Browsing by Subject "Intervertebral Disc Degeneration"

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    ItemOpen Access
    A magnetic resonance imaging framework for quantifying intervertebral disc deformation in vivo: reliability and application to diurnal variations in lumbar disc shape
    (Journal of biomechanics, 2018-04) DeFrate, LE
    Low back pain is a significant socioeconomic burden in the United States and lumbar intervertebral disc degeneration is frequently implicated as a cause. The discs play an important mechanical role in the spine, yet the relationship between disc function and back pain is poorly defined. The objective of this work was to develop a technique using magnetic resonance imaging (MRI) and three-dimensional modeling to measure in vivo disc deformations. Using this method, we found that disc geometry was measurable with precision less than the in-plane dimensions of a voxel (≈100 µm, 10% of the MRI pixel size). Furthermore, there was excellent agreement between mean disc height, disc perimeter, disc volume and regional disc height measurements for multiple trials from an individual rater (standard deviation <3.1% across all measurements) and between mean height, perimeter, and volume measurements made by two independent raters (error <1.5% across all measurements). We then used this measurement system to track diurnal deformations in the L5-S1 disc in a young, healthy population (n = 8; age 24.1 ± 3.3 yrs; 2 M/6F). We measured decreases in the mean disc height (-8%) and volume (-9%) with no changes in perimeter over an eight-hour workday. We found that the largest height losses occurred in the posterior (-13%) and posterior-lateral (-14%) regions adjacent to the outer annulus fibrosus. Diurnal annulus fibrosus (AF) strains induced by posterior and posterior-lateral height loss may increase the risk for posterior disc herniation or posterior AF tears. These preliminary findings lay a foundation for determining how deviations from normal deformations may contribute to back pain.
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    ItemOpen Access
    An analysis from the Quality Outcomes Database, Part 2. Predictive model for return to work after elective surgery for lumbar degenerative disease.
    (Journal of neurosurgery. Spine, 2017-10) Asher, Anthony L; Devin, Clinton J; Archer, Kristin R; Chotai, Silky; Parker, Scott L; Bydon, Mohamad; Nian, Hui; Harrell, Frank E; Speroff, Theodore; Dittus, Robert S; Philips, Sharon E; Shaffrey, Christopher I; Foley, Kevin T; McGirt, Matthew J
    OBJECTIVE Current costs associated with spine care are unsustainable. Productivity loss and time away from work for patients who were once gainfully employed contributes greatly to the financial burden experienced by individuals and, more broadly, society. Therefore, it is vital to identify the factors associated with return to work (RTW) after lumbar spine surgery. In this analysis, the authors used data from a national prospective outcomes registry to create a predictive model of patients' ability to RTW after undergoing lumbar spine surgery for degenerative spine disease. METHODS Data from 4694 patients who underwent elective spine surgery for degenerative lumbar disease, who had been employed preoperatively, and who had completed a 3-month follow-up evaluation, were entered into a prospective, multicenter registry. Patient-reported outcomes-Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain (BP) and leg pain (LP), and EQ-5D scores-were recorded at baseline and at 3 months postoperatively. The time to RTW was defined as the period between operation and date of returning to work. A multivariable Cox proportional hazards regression model, including an array of preoperative factors, was fitted for RTW. The model performance was measured using the concordance index (c-index). RESULTS Eighty-two percent of patients (n = 3855) returned to work within 3 months postoperatively. The risk-adjusted predictors of a lower likelihood of RTW were being preoperatively employed but not working at the time of presentation, manual labor as an occupation, worker's compensation, liability insurance for disability, higher preoperative ODI score, higher preoperative NRS-BP score, and demographic factors such as female sex, African American race, history of diabetes, and higher American Society of Anesthesiologists score. The likelihood of a RTW within 3 months was higher in patients with higher education level than in those with less than high school-level education. The c-index of the model's performance was 0.71. CONCLUSIONS This study presents a novel predictive model for the probability of returning to work after lumbar spine surgery. Spine care providers can use this model to educate patients and encourage them in shared decision-making regarding the RTW outcome. This evidence-based decision support will result in better communication between patients and clinicians and improve postoperative recovery expectations, which will ultimately increase the likelihood of a positive RTW trajectory.
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    ItemOpen Access
    Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.
    (Spine, 2011-07) Sinclair, S Michael; Shamji, Mohammed F; Chen, Jun; Jing, Liufang; Richardson, William J; Brown, Christopher R; Fitch, Robert D; Setton, Lori A

    Study design

    The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro.

    Objective

    To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro.

    Summary of background data

    TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown.

    Methods

    IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells.

    Results

    Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively.

    Conclusion

    Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.
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    ItemOpen Access
    Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.
    (2010) Sinclair, Steven Michael
    STUDY DESIGN: The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro. OBJECTIVE: To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro. SUMMARY OF BACKGROUND DATA: TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown. METHODS: IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells. RESULTS: Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively. CONCLUSION: Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.
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    ItemOpen Access
    Complications in adult spinal deformity surgery: an analysis of minimally invasive, hybrid, and open surgical techniques.
    (Neurosurgical focus, 2014-05) Uribe, Juan S; Deukmedjian, Armen R; Mummaneni, Praveen V; Fu, Kai-Ming G; Mundis, Gregory M; Okonkwo, David O; Kanter, Adam S; Eastlack, Robert; Wang, Michael Y; Anand, Neel; Fessler, Richard G; La Marca, Frank; Park, Paul; Lafage, Virginie; Deviren, Vedat; Bess, Shay; Shaffrey, Christopher I; International Spine Study Group

    Object

    It is hypothesized that minimally invasive surgical techniques lead to fewer complications than open surgery for adult spinal deformity (ASD). The goal of this study was to analyze matched patient cohorts in an attempt to isolate the impact of approach on adverse events.

    Methods

    Two multicenter databases queried for patients with ASD treated via surgery and at least 1 year of follow-up revealed 280 patients who had undergone minimally invasive surgery (MIS) or a hybrid procedure (HYB; n = 85) or open surgery (OPEN; n = 195). These patients were divided into 3 separate groups based on the approach performed and were propensity matched for age, preoperative sagittal vertebral axis (SVA), number of levels fused posteriorly, and lumbar coronal Cobb angle (CCA) in an attempt to neutralize these patient variables and to make conclusions based on approach only. Inclusion criteria for both databases were similar, and inclusion criteria specific to this study consisted of an age > 45 years, CCA > 20°, 3 or more levels of fusion, and minimum of 1 year of follow-up. Patients in the OPEN group with a thoracic CCA > 75° were excluded to further ensure a more homogeneous patient population.

    Results

    In all, 60 matched patients were available for analysis (MIS = 20, HYB = 20, OPEN = 20). Blood loss was less in the MIS group than in the HYB and OPEN groups, but a significant difference was only found between the MIS and the OPEN group (669 vs 2322 ml, p = 0.001). The MIS and HYB groups had more fused interbody levels (4.5 and 4.1, respectively) than the OPEN group (1.6, p < 0.001). The OPEN group had less operative time than either the MIS or HYB group, but it was only statistically different from the HYB group (367 vs 665 minutes, p < 0.001). There was no significant difference in the duration of hospital stay among the groups. In patients with complete data, the overall complication rate was 45.5% (25 of 55). There was no significant difference in the total complication rate among the MIS, HYB, and OPEN groups (30%, 47%, and 63%, respectively; p = 0.147). No intraoperative complications were reported for the MIS group, 5.3% for the HYB group, and 25% for the OPEN group (p < 0.03). At least one postoperative complication occurred in 30%, 47%, and 50% (p = 0.40) of the MIS, HYB, and OPEN groups, respectively. One major complication occurred in 30%, 47%, and 63% (p = 0.147) of the MIS, HYB, and OPEN groups, respectively. All patients had significant improvement in both the Oswestry Disability Index (ODI) and visual analog scale scores after surgery (p < 0.001), although the MIS group did not have significant improvement in leg pain. The occurrence of complications had no impact on the ODI.

    Conclusions

    Results in this study suggest that the surgical approach may impact complications. The MIS group had significantly fewer intraoperative complications than did either the HYB or OPEN groups. If the goals of ASD surgery can be achieved, consideration should be given to less invasive techniques.
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    ItemOpen Access
    Complications, revision fusions, readmissions, and utilization over a 1-year period after bone morphogenetic protein use during primary cervical spine fusions.
    (The spine journal : official journal of the North American Spine Society, 2014-09) Goode, Adam P; Richardson, William J; Schectman, Robin M; Carey, Timothy S

    Background context

    Nationwide estimates examining bone morphogenetic protein (BMP) use with cervical spine fusions have been limited to perioperative outcomes.

    Purpose

    To determine the 1-year risk of complications, cervical revision fusions, hospital readmissions, and health care services utilization.

    Study design

    A retrospective cohort study from 2002 to 2009 using a nationwide claims database.

    Patient sample

    There were 61,937 primary cervical spine fusions of which 1,677 received BMP.

    Outcome measures

    Complications, revision fusions, 30-day hospital readmission, and health care utilization.

    Methods

    Data for these analyses come from the Thomson Reuters MarketScan Commercial Claims and Encounters Database 2010. Patients were aged 18 to 64 years, receiving and not receiving BMP with a primary (C2-C7) cervical spine fusion. All outcomes were defined by International Classification of Diseases, 9th edition Clinical Modification and Current Procedural and Terminology, 4th edition codes. Complications were analyzed as any complication and stratified by nervous system, wound, and dysphagia or hoarseness. Cervical revision fusions were determined in the 1-year follow-up. Hospital readmission discharge records defined 30-day hospital readmission and reason for the readmission. The utilization of at least one health care service of cervical spine imaging, epidural usage or rehabilitation service was examined. Poisson regression models were used to estimate the relative risk and 95% confidence interval (CI). Linear regression was used to determine the time to hospital readmission. Results were stratified by anterior or posterior and circumferential approaches.

    Results

    Patients receiving BMP were 29% more likely to have a complication (adjusted relative risk [aRR]=1.29 [95% CI, 1.14-1.46]) and a nervous system complication (aRR=1.42 [95% CI, 1.10-1.83]). Cervical revision fusions were more likely among patients receiving BMP (aRR=1.69 [95% CI, 1.35-2.13]). The risk of 30-day readmission was greater with BMP use (aRR=1.37 [95% CI, 1.07-1.73]) and readmission occurred 27.4% sooner on an average. Patients receiving BMP were more likely to receive computed tomography scans (aRR=1.34 [95% CI, 1.06-1.70]) and epidurals with anterior surgical approaches (aRR=1.29 [95% CI, 1.00-1.65]).

    Conclusions

    These findings question both the safety and effectiveness of off-label BMP use in primary cervical spine fusions.
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    ItemOpen Access
    Degenerative Spinal Deformity.
    (Neurosurgery, 2015-10) Ailon, Tamir; Smith, Justin S; Shaffrey, Christopher I; Lenke, Lawrence G; Brodke, Darrel; Harrop, James S; Fehlings, Michael; Ames, Christopher P
    Degenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22°, and lumbopelvic mismatch <±9°; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes.
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    ItemOpen Access
    Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro.
    (PLoS One, 2013) Chen, Jun; Lee, Esther J; Jing, Liufang; Christoforou, Nicolas; Leong, Kam W; Setton, Lori A
    A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration - a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient's own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated. The overall objective of this study was to assess the possibility of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely derived from notochord. This study employed magnetic activated cell sorting (MACS) to isolate a CD24(+) iPSC subpopulation. Notochordal cell-related gene expression was analyzed in this CD24(+) cell fraction via real time RT-PCR. CD24(+) iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the mouse NP phenotype was assessed by immunostaining. This study also focused on producing a more conducive environment for NP differentiation of mouse iPSCs with addition of low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination of immunostaining and biochemical assays. Results demonstrated that a CD24(+) fraction of mouse iPSCs could be retrieved and differentiated into a population that could synthesize matrix components similar to that in native NP. Likewise, the addition of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion, this study suggests that mouse iPSCs have the potential to differentiate into NP-like cells and suggests the possibility that they may be used as a novel cell source for cellular therapy in the IVD.
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    ItemOpen Access
    Editorial: Recombinant human bone morphogenetic protein-2.
    (Journal of neurosurgery. Spine, 2013-02) Shaffrey, Christopher I; Smith, Justin S
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    ItemOpen Access
    Frequency, risk factors, and treatment of distal adjacent segment pathology after long thoracolumbar fusion: a systematic review.
    (Spine, 2012-10) Kasliwal, Manish K; Shaffrey, Christopher I; Lenke, Lawrence G; Dettori, Joseph R; Ely, Claire G; Smith, Justin S

    Study design

    Systematic review.

    Objective

    To systematically review the literature related to distal adjacent segment pathology (ASP) after long thoracolumbar fusions for deformity including frequency, risk factors, frequency differences between adolescents and adults, surgical approach for revision, and revision complications.

    Summary of background data

    Spinal deformity surgery complications include ASP. Although ASP at the rostral end of instrumented fusions has been well described, substantially less has been documented about distal ASP.

    Methods

    A systematic search was conducted in Medline and the Cochrane Collaboration Library for articles published between January 1, 1983, and March 15, 2012. We included all articles that described distal ASP after long thoracolumbar fusion for deformity. Radiographical ASP (RASP) was defined as evidence of ASP based on imaging, and clinical ASP (CASP) was defined as symptomatic ASP.

    Results

    Seven retrospective cohort studies met inclusion criteria. Distal CASP developed in 17.7% at 2- 6-year follow-up and 19.8% at 9-year follow-up, whereas reoperation due to CASP was reported in 15.6% at 2 to 6 years and 14.4% at 9 years. Distal RASP was more frequent (44.7%-65.5%). Preoperative sagittal imbalance was associated with increased risk of distal ASP. There was increased risk of CASP in patients with higher postoperative fractional curve and increased risk of RASP in younger patients and those with preoperative disc degeneration, longer fusions, circumferential procedures, and postoperative L5-S1 disc space narrowing. No studies meeting inclusion criteria compared distal ASP in adults and adolescents or defined the best approach or complications for distal ASP revision.

    Conclusion

    Low-quality evidence suggests a cumulative rate of 18% to 20% for CASP and 45% to 65% for RASP after long thoracolumbar fusion for spinal deformity during 9-year follow-up. Low-quality evidence suggests an association between preoperative sagittal imbalance and distal ASP, with greater risk of distal ASP in patients with sagittal imbalance. Low-quality evidence suggests increased risk of CASP in patients with higher postoperative fractional curve and increased risk of RASP in younger patients and those with preoperative disc degeneration, longer fusions, circumferential procedures, and postoperative L5-S1 disc space narrowing.

    Consensus statement

    1. The risk of developing new symptoms secondary to distal adjacent segment pathology following long thoracolumbar fusion for deformity is approximately 18–20% during a period of 9 years follow up, and most of these patients will require revision surgery. Strength of Statement: Weak. 2. The risk of developing distal adjacent segment pathology may be higher in those with preoperative sagittal imbalance, preoperative disc degeneration, longer fusions, circumferential procedures, and postoperative L5–S1 disc space narrowing. Strength of Statement: Weak.
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    ItemOpen Access
    Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration.
    (Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2016-08) Tang, Xinyan; Jing, Liufang; Richardson, William J; Isaacs, Robert E; Fitch, Robert D; Brown, Christopher R; Erickson, Melissa M; Setton, Lori A; Chen, Jun
    Previous study claimed that disc degeneration may be preceded by structure and matrix changes in the intervertebral disc (IVD) which coincide with the loss of distinct notochordally derived nucleus pulposus (NP) cells. However, the fate of notochordal cells and their molecular phenotype change during aging and degeneration in human are still unknown. In this study, a set of novel molecular phenotype markers of notochordal NP cells during aging and degeneration in human IVD tissue were revealed with immunostaining and flow cytometry. Furthermore, the potential of phenotype juvenilization and matrix regeneration of IVD cells in a laminin-rich pseudo-3D culture system were evaluated at day 28 by immunostaining, Safranin O, and type II collagen staining. Immunostaining and flow cytometry demonstrated that transcriptional factor Brachyury T, neuronal-related proteins (brain abundant membrane attached signal protein 1, Basp1; Neurochondrin, Ncdn; Neuropilin, Nrp-1), CD24, and CD221 were expressed only in juvenile human NP tissue, which suggested that these proteins may be served as the notochordal NP cell markers. However, the increased expression of CD54 and CD166 with aging indicated that they might be referenced as the potential biomarker for disc degeneration. In addition, 3D culture maintained most of markers in juvenile NP, and rescued the expression of Basp1, Ncdn, and Nrp 1 that disappeared in adult NP native tissue. These findings provided new insight into molecular profile that may be used to characterize the existence of a unique notochordal NP cells during aging and degeneration in human IVD cells, which will facilitate cell-based therapy for IVD regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1316-1326, 2016.
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    ItemOpen Access
    Impact of Dominant Symptom on 12-Month Patient-Reported Outcomes for Patients Undergoing Lumbar Spine Surgery.
    (Neurosurgery, 2020-10) Devin, Clinton J; Asher, Anthony L; Archer, Kristin R; Goyal, Anshit; Khan, Inamullah; Kerezoudis, Panagiotis; Alvi, Mohammed Ali; Pennings, Jacquelyn S; Karacay, Bernes; Shaffrey, Christopher I; Bisson, Erica F; Knightly, John J; Mummaneni, Praveen V; Foley, Kevin T; Bydon, Mohamad

    Background

    The impact of symptom characteristics on outcomes of spine surgery remains elusive.

    Objective

    To determine the impact of symptom location, severity, and duration on outcomes following lumbar spine surgery.

    Methods

    We queried the Quality Outcomes Database (QOD) for patients undergoing elective lumbar spine surgery for lumbar degenerative spine disease. Multivariable regression was utilized to determine the impact of preoperative symptom characteristics (location, severity, and duration) on improvement in disability, quality of life, return to work, and patient satisfaction at 1 yr. Relative predictor importance was determined using an importance metric defined as Wald χ2 penalized by degrees of freedom.

    Results

    A total of 22 022 subjects were analyzed. On adjusted analysis, we found patients with predominant leg pain were more likely to be satisfied (P < .0001), achieve minimum clinically important difference (MCID) in Oswestry Disability Index (ODI) (P = .002), and return to work (P = .03) at 1 yr following surgery without significant difference in Euro-QoL-5D (EQ-5D) (P = .09) [ref = predominant back pain]. Patients with equal leg and back pain were more likely to be satisfied (P < .0001), but showed no significant difference in achieving MCID (P = .22) or return to work (P = .07). Baseline numeric rating scale-leg pain and symptom duration were most important predictors of achieving MCID and change in EQ-5D. Predominant symptom was not found to be an important determinant of return to work. Worker's compensation was found to be most important determinant of satisfaction and return to work.

    Conclusion

    Predominant symptom location is a significant determinant of functional outcomes following spine surgery. However, pain severity and duration have higher predictive importance. Return to work is more dependent on sociodemographic features as compared to symptom characteristics.
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    ItemOpen Access
    Impact of occupational characteristics on return to work for employed patients after elective lumbar spine surgery.
    (The spine journal : official journal of the North American Spine Society, 2019-12) Khan, Inamullah; Bydon, Mohamad; Archer, Kristin R; Sivaganesan, Ahilan; Asher, Anthony M; Alvi, Muhammad Ali; Kerezoudis, Panagiotis; Knightly, John J; Foley, Kevin T; Bisson, Erica F; Shaffrey, Christopher; Asher, Anthony L; Spengler, Dan M; Devin, Clinton J

    Background context

    Low back pain has an immense impact on the US economy. A significant number of patients undergo surgical management in order to regain meaningful functionality in daily life and in the workplace. Return to work (RTW) is a key metric in surgical outcomes, as it has profound implications for both individual patients and the economy at large.

    Purpose

    In this study, we investigated the factors associated with RTW in patients who achieved otherwise favorable outcomes after lumbar spine surgery.

    Study design/setting

    This study retrospectively analyzes prospectively collected data from the lumbar module of national spine registry, the Quality Outcomes Database (QOD).

    Patient sample

    The lumbar module of QOD includes patients undergoing lumbar surgery for primary stenosis, disc herniation, spondylolisthesis (Grade I) and symptomatic mechanical disc collapse or revision surgery for recurrent same-level disc herniation, pseudarthrosis, and adjacent segment disease. Exclusion criteria included age under 18 years and diagnoses of infection, tumor, or trauma as the cause of lumbar-related pain.

    Outcome measures

    The outcome of interest for this study was the return to work 12-month after surgery.

    Methods

    The lumbar module of QOD was queried for patients who were employed at the time of surgery. Good outcomes were defined as patients who had no adverse events (readmissions/complications), had achieved 30% improvement in Oswestry disability index (ODI) and were satisfied (NASS satisfaction) at 3-month post-surgery. Distinct multivariable logistic regression models were fitted with 12-month RTW as outcome for a. overall population and b. the patients with good outcomes. The variables included in the models were age, gender, race, insurance type, education level, occupation type, currently working/on-leave status, workers' compensation, ambulatory status, smoking status, anxiety, depression, symptom duration, number of spinal levels, diabetes, motor deficit, and preoperative back-pain, leg-pain and ODI score.

    Results

    Of the total 12,435 patients, 10,604 (85.3%) had successful RTW at 1-year postsurgery. Among patients who achieved good surgical outcomes, 605 (7%) failed to RTW. For both the overall and subgroup analysis, older patients had lower odds of RTW. Females had lower odds of RTW compared with males and patients with higher back pain and baseline ODI had lower odds of RTW. Patients with longer duration of symptoms, more physically demanding occupations, worker's compensation claim and those who had short-term disability leave at the time of surgery had lower odds of RTW independent of their good surgical outcomes.

    Conclusions

    This study identifies certain risk factors for failure to RTW independent of surgical outcomes. Most of these risk factors are occupational; hence, involving the patient's employer in treatment process and setting realistic expectations may help improve the patients' work-related functionality.
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    In-Hospital Complications and Resource Utilization Following Lumbar Spine Surgery in Patients with Parkinson Disease: Evaluation of the National Inpatient Sample Database.
    (World neurosurgery, 2017-10) Baker, Joseph F; McClelland, Shearwood; Line, Breton G; Smith, Justin S; Hart, Robert A; Ames, Christopher P; Shaffrey, Chris; Bess, Shay

    Background

    Previous reports suggest that patients with Parkinson disease (PD) have elevated rates of complications following spine surgery; however, these reports are limited by small patient series. In this study, we used the National Inpatient Sample (NIS) database to compare in-hospital complications following elective lumbar spine surgery in patients with a diagnosis of PD and patients without PD.

    Methods

    The NIS database was accessed to identify patients with PD and those without PD who underwent lumbar spine surgery. All patients identified had a diagnosis code consistent with degenerative lumbar spine pathology. The patients were evaluated for the presence or absence of PD and divided into 4 lumbar spine procedure groups: decompression alone, lateral fusion, posterior fusion, and anterior fusion technique. Propensity score matching (PSM) was performed for the PD versus non-PD patients in each procedure group to control for confounding demographic variables, and in-hospital complications were compared between the 2 groups.

    Results

    Between 2001 and 2012, a total of 613,522 lumbar spine surgery patient episodes were identified, of which 4492 (0.7%) involved a diagnosis of PD. Following PSM for patient age, sex, and race, the patients with PD were at increased risk for acute postoperative hemorrhagic anemia, increased blood transfusion requirements, and increased genitourinary, neurologic, and cardiac complications compared with the patients without PD.

    Conclusions

    PSM analysis of the NIS database demonstrated that patients with PD are at increased risk for acute in-hospital complications and greater blood transfusion requirements than those without PD. Surgeons should be aware of the increased risks and differing requirements when treating spinal pathology in patients with PD.
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    Interleukin-17 synergizes with IFNγ or TNFα to promote inflammatory mediator release and intercellular adhesion molecule-1 (ICAM-1) expression in human intervertebral disc cells.
    (Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2011-01) Gabr, Mostafa A; Jing, Liufang; Helbling, Antonia R; Sinclair, S Michael; Allen, Kyle D; Shamji, Mohammed F; Richardson, William J; Fitch, Robert D; Setton, Lori A; Chen, Jun
    Interleukin-17 (IL-17) is a cytokine recently shown to be elevated, along with interferon-γ (IFNγ) and tumor necrosis factor (TNFα), in degenerated and herniated intervertebral disc (IVD) tissues, suggesting a role for these cytokines in intervertebral disc disease. The objective of our study was to investigate the involvement of IL-17 and costimulants IFNγ and TNFα in intervertebral disc pathology. Cells were isolated from anulus fibrosus and nucleus pulposus tissues of patients undergoing surgery for intervertebral disc degeneration or scoliosis. The production of inflammatory mediators, nitric oxide (NOx), prostaglandin E2 (PGE2) and interleukin-6 (IL-6), as well as intercellular adhesion molecule (ICAM-1) expression, were quantified for cultured cells following exposure to IL-17, IFNγ, and TNFα. Intervertebral disc cells exposed to IL-17, IFNγ, or TNFα showed a remarkable increase in inflammatory mediator release and ICAM-1 expression (GLM and ANOVA, p < 0.05). Addition of IFNγ or TNFα to IL-17 demonstrated a synergistic increase in inflammatory mediator release, and a marked increase in ICAM-1 expression. These findings suggest that IVD cells not only respond with a catabolic phenotype to IL-17 and costimulants IFNγ and TNFα, but also express surface ligands with consequent potential to recruit additional lymphocytes and immune cells to the IVD microenvironment. IL-17 may be an important regulator of inflammation in the IVD pathologies.
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    ItemOpen Access
    Lumbar intervertebral disc diurnal deformations and T2 and T1rho relaxation times vary by spinal level and disc region.
    (European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2022-03) Martin, John T; Oldweiler, Alexander B; Kosinski, Andrzej S; Spritzer, Charles E; Soher, Brian J; Erickson, Melissa M; Goode, Adam P; DeFrate, Louis E

    Purpose

    Magnetic resonance imaging (MRI) is routinely used to evaluate spine pathology; however, standard imaging findings weakly correlate to low back pain. Abnormal disc mechanical function is implicated as a cause of back pain but is not assessed using standard clinical MRI. Our objective was to utilize our established MRI protocol for measuring disc function to quantify disc mechanical function in a healthy cohort.

    Methods

    We recruited young, asymptomatic volunteers (6 male/6 female; age 18-30 years; BMI < 30) and used MRI to determine how diurnal deformations in disc height, volume, and perimeter were affected by spinal level, disc region, MRI biomarkers of disc health (T2, T1rho), and Pfirrmann grade.

    Results

    Lumbar discs deformed by a mean of -6.1% (95% CI: -7.6%, -4.7%) to -8.0% (CI: -10.6%, -5.4%) in height and -5.4% (CI: -7.6%, -3.3%) to -8.5% (CI: -11.0%, -6.0%) in volume from AM to PM across spinal levels. Regional deformations were more uniform in cranial lumbar levels and concentrated posteriorly in the caudal levels, reaching a maximum of 13.1% at L5-S1 (CI:-16.1%, -10.2%). T2 and T1rho relaxation times were greatest in the nucleus and varied circumferentially within the annulus. T2 relaxation times were greatest at the most cranial spinal levels and decreased caudally. In this young healthy cohort, we identified a weak association between nucleus T2 and the diurnal change in the perimeter.

    Conclusions

    Spinal level is a key factor in determining regional disc deformations. Interestingly, deformations were concentrated in the posterior regions of caudal discs where disc herniation is most prevalent.
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    ItemOpen Access
    Operative and nonoperative treatment approaches for lumbar degenerative disc disease have similar long-term clinical outcomes among patients with positive discography.
    (World neurosurgery, 2014-11) Smith, Justin S; Sidhu, Gursukhman; Bode, Ken; Gendelberg, David; Maltenfort, Mitchell; Ibrahimi, David; Shaffrey, Christopher I; Vaccaro, Alexander R

    Objective

    It remains unclear whether fusion for lumbar degenerative disc disease with positive discography produces better outcomes compared with nonoperative treatment. The aim of this study was to compare outcomes of patients with discography-concordant lumbar degenerative disc disease electing for fusion versus nonoperative treatment.

    Methods

    We retrospectively reviewed consecutive patients with back pain and concordant lumbar discogram who were offered fusion. Follow-up questionnaires included pain score, Oswestry disability index, short form-12, and satisfaction scale. Patients were stratified based on whether they elected for fusion or nonoperative treatment.

    Results

    Overall follow-up was 48% (96/200). Patients lacking follow-up were slightly older (P = 0.021) and less likely to be smokers (P = 0.013). Between patients with and without follow-up, there were no significant differences in pain score at initial visit, body mass index, or gender (P ≥ 0.40). The 96 patients for whom follow-up was obtained included 53 in the operative and 43 in the nonoperative groups. At baseline, there were no significant differences between these groups based on age, pain score, body mass index, smoking, or gender (P ≥ 0.25). Mean follow-up was 63 months for operative and 58 months for nonoperative patients (P = 0.20). The mean pain score at last follow-up improved significantly for operative and nonoperative patients (P < 0.001). At follow-up, operative and nonoperative groups did not differ significantly with regard to pain scores, Oswestry disability index, short form-12, or satisfaction scale.

    Conclusions

    Comparison of long-term outcomes for patients with back pain and concordant discography did not demonstrate a significant difference in outcome measures of pain, health status, satisfaction, or disability based on whether the patient elected for fusion or nonoperative treatment.
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    Patient characteristics of smokers undergoing lumbar spine surgery: an analysis from the Quality Outcomes Database.
    (Journal of neurosurgery. Spine, 2017-12) Asher, Anthony L; Devin, Clinton J; McCutcheon, Brandon; Chotai, Silky; Archer, Kristin R; Nian, Hui; Harrell, Frank E; McGirt, Matthew; Mummaneni, Praveen V; Shaffrey, Christopher I; Foley, Kevin; Glassman, Steven D; Bydon, Mohamad
    OBJECTIVE In this analysis the authors compare the characteristics of smokers to nonsmokers using demographic, socioeconomic, and comorbidity variables. They also investigate which of these characteristics are most strongly associated with smoking status. Finally, the authors investigate whether the association between known patient risk factors and disability outcome is differentially modified by patient smoking status for those who have undergone surgery for lumbar degeneration. METHODS A total of 7547 patients undergoing degenerative lumbar surgery were entered into a prospective multicenter registry (Quality Outcomes Database [QOD]). A retrospective analysis of the prospectively collected data was conducted. Patients were dichotomized as smokers (current smokers) and nonsmokers. Multivariable logistic regression analysis fitted for patient smoking status and subsequent measurement of variable importance was performed to identify the strongest patient characteristics associated with smoking status. Multivariable linear regression models fitted for 12-month Oswestry Disability Index (ODI) scores in subsets of smokers and nonsmokers was performed to investigate whether differential effects of risk factors by smoking status might be present. RESULTS In total, 18% (n = 1365) of patients were smokers and 82% (n = 6182) were nonsmokers. In a multivariable logistic regression analysis, the factors significantly associated with patients' smoking status were sex (p < 0.0001), age (p < 0.0001), body mass index (p < 0.0001), educational status (p < 0.0001), insurance status (p < 0.001), and employment/occupation (p = 0.0024). Patients with diabetes had lowers odds of being a smoker (p = 0.0008), while patients with coronary artery disease had greater odds of being a smoker (p = 0.044). Patients' propensity for smoking was also significantly associated with higher American Society of Anesthesiologists (ASA) class (p < 0.0001), anterior-alone surgical approach (p = 0.018), greater number of levels (p = 0.0246), decompression only (p = 0.0001), and higher baseline ODI score (p < 0.0001). In a multivariable proportional odds logistic regression model, the adjusted odds ratio of risk factors and direction of improvement in 12-month ODI scores remained similar between the subsets of smokers and nonsmokers. CONCLUSIONS Using a large, national, multiinstitutional registry, the authors described the profile of patients who undergo lumbar spine surgery and its association with their smoking status. Compared with nonsmokers, smokers were younger, male, nondiabetic, nonobese patients presenting with leg pain more so than back pain, with higher ASA classes, higher disability, less education, more likely to be unemployed, and with Medicaid/uninsured insurance status. Smoking status did not affect the association between these risk factors and 12-month ODI outcome, suggesting that interventions for modifiable risk factors are equally efficacious between smokers and nonsmokers.
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    ItemOpen Access
    Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues.
    (Arthritis and rheumatism, 2010-07) Shamji, Mohammed F; Setton, Lori A; Jarvis, Wingrove; So, Stephen; Chen, Jun; Jing, Liufang; Bullock, Robert; Isaacs, Robert E; Brown, Christopher; Richardson, William J

    Objective

    Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue.

    Methods

    Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions.

    Results

    Immunoreactivity for IL-4, IL-6, IL-12, and interferon-gamma (IFNgamma) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes.

    Conclusion

    Greater IFNgamma positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration.
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    ItemOpen Access
    Randomized controlled trials for degenerative lumbar spondylolisthesis: which patients benefit from lumbar fusion?
    (Journal of neurosurgery. Spine, 2017-02) Ghogawala, Zoher; Resnick, Daniel K; Glassman, Steven D; Dziura, James; Shaffrey, Christopher I; Mummaneni, Praveen V