Browsing by Subject "Intervertebral Disc Displacement"
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Item Open Access A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.(J Control Release, 2013-10-10) Sinclair, S Michael; Bhattacharyya, Jayanta; McDaniel, Jonathan R; Gooden, David M; Gopalaswamy, Ramesh; Chilkoti, Ashutosh; Setton, Lori ARadiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.Item Open 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, LELow 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.Item Open 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 SBackground 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.Item Open Access Fusion Extension Leads to Spontaneous Resolution of Symptomatic Disc Herniations Associated With Proximal Junctional Kyphosis: A Report of 3 Cases.(JBJS case connector, 2022-10) Rocos, Brett; Wong, Ian HY; Kato, So; Oitment, Colby; Nielsen, Christophen; Jentzsch, Thorsten; Ravinsky, Robert; Wener, Emily; Bensky, Hailey; Lewis, Stephen JCases
A retrospective chart and radiographic review was performed of 3 patients presenting with neurological deficits secondary to soft thoracic disc herniation associated with proximal junctional kyphosis. The patients were treated with proximal extension of the construct, correction of the focal sagittal malalignment, and posterior decompressive laminectomy without excision of the herniated disc. All 3 patients made complete neurological recovery and subsequent magnetic resonance imaging showed resolution of the herniated discs.Conclusions
Laminectomy in conjunction with proximal extension of the construct without formal thoracic discectomy was associated with complete neurological recovery and spontaneous resolution of soft thoracic disc herniations associated with junctional failures.Item Open 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 JBackground 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.Item Open Access Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.(J Orthop Res, 2013-10) Bridgen, DT; Gilchrist, CL; Richardson, WJ; Isaacs, RE; Brown, CR; Yang, KL; Chen, J; Setton, LAThe extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics.Item Open Access 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, JunInterleukin-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.Item Open 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 EPurpose
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.Item Open Access Medical management.(Journal of neurosurgery. Spine, 2014-08) Shaffrey, Christopher I; Smith, Justin SItem Open Access Predictive value of 3-month lumbar discectomy outcomes in the NeuroPoint-SD Registry.(Journal of neurosurgery. Spine, 2015-10) Whitmore, Robert G; Curran, Jill N; Ali, Zarina S; Mummaneni, Praveen V; Shaffrey, Christopher I; Heary, Robert F; Kaiser, Michael G; Asher, Anthony L; Malhotra, Neil R; Cheng, Joseph S; Hurlbert, John; Smith, Justin S; Magge, Subu N; Steinmetz, Michael P; Resnick, Daniel K; Ghogawala, ZoherObject
The authors have established a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures using prospectively collected outcomes. Collection of these data requires an extensive commitment of resources from each site. The aim of this study was to determine whether outcomes data from shorter-interval follow-up could be used to accurately estimate long-term outcome following lumbar discectomy.Methods
An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level lumbar discectomy for treatment of disc herniation were included. SF-36 and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Quality-adjusted life year (QALY) data were calculated using SF-6D utility scores. Correlations among outcomes at each follow-up time point were tested using the Spearman rank correlation test.Results
One hundred forty-eight patients were enrolled over 1 year. Their mean age was 46 years (49% female). Eleven patients (7.4%) required a reoperation by 1 year postoperatively. The overall 1-year follow-up rate was 80.4%. Lumbar discectomy was associated with significant improvements in ODI and SF-36 scores (p < 0.0001) and with a gain of 0.246 QALYs over the 1-year study period. The greatest gain occurred between baseline and 3-month follow-up and was significantly greater than improvements obtained between 3 and 6 months or 6 months and 1 year(p < 0.001). Correlations between 3-month, 6-month, and 1-year outcomes were similar, suggesting that 3-month data may be used to accurately estimate 1-year outcomes for patients who do not require a reoperation. Patients who underwent reoperation had worse outcomes scores and nonsignificant correlations at all time points.Conclusions
This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. Three-month outcome data may be used to accurately estimate outcome at future time points and may lower costs associated with registry data collection. This registry effort provides a practical foundation for the acquisition of outcome data following lumbar discectomy.Item Open 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 JObjective
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.Item Open Access Return to sport after open and microdiscectomy surgery versus conservative treatment for lumbar disc herniation: a systematic review with meta-analysis.(Br J Sports Med, 2016-02) Reiman, Michael P; Sylvain, Jonathan; Loudon, Janice K; Goode, AdamBACKGROUND: Lumbar disc herniation has a prevalence of up to 58% in the athletic population. Lumbar discectomy is a common surgical procedure to alleviate pain and disability in athletes. We systematically reviewed the current clinical evidence regarding athlete return to sport (RTS) following lumbar discectomy compared to conservative treatment. METHODS: A computer-assisted literature search of MEDLINE, CINAHL, Web of Science, PEDro, OVID and PubMed databases (from inception to August 2015) was utilised using keywords related to lumbar disc herniation and surgery. The design of this systematic review was developed using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Methodological quality of individual studies was assessed using the Downs and Black scale (0-16 points). RESULTS: The search strategy revealed 14 articles. Downs and Black quality scores were generally low with no articles in this review earning a high-quality rating, only 5 articles earning a moderate quality rating and 9 of the 14 articles earning a low-quality rating. The pooled RTS for surgical intervention of all included studies was 81% (95% CI 76% to 86%) with significant heterogeneity (I(2)=63.4%, p<0.001) although pooled estimates report only 59% RTS at same level. Pooled analysis showed no difference in RTS rate between surgical (84% (95% CI 77% to 90%)) and conservative intervention (76% (95% CI 56% to 92%); p=0.33). CONCLUSIONS: Studies comparing surgical versus conservative treatment found no significant difference between groups regarding RTS. Not all athletes that RTS return at the level of participation they performed at prior to surgery. Owing to the heterogeneity and low methodological quality of included studies, rates of RTS cannot be accurately determined.