of graft fragmentation, settling, and instrumentation problems compared with iliac crest bone graft.

The overall quality of evidence evaluating the potential use and superiority of the synthetic biological materials for lumbar and cervical fusion in this systematic review was low or insufficient, largely due to the high potential for bias and small sample sizes. Thus, definitive conclusions or recommendations regarding the use of these synthetic materials should be made cautiously and within the context of the limitations of the evidence.

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Shian Liu, Renaud Lafage, Justin S. Smith, Themistocles S. Protopsaltis, Virginie C. Lafage, Vincent Challier, Christopher I. Shaffrey, Kris Radcliff, Paul M. Arnold, Jens R. Chapman, Frank J. Schwab, Eric M. Massicotte, S. Tim Yoon, Michael G. Fehlings and Christopher P. Ames

OBJECT

Cervical stenosis is a defining feature of cervical spondylotic myelopathy (CSM). Matsunaga et al. proposed that elements of stenosis are both static and dynamic, where the dynamic elements magnify the canal deformation of the static state. For the current study, the authors hypothesized that dynamic changes may be associated with myelopathy severity and neck disability. This goal of this study was to present novel methods of dynamic motion analysis in CSM.

METHODS

A post hoc analysis was performed of a prospective, multicenter database of patients with CSM from the AOSpine North American study. One hundred ten patients (34%) met inclusion criteria, which were symptomatic CSM, age over 18 years, baseline flexion/extension radiographs, and health-related quality of life (HRQOL) questionnaires (modified Japanese Orthopaedic Association [mJOA] score, Neck Disability Index [NDI], the 36-Item Short Form Health Survey Physical Component Score [SF-36 PCS], and Nurick grade). The mean age was 56.9 ± 12 years, and 42% of patients were women (n = 46). Correlations with HRQOL measures were analyzed for regional (cervical lordosis and cervical sagittal vertical axis) and focal parameters (kyphosis and spondylolisthesis between adjacent vertebrae) in flexion and extension. Baseline dynamic parameters (flexion/extension cone relative to a fixed C-7, center of rotation [COR], and range of motion arc relative to the COR) were also analyzed for correlations with HRQOL measures.

RESULTS

At baseline, the mean HRQOL measures demonstrated disability and the mean radiographic parameters demonstrated sagittal malalignment. Among regional parameters, there was a significant correlation between decreased neck flexion (increased C2–7 angle in flexion) and worse Nurick grade (R = 0.189, p = 0.048), with no significant correlations in extension. Focal parameters, including increased C-7 sagittal translation overT-1 (slip), were significantly correlated with greater myelopathy severity (mJOA score, Flexion R = −0.377, p = 0.003; mJOA score, Extension R = −0.261, p = 0.027). Sagittal slip at C-2 and C-4 also correlated with worse HRQOL measures. Reduced flexion/extension motion cones, a more posterior COR, and smaller range of motion correlated with worse general health SF-36 PCS and Nurick grade.

CONCLUSIONS

Dynamic motion analysis may play an important role in understanding CSM. Focal parameters demonstrated a significant correlation with worse HRQOL measures, especially increased C-7 sagittal slip in flexion and extension. Novel methods of motion analysis demonstrating reduced motion cones correlated with worse myelopathy grades. More posterior COR and smaller range of motion were both correlated with worse general health scores (SF-36 PCS and Nurick grade). To our knowledge, this is the first study to demonstrate correlation of dynamic motion and listhesis with disability and myelopathy in CSM.

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Christopher K. Kepler, Alexander R. Vaccaro, Eric Chen, Alpesh A. Patel, Henry Ahn, Ahmad Nassr, Christopher I. Shaffrey, James Harrop, Gregory D. Schroeder, Amit Agarwala, Marcel F. Dvorak, Daryl R. Fourney, Kirkham B. Wood, Vincent C. Traynelis, S. Tim Yoon, Michael G. Fehlings and Bizhan Aarabi

OBJECT

In this clinically based systematic review of cervical facet fractures, the authors’ aim was to determine the optimal clinical care for patients with isolated fractures of the cervical facets through a systematic review.

METHODS

A systematic review of nonoperative and operative treatment methods of cervical facet fractures was performed. Reduction and stabilization treatments were compared, and analysis of postoperative outcomes was performed. MEDLINE and Scopus databases were used. This work was supported through support received from the Association for Collaborative Spine Research and AOSpine North America.

RESULTS

Eleven studies with 368 patients met the inclusion criteria. Forty-six patients had bilateral isolated cervical facet fractures and 322 had unilateral isolated cervical facet fractures. Closed reduction was successful in 56.4% (39 patients) and 63.8% (94 patients) of patients using a halo vest and Gardner-Wells tongs, respectively. Comparatively, open reduction was successful in 94.9% of patients (successful reduction of open to closed reduction OR 12.8 [95% CI 6.1–26.9], p < 0.0001); 183 patients underwent internal fixation, with an 87.2% success rate in maintaining anatomical alignment. When comparing the success of patients who underwent anterior versus posterior procedures, anterior approaches showed a 90.5% rate of maintenance of reduction, compared with a 75.6% rate for the posterior approach (anterior vs posterior OR 3.1 [95% CI 1.0–9.4], p = 0.05).

CONCLUSIONS

In comparison with nonoperative treatments, operative treatments provided a more successful outcome in terms of failure of treatment to maintain reduction for patients with cervical facet fractures. Operative treatment appears to provide superior results to the nonoperative treatments assessed.

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Michael G. Fehlings, Justin S. Smith, Branko Kopjar, Paul M. Arnold, S. Tim Yoon, Alexander R. Vaccaro, Darrel S. Brodke, Michael E. Janssen, Jens R. Chapman, Rick C. Sasso, Eric J. Woodard, Robert J. Banco, Eric M. Massicotte, Mark B. Dekutoski, Ziya L. Gokaslan, Christopher M. Bono and Christopher I. Shaffrey

Object

Rates of complications associated with the surgical treatment of cervical spondylotic myelopathy (CSM) are not clear. Appreciating these risks is important for patient counseling and quality improvement. The authors sought to assess the rates of and risk factors associated with perioperative and delayed complications associated with the surgical treatment of CSM.

Methods

Data from the AOSpine North America Cervical Spondylotic Myelopathy Study, a prospective, multicenter study, were analyzed. Outcomes data, including adverse events, were collected in a standardized manner and externally monitored. Rates of perioperative complications (within 30 days of surgery) and delayed complications (31 days to 2 years following surgery) were tabulated and stratified based on clinical factors.

Results

The study enrolled 302 patients (mean age 57 years, range 29–86) years. Of 332 reported adverse events, 73 were classified as perioperative complications (25 major and 48 minor) in 47 patients (overall perioperative complication rate of 15.6%). The most common perioperative complications included minor cardiopulmonary events (3.0%), dysphagia (3.0%), and superficial wound infection (2.3%). Perioperative worsening of myelopathy was reported in 4 patients (1.3%). Based on 275 patients who completed 2 years of follow-up, there were 14 delayed complications (8 minor, 6 major) in 12 patients, for an overall delayed complication rate of 4.4%. Of patients treated with anterior-only (n = 176), posterior-only (n = 107), and combined anterior-posterior (n = 19) procedures, 11%, 19%, and 37%, respectively, had 1 or more perioperative complications. Compared with anterior-only approaches, posterior-only approaches had a higher rate of wound infection (0.6% vs 4.7%, p = 0.030). Dysphagia was more common with combined anterior-posterior procedures (21.1%) compared with anterior-only procedures (2.3%) or posterior-only procedures (0.9%) (p < 0.001). The incidence of C-5 radiculopathy was not associated with the surgical approach (p = 0.8). The occurrence of perioperative complications was associated with increased age (p = 0.006), combined anterior-posterior procedures (p = 0.016), increased operative time (p = 0.009), and increased operative blood loss (p = 0.005), but it was not associated with comorbidity score, body mass index, modified Japanese Orthopaedic Association score, smoking status, anterior-only versus posterior-only approach, or specific procedures. Multivariate analysis of factors associated with minor or major complications identified age (OR 1.029, 95% CI 1.002–1.057, p = 0.035) and operative time (OR 1.005, 95% CI 1.002–1.008, p = 0.001). Multivariate analysis of factors associated with major complications identified age (OR 1.054, 95% CI 1.015–1.094, p = 0.006) and combined anterior-posterior procedures (OR 5.297, 95% CI 1.626–17.256, p = 0.006).

Conclusions

For the surgical treatment of CSM, the vast majority of complications were treatable and without long-term impact. Multivariate factors associated with an increased risk of complications include greater age, increased operative time, and use of combined anterior-posterior procedures.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010