Ravi K Ponnappan

Thomas Jefferson University, Philadelphia, Pennsylvania, United States

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Publications (19)46.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Intervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process. To review the current understanding of the molecular basis of disc degeneration. Review article. A literature review was performed to identify recent investigations and current knowledge regarding the molecular basis of IVD degeneration. The unique structural requirements and biochemical properties of the disc contribute to its propensity toward degeneration. Mounting evidence suggests that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process. Decreased extracellular matrix production, increased production of degradative enzymes, and increased expression of inflammatory cytokines contribute to the loss of structural integrity and accelerate IVD degeneration. Neurovascular ingrowth occurs, in part, because of the changing degenerative phenotype. A detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies.
    The spine journal: official journal of the North American Spine Society 03/2013; 13(3):318-30. · 2.90 Impact Factor
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    ABSTRACT: Retrospective review of 750 consecutive multilevel cervical spine decompression surgeries performed by a single spine surgeon. To determine the incidence of C5 palsy in a large consecutive series of multilevel cervical spine decompression procedures. Palsy of the C5 nerve is a well-known potential complication of cervical spine surgery with reported rates ranging from 0% to 30%. The etiology remains uncertain but has been attributed to iatrogenic injury during surgery, tethering from shifting of the spinal cord, spinal cord ischemia, and reperfusion injury of the spinal cord. We included patients undergoing multilevel cervical corpectomy, corpectomy with posterior fusion, posterior laminectomy and fusion, and laminoplasty. Exclusion criteria included lack of follow-up data, spinal cord injury preventing preoperative or postoperative motor testing, or surgery not involving the C5 level. Incidence of C5 palsy was determined and compared to determine whether significant differences existed among the various procedures, patient age, sex, revision surgery, preoperative weakness, diabetes, smoking, number of levels decompressed, and history of previous upper extremity surgery. Of the 750 patients, 120 were eliminated on the basis of the exclusion criteria. The 630 patients included in the analysis consisted of 292 females and 338 males. The mean age was 58 years (range, 19-87). The incidence of C5 nerve palsy for the entire group was 42 of 630 (6.7%). The incidence was highest for the laminectomy and fusion group (9.5%), followed by the corpectomy with posterior fusion group (8.4%), the corpectomy group (5.1%), and finally the laminoplasty group (4.8%), although these differences did not reach statistical significance. There was a significantly higher incidence in males (8.6% vs. 4.5%, P = 0.05). Incidence of C5 nerve palsy after cervical spine decompression was 6.7%. This is consistent with previously published studies and represents the largest series of North American patients to date. There is no statistically significant difference in incidence of C5 palsy based on surgical procedure, although there was a trend toward higher rates with laminectomy and fusion.
    Spine 02/2012; 37(3):174-8. · 2.16 Impact Factor
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    ABSTRACT: Back pain, a significant source of morbidity in our society, is related to the degenerative changes of the intervertebral disc. At present, the treatment of disc disease consists of therapies that are aimed at symptomatic relief. This shortcoming stems in large part from our lack of understanding of the biochemical and molecular events that drive the disease process. The goal of this study is to develop a model of early disc degeneration using an organ culture. This approach is based on our previous studies that indicate that organ culture closely models molecular events that occur in vivo in an ex vivo setting. To mimic a degenerative insult, discs were cultured under low oxygen tension in the presence of TNF-α, IL-1β and serum limiting conditions. Treatment resulted in compromised cell survival and changes in cellular morphology reminiscent of degeneration. There was strong suppression in the expression of matrix proteins including collagen types 1, 2, 6 and 9, proteoglycans, aggrecan and fibromodulin. Moreover, a strong induction in expression of catabolic matrix metalloproteinases (MMP) 3, 9 and 13 with a concomitant increase in aggrecan degradation was seen. An inductive effect on NGF expression was also noticed. Although similar, nucleus pulposus and annulus fibrosus tissues showed some differences in their response to the treatment. Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function.
    Arthritis research & therapy 10/2011; 13(5):R171. · 4.27 Impact Factor
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    ABSTRACT: Although understanding of the biologic basis of intervertebral disk (IVD) degeneration is rapidly advancing, the unique IVD environment presents challenges to the development and delivery of biologic treatments. Acceleration of cellular senescence and apoptosis in degenerative IVDs and the depletion of matrix proteins have prompted the development of treatments based on replacing IVD cells using various cell sources. However, this strategy has not been tested in animal models. IVD degeneration and associated pain have led to interest in pathologic innervation of the IVD and ultimately to the development of percutaneous devices to ablate afferent nerve endings in the posterior annulus. Degeneration leads to changes in the expression of matrix protein, cytokines, and proteinases. Injection of growth factors and mitogens may help overcome these degenerative changes in IVD phenotype, and these potential treatments are being explored in animal studies. Gene therapy is an elegant method to address changes in protein expression, but efforts to apply this technology to IVD degeneration are still at early stages.
    The Journal of the American Academy of Orthopaedic Surgeons 09/2011; 19(9):543-53. · 2.46 Impact Factor
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    ABSTRACT: Prospective study of 29 patients who underwent anterior cervical (AC) or posterior lumbar (PL) spinal surgery. A validated measure of dysphagia, the Swallowing-Quality of Life (SWAL-QOL) survey, was used to assess the degree of postoperative dysphagia. To determine the degree of dysphagia preoperatively and postoperatively in patients undergoing AC surgery compared with a control group that underwent PL surgery. Dysphagia is a well-known complication of AC spine surgery and has been shown to persist for up to 24 months or longer. A total of 18 AC patients and a control group of 11 PL patients were prospectively enrolled in this study and were assessed preoperatively and at 3 weeks and 1.5 years postoperatively using a 14-item questionnaire from the SWAL-QOL survey to determine degree of dysphagia. Other patient factors and anesthesia records were examined to evaluate their relationship to dysphagia. There were no significant differences between the AC and PL groups with respect to age, sex, body mass index, or length of surgery. The SWAL-QOL scores at 3 weeks were significantly lower for the AC group than for the PL group (76 vs. 96; P = 0.001), but there were no differences between the groups preoperatively or at final follow-up. Smokers, patients with chronic obstructive pulmonary disease, and women had lower SWAL-QOL scores at one or more time point. Patients undergoing AC surgery had a significant increase in the degree of dysphagia 3 weeks after surgery compared with patients undergoing PL surgery. By final follow-up, swallowing in the AC group recovered to a level similar to preoperative and comparable to that in patients undergoing lumbar surgery at 1.5 years. Smoking, chronic obstructive pulmonary disease, and female sex are possible factors in the development of postoperative dysphagia.
    Spine 08/2011; 36(17):1387-91. · 2.16 Impact Factor
  • Spine 03/2011; 36(5):E320-5. · 2.16 Impact Factor
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    ABSTRACT: A structured questionnaire. The purpose of this study was to determine whether material rod composition and its imaging characteristics can determine patient perceptions of pain, outcome, and need for revision surgery in the context of the failure of spinal instrumentation following lumbar arthrodesis. Patient perceptions of radiographic images in the context of failed spinal instrumentation may influence clinical outcomes and patient satisfaction. Due to radiolucency, failed polyetheretherketone (PEEK) rods may be perceived differently by patients than more traditional materials. Patients presenting primarily with chief complaints of back pain completed a 2-page, 22-question questionnaire containing 3 alternative radiographic images of failed rod instrumentation following posterolateral lumbar arthrodesis. The images represented failed rods composed of either PEEK, PEEK with a longitudinal radio-opaque marker, or traditional titanium. Statistical analysis with the Cochran Q test was performed to determine whether there were statistical differences in the responses. The responses suggested a preference for the images representing PEEK instrumentation as being associated with superior clinical outcomes, the least pain, the most comfort, and the least likelihood of required revision surgery. PEEK rods possess radiolucent properties that can alter patient perceptions of clinical outcomes when compared with images of other equally unfavorable scenarios. The significance of these patient perceptions must still be demonstrated. However, they may play an important role in clinical outcomes and patient satisfaction.
    Spine 08/2010; 35(17):E843-8. · 2.16 Impact Factor
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    ABSTRACT: Study Design. Retrospective analysis of a cohort of patients treated between April 2006 and January 2008, and diagnosed with cervical degenerative disease. Objective. To determine the correlation of the clinical findings associated with cervical myelopathy to the presence of spinal cord compression or cord signal abnormalities on magnetic resonance imaging (MRI). Summary of Background Data. There are numerous reports describing the radiographic features of cervical spondylosis, however, no publication specifically describes the association between the physical signs of cervical myelopathy and the presenting imaging findings. Methods. Myelopathy was defined as the presence of greater than one long-tract sign localized to the cervical spinal cord (Hoffman or Babinski signs, clonus, hyper-reflexia, crossed abductor sign, and/or gait dysfunction) on physical examination in the absence of other neurologic condition(s). The presence of these signs, MRI imaging features of spinal cord compression and hyperintense T2 intraparenchymal cord signal abnormality, and patient demographics were recorded. Results. One hundred three patients met inclusion criteria (age >18, symptomatic cervical degenerative disease and complete neurologic assessment). Of these, 54 had clinical findings of cervical myelopathy. Radiographic features of cord compression were present in 62% of patients, and 84% had myelopathy on examination. No patients without cord compression presented with myelopathy (P < 0.0001). Thirty-five percent of the patients presented with hyperintense signal on T2 MRI within the spinal cord parenchyma. This finding correlated with the presence of myelopathy (P < 0.0001). Multivariate analysis on the subset with cord compression indicates that the likelihood of myelopathy increased with the presence of cord signal hyperintensity (odds ratio [OR], 11.4), sensory loss (OR, 16.9), and age (OR, 1.10 per year). Conclusion. The diagnosis of cervical myelopathy is based on presenting symptoms and physical examination. This analysis illustrates that radiographic cervical spinal cord compression and hyperintense T2 intraparen chymal signal abnormalities correlate with the presence of myelopathic findings on physical examination.
    Spine 03/2010; 35(6):620-624. · 2.16 Impact Factor
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    ABSTRACT: To investigate transforming growth factor beta (TGFbeta) regulation of connective tissue growth factor (CTGF) expression in cells of the nucleus pulposus of rats, mice, and humans. Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to measure CTGF expression in the nucleus pulposus. Transfections were used to measure the effects of Smads 2, 3, and 7 and activator protein 1 (AP-1) on TGFbeta-mediated CTGF promoter activity. CTGF expression was lower in neonatal rat discs than in skeletally mature rat discs. An increase in CTGF expression and promoter activity was observed in rat nucleus pulposus cells after TGFbeta treatment. Deletion analysis indicated that promoter constructs lacking Smad and AP-1 motifs were unresponsive to treatment. Analysis showed that full-length Smad3 and the Smad3 MH-2 domain alone increased CTGF activity. Further evidence of Smad3 and AP-1 involvement was seen when DN-Smad3, SiRNA-Smad3, Smad7, and DN-AP-1 suppressed TGFbeta-mediated activation of the CTGF promoter. When either Smad3 or AP-1 sites were mutated, CTGF promoter induction by TGFbeta was suppressed. We also observed a decrease in the expression of CTGF in discs from Smad3-null mice as compared with those from wild-type mice. Analysis of human nucleus pulposus samples indicated a trend toward increasing CTGF and TGFbeta expression in the degenerated state. TGFbeta, through Smad3 and AP-1, serves as a positive regulator of CTGF expression in the nucleus pulposus. We propose that CTGF is a part of the limited reparative response of the degenerated disc.
    Arthritis & Rheumatology 03/2010; 62(7):1983-92. · 7.48 Impact Factor
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    ABSTRACT: A survey on thromboprophylaxis in spinal surgery and trauma was conducted among spine trauma surgeons. Neurosurgeons and orthopedic surgeons from the Spinal Trauma Study Group were surveyed in an attempt to understand current practices in the perioperative administration of thromboprophylaxis in spinal surgery. Although much research has been invested in the prevention of thromboembolic events following surgical procedures, there have been few investigations specific to spinal surgery, especially in the context of trauma. A total of 47 spine surgeons were provided with a 24-question survey pertaining to deep vein thrombosis prophylaxis in spine surgical patients. There was 100% response to the survey, and 46 of the 47 physicians (98%) responded to the case scenarios. Institutional protocols for deep vein thrombosis prophylaxis existed for 42 (89%) of the respondents; however, only 27 (57%) indicated that these protocols included spinal cord injury (SCI) patients. Before surgery, no prophylaxis or mechanical prophylactic measures for SCI and non-SCI spinal fracture patients were routinely used by 36 (77%) and 40 (85%) respondents, respectively. After surgery, pharmacologic prophylaxis was prescribed by 42 (91%) and 28 (62%) surgeons for SCI and non-SCI spinal fracture patients, respectively. There was a statistically significant tendency to use more intensive prophylactic measures for patients with SCI (x2, 10.86; P < 0.01) as well as a statistically significant longer duration of proposed thromboprophylaxis (x2, 24.62; P < 0.001). Postoperative pharmacologic thromboprophylaxis for elective anterior thoracolumbar spine surgery was reported by 23 (51%) of the respondents, whereas only 18 (40%) used pharmacological prophylaxis in elective posterior thoracolumbar spine cases. Spine complications from low-molecular weight heparin were reported by 22 (47%) surgeons, including fatal pulmonary embolism by 19 (40%) surgeons. A basis for a consensus protocol on thromboprophylaxis in spinal trauma was attempted. No more than mechanical prophylaxis was recommended before surgery for non-SCI patients or after surgery for elective cervical spine cases. Chemical prophylaxis was commonly used after surgery in patients with SCI and in patients with elective anterior thoracolumbar surgery.
    Spine 02/2010; 35(3):323-9. · 2.16 Impact Factor
  • The Spine Journal. 01/2010; 10(9):S9–S10.
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    ABSTRACT: The aim of this study was to determine if treatment with reversine, a purine analog, promoted generation of skeletal progenitor cells from lineage-committed annulus fibrosus cells. Reversine modulated cell growth, morphology, and the actin cytoskeleton of annulus fibrosus cells. Microarray profiling coupled with Ingenuity Pathway Analysis revealed that reversine treatment resulted in a significant expression change in many genes including those required for cell-cell interaction, cell movement, cell growth, and development. Further analysis revealed that there was involvement of gene networks concerned with cellular assembly and organization, DNA replication and repair, tissue morphology, and cell-to-cell signaling. The gene expression profile was dependent on reversine concentration. In osteogenic media, cells pretreated with 300 nM reversine exhibited an increased induction in alkaline phosphatase activity and enhanced expression of alkaline phosphatase, bone sialoprotein, osteocalcin, and collagen type I mRNA. Maintained in adipogenic media, the reversine-pretreated annulus cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of PPAR-gamma2, LPL, and Fabp mRNA. In chondrogenic media, cells pretreated with reversine exhibited marked increase in the induction of aggrecan, collagen types II, IX, and XI, and versican. It is concluded that reversine treatment induced annulus fibrosus cell plasticity and promoted their differentiation along mesenchymal lineages. This agent could be used to generate skeletal progenitor cells to orchestrate the repair of the intervertebral disc.
    Tissue Engineering Part A 12/2009; 16(4):1443-55. · 4.64 Impact Factor
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    ABSTRACT: The increased risk for venous thromboembolic events following spinal trauma is well established. The purpose of the present study was to examine the literature in order to determine the optimum thromboprophylaxis regimen for patients with acute spinal injuries with or without spinal cord injury. EMBASE, MEDLINE, and Cochrane databases were searched from the earliest available date to April 2008 for clinical trials comparing different methods of thromboprophylaxis in adult patients following acute spinal injuries (with or without spinal cord injury). Outcome measures included the prevalences of deep-vein thrombosis and pulmonary embolism and treatment-related adverse events. The search yielded 489 studies, but only twenty-one of them fulfilled the inclusion criteria. The prevalence of deep-vein thrombosis was significantly lower in patients without spinal cord injury as compared with patients with spinal cord injury (odds ratio = 6.0; 95% confidence interval = 2.9 to 12.7). Patients with an acute spinal cord injury who were receiving oral anticoagulants had significantly fewer episodes of pulmonary embolism (odds ratio = 0.1; 95% confidence interval = 0.01 to 0.63) than those who were not receiving oral anticoagulants (either untreated controls or patients managed with low-molecular-weight heparin). The start of thromboprophylaxis within the first two weeks after the injury resulted in significantly fewer deep-vein-thrombosis events than delayed initiation did (odds ratio = 0.2; 95% confidence interval = 0.1 to 0.4). With regard to heparin-based pharmacoprophylaxis in patients with spinal trauma, low-molecular-weight heparin significantly reduced the rates of deep-vein thrombosis and bleeding episodes in comparison with the findings in patients who received unfractionated heparin, with odds ratios of 2.6 (95% confidence interval = 1.2 to 5.6) and 7.5 (95% confidence interval = 1.0 to 58.4) for deep-vein thrombosis and bleeding, respectively. The prevalence of deep-vein thrombosis following a spine injury is higher among patients who have a spinal cord injury than among those who do not have a spinal cord injury. Therefore, thromboprophylaxis in these patients should start as early as possible once it is deemed safe in terms of potential bleeding complications. Within this population, low-molecular-weight heparin is more effective for the prevention of deep-vein thrombosis, with fewer bleeding complications, than unfractionated heparin is. The use of vitamin K antagonists appeared to be effective for the prevention of pulmonary embolism.
    The Journal of Bone and Joint Surgery 11/2009; 91(11):2568-76. · 3.23 Impact Factor
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    ABSTRACT: Although there are several studies evaluating the necessity and efficacy of thromboprophylaxis after spinal trauma with or without spinal cord injury (SCI), to date there is no established standard of practice pertaining to this specific patient population with regards to venous thromboembolism (VTE) prophylaxis. To reach a consensus opinion in the administration of thromboprophylaxis in both preoperative and postoperative care in the settings of spinal trauma and SCI. A live survey on thromboprophylaxis after spinal surgery in the setting of trauma was conducted at a meeting among spine trauma surgeons. Twenty-five spine surgeons (Neurosurgeons and Orthopedic surgeons), all members of the Spine Trauma Study Group, participated in a live survey in which they attempted to reach consensus pertaining to the management of deep vein thrombosis prophylaxis in patients with spine fractures (with and without a concomitant SCI). The consensus survey consisted of a 10-item questionnaire. Chi-square test was used for group comparisons in questionnaire responses. Complete agreement was reached for the need of postoperative pharmacologic thromboprophylaxis in cervical spine injuries with SCI and anterior thoracolumbar procedures with or without SCI. Postoperative pharmacologic thromboprophylaxis after cervical spine injuries without SCI was agreed not to be needed. In cases of delayed surgery for patients with SCI, pharmacologic thromboprophylaxis was recommended to be started as soon as possible in the presurgical period. The optimal duration of pharmacologic VTE prophylaxis was determined to be 3 months. Only 53% agreement was noted for the withholding of preoperative chemical prophylaxis in cervical or thoracolumbar spinal injuries with SCI (and 68% without SCI). Only 80% of the surgeons agreed that postoperative pharmacologic thromboprophylaxis is needed after posterior thoracolumbar procedures in patients with or without SCI. The use of vena cava filter after SCI was not universally recommended. Postoperative pharmacologic thromboprophylaxis was opined to be unnecessary in patients with cervical spine injuries without SCI, however, it is recommended for cervical spine trauma with SCI or anterior thoracolumbar procedures irrespective of SCI. Pharmacologic thromboprophylaxis was recommended to start preoperatively as soon as possible in SCI cases or in cases with surgical delay. Pharmacologic prophylaxis was recommended to be administered for at least 3 months postinjury. Although these recommendations met complete consensus by this group, individual patient factors should also be considered in determining optimal thromboprophylaxis in this patient population. Future research recommendations on thromboprophylaxis in spinal trauma are proposed.
    The spine journal: official journal of the North American Spine Society 03/2009; 9(7):530-6. · 2.90 Impact Factor
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    ABSTRACT: Polyetheretherketone (PEEK) has been increasingly used as a biomaterial for spinal implants. PEEK lumbar fusion rods have recently become available for use in posterior lumbar fusion procedures. To compare Polyetheretherketone Rod System to traditional titanium rod fixation in a cadaveric model and provide mechanical test data for the PEEK system. Biomechanical testing. Cadaveric biomechanical testing was conducted to compare Expedium 5.5 mm PEEK rods to titanium rods of equivalent diameter. Biomaterials testing was performed to determine static and dynamic performance of Expedium 5.5 mm PEEK rods with 6% BaSo4 in compressive bending and torsion. Cadaveric testing demonstrated that PEEK rods can significantly reduce the range of motion of a destabilized segment. The testing showed no significant difference in the stability provided by PEEK and titanium rods in posterolateral fusion (PLF) or posterior lumbar interbody fusion (PLIF) constructs. PEEK static compressive bending tests showed 67 degrees displacement without fracture of the rod. Torsion testing showed 30 degrees of rotation without yield or plastic deformation. Dynamic compression testing revealed two fatigue runouts at 23 degrees. PEEK rods provide comparable stability to titanium rods of equivalent diameter in cadaveric testing. Mechanical testing suggests PEEK rods can withstand far beyond the angular displacements suggested by cadaveric testing and that of normal physiologic range of motion. Potential advantages to PEEK rods include better anterior column load sharing, reduced stress at bone-to-screw interface, and reduced computed tomography and magnetic resonance imaging scatter and artifact.
    The spine journal: official journal of the North American Spine Society 10/2008; 9(3):263-7. · 2.90 Impact Factor
  • Ravi K Ponnappan, Alan S Hilibrand
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    ABSTRACT: Purpose of review: Recent innovation and controversy in spine surgery has centered on the incidence, treatment and prevention of adjacent segment degeneration. This review will focus on the recent published literature pertaining to adjacent segment degeneration and disease of the cervical spine from 2006–2007 and highlight the current controversy, advancements and failures of treatment options. Recent findings: Recent publications continue to show increased rates of adjacent segment degenerative changes at long-term follow-up, with a constant rate of symptomatic disease. Biomechanical analyses indicate that increased stress may be a factor in precipitating accelerated degeneration, however, a clinical evaluation of post patients after surgery shows more global distribution of adjacent segment motion. Technique-related factors also may play a role in adjacent segment degeneration, that is kyphotic alignment and plate position. Short-term clinical results from total disk replacement have shown clinical equivalence to anterior decompression and fusion; however, reoperation for adjacent segment disease continues to be reported. Summary: Adjacent segment disease continues to be a concern as more long-term clinical outcome data of anterior fusions emerge. The etiology of the problem continues to be elusive and is likely multifactorial. The effect of motion-sparing technology will be further revealed as long-term outcomes data become available.
    Current Orthopaedic Practice 07/2008; 19(4):420–424.
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    ABSTRACT: Study DesignThis study is a systematic review of published biomechanical studies involving pedicle screw-based posterior dynamic stabilization devices (PDS) with a special focus on kinematics and load transmission through the functional spine unit (FSU).
    SAS Journal 01/2008; 2(4):159-170.
  • Joon Y Lee, Ahmad Nassr, Ravi K Ponnappan
    The Journal of Bone and Joint Surgery 10/2007; 89(9):2037-9. · 3.23 Impact Factor
  • The Spine Journal. 11(10):S12.

Publication Stats

133 Citations
46.97 Total Impact Points

Institutions

  • 2009–2010
    • Thomas Jefferson University
      • Department of Orthopaedic Surgery
      Philadelphia, Pennsylvania, United States
  • 2008
    • Thomas Jefferson University Hospitals
      Philadelphia, Pennsylvania, United States
    • Rothman Institute
      Philadelphia, Pennsylvania, United States
  • 2007
    • University of Pittsburgh
      • Department of Orthopaedic Surgery
      Pittsburgh, PA, United States