Evaluating the Efficacy and Safety of Hemofence (Thorombin Cross-linked Sodium Hyaluronate Gel Matrix) in Hemostasis for Intractable Exudative Bleeding in Spinal Surgery: A Multicenter, Randomized, Phase III Clinical Trial.

Objective: To demonstrate the non-inferiority of the novel hemostatic agent, Hemofence® (BMI Korea Co. Ltd., Jeju Korea, thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. Methods: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For non-inferiority test, a 97.5% one-sided confidence interval was used; the test group was deemed non-inferior if the lower limit exceeded -10%. Results: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% confidence interval (-4.90%, 7.44%) confirmed the test drug's non-inferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.0000, p=0.2427, and p=0.9663, respectively). Conclusion: A novel hemostatic agent, Hemofence®, demonstrated an efficacy and safety profile comparable to that of Floseal.

Current Concepts in the Treatment of Traumatic C2 Vertebral Fracture : A Literature Review.

The integrity of the high cervical spine, the transition zone from the brainstem to the spinal cord, is crucial for survival and daily life. The region protects the enclosed neurovascular structure and allows a substantial portion of the head motion. Injuries of the high cervical spine are frequent, and the fractures of the C2 vertebra account for approximately 17-25% of acute cervical fractures. We review the two major types of C2 vertebral fractures, odontoid fracture and Hangman's fracture. For both types of fractures, favorable outcomes could be obtained if the delicately selected conservative treatment is performed. In odontoid fractures, as the most common fracture on the C2 vertebrae, anterior screw fixation is considered first for type II fractures, and C1-2 fusion is suggested when nonunion is a concern or occurs. Hangman's fractures are the second most common fracture. Many stable extension type I and II fractures can be treated with external immobilization, whereas the predominant flexion type IIA and III fractures require surgical stabilization. No result proves that either anterior or posterior surgery is superior, and the surgeon should decide on the surgical method after careful consideration according to each clinical situation. This review will briefly describe the basic principles and current treatment concepts of C2 fractures.

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.

True Continuous Segment of Ossification of Posterior Longitudinal Ligament is Protective Against Postoperative Early Kyphosis Progression After Laminoplasty.

BACKGROUND AND OBJECTIVES: Ossification of the posterior longitudinal ligament (OPLL) is a potentially catastrophic disease. Laminoplasty (LP) is a common surgical intervention, but postoperative kyphosis progression is a major complication, for which various risk factors have been identified and used in surgical decision-making. Our focus is on the ability of OPLL with specific morphological traits, designated as the true continuous segment (TCS), to stabilize alignment and prevent postoperative kyphosis after LP. METHODS: This retrospective case-control study included patients who underwent cervical LP for OPLL treatment with a minimum 1-year follow-up. Demographic, operative, and radiographic parameters were analyzed. TCS is defined as a continuous segment of OPLL that spans the disk space more than half of the adjacent vertebral body height without crack, or OPLL segment attached to both upper and lower adjacent vertebral bodies by bridging, or obvious interbody autofusion, and is identified from preoperative computed tomography. A subgroup analysis for preoperatively lordotic patients, divided into 2 groups based on cervical alignment at the final follow-up, was conducted to identify risk factors for kyphosis progression. Difference analysis, linear regression analysis for loss of lordosis (LoL), and logistic regression analysis for kyphosis progression were used. RESULTS: A total of 84 patients were identified. Among them, 78 patients with preoperatively lordotic alignment were divided into 2 groups: those who maintained lordotic alignment (n = 60) and those who progressed to kyphosis (n = 18). Regression analyses revealed a significant protective effect of TCS count against LoL and postoperative kyphosis, with a TCS count of 3 or more conclusively preventing kyphosis (sensitivity 1.000, specificity 0.283, area under the curve 0.629). CONCLUSION: For patients with OPLL, TCS was shown to protect against the LoL after LP. Therefore, TCS should be identified and considered when planning surgical treatment for OPLL.

Radiological evaluation of atlantoaxial fusion using C2 translaminar screws and C2 pedicle screws: Does the screw halo sign imply fusion failure?

The purpose of this study was to identify the criteria for atlantoaxial (AA) fusion by comparing follow-up lateral radiographs and computed tomography (CT) images. We retrospectively analyzed data from 161 consecutive patients undergoing AA fusion. Patients with a minimum of 1 year of CT follow-up after AA fusion surgery using C2 pedicle screws or translaminar screws (C2TLS) were included. Patients were followed up radiographically at 3, 6, and 12 months after surgery, and dynamic lateral radiographs were also evaluated. A total of 49 patients were analyzed, with a mean CT image follow-up of 41.6 ±â€…37.6 months. Thirty eight patients had C2 pedicle screw placement, and 11 patients underwent planned C2TLS. AA fusion with bridging bone mass formation was achieved in 45/49 (91.8%) patients. Screw halos were observed in 14/49 (28.6%) patients. Among them, final fusion failure occurred in 2 (14.3%) patients. The last follow-up CT showed no difference in the fusion failure rate according to the presence or absence of a screw halo (no halo, 5.7%; halo, 14.3%; P = .33). The differences in C1-2 segmental angles (SA) in flexion-extension dynamic lateral radiographs were 1.99 ±â€…1.62° in the fusion group and 4.37 ±â€…2.13° in the non-fusion group (P = .01). The likelihood of fusion failure increased when the SA gap was greater than 2.62° (P = .05). C2TLS placement had a significantly higher incidence of screw halos. However, the halo sign was not significantly related to final bone fusion. Bone fusion could be predicted when the SA gap of C1-2 was less than 2.62° on the dynamic radiograph.

Ligamentum flavum hypertrophy significantly contributes to the severity of neurogenic intermittent claudication in patients with lumbar spinal canal stenosis.

Ligamentum flavum hypertrophy (LFH) is a known contributor to lumbar spinal canal stenosis (LSCS). However, the clinical significance and quantitative role of LFH compared to other components, such as disc bulging and facet hypertrophy, have not yet been examined. We investigated the correlation between the quantitative radiological factors, clinical symptoms, and outcomes in patients with LSCS. In total, 163 patients diagnosed with single-level (L4-L5) stenosis were included. The patients were divided into 2 groups according to claudication severity: >100 m for mild (n = 92) and < 100 m for severe (n = 71). The visual analog scale (VAS) was used to quantify back and leg pain, and the Oswestry Disability Index (ODI) and Short form-36 (SF-36) physical component summary (PCS) scores, and Macnab criteria were evaluated as clinical factors 6 months after treatment. We measured the baseline canal cross-sectional area, ligamentum flavum (LF) area, disc herniation area, dural sac area, fat area, and LF thickness using MRI. A comparative analysis was performed to evaluate the association between radiologic and clinical factors. Additionally, further comparative analyses between the types of surgeries were performed. Among various radiologic factors, the baseline LF thickness (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.25-2.41) was the only major contributing factor to the severity of claudication in the multivariate logistic regression analysis. The types of surgery (decompression alone vs fusion) did not significantly differ in terms of their clinical outcomes, including back and leg VAS, ODI, SF-36 PCS, and satisfaction with the MacNab classification. LF thickness is a major factor contributing to claudication severity.

CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease In Vivo.

Mutations in specific genes, including synuclein alpha (SNCA) that encodes the α-synuclein protein, are known to be risk factors for sporadic Parkinson's disease (PD), as well as critical factors for familial PD. In particular, A53T-mutated SNCA (A53T-SNCA) is a well-studied familial pathologic mutation in PD. However, techniques for deletion of the mutated SNCA gene in vivo have not been developed. Here, we used the CRISPR-Cas9 system to delete A53T-SNCA in vitro as well as in vivo. Adeno-associated virus carrying SaCas9-KKH with a single-guide RNA targeting A53T-SNCA significantly reduced A53T-SNCA expression levels in vitro. Furthermore, we tested its therapeutic potential in vivo in a viral A53T-SNCA-overexpressing rat model of PD. Gene deletion of A53T-SNCA significantly rescued the overexpression of α-synuclein, reactive microgliosis, dopaminergic neurodegeneration, and parkinsonian motor symptoms. Our findings propose CRISPR-Cas9 system as a potential prevention strategy for A53T-SNCA-specific PD.

Label-Free Quantitative Proteome Profiling of Cerebrospinal Fluid from a Rat Stroke Model with Stem Cell Therapy.

Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.

Kinematics after cervical laminoplasty: risk factors for cervical kyphotic deformity after laminoplasty.

BACKGROUND CONTEXT: Laminoplasty of the cervical spine is widely used as an effective surgical method to treat compressive myelopathy of the cervical spine; however, there is an adverse effect of kyphosis after surgery. The risk factors or predictors of kyphosis have not been sufficiently evaluated. PURPOSE: To assess the risk factors for kyphosis following laminoplasty. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Patients diagnosed with cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL) who underwent laminoplasty between May 2011 and October 2018 were enrolled. OUTCOME MEASURES: Changes in lordosis and range of motion (ROM). METHODS: Radiological imaging data were collected from simple neutral and flexion-extension radiographs at baseline and at 2-year follow-up. The ROM from the neutral position to complete flexion was defined as the flexion capacity, and the ROM from the neutral position to complete extension was defined as the extension capacity. RESULTS: This study included 53 patients (mean age, 59.3 years). Multivariate linear regression analysis revealed that, the smaller the preoperative extension capacity, the greater was the decrease in lordosis (p=.025), while the larger the T1 slope, the greater was the decrease in lordosis following laminoplasty (p= .008). Correlation analysis revealed that C2-7 lordosis increased with increasing baseline T1 slope before surgery (p< .01). In patients with large preoperative C2-7 lordosis, the postoperative decrease in ROM tended to be greater (p= .028). However, the degree of lordosis and ROM reduction did not demonstrate a clear correlation with the clinical outcomes at 2 years after surgery. CONCLUSIONS: Kyphotic changes in the cervical spine following laminoplasty were related to preoperative radiological parameters. The greater the preoperative extension capacity, the lower was the decrease in lordosis, and the greater the T1 slope, the greater was the decrease in lordosis.

Multidisciplinary team training reduces the error rate of DXA image.

Establishing the hospital's own standard operating procedures (SOPs) and team training including physicians and technologists reduces the error rate of dual-energy X-ray absorptiometry (DXA) measurement. In addition, when monitoring DXA images, it is necessary to check whether region of interest (ROI) and bone mapping are properly set as well as patient positioning. INTRODUCTION: Physicians often experience poor quality DXA images, which affects osteoporosis treatment. The purpose of this study is to analyze the change in the error rate of DXA images after a multidisciplinary team training including physicians and technologists. METHODS: Experienced physicians and DXA technologists formed a training team to establish SOPs for DXA measurement. The training team instructed the other related hospital personnel for a month. We set the criteria of measurement errors (9 items for the lumbar spine image and 8 items for the proximal femur image). With these criteria, a total of 637 images (320 images before training and 317 images after training) were analyzed to check the frequency and distribution of errors before and after training. RESULTS: The most common error when measuring the lumbar spine image before training was inadequate bone mapping (51.9%), and when measuring the proximal femur image was the incorrect area of the ROI of the femoral neck (37.2%). The most improved error after training was inadequate bone mapping (33.3% improvement) in the lumbar spine image and inadequate internal rotation (13.6% improvement) in the proximal femur image. Errors were significantly reduced by 23.2% in the lumbar spine, 9.0% in the proximal femur, and 9.2% in both the regions. CONCLUSIONS: Establishing SOPs and multidisciplinary team training effectively reduced the error rate of DXA images.

CCN5 Reduces Ligamentum Flavum Hypertrophy by Modulating the TGF-ß Pathway.

Ligamentum flavum hypertrophy (LFH) is the most important component of lumbar spinal canal stenosis. Although the pathophysiology of LFH has been extensively studied, no method has been proposed to prevent or treat it. Since the transforming growth factor-ß (TGF-ß) pathway is known to be critical in LFH pathology, we investigated whether LFH could be prevented by blocking or modulating the TGF-ß mechanism. Human LF cells were used for the experiments. First, we created TGF-ß receptor 1 (TGFBR1) knock out (KO) cells with CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 biotechnology and treated them with TGF-ß1 to determine the effects of blocking the TGF-ß pathway. Subsequently, we studied the effect of CCN5, which has recently been proposed to modulate the TGF-ß pathway. To assess the predisposition toward fibrosis, α-smooth muscle actin (αSMA), fibronectin, collagen-1, collagen-3, and CCN2 were evaluated with quantitative real-time polymerase chain reaction, western blotting, and immunocytochemistry. The TGFBR1 KO LF cells were successfully constructed with high KO efficiency. In wild-type (WT) cells, treatment with TGF-ß1 resulted in the overexpression of the messenger RNA (mRNA) of fibrosis-related factors. However, in KO cells, the responses to TGF-ß1 stimulation were significantly lower. In addition, CCN5 and TGF-ß1 co-treatment caused a notable reduction in mRNA expression levels compared with TGF-ß1 stimulation only. The αSMA protein expression increased with TGF-ß1 but decreased with CCN5 treatment. TGF-ß1 induced LF cell transdifferentiation from fibroblasts to myofibroblasts. However, this cell transition dramatically decreased in the presence of CCN5. In conclusion, CCN5 could prevent LFH by modulating the TGF-ß pathway. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2634-2644, 2019.

Evolution of CRISPR towards accurate and efficient mammal genome engineering.

The evolution of genome editing technology based on CRISPR (clustered regularly interspaced short palindromic repeats) system has led to a paradigm shift in biological research. CRISPR/Cas9-guide RNA complexes enable rapid and efficient genome editing in mammalian cells. This system induces double-stranded DNA breaks (DSBs) at target sites and most DNA breakages induce mutations as small insertions or deletions (indels) by non-homologous end joining (NHEJ) repair pathway. However, for more precise correction as knock-in or replacement of DNA base pairs, using the homology-directed repair (HDR) pathway is essential. Until now, many trials have greatly enhanced knock-in or substitution efficiency by increasing HDR efficiency, or newly developed methods such as Base Editors (BEs). However, accuracy remains unsatisfactory. In this review, we summarize studies to overcome the limitations of HDR using the CRISPR system and discuss future direction. [BMB Reports 2019; 52(8): 475-481].

Recent trends in CRISPR-Cas system: genome, epigenome, and transcriptome editing and CRISPR delivery systems.

BACKGROUND: The CRISPR-Cas systems have emerged as a robust genome editing tool useful in various fields of research. With the discovery and development of the orthologous CRISPR-Cas systems, their genome editing efficiency have improved. OBJECTIVE: In this review, we aim to present the recent developments and applications of the CRISPR-Cas systems. METHODS: First, we introduce how the advancements of CRISPR technology enabled genome editing to single base precision. Then, we discuss the CRISPR based methods for targeted transcriptional regulation, epigenome editing, and RNA editing. Finally, we review the CRISPR delivery systems highlighting recent attempts to integrate nanotechnology to develop novel CRISPR delivery modalities. CONCLUSION: Here, we review the recent trends in CRISPR-based biotechnologies, encompassing genome editing, epigenome regulation and direct RNA targeting and provide an overview of methods employed for CRISPR delivery with an emphasis on the most recent nanotechnology-based delivery strategies. We anticipate that the development of CRISPR based technology will continue to explore novel methods.

Extraocular Pressure Measurements to Avoid Orbital Compartment Syndrome in Aneurysm Surgery.

BACKGROUND: Orbital compartment syndrome (OCS) is a rare but devastating complication following pterional craniotomy. Although the causes of OCS are unclear, external compression of the orbit by a myocutaneous flap is commonly mentioned as a major factor. We evaluated the ocular influence of external compression using an extraocular pressure monitor. METHODS: We measured extraocular pressure in 86 patients who underwent surgery for cerebral aneurysm via a pterional approach. Clinical information and radiologic parameters, including the area of the medial rectus muscle (MRM) and the craniotomy height from the bottom of the anterior skull base, were collected. As a control group, 117 patients who underwent surgery without pressure monitoring were also evaluated. RESULTS: Extraocular pressure reached a maximum during craniotomy (mean, 22.0 mm Hg; range, 18.4-51.0 mm Hg) and decreased after myocutaneous flap adjustment (mean, 7.9 mm Hg; range, 5.4-17.5 mm Hg). Pressure before myocutaneous flap manipulation differed between patients with anterior communicating artery (Acomm) aneurysms and other patients (mean, 16.5 mm Hg vs. 9.4 mm Hg; P = 0.003). Among Acomm aneurysm cases, the monitored group showed a significantly lower MRM swelling ratio (postoperative MRM area/preoperative MRM area) compared with the control group (1.03 ± 0.10 vs. 1.17 ± 0.15; P = 0.036). CONCLUSIONS: Myocutaneous flaps can produce unnoticed overpressure on the orbit, resulting in OCS-related blindness during aneurysm clipping surgery, especially in cases involving mandatory lower craniotomy. The continuous extraocular compressive pressure monitoring technique is a simple and effective approach to prevent such a serious complication.

Myofibroblast in the ligamentum flavum hypertrophic activity.

PURPOSE: Majority of the previous studies compared lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) patients for analyses of LFH. However, the separation of normal/hypertrophied LF has often been ambiguous and the severity of hypertrophic activity differed. Here, we present a novel analysis scheme for LFH in which myofibroblast is proposed as a major etiological factor for LFH study. METHODS: Seventy-one LF patient tissue samples were used for this study. Initially, mRNA levels of the samples were assessed by qRT-PCR: angiopoietin-like protein-2 (ANGPTL2), transforming growth factor-beta1 (TGF-ß1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using α-smooth muscle actin (αSMA) as a marker. To study the myofibroblast in TGF-ß pathway, LF tissues were analyzed for protein levels of αSMA/TGF-ß1 by Western blot. In addition, from LF cells cultured with exogenous TGF-ß1 conditioned medium, expression of αSMA/collagen-1 was assessed and the cell morphology was identified. RESULTS: The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-ß1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-ß1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by αSMA staining, and the protein levels of αSMA were positively correlated with TGF-ß1. In LF cell culture, exogenous TGF-ß1 upregulated αSMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. CONCLUSIONS: We conclude that the transition of fibroblast to myofibroblasts via TGF-ß pathway is a key linker between inflammation and fibrosis in LFH mechanism.

Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PURPOSE: Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. METHODS: A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. RESULTS: Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. CONCLUSIONS: Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

Surgery versus Nerve Blocks for Lumbar Disc Herniation : Quantitative Analysis of Radiological Factors as a Predictor for Successful Outcomes.

OBJECTIVE: To assess the clinical and radiological factors as predictors for successful outcomes in lumbar disc herniation (LDH) treatment. METHODS: Two groups of patients with single level LDH (L4-5) requiring treatment were retrospectively studied. The surgery group (SG) included 34 patients, and 30 patients who initially refused the surgery were included in the nerve blocks group (NG). A visual analogue scale (VAS) for leg and back pain and motor deficit were initially evaluated before procedures, and repeated at 1, 6, and 12 months. Radiological factors including the disc herniation length, disc herniation area, canal length-occupying ratio, and canal area-occupying ratio were measured and compared. Predicting factors of successful outcomes were determined with multivariate logistic regression analysis after the optimal cut off values were established with a receiver operating characteristic curve. RESULTS: There was no significant demographic difference between two groups. A multivariate logistic regression analysis with radiological and clinical (12 months follow-up) data revealed that the high disc herniation length with cutoff value 6.31 mm [odds ratio (OR) 2.35; confidence interval (CI) 1.21-3.98] was a predictor of successful outcomes of leg pain relief in the SG. The low disc herniation length with cutoff value 6.23 mm (OR 0.05; CI 0.003-0.89) and high baseline VAS leg (OR 12.63; CI 1.64-97.45) were identified as predictors of successful outcomes of leg pain relief in the NG. CONCLUSION: The patients with the disc herniation length larger than 6.31 mm showed successful outcomes with surgery whereas the patients with the disc herniation length less than 6.23 mm showed successful outcomes with nerve block. These results could be considered as a radiological criteria in choosing optimal treatment options for LDH.

Risk Factors for Delayed Hinge Fracture after Plate-Augmented Cervical Open-Door Laminoplasty.

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<0.05). Initial hinge status seemed to be the most powerful risk factor for HF (p=0.000) and thus was collinear with other variables. Therefore, multivariate logistic regression analysis was performed excluding initial hinge status, and the results indicated that medially placed hinge gutter, double screw fixation on the elevated lamina, and upper surgical level were risk factors for HF after adjustment for other confounding factors. CONCLUSION: To prevent HF and to draw a successful postoperative outcome after cervical laminoplasty, surgical and clinical precautions should be considered.

Expression of matrix metalloproteinase-2 and -9 in human ligamentum flavum cells treated with tumor necrosis factor-α and interleukin-1ß.

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-1ß (IL-1ß). 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-1ß, 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-1ß-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-1ß promote proMMP-2 and proMMP-9 secretion. IL-1ß 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.