bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disc Space Excessive Distraction is a Potent Risk Factor for Adjacent Segment Degeneration after Anterior Cervical Discectomy and Fusion
Authors: Huang X. , Li F. , Shen H. , Li M. 
Published: May 2014

Introduction We reported that excessive disc space distraction caused by insertion of large cages during anterior cervical discectomy and fusion (ACDF) induces adjacent segment degeneration (ASD). Previous reports indicated that over distraction of disc space was an independent risk factor for ASD after posterior lumbar interbody fusion. We therefore hypothesize that the incidence of ASD after ACDF with larger size of cages should be higher than that ACDF with normal cages due to this loss of disc space distraction. Materials and Methods Radiographic ASD is defined as development of spondylolisthesis >3 mm, decrease in disc height >3 mm, or intervertebral angle at flexion lesser than −5 degrees. Symptomatic ASD is defined by a decrease of ≥ 4 points in Japanese Orthopedic Association score. A 130 patients with cervical spondylotic radiculopathy were treated with either ACDF with larger size of cages ( n = 45) or ACDF with normal cages ( n = 85) and followed up for a minimum of 2 years (mean, 39.2 months). Results Disc space distraction in the normal cage group was significantly smaller (0.4 mm) as compared with the larger size group (1.8 mm). The incidence of clinical ASD in the normal cage group (2%, 1/45) was also significantly less than that in the larger size group (15%, 13/85). Multivariate analysis showed that disc space distraction was the most significant risk factor. Conclusion Among various risk factors for ASD after ACDF, the excessive distraction of disc space proved to be a potent risk factor for ASD. Disclosure of Interest None declared
Correlation of Intervertebral Disc Degeneration among Different Spinal Regions in the Entire Spine in a Population-Based Cohort: The Wakayama Spine Study
Authors: Teraguchi M. , Hashizume H. , Yoshimura N. , Yamada H. , Akune T. , Yoshida M. 
Published: May 2014

Introduction A thorough literature review about the correlation of disc degeneration (DD) among the cervical, thoracic, and lumbar region revealed no studies that focused on a population-based cohort analysis of DD in the entire spine in humans using MRI. To further elucidate the role of intraindividual factors in the development of DD, we should examine DD in the entire spine. The purpose of this study, was to examine the correlation of DD in the cervical, thoracic, and lumbar region, respectively. Materials and Methods This was a cross-sectional study of a cohort from western Japan, comprising 975 (men, 324; women, 641) of 1,011 participants (age, 21-97 years). The participants were subjected to the entire spine MRI and all intervertebral discs in the cervical (C2/3-7/Th1), thoracic (Th1/2-Th12/L1), and lumbar (L1/2-L5/S) region on sagittal T2-weighted images were evaluated according to the Pfirrmann classification system (1-3= nondegeneration; 4, 5=degeneration). The Spearman rank correlation analysis was used to determine the correlation among the number of DD at each region mutually after adjustment for age. Results The Spearman rank correlation coefficient was 0.347 (95%CI: 0.5-0.59) between the cervical region and thoracic region, 0.300 (95%CI: 0.42-0.52) between the lumbar region and thoracic region, and 0.246 (95%CI: 0.34-0.44) between the cervical region and lumbar region. Conclusion Our population-based study using the whole spine MRI revealed a highly significant intraindividual correlation between DD in the cervical region and DD in the thoracic or lumbar region. Needless to say, the biomechanical environments among the three regions are fundamentally different. This distinct individual correlation for DD could be attributed to underlying genetic factor or endogenous factors, and so on. To further elucidate the role of intraindividual factors to DD, investigations on the extent of degenerative changes using the whole spine MRI could provide useful fundamental data concerning degenerative spinal change. Disclosure of Interest None declared
Body Mass Index and its Association with Lumbar Disc Herniation and Sciatica: A Large-Scale, Population-Based Study
Authors: Samartzis D. , Karppinen J. , Luk K. DK , Cheung K. MC 
Published: May 2014

Introduction Elevated body mass index (BMI) or overweight and obesity are pandemics. Lumbar disc herniation and sciatica occur in every population and present severe socioeconomic consequences. However, little is known regarding the role of BMI with lumbar disc herniation and sciatica. As such, the following large-scale study addressed the association of BMI, in particular overweight and obesity, with disc herniation, its global lumbar involvement and its implications with the development of sciatica. Materials and Methods A cross-sectional study of 2,596 Southern Chinese (mean age: 42 years; 60% females) was conducted assessing T2-weighted MRI, environmental and lifestyle factors, as well as clinical profiles of sciatica. On imaging, the presence of disc bulge/extrusion (DBE) and other spinal phenotypes from L1-S1 were assessed. Disc degeneration was assessed and graded based on the Schneiderman et al criteria and summated of all levels to produce a degenerative disc disease (DDD) score (potential score range: 0-15). A total DBE (TDBE) score of L1-S1 was calculated (potential score range: 0-10). Asian-modified BMI values and categories of underweight, normal weight, overweight, and obese were obtained for each subject. Results DBE was noted in 46.3% of the subjects, mainly occurring at L4-S1. The mean DDD and TDBE scores were 0.7 and 2.83, respectively. Historical prevalence of sciatica was 44.6%, with 17.9% reporting sciatica at the time of assessment. The mean BMI was 22.9 kg/m2 (7.2% underweight, 47.9% normal weight, 36.1% overweight, and 8.9% obese). Elevated DDD score was significantly correlated with an elevated TDBE score (r=0.610; p< 0.001). TDBE score significantly increased with elevated BMI categories ( p< 0.001). Multivariate analyses adjusting for covariates noted that elevated BMI was significantly associated with DBE (normal weight [Ref]; underweight OR: 0.71[95% CI: 0.49-1.03]; overweight OR: 1.26[95% CI: 1.04-1.52]; obese OR: 1.78[95% CI: 1.30-2.44]). TDBE score (OR: 1.36; 95% CI: 1.15-1.60) and obesity (OR: 1.68; 95% CI: 1.25-2.24) were significantly related with sciatica. Worse functional and disability scores were associated with sciatica ( p< 0.05). Conclusion Based on the largest population-based study to assess the role of BMI and its association with disc herniation, this study definitely noted that overweight and obesity significantly increased the likelihood of having lumbar disc herniation, its global severity, and the risk of developing sciatica. Disclosure of Interest None declared
Regeneration of the Intervertebral Disc with Nucleus Pulposus Cell-Seeded Collagen II/Hyaluronan/Chondroitin-6-Sulfate Tri-Copolymer Constructs in a Rabbit Disc Degeneration Model
Authors: Huang B. , Zhuang Y. , Li C. , Liu L. , Zhou Y. 
Published: May 2014

Introduction Advancement in tissue engineering provides a promising approach to recover the functionality of the degenerated intervertebral disc. In our study, a nucleus pulposus (NP) cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate (CII/HyA/CS) tri-copolymer construct was implanted into the disc space directly after nucleotomy in a rabbit model. The aim of this study was to investigate whether the NP cell-seeded CII/HyA/CS tri-copolymer constructs could regenerate the degenerated disc in vivo after implantation into the rabbit nucleotomy model. Materials and Methods NP cells isolated from thoracic and lumbar spines of New Zealand white rabbits of about 3 weeks of age and 1 kg in weight were labeled with a 5- (and-6)-carboxyflurescein diacetate succinimidyl ester (CFDA-SE) fluorescent dye and seeded within the CII/HyA/CS scaffold by a centrifugation method. After in vitro culture for 1 week, NP cell-seeded CII/HyA/CS tri-copolymer constructs were allografted into the disc defects of recipient rabbit immediately after nucleotomy of the lumbar spine. The Bradner disc index and the T2-weighted signal intensity index were determined using lateral plane radiographs and magnetic resonance imaging at 4, 12, and 24 weeks after the operation. Finally, the operated discs were explanted for gross morphological observation, histological evaluation, and cell viability assessment. Animals with only nucleotomy and cell-free CII/HyA/CS scaffold implantation served as controls. Results In our study, we could demonstrate that the T2-weighted signal intensity index of the operated discs decreased in all three groups 1 month after surgery and the index of the cell-containing scaffold insertion group was significantly higher than that of the other two groups. After 24 weeks, the index of the cell-containing scaffold insertion group increased significantly. However, further decline was observed in both the noninsertion group and the scaffold insertion group. In radiographic analysis, the narrowing of the intervertebral disc space was significantly retarded by the cell-scaffold hybrids implantation up to 24 postoperative weeks. Moreover, the gross morphology and histological evaluation indicated that the allografted NP cells were viable and showed extracellular matrix production. Conclusion In our study, we had constructed rabbit NP cell-seeded CII/HyA/CS tri-copolymer implants in vitro. Immediately after nucleotomy of the recipient rabbit, we allografted the precultured cell-scaffold hybrids into the lacuna of the disc. Results documented survival of the allografted NP cells and extracellular matrix deposition, which finally resulted in maintenance of disc height and restoration of T2-weighted signal intensity on magnetic resonance imaging. Disclosure of Interest None declared
Pathogenesis of Ossification of Ligamentum Flavum
Authors: N. B. J.  , S. L. J.  , N. G.  
Published: May 2014

Introduction Ossification of ligamentum flavum (OLF) is a rare disorder. The present study aims at histopathological analysis of OLF with special emphasis on the alterations in the elastin fibers, collagen, matrix, cellularity, chodrocyte proliferation, and osteoid metaplasia. Materials and Methods The study involves histopathologic examination of surgically harvested ligamentum flavum (LF) specimens from 10 OLF, 5 with degenerative spinal stenosis and 5 normal LF as controls. The specimens were studied with hematoxylin and eosin, Verhoff van Gieson, toluidine blue, Masons trichrome, and Alcian blue. All specimens were analyzed qualitatively for (1) elastic fiber orientation, integrity, and loss, (2) collagen bundles,(3) fibrosis,(4) chondroid metaplasia,(5) chondrocyte proliferation, and (6) Osteoid metaplasia. The quantitative analysis was done using SCION image analysis software. Results All the 10 OLF specimens showed extensive loss of elastic fibers associated with cartilage matrix formation. There were many areas of irregularly oriented elastic fibers, areas of ossification and in between there was a transitional area of cartilage matrix with chondrocytes progressing toward ossification. Elastic fiber occupying ratio was 60.96, 40.25, and 22.66%; number of chondrocytes per mm2 was 37.56, 93.35, and 117.68; area of chondroid matrix (%) was 11.34, 32.37, and 73.56, respectively, and the area of osteoid matrix (%) was 0, 9.37, and 33.43 respectively for normal controls, degenerative group, and OLF group. The areas of cartilage matrix were more on the dorsal side compared with the dural side of LF. In contrast, cartilage matrix osteogenesis was more in dural than dorsal surface of LF. Conclusion In OLF, loss of elastic fibers was associated with proliferation of collagen fibers, fibrosis, chondrogenesis, and osteogenesis. The pathological process initiates in the dorsal surface with chondroid metaplasia gradually elevating the mature cartilage matrix toward the dural surface, where the initial ossification occurs. Disclosure of Interest None declared References Jolly SS. Fluoride balance studies in endemic fluorosis. Fluoride 1976;8:138–147 Jolly SS, Singh BM, Mathur OC, Malhotra KC. Epidemiological, clinical, and biochemical study of endemic dental and skeletal fluorosis in punjab. BMJ 1968;4(5628):427–429 Jolly SS, Singh ID, Prasad S, Sharma R, Singh BM, Mathur OC. An epidemiological study of endemic fluorosis in Punjab. Indian J Med Res 1969;57(7):1333–1346 Jolly SS, Prasad S, Sharma R, Rai B. Human fluoride intoxication in the Punjab. Fluoride 1971;4:64–79 Jolly SS, Prasad S, Sharma R, Chander R. Endemic fluorosis in Punjab-skeletal aspects. Fluoride 1973;6:4–18 Naidu MRC, Reddy DR, Reddy PK, Sastry Kolluri VR. [Fluorotic cervical spinal cord disease]. Rev Chir Orthop Repar Appar Mot 1989;75(4):228–231 Siddiqui AH. Fluorosis in Nalgonda District, Hyderabad-Deccan. BMJ 1955;2(4953):1408–1413
Collagen-Derived Peptide N-Acetylated Proline-Glycine-Proline in Intervetebral Disc Recruits Cartilage Endplate Stem Cells by Binding with CXC Receptor 2
Authors: Feng C. 
Published: May 2014

Introduction Degenerative disc disease (DDD) is a prevalent musculoskeletal disorder and is the major cause of low back pain. But our comprehension about development of the intervertebral disc (IVD) and pathogenesis of disc degeneration is unclear, which is an obstacle for appropriate therapies. Recently, some reports identified stem/progenitor cells within particular IVD niches and cartilage endplate. These cells together with mesenchymal stem cells (MSC) are recruited to nucleus pulposus(NP) and annulus fibrosus(AF) to generate regenerative functions in a healthy IVD. The possibility of stimulating these stem cells holds promise for future therapy for DDD. But factors which recruit stem cells to NP and AF are unknown. There are increasing evidences that N-acetylated proline-glycine-proline (N-AC-PGP), which is a degradation fragment of collagen, plays an important role in inflammatory cell recruitment. But whether it presents in IVD and whether it is a chemokine of stem cell have remained elusive. Materials and Methods In this study, we detected the presence of N-AC-PGP by liquid chromatography-mass spectrum in IVD with different degeneration grade and the enzymes responsible for generating N-AC-PGP, matrix metalloproteases 8 and 9 and prolyl endopeptidase (PE), are also quantified by ELISA in these IVD samples. To found out the role of N-AC-PGP in IVD, cartilage endplate stem cells (CESC) chemotaxis assay was performed by Tanswell assay. Results We demonstrate the correlation between N-AC-PGP content in IVD and content of MMP-8and9 and PE.N-AC-PGP increase with increasing degeneration grade of IVD. Then, we described the generation pathway of N-AC-PGP in IVD. Finally, we demonstrated that N-AC-PGP can recruit CESC by binding with CXC receptors 2 on CESC. Conclusion These findings reveal a possible regeneration mechanism in IVD, which depends on the chemotaxis of N-AC-PGP for CESC and indicate a new therapy by using N-AC-PGP to stimulate stem cells in IVD. Disclosure of Interest None declared References Snelgrove RJ, Jackson PL, Hardison MT, et al. A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. Science 2010;330(6000):90–94 Gaggar A, Jackson PL, Noerager BD, et al. A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation. J Immunol 2008;180(8):5662–5669 Weathington NM, van Houwelingen AH, Noerager BD, et al. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 2006;12(3):317–323
Role of Semaphorins in Angiogenesis and Innervation in Human Intervertebral Disc Degeneration
Authors: Binch A. LA. , Phillips K. L , Chiverton N. , Cole A. , Michael A. R. , Breakwell L. , Cross A. K. , Le Maitre C. L. 
Published: May 2014

Introduction Although the intervertebral disc (IVD) is considered the largest aneural structure within the human body, during degeneration nociceptive nerves are seen to accompany blood vessels into the IVD yet it remains unclear how this process occurs. Semaphorins are axonal guidance molecules known to repulse nerves by altering the actin cytoskeleton of growth cones. Semaphorin 3A (sema3A) has recently been localized in healthy IVDs, suggesting an inhibitory role toward neural and vascular ingrowth. This study aimed to first identify the presence of the class 3 semaphorins and sema4D shown to be involved in promoting angiogenesis and their receptors within nucleus pulposus(NP) cells and an endothelial cell line and determine whether their expression could be altered by cytokine treatment. Materials and Methods Real-time PCR (RT-PCR) was performed to investigate gene expression of class 3 semaphorins; Sema3A-3F, sema4D, their receptors plexin A1-A4 and plexin D1 and neuropilin-1 (NRP-1) and NRP-2 in directly extracted RNA from human NP cells and NP cells cultured in alginate for 2weeks before treatment for 48hours with interleukin (IL)-1, IL-6, or tumor necrosis factor α(TNFα) at 0 to 100ng/mL. Similarly, HDMEC-1 endothelial cells were treated with IL-1, IL-6, or TNFα at 0 and 10ng/mL for 48hours, after which mRNA expression was investigated by RT-PCR. Results Expression of semaphorins and their receptors were present in normal and degenerate disc samples. In human NP cells, IL-6 inhibited semaphorin expression, whereas IL-1 and TNFα significantly increased sema3D over 10-fold ( p≤0.05). IL-1 upregulated all plexins, conversely TNFα significantly decreased plexin A2. NRP-2 showed a significant increase in response to IL-1. While NRP-1 was significantly decreased in response to IL-1. In HDMEC-1 cells IL-1 significantly increased sema3C and sema3D while TNF significantly increased sema3C. TNF significantly increased NRP-2 expression, however, NRP-1 was decreased by all cytokines. Plexin receptor expression was increased upon IL-6 and TNF treatment whereas IL-1 caused significant decrease in plexin A3 expression. Conclusion Here, we have demonstrated that several cytokines known to be upregulated during disc degeneration and disc prolapse, regulate expression of certain members of class 3 semaphorins, as well as their receptors in human NP cells and HDMEC-1 cells. This data suggests that the presence of these factors within the degenerate disc may be responsible for modulating the ingrowth of blood vessels and promote nerve ingrowth leading to discogenic pain. Disclosure of Interest None declared
Disc Degeneration after Temporary Fixation of the Motion Segment in Unstable Thoracolumbar A and B Fractures
Authors: Hoppe S. , Keel M. , Aghayev E. , Benneker L. 
Published: May 2014

Introduction Anterior stabilization with cages/iliac bone graft and corpectomy in addition with posterior spondylodesis is the gold standard for the treatment of anterior unstable Magerl types A and B fractures of the thoracolumbar junction.1,2 The effect of temporary fixation on the intervertebral disc as well as on progression of kyphosis, especially after dorsal implant removal to unblock the caudal nonfused segment, is unclear. Materials and Methods Retrospective case series of all patients treated with posterior stabilization in combination with vertebroplasty/kyphoplasty between 2000 and 2010 with secondary implant removal 8 to 12 months after the index operation. All cases were assessed for loss of reduction, Cobb angle, and disc height after implant removal by anteroposterior and lateral radiographs. Results Overall 20 (m: 13; f: 7) (age: 40.9 ± 14.4 years) out of 59 patients treated with bridging dorsal instrumentation with transpedicular vertebroplasty underwent implant removal. Fractures were classified as A 3.21 in 15, A 3.1 in 3, and B 2.3 in 2 cases. The fracture location was Th12 in 5, L1 in 11, L2 and L3 in 2 cases. The implant removal was performed 9.6 ± 3.2 month after initial surgery. In all but one case increase of kyphosis was found 6 month later. The mean increase of kyphosis was 8 ± 6 degrees (max: 12 degrees; min: 0 degrees), mainly in the upper motion segment. Significant loss of disc height was found in the upper motion segment compared with before implant removal, whereas vertebral height remains stable. Age highly correlated to loss of reduction and disc height (r = 0.51). No differences between the fracture location and types were found. Conclusion After temporary fixation of the intervertebral disc by internal fixation an increase of kyphosis in the segment above the augmented/fractured vertebra is to be expected, especially because of degeneration of the disc above the affected vertebra. This effect is age dependent. In how far this has clinical relevance is topic of ongoing investigations. Disclosure of Interest None declared References Harris MB. The role of anterior stabilization with instrumentation in the treatment of thoracolumbar burst fractures. Orthopedics 1992;15(3):347–350 Mariotti AJ, Diwan AD. Current concepts in anterior surgery for thoracolumbar trauma. Orthop Clin North Am 2002;33(2):403–412
Simulation of Degenerative and Proinflammatory Conditions for Testing of Cell Therapy Approaches in a Disc Organ Culture System
Authors: Teixeira G. Quelhas , Gonçalves R. , Boldt A. , Wilke H.-J. , Ignatius A. , Barbosa M. , Neidlinger-Wilke C. 
Published: May 2014

Introduction A successful cell therapy of disc degeneration requires long-term survival and metabolic activity of injected cells in the degenerative disc environment that is affected by low nutrient supply, decreased osmolarity, and proinflammatory conditions. A bovine disc organ culture system with simulation of degenerative and proinflammatory conditions was evaluated with regard to its suitability for testing the fate of injected cells. Materials and Methods Bovine caudal disc punches (up to six discs from each specimen) were exposed to needle puncture and proinflammatory factors (LPS, interleukin [IL]1β) for 2 days after a 6-day culture without stimulus, while untreated samples were used as controls. The induction of a proinflammatory response was evaluated by quantification of prostaglandin E2 (PGE2) in culture supernatants and gene expression analysis of proinflammatory cytokines, matrix metalloproteases (MMPs), collagen type II, and aggrecan was measured in isolated disc cells. The metabolic profile of disc punches was traced by quantification of glucose consumption and lactic acid production. To simulate normal versus degenerative conditions, cultures were maintained at 5 mM glucose and 400 mOsm or exposed to low glucose (0.05 mM) and reduced osmolarity (300 mOsm). PKH-labeled cells were injected within an albumin-based hydrogel scaffold. Discs were analyzed by histochemistry and by determination of glycosaminoglycan (GAG) content after 2 weeks. Results PGE2 increased for LPS 10 µg/mL, IL1β 10 ng/mL or 100 ng/mL treatments of 21.7 ± 0.8-fold, 5.5 ± 0.9-fold, and 9.6 ± 0.8-fold, respectively, when compared with control (Fig. 1A). Preliminary evaluations showed that LPS- and IL1β-treated discs increased expression of IL-6 and 8, MMP1 and MMP3, and decreased collagens type II and aggrecan expression (Fig. 1B). GAG content of the disc explants decreased (62.4 ± 9%) within 2 weeks. However, treated samples and controls showed similar glucose consumption and lactic acid production, with the concentrations never reaching levels of starvation or toxic environment. Fluorescent cells could be detected at each sampling time point with only little differences between culture conditions. Conclusion Simulation of degenerative or inflammatory conditions increased PGE2 release and expression of MMPs and ILs, and decreased matrix protein expression by disc cells. Monitoring of injected fluorescence-labeled cells allows characterization of cell reactions in a simulated degenerative environment. This approach is suitable for in vitro testing of regenerative or anti-inflammatory treatment strategies of disc degeneration. Acknowledgments The research described was financially supported by PEST founds, FP7-EU project GENODISC, Luso-German Integrated Actions 2012: CRUP/DAAD and by the German Spine Foundation. Disclosure of Interest None declared