Lumbar fusion surgery in the era of an aging society: analysis of a nationwide population cohort with minimum 8-year follow-up.

BACKGROUND CONTEXT: Fusions for lumbar spine diseases are widely performed and have a growing incidence, especially in elderly population. PURPOSE: The goal of this study was to assess national trends of lumbar spinal fusions and examine the risk for re-operations after a lumbar fusion with a focus on 'epidemiologic transition' relating to age. STUDY DESIGN/SETTING: The prospectively collected Korean Health Insurance Review and Assessment Service (HIRA) nationwide cohort database was retrospectively reviewed. PATIENT SAMPLE: The total 278,815 patients who underwent lumbar spinal fusions for degenerative spine diseases between 2010 and 2018 were reviewed and used to assess trends in operative incidence. The 37,050 patients who underwent lumbar fusions between 1/2010 and 12/2011 were enrolled to determine 8-year reoperation rates. OUTCOME MEASURES: The overall number of lumbar spinal fusions were analyzed for the national annual trend. Demographic data, reoperation rates, and confounding clinical factors were evaluated. METHODS: The overall number of lumbar spinal fusions was analyzed to determine the national annual trend of operative incidence. For the reoperation rate analysis, the primary outcome measured was the cumulative incidence of revision operations within a minimum 8-year follow-up period. Additional outcomes included comparative analyses of the reoperation rate with respect to age, sex, or other underlying comorbidities. RESULTS: Over time, elderly patients comprised a larger portion of the cohort (2010:24.2%; 2018:37.6%), while operations in younger patients decreased over time (2010:40.3%; 2018:27.0%). In the cohort of patients with a minimum 8-year follow-up (n=37,050), rates of reoperation peaked in patients aged 60-69 years (17.6 per 1000 person-years [HR 2.20 compared to <40years]) and decreased for more elderly patients (14.3 per 1000 person-years [HR 1.80 compared to <40years]). Age was the most significant risk factor for reoperation. Osteoporosis was also a risk factor for reoperation in post-menopausal females. CONCLUSIONS: Increasing incidence of lumbar fusions in elderly patients was seen however the risk of reoperation decreased in patients aged 70 or more. Lumbar fusion for elderly patients should not be hesitated in the decision-making process because of concerns about reoperation.

Postoperative survival after lumbar instrumented surgery for metastatic spinal tumors: a nationwide population-based cohort analysis.

BACKGROUND: It is difficult to predict the expected survival after lumbar instrumented surgery for metastases owing to the difference among different cancer origins and the relatively short survival after surgery. AIMS: The aim of this study is to analyze the postoperative survival period of lumbar spinal metastasis patients who underwent lumbar instrumented surgery. METHODS: Data were collected from the Korean National Health Insurance Review and Assessment Service database. Patients who underwent lumbar spinal surgery with instrumentation between January 2011 and December 2015 for metastatic lumbar diseases were reviewed. The mean postoperative survival period of patients with metastatic lumbar cancer according to each primary cancer type was evaluated. RESULTS: A total of 628 patients were enrolled and categorized according to primary cancer type. The overall median survival rate was 1.11±1.30 years. The three most prevalent primary cancer groups were lung, hepatobiliary, and colorectal cancers, presenting relatively short postoperative survival rates (0.93±1.25, 0.74±0.75 and 0.74±0.88 years, respectively). The best postoperative survival period was observed in breast cancer (2.23±1.83 years), while urinary tract cancer showed the shortest postoperative survival period (0.59±0.69 years). CONCLUSION: The postoperative survival period of patients with lumbar metastatic spinal tumors according to different primary cancers after instrumented fusion was ˃1 year overall, with differences according to different primary origins. This result may provide information regarding the expected postoperative survival after instrumented surgery for lumbar spinal metastases.

Radiologic risk factors associated with development of myelopathy in patients with ossification of the posterior longitudinal ligament of the cervical spine.

STUDY DESIGN: Retrospective Cohort Study OBJECTIVE: Myelopathy following ossification of the posterior longitudinal ligament (OPLL) is one of the devastating clinical features in these patients, while we still know little about which factors are associated with development of myelopathy. We evaluated the difference of radiologic measurements between OPLL patients with or without myelopathy and searched for the clinical significance with emphasis on the impact of dynamic motion. METHODS: 305 patients diagnosed of OPLL were enrolled for retrospective review. They were divided into two groups according to the coexistence of radiographic evidence of myelopathy. Demographic data as well as radiologic measures including the presence of disc degeneration (DD), anterior-posterior diameter (APD) of central canal, canal compromise (CC) ratio, global and segmental range of motion (gROM and sROM), OPLL type (morphologic classification) and K-line were collected. RESULTS: APD (odds ratio (OR); 0.411), CC ratio (OR; 1.100) and sROM (OR; 1.371) were significantly associated with the presence of myelopathy in the multivariate analysis. While the statistically significant factors were same in OPLLs with CC larger than 50%, presence of DD (OR; 4.509) and sROM (OR; 1.295) were significantly associated with myelopathy but not the CC itself in OPLLs with CC smaller than 50%. CONCLUSIONS: We discovered that the APD, CC ratio and sROM had significant association with development of myelopathy in OPLLs. And the presence of dynamic factors had significant association with myelopathy in OPLLs with smaller CC ratios. This observation and its clinical significance on development of myelopathy might enhance our understanding of OPLL.

Use of prophylactic perioperative antibiotics for lumbar spinal fusions: A nationwide population-based cohort study.

BACKGROUND: Perioperative prophylactic antibiotic (PPA) use in spine surgery is known to reduce the rate of surgical site infections. In the past decade, several evidence-based guidelines have been published and surveillance systems to monitor the proper use of antimicrobials had been adapted by many institutes. OBJECTIVE: To report the trends of PPA prescription in lumbar fusion surgeries nationwide in the Republic of Korea. METHODS: This is a nationwide registry study. Using the population-based data from the Republic of Korea provided by the Korean Health Insurance Review and Assessment Service, data of all lumbar spinal fusion surgeries performed between 2010 and 2018 in adult patients (age ≥19 years) were reviewed. RESULTS: The most frequently used antibiotics were first-generation cephalosporins, which accounted for 38.2 % of total PPA prescriptions and were prescribed in 58.96 % of lumbar fusion surgeries. A gradual increase in prescription trends was observed. The second most frequently used PPAs were second-generation cephalosporins, which showed decrease in use from 2016. The frequency of vancomycin prescriptions gradually increased over the observation period and showed an almost four-fold increase in 2018 compared to 2010. First- and second-generation cephalosporins were prescribed less frequently to patients with renal disease. CONCLUSION: The pattern of PPA use has changed remarkably over the observation period. Furthermore, specific differences in PPA prescriptions were observed among patients with certain co-morbidities.

Elucidating the effect of mechanical stretch stress on the mechanism of ligamentum flavum hypertrophy: Development of a novel in vitro multi-torsional stretch loading device.

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.

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to the mouse lumbar intervertebral disc.

A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries.

Characteristics of Sagittal Spinopelvic Alignment Changes After Symptom Relief After Simple Lumbar Decompression.

BACKGROUND: 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. OBJECTIVE: To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of global alignment and proportion score in an independent database.

BACKGROUND CONTEXT: Sagittal spinopelvic alignment has been associated with patient-reported outcome measures and mechanical complication rates. Recently, it was claimed that linear numerical values of pelvic tilt and lumbar lordosis measurements may be misleading for patients that have different magnitudes of pelvic incidence. The use of "relative" measurements embedded in a weighted scoring of Global Alignment and Proportion (GAP) was proposed. PURPOSE: The purpose was to evaluate the GAP scorein an independent database. STUDY DESIGN/SETTING: Retrospective Cohort Study PATIENT SAMPLE: Adult spinal deformity patients who underwent ≥7 levels posterior fusion to the pelvis between 2004 and 2014 were included. OUTCOME MEASURES: Mechanical Complication Rates. METHODS: Demographic, clinical, surgical and radiographic patient characteristics were recorded. Cochran-Armitage tests were used to compare mechanical complication rates in GAP categories. Uni and multivariable logistic regression analyses were used to obtain crude and adjusted Odds Ratios, of predictor (GAP categories) and the outcome (mechanical complication), and Risk Ratios were calculated. The diagnostic performance of the GAP score was tested using the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value and accuracy in predicting mechanical complications. RESULTS: A total of 322 patients (285F, 37M) with a mean age of 58.2±9.6 were analyzed. Mean follow-up was 69.7 months (range 24 to 177). Mechanical complications occurred in 52.2% of the patients. Mechanical complication rates in proportioned (GAP-P), moderately (GAP-MD) and severely disproportioned (GAP-SD) patients were 21.8%, 55.1%, and 70.4%, respectively. AUC for the GAP score, at 2 years, was 0.682 (95% CI, 0.624 to 0.741, p<.001). AUC at minimum 5 years follow-up was similar at 0.708, while AUC at minimum 7- and 12-year follow-up were 78.5 and 90.7, respectively. Having a postoperative spinopelvic alignment of GAP-MD and GAP-SD resulted in 2.5 and 3.2 folds of relative risk in incurring a mechanical complication when compared to having a proportioned spinopelvic state, respectively. CONCLUSIONS: This study reports an association between the GAP Score and mechanical complications in an independent database. Increased association was noted as the years of follow-up increased. Aiming to achieve proportionate GAP Score postoperatively seems to be a viable option as lower GAP scores were associated with lower rates of mechanical complications, and vice versa.

Extra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma.

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.

A New Classification for Cervical Ossification of the Posterior Longitudinal Ligament Based on the Coexistence of Segmental Disc Degeneration.

OBJECTIVE: Classification systems for cervical ossification of the posterior longitudinal ligament (OPLL) have traditionally focused on the morphological characteristics of ossification. Although the classification describes many clinical features associated with the shape of the ossification, including the concept of spondylosis seems necessary because of the similarity in age distribution. METHODS: Patients diagnosed with OPLL who presented with increase signal intensity (ISI) on magnetic resonance imaging were surgically treated in our department. The patients were divided into two groups (pure versus degenerative) according to the presence of disc degeneration. RESULTS: Of 141 patients enrolled in this study, more than half (61%) were classified into the degenerative group. The pure group showed a profound male predominance, early presentation of myelopathy, and a different predilection for ISI compared to the degenerative group. The mean canal compromise ratio (CC) of the ISI was 47% in the degenerative group versus 61% in the pure group (p<0.0000). On the contrary, the global and segment motions were significantly larger in the degenerative group (p<0.0000 and p=0.003, respectively). The canal diameters and global angles did not differ between groups. CONCLUSION: Classifying cervical OPLL based on the presence of combined disc degeneration is beneficial for understanding the disorder's behavior. CC appears to be the main factor in the development of myelopathy in the pure group, whereas additional dynamic factors appear to affect its development in the degenerative group.

Thoracolumbar Junction Orientation: A Novel Guide for Sagittal Correction and Proximal Junctional Kyphosis Prediction in Adult Spinal Deformity Patients.

BACKGROUND: Novel radiographic sagittal parameters of the thoracolumbar junction orientation (TLJO, thoracolumbar slope [TLS] and thoracolumbar tilt [TLT]) have been introduced and correlated with lumbopelvic parameters and thoracic kyphosis. OBJECTIVE: To determine a predictive model for reciprocal thoracic kyphosis and proximal junctional kyphosis (PJK) based on the TLJO. METHODS: A total of 127 patients who had fusion from sacrum to T10-L2 from 2004 to 2014 were reviewed. TK (T5-T12), PI, SS, PT, LL, and proximal junctional angle (PJA) were measured preoperatively, 6 wk postoperatively, and at final follow-up. TLJO was measured by TLS and TLT. Changes between time points were determined (preop-6 wk = ΔParameterPre6wk and preop-final follow/up = ΔParameterPreFinal). Scoliosis Research Society (SRS) and Oswestry Disability Index (ODI) questionnaires were evaluated at final follow-up. Patients were divided into 2 groups based on the presence of PJK (ΔPJAPreFinal >15°). Independent t-tests and receiver operating characteristic (ROC) curves were used to investigate the significance of differences and cut-off values. Pearson correlations and linear regressions were used to analyze the entire cohort to determine the relationship between the changes in parameters. RESULTS: Compared to patients without PJK (n = 100), those with PJK (n = 27) had significantly lower SRS scores and significantly greater ΔTKPreFinal, ΔLLPre6wk, and ΔTLSPre6wk. To maintain in the nonPJK group, ROC curves demonstrated a cut-off value of -9.4° for ΔTLSPre6wk. PJK was significantly correlated with ΔTKPreFinal and ΔTLSPre6wk. The linear correlation revealed that ΔTLSPre6wk < -25.3° is the risk factor of PJK > 15°. CONCLUSION: As change of TLS reflects lumbopelvic realignment and influences reciprocal TK, reducing the change of TLS may be a sagittal realignment guideline to reduce the risk of PJK.

Coronavirus Disease (COVID-19) Outbreak and Its Impact on Spinal Daily Practice : Preliminary Report from a Single (Regional) University Hospital in Republic of Korea.

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.

Thoracolumbar junction orientation: its impact on thoracic kyphosis and sagittal alignment in both asymptomatic volunteers and symptomatic patients.

PURPOSE: The thoracolumbar junction (TLJ) has not been explored in regard to its contribution to global sagittal alignment. This study aims to define novel sagittal parameters of the TLJ and to assess their roles within global sagittal alignment. METHODS: Included for cross-sectional, retrospective analysis were asymptomatic volunteers and symptomatic patients who had undergone operation for adult spinal deformity. Unique sagittal parameters of the TLJ were measured using the midline of the T12-L1 disk space: The TLJ orientation [TLJO; thoracolumbar tilt (TLT) and slope (TLS)]. Thoracic kyphosis (TK; T5-12), C7-S1 sagittal vertical axis (SVA), lumbar lordosis (LL; L1-S1), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI) were measured. Continuous variables were compared using the independent t test. Pearson correlations examined relationships between the parameters in each group. The asymptomatic TK was calculated using the measurement of the asymptomatic volunteer's TLJO by linear regression. RESULTS: One hundred fifteen asymptomatic volunteers and 127 symptomatic patients were included. Only LL among the lumbopelvic parameters correlated with TK (asymptomatic volunteers: r = - 0.42; symptomatic patients: r = - 0.40). All the pelvic parameters have no direct correlation with TK in both groups. TLJO had stronger correlation with TK [asymptomatic volunteers: r = - 0.68 (TLS), r = 0.41 (TLT); symptomatic patients: r = - 0.56 (TLS), r = 0.44 (TLT)] than the lumbopelvic parameters. TLS correlated with LL (asymptomatic volunteers: r = 0.78; symptomatic patients: r = 0.73). Most pelvic parameters correlated with TLJO except for PI. The asymptomatic TK was estimated by the derived formula: 20.847 + TLS × (- 1.198). CONCLUSION: The TLJO integrates the status of the lumbopelvic sagittal parameters and simultaneously correlates with thoracic and global sagittal alignment. These slides can be retrieved under Electronic Supplementary Material.

Serum and nutrient deprivation increase autophagic flux in intervertebral disc annulus fibrosus cells: an in vitro experimental study.

PURPOSE: The loss of nutrient supply is a suspected contributor of intervertebral disc degeneration. However, the extent to which low nutrition affects disc annulus fibrosus (AF) cells is unknown as nutrient deprivation has mainly been investigated in disc nucleus pulposus cells. Hence, an experimental study was designed to clarify the effects of limited nutrients on disc AF cell fate, including autophagy, the process by which cells recycle their own damaged components. METHODS: Rabbit disc AF cells were cultured in different media with varying serum concentrations under 5% oxygen. Cellular responses to changes in serum and nutrient concentrations were determined by measuring proliferation and metabolic activity. Autophagic flux in AF cells was longitudinally monitored using imaging cytometry and Western blotting for LC3, HMGB1, and p62/SQSTM1. Apoptosis (TUNEL staining and cleaved caspase-3 immunodetection) and cellular senescence (senescence-associated ß-galactosidase assay and p16/INK4A immunodetection) were measured. RESULTS: Markers of apoptosis and senescence increased, while cell proliferation and metabolic activity decreased under the withdrawal of serum and of nutrients other than oxygen, confirming cellular stress. Time-dependent increases in autophagy markers, including LC3 puncta number per cell, LC3-II expression, and cytoplasmic HMGB1, were observed under conditions of reduced nutrition, while an autophagy substrate, p62/SQSTM1, decreased over time. Collectively, these findings suggest increased autophagic flux in disc AF cells under serum and nutrient deprivation. CONCLUSION: Disc AF cells exhibit distinct responses to serum and nutrient deprivation. Cellular responses include cell death and quiescence in addition to reduced proliferation and metabolic activity, as well as activation of autophagy under conditions of nutritional stress. These slides can be retrieved under Electronic Supplementary Material.

Inflammation by activated macrophage-like THP-1 cells increases human dura mater cell adhesion with alteration of integrin α2 ß1 and matrix metalloproteinase.

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 α2 ß1 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 naïve 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 naïve 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 ß1 and environmental MMP-1, -3 and decreased MMP-9. Selective integrin subtype α2 ß1 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.

Decompression with Lateral Pediculectomy and Circumferential Reconstruction for Unstable Thoracolumbar Burst Fractures: Surgical Techniques and Results in 18 Patients.

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.

Spine-on-a-chip: Human annulus fibrosus degeneration model for simulating the severity of intervertebral disc degeneration.

The aetiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no effective fundamental therapies. Symptomatic IVD is known to be associated with nerve root compression. However, even in the absence of nerve compression, LBP occurs in patients with IVD degeneration. We hypothesize that this phenomenon is associated with a concentration of pro-inflammatory cytokines such as interleukin (IL)-1ß and tumour necrosis factor-alpha (TNF-α), which can lead to altered histologic features and cellular phenotypes observed during IVD degeneration. This study investigated the effects of the concentration of IL-1ß and macrophage derived soluble factor including IL-1ß and TNF-α on the painful response of human annulus fibrosus (AF) cells using a newly developed spine-on-a-chip. Human AF cells were treated with a range of concentrations of IL-1ß and macrophage soluble factors. Our results show that increasing the concentration of inflammatory initiator caused modulated expression of pain-related factors, angiogenesis molecules, and catabolic enzymes. Furthermore, accumulated macrophage derived soluble factors resulted in morphological changes in human AF cells and kinetic alterations such as velocity, dendritic length, cell area, and growth rate, similar to that reported within degenerative IVD. Thus, a better understanding of the relationships between molecular and kinetic alterations can provide fundamental information regarding the pathology of IVD degenerative progression.

The Role of Hypoxia in Angiogenesis and Extracellular Matrix Regulation of Intervertebral Disc Cells During Inflammatory Reactions.

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)-1ß-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-1ß-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 naïve 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-1ß 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.

The Korean Spinal Neurosurgery Society ; Are We Reimbursed Properly for Spinal Neurosurgical Practices under the Korean Resource Based Relative Value Scale Service?

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.

Analysis of Associating Factors With C2-7 Sagittal Vertical Axis After Two-level Anterior Cervical Fusion: Comparison Between Plate Augmentation and Stand-alone Cages.

STUDY DESIGN: A retrospective review. OBJECTIVE: 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). SUMMARY OF BACKGROUND DATA: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: 3.