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Extra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (~12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo. Results: Brain tumors had a 1.42-fold cancer-to-normal ratio (p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group (p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APTEDB-DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.

Objective Even if analyzed through meta-analyses or systemic reviews ensued lately, we could say that at least it is inconclusive which of the surgical or non-surgical treatment to lumbar spinal stenosis is better particularly in short to intermediate-term. This study compared non-surgical and surgical outcomes in surgical candidates for lumbar spinal stenosis (LSS). Methods Surgical candidates for LSS were prospectively screened. Patients were offered the option to be enrolled in a randomized cohort, an observational cohort, or not to participate. Patient-reported outcomes were evaluated at baseline, and at 1, 3, 6, and 12 months. The primary outcomes were measures of pain and functional outcomes such as the Korean version of the Oswestry Disability Index (K-ODI), the EuroQol 5-Dimension instrument (EQ-5D), and 36-Item Short-Form Health Survey (SF-36). Results One hundred and ten patients were enrolled in the randomized cohort and 37 patients in the observational cohort. Among them, 97 patients received non-surgical treatment, and 50 patients underwent surgical treatment. At 12 months, the non-surgical treatment group had less improvements in the primary outcome measures of back pain (mean change: non-surgery, 2.34 vs. surgery, 3.99), leg pain (2.92 vs. 3.40), K-ODI (5.12 vs. 8.31), EQ-5D utility index (0.19 vs. 0.25), and EQ-5D VAS (9.68 vs. 16.0). Most SF-36 section parameters also showed less improvement in the non-surgical treatment group than in the surgical treatment group throughout the 12-month follow-up. Conclusions In LSS patients without instability, non-surgical treatment resulted in less pain improvement and functional recovery through 1 year.

Objective: Since the first discovery of the 2019 novel coronavirus (COVID-19), rapid and wide spread of the disease has been reported and the World Health Organization announced that a 'pandemic' has started. Up to date there is little known regarding the impact of this outbreak on spinal specialists' daily clinical practice. We intended to evaluate how COVID-19 has affected the number of spinal disease patients we meet and operate in daily practice. Methods: The de-identified data regarding number of patients visiting the spine clinic at a tertiary referral hospital and a secondary level hospital from January, February and March of 2017 to 2020 were retrospectively reviewed. The number of out-patient department (OPD) visits, number of emergency room (ER) visits as well as number of surgeries performed during the reviewed period were collected and analyzed, comparing 2020 to the previous 3 years. Results: The number of daily OPD visits showed a steady decrease starting from January, and presented a statistically significant decrease by early March 2020, compared to the previous 3 years. During the same period, decrease in number of daily ER visits was statistically significant as well. The number of elective surgeries or number of surgeries for patients admitted via ER during COVID-19 outbreak remained similar to that of 2017-2019 suggesting, despite the decrease of patients visiting the hospital for spinal diseases, those whom required surgery still visited the hospital. The results were consistant among other hospital level. Conclusion: The outbreak of COVID-19 affected our daily practice as OPD and ER visits reduced but did not affect the number of surgeries. We believe that this report will be informative to spinal specialists worldwide fighting the COVID-19 pandemic.

Objective We developed a novel multi-torsional mechanical stretch stress loading device for ligamentum flavum cells and evaluated its influence on the development of ligamentum flavum hypertrophy, a common cause of lumbar spinal canal stenosis. Materials and methods Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human ligamentum flavum cells was performed and the results were compared to control (0% stress). Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay. Results Using our multi-torsional mechanical stretch stress loading device, 5% stress for 24 hour was optimal for ligamentum flavum cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMP-1, MMP-3, and TIMP-2 were significantly increased, compared to the control. Conclusion Using the novel multi-torsional mechanical stretch stress loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering ligamentum flavum hypertrophy.

Sagittal spinopelvic alignment (SSPA) parameters are essential for the diagnosis of adult spinal deformities (ASDs) and their progression. Certain clinical symptoms that occur in patients with lumbar spinal stenosis (LSS) and herniated nucleus pulposus (HNP) may distort the SSPA and mimic ASD.To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position.This retrospective cohort study evaluated changes in SSPA after simple lumbar decompression surgery in patients with LSS and HNP. Relative sagittal alignment (RSA), relative pelvic version, relative lumbar lordosis (RLL), Lordosis Distribution Index (LDI), and global alignment and proportion (GAP) values were calculated using the conventional Schwab classification method. First, the preoperative and postoperative SSPA parameters were compared. Second, patients were subgrouped into symptomatic within 10 minutes of standing (SP group) and other symptoms of LSS and HNP as controls. Changes in SSPA parameters after symptom relief after simple lumbar decompression surgery were compared between the two groups.Overall, all SSPA parameters improved after surgery. However, after subgrouping, patients in the control group did not show significant SSPA alterations, except for LDI, whereas patients in the SP group significantly improved in terms of their RSA, RLL, LDI, and GAP values after symptom relief after surgery.Patients with pain on standing within 10 minutes showed significant correction in RSA, RLL, and GAP values after simple lumbar decompression. Therefore, it is important to observe such clinical symptoms to avoid misdiagnosis of ASD.

Objective: Computed tomography (CT) is an often-used diagnostic imaging tool during the evaluation of the cervical spine pathology. CT scan can provide one’s bone density by measuring Hounsfield’s unit. In anterior cervical discectomy and fusion (ACDF) surgeries, bone density may play an important role as it may relate to non-union. Therefore, the evaluation and consideration of the Hounsfield’s unit of sub-axial cervical vertebral body is important, especially during multi-level ACDF.Methods: Patients who have taken cervical CT scan pre-operatively to multi-level (3 or 4 levels) anterior cervical discectomy and fusion with anterior plating between June 2010 and August 2018, at our department were retrospectively reviewed. The bone density was estimated by measuring Hounsfield Unit (HU) of sub-axial vertebrae - C3 to T1 - by using PiViewStar imaging software program. Radiological evaluation of fusion was done by assessing postoperative plain X-rays and CT scans of 4 months and 1-year follow-up. The difference in HU were evaluated between different segments of sub-axial vertebrae. Then the fusion rate of the ACDF ending at C6 were compared to C7. All grouped values were tested for normality using the Shapiro-Wilk test. Matched-ANOVA and Fisher’s exact test was used.Results: A total of eighty patients were who underwent 3 or 4 level ACDF with anterior plate fixation were retrospectively reviewed. Bone density estimated from Hounsfield unit (HU) measurement of the sub-axial vertebral bodies ranges from 112.2 to 594.9 with the mean of 280.91. When comparing C5 with 6, 6 with 7, and 7 with T1 they showed significantly decreasing HU value with p-value

We present a case of a L5/S1 extraforaminal stenosis (EFS), also known as far-out syndrome, in which ineffective multiple previous fusion surgeries were performed because of misdiagnosis. An 83-year-old man, complaining of back and left sided leg pain along the L5 dermatome for 5 years visited our institute claiming persistent pain even after 2 fusion surgeries at another hospital. A new magnetic resonance image (MRI) scan with a half coronal T1-weighted sequence revealed left L5/S1 EFS and resultant L5 nerve root compression. Because of the patient’s old age, history of angina and anti-platelet medications, a minimally invasive full-endoscopic decompression was performed. Afterwards the patient experienced immediate relief of the radicular pain, satisfied with the surgery. Diagnosis of L5/S1 EFS can be challenging especially when only routine sagittal/axial MRI scans are provided. Half coronal plane T1-weighted image MRI can be extremely helpful in diagnosis of this distinct pathology. Through this case report, we would like to emphasize the significance of half coronal MRI in diagnosis of L5/S1 EFS and also show a representative successful full-endoscopic decompression for the disease.

This study was designed to investigate (i) extracellular matrix to specify adhesive substrates to human dura mater cell (hDMC); (ii) the alteration on adhesion-related molecules in hDMC; and (iii) secreted matrix metalloproteinases (MMPs) linked with extracellular matrix remodeling after exposure to inflammation. The hDMC was cultured from human dura mater tissue, and the studies were performed with hDMC after co-culturing with macrophage like THP-1 cells (Mϕ). The adhesion of co-cultured hDMC through collagen I increased 6.4-fold and through collagen IV increased 5.0-fold compared with the adhesion of naive cells (p < 0.001). Integrin subtype α2 β1 expression was increased 6.3-fold (p < 0.001) and α1 expression was decreased 2.0-fold (p < 0.001) in the co-cultured cells compared with the naive cells. Co-culturing induced significant increases in MMP-1 (13.9-fold, p < 0.01), MMP-3 (7.6-fold, p < 0.01), and VEGF (VEGF: 3.8-fold, p < 0.05) expression and decreases in MMP-9 (0.1-fold, p < 0.01) compared with the sum of naive hDMC and Mϕ values. Increased hDMC adhesion under inflammatory conditions is caused by an increased cellular affinity for collagen I and IV mediated by increased hDMC levels of integrin subtype α2 β1 and environmental MMP-1, -3 and decreased MMP-9. Selective integrin subtype α2 β1 inhibition assay showed 37.8% and 35.7% reduction in adhesion of co-cultured hDMC to collagen I (p < 0.001) and IV (p = 0.057), respectively. The present study provides insight into the pathological conditions related to dura mater adhesion in inflammation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2019.

ObjectiveWe developed a novel multi-torsional mechanical stretch stress (MSS) loading device for ligamentum flavum (LF) cells and evaluated its influence on the development of ligamentum flavum hypertrophy (LFH), a common cause of lumbar spinal canal stenosis.Materials and MethodsStretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human LF cells was performed and the results were compared to control (0%) MSS. Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay.ResultsUsing our multi-torsional MSS loading device, 5% MSS for 24 h was optimal for LF cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMR-1, MMR-3, and TIMP-2 were significantly increased, compared to the control. ConclusionUsing the novel multi-torsional MSS loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering LFH. This discovery enhances our understating of the effects of mechanical stress on LFH.

Physicians often encounter surgical candidates with lumbar disc herniation (LDH) who request non-surgical management even though surgery is recommended. However, second opinions may differ among doctors. Therefore, a prospective comprehensive cohort study (CCS) was designed to assess outcomes of nonsurgical treatment for surgical candidates who were recommended to undergo surgery for LDH but requested a second opinion. The CCS includes both randomized and observational cohorts, comprising a nonsurgery cohort and surgery cohort, in a parallel fashion. Crossover between the nonsurgery and surgery cohorts was allowed at any time. The present study was an as-treated interim analysis of 128 cases (nonsurgery cohort, n = 71; surgery cohort, n = 57). Patient-reported outcomes included visual analogue scores for the back (VAS-B) and leg (VAS-L), the Oswestry Disability Index, the EuroQol 5-Dimension instrument, and the 36-Item Short-Form Health Survey (SF-36), which were evaluated at baseline and at 1, 3, 6, 12, and 24 months. At baseline, age and SF-36 physical function were significantly lower in the surgery cohort than in the nonsurgery cohort (p 0.01). Nonsurgical management may be a negotiable option even for surgical candidates in the shared decision-making process.

Fractures at the thoracolumbar region are commonly followed after major traumatic injuries, and up to 20% of these fractures are known to be burst fractures. Making surgical decisions for these patients are of great interest however there is no golden standard so far. Since the introduction of Thoracolumbar Injury Classification and Severity (TLICS) score in 2007, it has been widely used as a referential guideline for making surgical decisions in thoracolumbar fractures. However, there is still limitations in this system. In this clinical case report, we introduce a L1 burst fracture after motor vehicle injury, who was successfully treated conservatively even while she was graded as a TLICS 5 injury. A case report is presented as well as discussion on the limitations of this grading system.

A retrospective review.We investigated the longitudinal change of cervical alignment parameters including C2-7 lordosis, C2-7 sagittal vertical axis (SVA), T1 slope, and segmental angle (SA) after two-level anterior cervical discectomy and fusion (ACDF).Cervical alignment may influence postoperative clinical outcomes. Several studies have suggested that cervical alignment may serve as a parameter for assessing cervical deformities similar to those used to assess thoracolumbar spine deformities. However, to our knowledge, no studies have investigated the effect of ACDF on cervical sagittal alignment.We enrolled patients whom had ACDF, 23 patients with stand-alone cages and 22 with plate augmentation. Radiologic parameters including C2-7 lordosis, C2-7 SVA, T1 slope, and SA at the operated level were evaluated preoperatively and at 1 week and 6 months postoperatively. The differences between preoperative and 6-month postoperative parameter values were designated as Δvalues. T1S-CL was calculated as the T1 slope minus C2-7 lordosis. Clinical outcome were obtained by the Visual Analog Scale (VAS) and the Neck Disability Index (NDI).ΔC2-7 SVA was significantly correlated with ΔT1S-CL and ΔC2-7 lordosis. ΔC2-7 lordosis was significantly correlated with ΔSA. ΔC2-7 lordosis had a significantly greater impact on ΔT1S-CL than did ΔT1 slope. The ΔSA and ΔC2-7 lordosis in the ACDF-plate were significantly higher than those in the in ACDF-cage. ΔT1S-CL and ΔC2-7 SVA in the ACDF-plate were significantly lower than those in the ACDF-cage.C2-7 SVA after two-level ACDF was affected more significantly by the SA and C2-7 angle than by the T1 slope. Two-level ACDF with plate restored more cervical lordosis by obtaining more segmental lordosis at the operated level and was more effective in terms of cervical alignment compared with ACDF using stand-alone cages.3.

OBJECT An in vitro study was performed to understand the potential roles of matrix metalloproteinase (MMP)-2 and MMP-9 in the elastin degradation of human ligamentum flavum (LF) cells via treatment with tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β). Previous studies have identified a decreased elastin to collagen ratio in hypertrophic LF. Among the extracellular matrix remodeling endopeptidases, MMP-2 and MMP-9 are known to have elastolytic activity. The hypothesis that activated LF cells exposed to inflammation would secrete MMP-2 and MMP-9, thereby resulting in elastin degradation, was examined. METHODS To examine MMP-2 and MMP-9 expression in human LF, cells were isolated and cultured from LF tissues that were obtained during lumbar disc surgery. Isolated LF cells were equally divided into 3 flasks and subcultured. Upon cellular confluency, the LF cells were treated with TNFα, IL-1β, or none (as a control) and incubated for 48 hours. The conditioned media were collected and assayed for MMP-2 and MMP-9 using gelatin zymography and Western blot analysis. The electrophoresis bands were compared on densitometric scans using ImageJ software. RESULTS The conditioned media from the isolated human LF cells naturally expressed 72-kD and 92-kD gelatinolytic activities on gelatin zymography. The IL-1β-treated LF cells presented sustained increases in the proenzyme/zymogen forms of MMP−2 and −9 (proMMP-2 and proMMP-9), and activeMMP-9 expression (p = 0.001, 0.022, and 0.036, respectively); the TNFα-treated LF cells showed the most elevated proMMP9 secretion (p = 0.006), as determined by Western blot analyses. ActiveMMP-2 expression was not observed on zymography or the Western blot analysis. CONCLUSIONS TNFα and IL-1β promote proMMP-2 and proMMP-9 secretion. IL-1β appears to activate proMMP-9 in human LF cells. Based on these findings, selective MMP-9 blockers or antiinflammatory drugs could be potential treatment options for LF hypertrophy.

This study was designed to investigate (i) extracellular matrix to specify adhesive substrates to human dura mater cell (hDMC); (ii) the alteration on adhesion-related molecules in hDMC; and (iii) secreted matrix metalloproteinases (MMPs) linked with extracellular matrix remodeling after exposure to inflammation. The hDMC was cultured from human dura mater tissue, and the studies were performed with hDMC after co-culturing with macrophage like THP-1 cells (Mϕ). The adhesion of co-cultured hDMC through collagen I increased 6.4-fold and through collagen IV increased 5.0-fold compared with the adhesion of naïve cells (p 0.001). Integrin subtype α

Objective To introduce our technique and results of retropleural/peritoneal lateral pediculectomy for the decompression of thoracolumbar fractures and reconstruction using an expandable titanium cage and circumferential fixation at a single stage. Methods Eighteen patients who had single unstable, burst thoracolumbar fracture were treated by this technique between January 2014 and December 2016 (T12: n = 9, L1: n = 7, L2: n = 2). They were reviewed retrospectively in terms of radiologic outcomes (computed tomography [CT] scan and radiograph), clinical outcomes, and complications. The results were compared with another cohort of thoracolumbar fractures treated by posterior-only surgery. Results There were no radiologic complications implying pseudoarthrosis or instrument failure on the postoperative 6-month CT scan. There was also no neurologic deterioration or infection during the same period. Two patients (11.1%) of iatrogenic injury and 1 patient of trauma-related injury of the dura were secured without any delayed complications. Three patients (16.7%) with transient weakness in left hip flexion immediately after operation were observed and recovered within 2 weeks in all cases. Six patients (33.3%) complained of dysesthesia and/or hypoesthesia on the incision site. Conclusions In this study, we suggest lateral pediculectomy as a distinct anatomic landmark to access and remove bony fragments effectively and safely in unstable thoracolumbar burst fractures. This provides a more straightforward access to the burst fragment and helps the surgeon to make better intraoperative decompression strategies. Moreover, this circumferential instrumentation with anterior support and fusion revealed better restoration of the thoracolumbar spine alignment compared with posterior-only surgery, with acceptable complications rates.

BACKGROUND Biochemical alterations associated with mechanical stress have been explored as an initiating step in the pathological progression of ligamentum flavum hypertrophy (LFH); however, this mechanism remains poorly understood. Recently, the inflammation induced after mechanical stress and the subsequent response of ligamentum flavum (LF) cells have been implicated in LFH pathology. OBJECTIVE To investigate the hypothesis that angiogenesis may be a critical link between hypertrophy and a series of stimulating events, including mechanical stress. METHODS LF from 20 lumbar spinal canal stenosis (LSCS) patients and 16 non-LSCS patients (control group) were collected during surgery. Patient demographic and radiographic data were obtained. The levels of angiogenic factors (vascular endothelial growth factor [VEGF], angiopoietin-1, vascular cell adhesion molecule, and basic fibroblast growth factor) in the LF were investigated by using an enzyme-linked immunosorbent assay. Angiogenesis was also quantified by immunohistochemical detection of CD34-positive capillaries. The correlations among clinical factors, including radiographic factors, angiogenic factors, and angiogenesis, were statistically analyzed. RESULTS The LSCS group was older and exhibited a longer symptom duration, wider segmental motion, and thicker LF than the control group. The LSCS group showed significantly higher tissue concentrations of VEGF (P < .001) that positively correlated with LF thickness (r = 0.557, P < .001) and segmental motion (r = 0.586, P < .001). The LSCS group showed significantly more CD34-positive capillaries than the control group (P = .004). CONCLUSION The LSCS group showed greater segmental motion, higher VEGF concentrations, and more CD34-positive capillaries than the control group. These data indicate that VEGF-mediated angiogenesis following mechanical stress may be a critical step within the series of pathological events in LFH.

Background context Neck pain (NP) is a common musculoskeletal disorder, but little is known about the associated risk factors. Purpose We compared anatomic differences in the neck and trunk area of young adult patients with chronic NP and control subjects without NP to identify risk factors and predictors. Study design This is an age-, sex-, and body mass index–matched retrospective case-control study of a consecutive sample. Patient sample Patients with axial NP for longer than 6 months (23 males and 25 females) and pain-free volunteers (23 males and 25 females) were included. Outcome measures Outcome measures were linear and angular dimensions of the cervicothoracic junction. Methods Midsagittal magnetic resonance imaging scans of the cervicothoracic spine were obtained. Four linear and four angular parameters were identified and measured. These parameters included depth of the T1-manubrium arch (T 1A D), depth of the thoracic cage (T X D), tangential height of T1 (T 1 H 1 ), relative height of T1 (T 1 H 2 ), T1 slope (T 1 S), thoracic inlet inclination (T i I), T1-manubrium arch inclination (T 1A I), and the angular difference between T i I and T 1A I (T i I−T 1A I). The measurements were taken by two neurosurgeons. Results Depth of the T1-manubrium arch and T i I were identified as predictors for NP in the binary logistic regression analysis. Each millimeter increase in T 1A D lessened the probability of NP with an adjusted odds ratio (OR) of 0.823 (95% confidence interval [CI], 0.701–0.966) in females and 0.809 (95% CI, 0.681–0.959) in males. Each degree increase in T i I was associated with the probability of NP with an adjusted OR of 1.247 (95% CI, 1.060–1.466) in males. Conclusions Measurement of cervicothoracic junctional structures is a reliable and feasible method of estimating potential predictor of chronic NP in young adults. Forward inclination of the thoracic inlet in males and a shallow thoracic cage in females were identified as important predictors.

Objective : Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro coculture system. We also examined the effect of notochordal cells on annular inflammation. Methods : Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate–stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results : MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased ( p

Anterior foraminotomy (AF) is a surgical treatment for unilateral cervical radiculopathy that avoids fusion-related complications, but its long-term outcome has yet to be investigated. To clarify the efficacy of AF, the author retrospectively collected long-term data regarding the results of this technique.Of 50 patients who underwent AF between November 1999 and June 2005, those who were followed for more than 6 years (n = 44) were enrolled in this study. The parameters studied included the number of revisions, additional surgeries, VAS/NDI, and Odom's criteria. Plain radiographs were also obtained pre- and postoperatively.At discharge, 98% of patients reported improvement, although 20 % temporarily experienced some residual symptoms. There were no other major postoperative complications. At final follow-up (FU, mean of 8.8 years), an excellent or good outcome was achieved in 39 patients (89%). There was no index level reoperation required, but two additional operations for symptomatic adjacent-segment degeneration were needed (4.5%). Six patients suffered from shoulder pain on the same side after surgery (mean onset: 3.6 years). At final FU, significant degeneration at the operated level was demonstrated on plain radiographs, resulting in a decreased range of motion. However, loss of lordosis of the segment was minimal. Radiographically, adjacent segment degeneration was noted in only 6 and 11% at the cranial and caudal segments, respectively.In this retrospective study, patients who underwent AF for one- or two- level cervical radiculopathy showed a good long-term outcome with minimal adjacent segment degeneration. However, more data should be collected to clarify possible associations with these findings, such as delayed shoulder problems and aggravation of degeneration at the operated level.

Background The intervertebral disc (IVD) is an avascular structure, and is therefore stable under hypoxic conditions. Previous studies have demonstrated that hypoxia might be related to symptomatic degenerative disc diseases (DDDs); however, the pathomechanism is still poorly understood. Objective To identify the effect of hypoxia on the production of inflammatory mediators, angiogenic factors, and extracellular matrix-regulating enzymes of IVD cells during inflammatory reactions. Methods Human nucleus pulposus (NP) and annulus fibrosus (AF) cells harvested during surgery for DDDs were cultured in macrophage conditioned media or interleukin (IL)-1β-stimulated media under hypoxic (2%) and normoxic (21%) conditions. Hypoxia-inducible factor-1α transcription factor activation was analyzed by western blotting. IL-6, IL-8, vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloprotease (TIMP)-1, and TIMP-2 in conditioned media were measured by an enzyme-linked immunosorbent assay. Results NP cells expressed higher hypoxia-inducible factor-1α in the IL-1β-stimulated group under hypoxic condition. MMP-1 was significantly increased in the AF cells under hypoxic condition; TIMP-1 and TIMP-2 were significantly decreased in both naive NP and AF cells during hypoxia. Both cells in macrophage conditioned media significantly diminished the production of IL-6 and VCAM, while VEGF significantly increased during hypoxia. After 1 ng/mL IL-1β stimulation, IL-8, VEGF, MMP-1, and MMP-3 were significantly increased in both cell types during hypoxia, while VCAM, TIMP-1, and TIMP-2 were decreased. Conclusion We found that hypoxia can enhance the angiogenic ability of IVD during inflammatory reactions, and cause progress in development of DDD via extracellular matrix regulation in this in vitro study.

OBJECTIVES The Korean Resource Based Relative Value Scale (K-RBRVS) was introduced in 2001 as an alternative of the previous medical fee schedule. Unfortunately, most neurosurgeons are unfamiliar with the details of the K-RBRVS and how it affects the reimbursement rates for the surgical procedures we perform. We summarize the K-RBRVS in brief, and discuss on how the relative value (RV) of the spinal neurosurgical procedures have changed since the introduction in 2001. METHODS We analyzed the change of spinal procedure RVs since 2001, and compared it with the change of values in the brain neurosurgical procedures. RVs of 88 neurospinal procedures on the list of K-RBRVS were analyzed, while 24 procedures added during annual revisions were excluded. RESULTS During the past 15 years, RVs for spinal procedures have increased 62.8%, which is not so different with the cumulative increase of consumer prices during this time period or the increase rate of 92.3% for brain surgeries. When comparing the change of RVs in more complex procedures between spinal and brain neurosurgery, the increase rate was 125.3% and 133%, respectively. CONCLUSION More effort of the society of spinal surgeons seems to be needed to get adequate reimbursement, as there have been some discrimination compared to brain surgeons in the increase of RVs. And considering the relative underestimation of spinal neurosurgeons' labor, more objective measures of neurospinal surgeons' work and productivity should be developed for impartial reimbursement.

STUDY DESIGN We evaluated the influence of rabbit notochordal cells on the expression of inflammatory mediators by human annulus fibrosus (AF) cells cocultured with macrophage-like cells. OBJECTIVE To identify the protective effect of rabbit notochordal cells on AF during in vitro inflammation. SUMMARY OF BACKGROUND DATA Discogenic pain, which is an important cause of intractable lower back pain, is associated with macrophage-mediated inflammation in the AF. Although rabbit notochordal cells prevent intervertebral disc degeneration, their effects on human AF inflammation remain unknown. METHODS Human AF pellets were cocultured for 48 hours with notochordal cell clusters from adult New Zealand White rabbits and phorbol myristate acetate (PMA)-stimulated human macrophage-like THP-1 cells. Conditioned media (CM) from the cocultures were assayed by enzyme-linked immunosorbent assay. The expression of inflammatory mediators in the AF pellets was evaluated by real-time reverse-transcription polymerase chain reaction. RESULTS The levels of mRNA for interleukin (IL)-6, IL-8, and inducible nitric oxide synthase (iNOS) in the AF pellets cocultured with notochordal cells and macrophages (hAF[rNC-M]) were significantly lower than those in the AF pellets cultured with macrophages alone (hAF[M]) (P < 0.05). The levels of IL-6 and IL-8 proteins in the CM of hAF(rNC-M) were significantly lower than those in the CM of hAF(M) (P < 0.05). Coculturing with notochordal cells significantly decreased the levels of mRNA for IL-6, IL-8, and iNOS in the macrophage-exposed AF pellets (P < 0.05). After 1 ng/mL IL-1β stimulation, the levels of IL-6 and IL-8 mRNA and the level of IL-8 protein production were significantly decreased in the AF pellets with notochordal cells compared with naive AF pellets (P < 0.05). CONCLUSION In an in vitro coculture system, rabbit notochordal cells reduced the levels of main inflammatory mediators and gene expression in the human AF during inflammation. Therefore, rabbit notochordal cells may constitute an important protective tool against symptomatic disc development.

We report two cases of cervical spinal epidural abscess (SEA), which are related to anterior cervical surgeries. The first case reveals a late postoperative infection without any predisposing factor. The second case reveals combined complication of infection and instrument failure (artificial disc). Both two cases manifested ascending infections that are unusual courses of anterior cervical infections. The abscess extended upwards and, finally, caused life threatening bacterial meningitis. We suggest aggressive surgical interventions with anti-bacterial therapies in such cases.

Study design In vitro study about angiogenic potentiality of ligamentum flavum (LF) cells using coculture of human lumbar LF cells and activated macropage-like THP-1 cells. Objective To test our hypothesis that activated LF, which was exposed to inflammation, induces angiogenesis, thus resulting in hypertrophy. Summary of background data Inflammatory reactions after mechanical stress produce fibrosis and scarring of the LF that result in hypertrophy, a major pathological feature of spinal stenosis. This study evaluated the roles of LF cells in the pathomechanism of hypertrophy, focusing on angiogenesis. Methods To determine their response to the inflammatory reaction, human LF cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. The conditioned media were assayed for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1. Naive and macrophage-exposed LF cells that responded to TNF-α/IL-1β were compared using the same outcome measures. Hypertrophied LF tissue was stained by TGF-β1 primary antibody using immunohistochemical method. Results Larger quantities of IL-6, IL-8, and VEGF were secreted by cocultured cells than by macrophages alone and LF cells alone combined. Prior macrophage exposure increased the secretion of IL-8 and VEGF in response to TNF-α/IL-1β stimulation whereas IL-6 production was increased in response to IL-1β. The coculture appeared to increase TGF-β1 secretion but the level was lower than that for macrophage-like cells alone and LF cells alone combined. Conclusion LF cells interact with macrophage-like cells to produce angiogenesis-related factors except TGF-β1. Activated LF cells that have been exposed to macrophage, can impact the inducement of angiogenesis-related factors, suggesting that fibrosis and scarring during inflammatory reaction is the major pathomechanism of LF hypertrophy.

A 69-year-old male presented with a rare spinal angiolipoma manifesting as history of back pain, and numbness in both lower limbs, which progressed over a period of 5 years. Total T10-T12 laminectomy was performed and the tumor was removed en bloc. The symptoms gradually improved postoperatively. Spinal angiolipoma is an uncommon benign extradural tumor of spine, which accounts for 0.14-1.2% of all spinal tumors and is a rare cause of spinal cord compression. Recognition of this entity is crucial as a benign and curable cause of paraplegia and back pain.

Intramedullary teratomas, particularly adult cervicothoracic lesions, are extremely rare. Up to now only 6 cases of intramedullary cervical teratomas have been reported in adults, and all of these were histologically mature. The authors present the case of a 35-year-old man with progressive myelopathic symptoms who was admitted through an outpatient clinic and was surgically treated. The characteristics, diagnosis, epidemiology, and treatment of cervical intramedullary teratomas in adults are also reviewed. Postoperative MR imaging showed that the tumor had been near totally removed, and severely adherent tissue remained ventrocranially with tiny focal enhancement on follow-up MR imaging. Pathological examinations revealed immature teratoma without any malignant component. Adjuvant therapy was not performed. Although no change in neurological findings and symptoms was apparent postoperatively, lesion regrowth was demonstrated on MR imaging 4 months after surgery. At 8 months postoperatively, myelopathic symptoms had developed and a huge intramedullary tumor recurred according to MR imaging. This case is the seventh reported instance of intramedullary cervical teratoma in an adult, and the first case report of the immature type with malignant features.

Increased potassium conductance during hypoxia causes membrane hyperpolarization and a resultant increase in extracellular potassium concentration ([K(+)](o)). In addition, glial buffering of [K(+)](o) is the key mechanism for clearing excess K(+) and is important for neuronal function and survival. Here, we studied the effect of glial buffering of [K(+)](o) on neural impulse conduction during hypoxia using a potassium-selective electrode and evoked potential recording in rat hippocampal slices. The increase in [K(+)](o) during hypoxia was modest and there were no significant differences between the layers. The [K(+)](o) during hypoxia was significantly elevated by addition of barium (1 mM), especially in the stratum pyramidale and stratum oriens. Although synaptic transmission was depressed during hypoxia, the presynaptic volley and antidromic population spike mostly remained unchanged. With the addition of barium, antidromic conduction was more profoundly affected than the presynaptic volley. When presynaptic inhibition was precluded by including a selective A1 adenosine receptor blocker to restore synaptic transmission, blockade of the antidromic conduction became more evident compared with the blockade of other recorded field potentials. These findings are compatible with regional differences in the increase of [K(+)](o) and suggest that glial buffering of high [K(+)](o) is important in antidromic conduction during hypoxia.

Background The dumbbell tumor is considered a distinct group of tumors of the spinal nerve sheath owing to its intriguing clinical and radiological characteristics. More than half of dumbbell tumors are completely restricted to the extradural space, although preoperative MRI in some cases suggests the presence of intradural/extradural tumors. The aim of this retrospective investigation is to elucidate the clinical features and to suggest the surgical strategy to reduce the operating time and prevent additional complications in extradural type. Methods The medical records and radiological studies of 7 consecutive cases (4 male, 3 female, mean age 40.4 years) who underwent removal of the intraspinal component of their extradural dumbbell tumors between January 1996 and December 2005 were analyzed. Diagnosis and preoperative evaluation were performed with MRI and myelogram/CTs. Results The relationship of the tumor mass to dural sac in preoperative MRIs was so indistinct as to suggest an intradural mass in 5 cases. We found that extradural portion was covered with an attenuated dura and that the dural ring was invaginated into the intradural portion in these cases. Therefore, the author began with the epidural removal of the intraspinal and extraspinal component, followed by carefully extracting the intradural-like mass. Conclusions In conclusion, we suggest that invagination of the dural ring is the anatomical feature that may be confused with an intradural/extradural tumor during operations for extradural dumbbell tumors. Initial epidural mass removal, extraction of intradural/extradural tumors subsequent to dural opening, and affirmation of presence of intradural tumor remnant could save time during dumbbell tumor surgery.

An 11-year-old girl presented with a very rare traumatic retroclival epidural hematoma manifesting as bilateral abducens nerve palsy, deviation of the uvula to the left, and weakened movement of tongue, which developed after a motor vehicle accident. The patient was treated conservatively and showed good outcome. Retroclival hematoma is a mainly pediatric entity usually associated with ligamentous injury at the craniocervical junction, and can be treated conservatively with good outcome.

A 13-year-old boy presented with a rare spontaneous spinal chronic subdural hematoma (SCSDH) with no associated trauma or medical problems manifesting as back and bilateral lower extremity pain persisting for 10 days. Neurological examination revealed mild weakness and paresthesia in both lower extremities. Magnetic resonance (MR) imaging performed 1 week after the appearance of symptoms revealed a chronic subdural hematoma at the thoracolumbosacral region. Follow-up MR imaging performed 1 week later showed significant resolution of the hematoma without the need for surgery. The patient was discharged with only conservative management. This case of spontaneous SCSDH with rapid spontaneous remission in a child not associated with coagulopathy indicates that aggressive surgical treatment should be delayed as long as possible in pediatric patients because the spinal structure is still developing.

OBJECT To determine the role played by mitogen-activated protein kinase (MAPK) signaling in the interactions between macrophages and intervertebral disc (IVD) cells, it was hypothesized that MAPK inhibition would modulate the production of the proinflammatory cytokines associated with inflammatory reaction in IVD cells. METHODS Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells, with and without SB202190 (a p38-α and -β inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), and PD98059 (an extracellular signal-regulated kinase [ERK] 1/2 inhibitor). The cytokines in conditioned media from cocultured and macrophage-exposed (nemotic) cells were assayed using enzyme-linked immunosorbent assays (ELISAs). RESULTS Interleukin (IL)-6 and IL-8 were secreted in greater quantities by the cocultured cells compared with naive IVD cells and macrophages (MΦ) cultured alone. The tumor necrosis factor (TNF)- α and IL-6 levels produced by the NP cells cocultured with MΦs (NP-MΦ) were significantly lower than those produced by AF cells cocultured with MΦs (AF-MΦ). SB202190 dose-dependently suppressed IL-6 secretion by AF-MΦ and NP-MΦ cocultures, and 10 μM SB202190 significantly decreased IL-6 and IL-8 production in nemotic AF and NP pellets. SP600125 at 10 μM significantly suppressed the production of TNF α IL-6. and IL-8 in AF-MΦ and NP-MΦ cocultures and significantly suppressed IL-1β production in the NP-MΦ coculture. Administration of 10 μM PD98059 significantly decreased IL-6 levels in the AF-MΦ coculture, and decreased the levels of TNF α and IL-8 in both the AF-MΦ and NP-MΦ cocultures. CONCLUSIONS The present study shows that inhibitors of p38 MAPK effectively controlled IL-6 production during inflammatory reactions and that JNK and ERK1/2 inhibitors successfully suppressed the production of major proinflammatory cytokines during interactions between macrophages and IVD cells. Therefore, selective blockade of these signals may serve as a therapeutic approach to symptomatic IVD degeneration.

OBJECTIVE Delayed hinge fracture (HF) that develops after cervical open door laminoplasty can be a source of postoperative complications such as axial pain. However, risk factors related to this complication remain unclear. We performed a retrospective clinical series to determine risk factors for delayed HF following plate-only open-door cervical laminoplasty. METHODS Patients who underwent plate-only open-door laminoplasty and had available postoperative computed tomography (CT) scans (80 patients with 270 laminae) were enrolled. Hinge status, hinge gutter location, open location, hinge width, number of screws used, operation level, and open angle were observed in the CT to determine radiographic outcome. Demographic data were collected as well. Radiographic and clinical parameters were analyzed using univariate and multivariate logistic regression analysis to determine the risk factors for HF. RESULTS Univariate logistic regression analysis results indicated poor initial hinge status, medially placed hinge gutter, double screw fixation on the elevated lamina, upper surgical level, and wide open angle as predictors for HF (p

Adenosine plays the principal role in synaptic depression during various energy-depleted conditions. However, additional inhibitory factors not associated with A1 adenosine receptors appear to be involved in hypoxic insults. Monocarboxylate accumulation and consequent acidic changes during hypoxia may be responsible for this remaining depression in synaptic activity. Field evoked potentials were recorded in the CA1 region of rat hippocampal slices. Preincubation with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) disclosed 43% of DPCPX-resistant synaptic depression (DRSD) during oxygen deprivation (OD). In contrast, no DRSD was detected in various conditions with limited glucose utilization, such as glucose deprivation and oxygen-glucose deprivation. Inhibition of anaerobic glycolysis (iodoacetate, sodium fluoride) abolished DRSD during OD, whereas blockade of monocarboxylate utilization with alpha-cyano-4-hydroxycinnamic acid (4-CIN) provoked DRSD in normoxic medium. These observations suggest that an intracellular accumulation of monocarboxylates is responsible for DRSD during hypoxia.

Transient recovery (TR) of evoked synaptic potential during the late stage of hypoxic hypoglycemia (HH) insult was investigated in rat hippocampal slices using extracellular recording methods. TR was observed in association with a rapid deterioration of antidromic population spikes (aPSs) following HH insult. TR was not elicited in normoglycemic hypoxia (NH), in which a gradual and delayed deterioration of aPSs was noted. TR was not modulated by either Ca(2+)- or PKC-dependent processes. When a glycolytic inhibitor was added, NH resulted in a rapid deterioration of aPSs and prompted appearance of TR. TR was also seen in slices using lactate to generate energy via oxidative phosphorylation, when hypoxic conditions were subsequently created. Other pharmacological interventions that aimed to cause rapid deterioration of aPSs without depleting energy stores failed to reproduce TR. The evidence thus suggests that the underlying mechanisms of TR appearance during HH insult are highly correlated with rapid energy depletion.

Object The authors evaluate the biomechanical properties of vertebral bodies (VBs) stabilized with calcium phosphate (CaP) cements for use in vertebroplasty in comparison with polymethylmethacrylate (PMMA). Methods In the first phase of the study, 73 VBs (T3–L2; thoracic region [T3–8] and thoracolumbar region [T9–L2]) were collected from seven fresh human cadavers. Compression tests were performed before and after vertebroplasty using PMMA (compression strength 80 MPa) and three kinds of CaP cements—CaP1 (5 MPa), CaP2 (20 MPa), and CaP3 (50 MPa). The authors compared the maximal compression loads (MCLs) and stiffness before and after vertebroplasty in each of the four cement groups. In the second phase of the study, 18 paired spinal units (PSUs) were collected from three fresh human cadavers, and the authors injected two types of cement selected from the first phase of the study into the lower level of six PSUs. They compared the MCLs of the untreated and two treated groups (there were six PSUs in each type of group) to analyze the tendency of inducing compression fractures in the upper level of the PSUs. The MCLs of the PMMA-injected vertebrae were significantly increased after vertebroplasty. The MCL levels of the CaP3-injected vertebrae and the CaP2-injected thoracolumbar vertebrae were decreased from those of untreated vertebrae without being significant. The MCLs of CaP1-injected vertebrae and CaP2-injected thoracic vertebrae were significantly decreased after vertebroplasty. The stiffness of all cement groups was decreased after vertebroplasty compared with initial stiffness, significantly so in all three thoracic CaP groups. In the second compression test with PSUs, the MCLs of the CaP2- and CaP3-injected PSUs were not significantly different from those of the untreated control PSUs. Conclusions The CaP3-injected vertebrae restored the MCLs of human vertebrae closer to their initial levels than the PMMA-injected vertebrae did. The CaP2- and CaP3-injected PSUs showed no tendency to induce compression fractures in adjacent VBs.

Object. When performing surgery, the extraforaminal window is very narrow at the L5—S1 level. The authors describe a microsurgical method for decompression of the L-5 nerve root trapped between a marginal osteophyte of the vertebral body and the transverse process. The procedure was performed in 16 patients with extraforaminal stenosis. Methods. The cranial part of the L5—S1 facet joint and the caudal portion of the pedicle and transverse process of L-5 were removed via a midline skin incision and partial resection of the pars interarticularis; a high-speed drill was used as was a surgical microscope. The affected nerve root was decompressed and mobilized cranially. Postoperatively all patients reported excellent relief of their sciatic pain, and there were no technique-associated complications. There was no recurrence during the follow-up period, that ranged from 14 to 70 months. Conclusions. The authors recommend this technique for the effective decompression of symptomatic extraforaminal L5—S1 stenosis. The need for a dangerous and tedious removal of the vertebral osteophyte together with spinal fusion is avoided.