Role of the miR-133a-5p/FBXO6 axis in the regulation of intervertebral disc degeneration.

OBJECTIVE: Low back pain is a leading cause of disabilities worldwide, and intervertebral disc degeneration (IVDD)-related disorders have been recognised as one of the main contributors. Nevertheless, the underlying mechanism has not yet been fully understood. The aim of this study was to investigate the role of the miR-133a-5p/FBXO6 axis in the regulation of IVDD. METHODS: RT-qPCR, WB and IHC were performed to assess the expression of FBXO6 in human IVD tissues. Nucleus pulposus (NP) cells were treated with IL-1ß to induce IVDD cellular model. Silence of FBXO6 was achieved using specific siRNAs. CCK-8 assay, flow cytometry, TUNEL assay, RT-qPCR and WB were used to evaluate the role and mechanism of FBXO6 in the process of IVDD. Online tools, GSE datasets and RT-qPCR were used to search the candidate miRNAs targeting FBXO6. The direct binding sites between FBXO6 and miR-133a-5p were further verified by a dual luciferase assay. RT-qPCR, WB and rescue experiments were conducted to identify the regulatory function of miR-133a-5p on the expression of aggrecan, collagen Ⅱ, MMP3, ADAMTS5, IL-6 and COX2. In addition, the role of the NF-κB pathway in regulating miR-133a-5p was studied using lentiviral shRNA, WB and RT-qPCR. RESULTS: Results showed that FBXO6 mainly expressed in the NP tissue of IVD and the expression of FBXO6 decreased with the process of IVDD as well as under IL-1ß stimulation. The silence of FBXO6 led to the decreased expression of aggrecan and collagen Ⅱ and the increased expression of MMP3, ADAMTS5, IL-6 and COX2, which further induced the degeneration of NP cells. The bioinformatic analysis showed that miR-133a-5p was the candidate miRNA targeting FBXO6. miR-133a-5p was upregulated in IVDD tissues and significantly inhibited the expression of FBXO6. The inhibition of miR-133a-5p ameliorated the acceleration of IVDD induced by the silence of FBXO6 in vitro. Moreover, it was demonstrated that IL-1ß regulated the expression of the miR-133a-5p/FBXO6 axis via the NF-κB pathway in NP cells. CONCLUSION: miR-133a-5p was upregulated by IL-1ß to aggravate intervertebral disc degeneration via sponging FBXO6. Inhibiting miR-133a-5p expression or rescuing FBXO6 expression may be promising strategies for the treatment of IVDD. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study suggests that the miR-133a-5p/FBXO6 axis could regulate NP cells proliferation, apoptosis, synthesis and degradation of extracellular matrix, which provides a promising therapeutic target and strategy for the treatment of IVDD.

Lateral-anterior lumbar interbody fusion (LaLIF) for lumbar degenerative disease: Technical notes, surgical system, and mid-term outcomes.

BACKGROUND: Many modified lateral lumbar interbody fusion techniques for lumbar degenerative diseases have been described by different authors. However, relatively high rates of vascular injury, peritoneal laceration, and even ureteral injury have been reported. PURPOSE: The objectives of this study were firstly to present the detailed, standardized technical notes and describe the required standard characteristics of the designed surgical system of LaLIF and secondly to evaluate clinical outcomes and highlight the approach-related complications. METHODS: The mini-open LaLIF is described in a step-wise manner. The outcome measures were operative parameters, self-report measures, radiographic measures, and complications within 1 month of surgery. Operative parameters measured included operative time, intraoperative blood loss, and length of hospital stay. The self-report measures include Visual Analogue Scale (VAS), Oswestry disability index (ODI), and Short Form 36 Health Survey (SF-36) score. The radiographic measures including the intervertebral foraminal height (FH), intervertebral disc height (DH), and intervertebral foraminal area (FA) were assessed with plain radiography. The complication profiles were classified into intraoperative and postoperative (up to 1 month). Intraoperative complications were subcategorized into neurologic, vascular, ureteral, peritoneal, and vertebral injuries. Postoperative complications were subcategorized into infection, cage migration, and subsidence. RESULTS: A total of 126 patients who underwent LaLIF between April 2016 and December 2018 â€‹by a senior author were retrospectively reviewed. There were 54 males and 72 females (range 42-89 â€‹years old, average 65 â€‹± â€‹11 years old). The mean follow-up was 20 â€‹± â€‹11 â€‹months (range 6-38 â€‹months). The LaLIF was conducted at 188 levels in 126 patients, with 1 level in 75 cases, 2 levels in 42, 3 levels in 7, and 4 levels in 2 cases. There were 114 patients who underwent stand-alone LaLIF and 12 patients required secondary posterior fixation. The mean operative time, intraoperative blood loss, and length of hospital stay were recorded. The patient-reported outcome scores (VAS, ODI, and SF-36) and radiographic parameters (FH, DH, and FA) demonstrated a significant improvement after surgery and at the last follow-up. There were 25 (19.8%) complications in the 126 patients. The intraoperative complications accounted for 19 cases (15.1%) and postoperative accounted for 6 cases (4.8%). The most frequent complications were neurological injury (6.3%) and temporary psoas injury (6.3%). CONCLUSIONS: The mini-open LaLIF, as a reproducible novel technique, can be performed safely at L2-L5. It is associated with reliable mid-term clinical outcomes and an acceptable complication profile when compared to traditional LLIF due to the advancements in the modified incision site, direct visualization, and usage of strictly vertical trajectory in multiple steps with the specially designed LaLIF system. TRANSLATIONAL POTENTIAL STATEMENT: To make the lateral lumbar fusion process repeatable and also maintain a shallow learning curve, especially for surgeons in the early stages of learning, by using instruments with the required standard characteristics, the standardized surgical steps, modified incision site, vertical trajectory, and the direct visualization during the entire procedure.

Expert consensus for PVCR in severe, rigid and angular spinal deformity treatment: The Kunming consensus.

In the past decades, an increasing number of surgeons started using posterior vertebral column resection (PVCR) to treat severe, rigid and angular spinal deformities. Little high-level evidence is available to guide surgical treatment. The aims of our study were to identify important surgical strategies and key technical points of Chinese experts who have extensive experience in the management of severe, rigid and angular spinal deformities using PVCR, and to standardize and unify the current core concepts. Workgroups of consensus were formed by selecting nationwide representing experts and comprehensive consultations. Eight task forces for major issues were established, then retrieval of literature, collection of expert opinions and writing of review articles were carried out. A modified Delphi process was chosen in round-table forum with three face-to-face meetings. Consensus was reached with items graded more than seven points including: indications and contraindications of PVCR; review PVCR in the evolution of spinal osteotomies; The corrective mechanism and safety of spinal cord; monitoring and responses of spinal cord crisis; characteristics and therapeutic outcome of pulmonary function; management of bleeding during PVCR; relationship of pedicle screw insertion and spinal cord safety; and analysis of non-neurologic complications and prevention strategies. In conclusion, The essential properties regarding PVCR procedure are tightly linked with various factors such as medical and surgical indication, range and level of vertebral column resection, strategies of correction, corrective efficiency and control of neurological risk. PVCR is used mainly for severe, rigid spinal deformity that is not manageable by other osteotomy techniques.

[Correlation of lumbar disc degeneration and spinal-pelvic sagittal balance].

OBJECTIVE: To elucidate the relationship between spino-pelvic sagittal balance parameters and lumbar intervertebral disc degeneration of each segment through retrospective analysis in lumbar degeneration patients. METHODS: Retrospective analysis was conducted for the follow-up data in 126 patients with lumbar degenerative disease from July 2009 to June 2012. There were 38 cases with whole spine plates and 88 cases with lumbar plates. All of them received magnetic resonance imaging (MRI) scans. Through software Image J, the following spino-pelvic sagittal balance parameters were measured: sagittal vertical axis (SVA, distance between C7 plumb line and posterior upper corner of S1 endplate), thoracic kyphosis (TK, T5-T12 Cobb angle), thoracolumbar kyphosis (TLK, T10-L2 Cobb angle), lumbar lordosis (LL, L1-L5 Cobb angle), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), T1 spino-pelvic inclination (T1-SPI), T9 spino-pelvic inclination (T9-SPI), spino-sacral angle (SSA), spino-pelvic angle (SPA) and C7 tilt (C7T). Based on the grading system of Pfirrmann et al, the intervertebral disc degeneration grades were acquired for each lumbar segment. According to the normal range of previous studies, each spino-pelvic sagittal balance parameter was classified into 3 groups, i.e. Group A (less than normal), Group B (normal) and Group C (more than normal). All statistical analyses were performed to compare the differences of each lumbar segment/intervertebral disc degeneration among groups by one-way ANOVA test via SPSS 18.0. And P-value < 0.05 was deemed significant. RESULTS: PI had a significant impact on the L5/S1 disc degeneration. And L5/S1 disc degeneration had a significant impact on sagittal balance. Among 57 cases of large PI, LL, PT, SS, SVA, C7T, SPA in L5/S1 of mild-to-moderate and severe degeneration groups was 36.91 ± 14.93 and 29.71 ± 11.30 (P = 0.045), 18.82 ± 8.27 and 25.18 ± 10.19 (P = 0.012), 39.45 ± 8.82 and 34.57 ± 8.88 (P = 0.042), 23.04 ± 26.63 and 62.15 ± 33.82 (P = 0.002), 88.85 ± 3.13 and 83.98 ± 4.62 (P = 0.003), 157.88 ± 11.20 and 147.75 ± 13.98 (P = 0.043) respectively. TLK in L1/L2 with mild-to-moderate and severe degeneration groups was 4.59 ± 7.81 and 14.91 ± 14.75 (P = 0.026). All of L1/L2, L2/L3 and L3/L4 disc degeneration had a significant impact on SPA. SPA in L1/L2, L2/L3, and L3/L4 with mild-to-moderate and severe degeneration groups was 158.47 ± 11.97 and 147.84 ± 12.72 (P = 0.031), 159.91 ± 10.78 and 148.75 ± 13.17 (P = 0.024), 158.46 ± 10.86 and 148.61 ± 13.93 (P = 0.047) respectively. CONCLUSION: With an important impact on lumbar disc degeneration, PI, either too big or too small, may predispose to the occurrences of lumbar disc degeneration. L5/S1 disc degeneration has a significant impact on pelvis postural parameters (PT, SS). L5/S1 degeneration is a key causative factor of pelvic posterior rotation and compensatory process. L5/S1 disc degeneration has an important impact on pelvis overall parameters (SVA, SPA, C7T). And the degeneration of L5/S1 is a key cause of trunk imbalance.

Expression of interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection.

BACKGROUND/OBJECTIVES: As a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis. MATERIALS AND METHODS: Whole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n = 47), liver cirrhosis (LC, n = 49), primary hepatocellular carcinoma (PHC, n = 44), chronic liver failure (CLF, n = 33), and a normal control group (n = 20). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n = 35), CHB (n = 57), and LC (n = 31) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry. RESULTS: Compared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage. CONCLUSIONS: IL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5306959258322482.

[Correlation of adult spinal sagittal imbalance and life quality].

OBJECTIVE: To evaluate the correlation of spinal sagittal imbalance and life quality. METHODS: Radiographic analysis for 48 consecutive symptomatic patients with spinal sagittal imbalance was performed with posteroanterior and lateral standing radiographs. There were 12 males and 36 females with an average age of (66.2 ± 8.5) yrs. The measurement parameters included C7PL, thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI) and sacral slope (SS). Life quality was assessed with SF-36 questionnaire. Pearman's method was employed to analyze the correlation. RESULTS: Mean C7PL was (44.7 ± 22.5) mm, TK (26.1 ± 13.1)°, TLK (11.9 ± 10.3)°, LL (23.5 ± 18.2)°, PT (32.1 ± 13.4)°, PI (57.4 ± 10.9)° and SS (22.5 ± 11.5)°. C7PL had a significant correlation with physical functioning (r = -0.428, P < 0.01) and general health (r = -0.428, P < 0.01). PI had a significant correlation with bodily pain (r = -0.374, P < 0.01), vitality (r = -0.303, P < 0.01), social functioning (r = -0.309, P < 0.01) and role emotional (r = -0.429, P < 0.05). TK had a significant correlation with physical functioning (r = -0.292, P < 0.05) and general health (r = -0.389, P < 0.01). LL had a significant correlation with physical functioning (r = 0.428, P < 0.01), general health (r = 0.340, P < 0.05) and vitality (r = 0.373, P < 0.01). PT had significant correlation with vitality (r = -0.385, P < 0.01) and social functioning (r = -0.417, P < 0.05). No significant correlation existed between TLK, SS and SF-36 categories. CONCLUSION: C7PL, TK, LL, PI and PT are significant parameters correlating with quality of life. PI is the most important one affecting bodily pain. TK, LL and C7PL are the main parameters affecting general health. PI, PT and LL affect vitality the most. Correcting these parameters while treating sagittal imbalance is important for a better life quality.

Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc.

Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulposus cell density decreased with degeneration process, and increased apoptotic ratio. ER pathway was predominant in mild stage of IVDD (GRP78, GADD153 upregulation and caspase-4 activation), death receptor pathway was predominant in mild and moderate stages (Fas, FasL up-regulation and caspase-8 activation) and mitochondrial pathway was predominant in moderate and severe stages (Bcl-2 down-regulation, Bax up-regulation, cytochrome-c accumulation in cytoplasm and caspase-9 activation). There were significant differences in the expressions of Fas, FasL, Bax, GADD153, cytochrome-c and cleaved caspase-8/9/3 between contained and non-contained discs. In conclusion, apoptosis occurs via these three apoptosis pathways together in IVDD. ER pathway plays a more critical role in the mild compared to moderate and severe stages, death receptor pathway in mild and moderate, and mitochondrial pathway in moderate and severe stages of IVDD. Disc cells apoptosis may progress rapidly after herniation, and may depend on the type of herniation.

[Experimental study of percutaneous vertebroplasty with a novel bone void filling container system].

OBJECTIVE: To investigate vertebral augmentation with a novel reticulate bone filling container system by polymethyl methacrylate (PMMA) injection in cadaveric simulated vertebral compressive fracture and explore the effect of reticulate bone filling container on cement distribution controlling within vertebral body and the restoration of biomechanical properties after augmentation. METHODS: A total of 28 freshly frozen human vertebrae specimens were randomly divided into 4 groups. After the measurements of bone mineral density (BMD) and vertebral height, each vertebra received an axle load by a MTS (material testing system) machine to test the initial strength and stiffness. Subsequently a simultaneous compressive fracture model was created to measure the stiffness and height of fractured vertebrae. Then the augmentation procedure was performed. Afterward the biomechanical properties and the vertebral height were similarly measured as pre-operatively. The expansion of bone filling container and the distribution of cement within vertebral body were morphologically observed by crossing the specimens in sagittal midline and also integrated with the radiographic results. RESULTS: Stiffness was significantly restored comparing with that of fractured level (P < 0.05). And the bipedicular groups had better restoration results than the unipedicular groups. The strength and height of specimens significantly increased after the augmentation procedure but without difference among groups. In axial radiographic view, the distribution of cement in vertebral body was oval or long oval-shaped in double-layer bone filling container groups while it was irregular in single-layer groups. After crossing, the double-layer version expanded well in vertebral body and could enwrap most of injected cement. There was only a little leakage near the vessel layer. But the single-layer version had a poor expansion and a large amount of cement leakage. CONCLUSION: This novel reticulate bone void filling container system with different layers may restore both the biomechanical properties and the height of fractured vertebrae. But, with the benefit of reducing cement leakage, a double-layer design can enwrap most of injected PMMA and has a brighter prospect of clinical application.

Biomechanical effects of insertion location and bone cement augmentation on the anchoring strength of iliac screw.

BACKGROUND: Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation. METHODS: 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed. FINDINGS: The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations. INTERPRETATION: The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw.

Biomechanical effects of the extent of sacrectomy on the stability of lumbo-iliac reconstruction using iliac screw techniques: What level of sacrectomy requires the bilateral dual iliac screw technique?

BACKGROUND: Although both single and dual iliac screw techniques are used in spino-pelvic reconstruction following sacrectomy for treating sacral tumors, the basis for choosing between the two techniques for different instability types remains undetermined. The purpose of this study was to evaluate the effects of the extent of sacrectomy on the stability of the lumbo-iliac fixation construct using single and dual iliac screw techniques. METHODS: Nine human L2-pelvic specimens were tested for their intact condition simulated by L3-L5 pedicle screw fixation. Sequential partial sacrectomies and L3-iliac fixation using bilateral single and dual iliac screws were conducted on the same specimens as follows: under-S1 sacrectomy+single screw, under-½S1 sacrectomy+single screw, one-side sacroiliac joint resection+single screw, total sacrectomy+single screw, and total sacrectomy+dual screw. Biomechanical testing was performed on a material testing machine for evaluating the stiffness of the L3-iliac fixation construct in compression and torsion. FINDINGS: Single iliac screw technique was found to effectively restore the local stability in under-½S1 sacrectomy. However, it could not provide adequate stability for further resection of one-side sacroiliac joint in torsion and total sacrectomy in compression (P<0.05). On the other hand, dual iliac screw technique could restore the stability to the intact condition after total sacrectomy in both compression and torsion. INTERPRETATION: The single iliac screw technique for L3-iliac fixation could effectively restore the local stability for under-½S1 sacrectomy. However, for instabilities of the under-½S1 sacrectomy with one-side sacroiliac joint resection or total sacrectomy, the dual iliac screw technique should be considered.

[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

OBJECTIVE: To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. METHODS: TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. RESULTS: Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. CONCLUSIONS: The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Biomechanical advantages of dual over single iliac screws in lumbo-iliac fixation construct.

The development of iliac screws has provided a markedly easier way for spino-pelvic instrumentation than the classical Galveston technique. However, high rates of iliac screw loosening and breakage are usually reported, especially in cases where bilateral single iliac screws are used. Therefore, there is a need for exploring more stable iliac fixation techniques. Thus, the objective of this study was to compare the biomechanical effects of bilateral single and dual iliac screws on the stability of L3-iliac fixation construct under total sacrectomy condition. In this study, L2-pelvic specimens were harvested from seven fresh human cadavers. After biomechanically testing the intact state simulated by L3-L5 pedicle screw fixation, destabilization was introduced by total sacrectomy. Upon destabilization, L3-iliac screw-rod reconstructions were performed by four different techniques as follows: (1) bilateral single short iliac screws (Single-Short); (2) bilateral single long iliac screws (Single-Long); (3) bilateral dual short iliac screws, placed in the upper and lower iliac columns (Dual-UL); and (4) bilateral dual short iliac screws, all placed in the lower iliac column (Dual-Lower). These four iliac screw fixation techniques were sequentially preformed in the same specimen, and the lengths of the short and long iliac screws were 70 and 130 mm, respectively. Biomechanical testing was performed on a material testing machine under 800 N compression and 7 Nm torsion loading modes to evaluate the construct stiffness. In compression, the stiffness of the L3-iliac fixation constructs of Single-Short, Single-Long, Dual-UL, and Dual-Lower techniques were 73, 76, 98, and 108% of the intact state, respectively. No significant differences were detected between Single-Short and Single-Long (P = 0.589) techniques. However, the compressive stiffness of these two techniques was significantly lower than the intact state, and the Dual-UL and Dual-Lower techniques (P < 0.05). There was no statistical difference between the intact condition and the Dual-Lower technique (P = 0.109). Interestingly, Dual-Lower exhibited notably higher compressive stiffness than Dual-UL (+10.3%, P = 0.049). In torsion, the stiffness of Single-Short, Single-Long, Dual-UL, and Dual-Lower techniques were 72, 79, 105, and 109% of the intact condition, respectively. No significant differences were detected between Single-Short and Single-Long techniques (P = 0.338), and also among Dual-UL, Dual-lower techniques, and the intact state (P > 0.05). However, Single-Short and Single-Long techniques provided markedly lower construct torsional stiffness than the other three groups (P < 0.05). For lumbo-illiac reconstruction after total sacrectomy, even the use of bilateral single, long iliac screws do not help in restoring the local stability to the intact condition. However, dual iliac screws provide much higher construct stability than single iliac screw techniques. Therefore, dual iliac screw technique should be preferred for treating the unstable situation caused by total sacrectomy.

Effect of the degree of osteoporosis on the biomechanical anchoring strength of the sacral pedicle screws: an in vitro comparison between unaugmented bicortical screws and polymethylmethacrylate augmented unicortical screws.

STUDY DESIGN: An in vitro laboratory study. OBJECTIVE: (i) To evaluate the effect of osteoporotic degree in determining the strength of sacral screw fixation and (ii) to compare the strength of unaugmented bicortical pedicle screw and polymethylmethacrylate (PMMA) augmented unicortical pedicle screw in sacral fixation. SUMMARY OF BACKGROUND DATA: Screw loosening is a clinical problem in lumbosacral fusions, especially in osteoporotic patients. To improve the screw anchoring strength of sacrum, bicortical and PMMA augmented sacral pedicle screw fixation techniques are widely used in clinical practice. However, the biomechanical strength of the bicortical and PMMA augmented sacral screw fixations remains undetermined in different degrees of osteoporosis. METHODS: Twenty-five fresh osteoporotic cadavers were used in this study. According to the value of lumbar bone mineral density (BMD) assessed by DEXA, specimens were divided into 3 groups: group A (N=9): BMD=0.7 to 0.8 g/cm, group B (N=8): BMD=0.6 to 0.7 g/cm, and group C (N=8): BMD<0.6 g/cm. In each specimen, S1 pedicle screw was inserted bicortically on the left side, and S1 pedicle screw with PMMA augmentation was inserted unicortically on the right side of the sacrum. Following a dynamic cyclic loading from 30 to 250 N on the screw head for 2000 cycles, the subsidence displacement and axial pull-out strength of each screw were measured. RESULTS: No anchoring failure (defined as the subsidence displacement exceeding 2 mm within 2000 loading cycles) occurred in group A and B. However, in group C, 6 cases (75%) in bicortical fixation and 5 cases (63%) in PMMA augmented fixation failed during cyclic loading. In group A, no significant difference between the bicortical and PMMA augmented fixations was detected in terms of the subsidence and maximal pull-out strength. In group B, significantly less subsidence and higher maximal pull-out strength were demonstrated in the PMMA augmented technique than that in the bicortical fixation. Both techniques exhibited lower subsidence of the screw in group A than in group B. The bicortical technique exhibited higher maximum pull-out strength in group A than that in group B. However, statistical difference in terms of PMMA augmentation was not detected between group A and B. CONCLUSION: For BMD value more than 0.70 g/cm, bicortical sacral pedicle screw fixation could obtain sufficient anchoring strength comparable with the PMMA augmented technique. When BMD value is within 0.6 to 0.7 g/cm, the PMMA augmented technique would be more beneficial in improving the fixation strength than the bicortical fixation. For BMD values less than 0.6 g/cm, early screw loosening may occur in both bicortical and PMMA augmented fixations.

Biomechanical comparison of 4 fixation techniques of sacral pedicle screw in osteoporotic condition.

STUDY DESIGN: An in vitro biomechanical cadaver study. OBJECTIVES: To compare the subsidence displacement after cyclic loading among 4 sacral pedicle screw fixations of bicortical, tricortical, standard polymethylmethacrylate (PMMA) augmentation, and sub-endplate PMMA augmentation in osteoporotic condition. SUMMARY OF BACKGROUND DATA: Implant failure caused by screw loosening is a clinical problem for lumbosacral fusions, especially in osteoporotic patients. To improve sacral screw anchoring strength, the main fixation techniques need to be evaluated biomechanically. METHODS: For this study, 11 fresh osteoporotic cadaver sacra were harvested and bone mineral density was measured with dual-energy radiograph absorptiometry. A 7 mm diameter monoaxial pedicle screw (S1) was randomly assigned by side (left vs. right) and placed bicortically or tricortically. The 2 screws, followed 2000 cyclic compression loading of 30 to 250 N, were removed. The screw tracts were filled up with PMMA, then, screws 5 mm shorter than the bicortical or tricortical fixation were reinserted (defined as standard and sub-endplate PMMA augmented sacral screw fixations, respectively). The PMMA augmented screws were then retested as before. Screw subsidence displacement after 2000 cyclic loading was measured and compared. RESULTS: The average bone mineral density of 11 specimens was 0.71 g/cm, ranged from 0.65 to 0.78 g/cm. No significant difference of subsidence displacement was detected between tricortical and standard PMMA augmented screws (P>0.05), however, the 2 fixations exhibited markedly less subsidence than bicortical screw (P<0.05). Sub-endplate PMMA augmented screw showed the least subsidence among all the screws (P<0.05). CONCLUSIONS: PMMA augmentation can increase the bonding strength of sacral screw-bone interface and the sub-endplate PMMA augmented sacral screw could obtain the highest stability among the 4 fixation techniques in osteoporotic condition.

[Predictive value of three surgical scoring systems for estimation of life expectancy in patients with extradural spinal metastasis].

OBJECTIVE: To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis. METHODS: From February 1996 to January 2009, spinal operations in 104 cases with spinal metastasis were performed in our hospital. There were 65 males and 39 females, with an average of 53.4 years (median 52.5 years). To calculate AUC (area under the curve) values of Receiver Operating Characteristic (ROC) curves of three scores, and to analyze the accuracy of prediction of life expectancy. To compare the actual survival time with the expected survival time of the three scores by Kaplan-Meier method. Spearman correlation analysis was performed between the survival time and three scoring systems. RESULTS: All cases were followed-up with an average duration of 10.9 months, and 77 patients died. AUC analysis of ROC curves showed that the difference of the accuracy of the three scores was not significant. AUC in all groups of Tokuhashi Score was low, with a poor diagnostic accuracy. In the "died within 3 months" and "died within 6 months" groups of revised Tokuhashi score, the accuracy was low, while high in the other two groups. The AUC values of Tomita score in "died within 6 months" and "died within 24 months" were high, with a great diagnostic accuracy while the other two groups were low with a low diagnostic accuracy. Kaplan-Meier survival curve analysis showed that the actual survival time in all three scores was not entirely consistent with the expected survival time. Tokuhashi score and revised score were positively correlated with the survival time while that of Tomita score was negative. CONCLUSION: All the three prognosis scores in patients with spinal metastasis were closely related with survival time. The combination of Tokuhashi score and Tomita score may be applied to better predict postoperative survival prognosis and guide the surgical options for patients with spinal metastasis.

The effect of screw length and bone cement augmentation on the fixation strength of iliac screws: a biomechanical study.

STUDY DESIGN: Comparison of the biomechanical fixation strengths offered by 3 iliac screw fixation techniques: short screw, short screw augmented with cement, and long screw. OBJECTIVE: Evaluate the effect of screw length and bone cement augmentation on the fixation strength of iliac screw upon fatigue loading. SUMMARY OF BACKGROUND DATA: Iliac screws have been used in treating spinal disorders such as spinal deformity, spondylolisthesis, and sacral tumor. In clinical practices, both short screws and long screws are being used. It has been reported that short iliac screws have a higher rate of loosening. Therefore, short iliac screws are being used with bone cement augmentation to improve fixation. To date, no biomechanical study has compared the strengths of these 3 different iliac screw fixation techniques. METHOD: Fresh, frozen human cadaveric pelvis specimens (n = 18, 12 males, 6 females, average age 61 y) were used. Bone density was measured to characterize bone quality. The specimens were randomly divided into 2 groups. In group 1 (n = 8), short screws of 7.0-mm diameter and 70 + or - 4 mm length (as the length of exceeding over ischial notch) and long screw of 7.0-mm diameter and 120 + or - 4 mm length were placed on either side of the pelvis (left and right). In group 2 (n = 10), short iliac screws were placed after augmentation with polymethyl methacrylate bone cement on 1 side of the pelvis and long iliac screw were placed on the other side (left and right). Cyclic loading ranging from 20 to 200 N was applied to each screw at a frequency of 2 Hz up to 5000 cycles. Pullout tests were then conducted at the rate of 5 mm/min after the fatigue test, and the maximum pullout strength for each screw was recorded and analyzed. RESULTS: The maximum pullout strength of the long screw and short screw groups after fatigue conditioning were 2386 + or - 1470 and 833 + or - 681 N respectively. Significant difference was found between the 2 groups (P < 0.05). The short iliac screw had a higher loosening rate. The pullout force of the short screw fixation with augmentation and the long screw fixation after cyclic loading were 2436 + or - 915 and 2529 + or - 1055 N, respectively. No significant difference was found between the 2 groups (P > 0.05). CONCLUSIONS: Short iliac screws are susceptible to loosening after cyclic loading. Bone cement augmentation of short screws has demonstrated a significant increase in the fixation strength of short screws to an extent similar to that of long iliac screws. Thus, short iliac screw fixation after augmentation with bone cement will be a viable clinical option for spino-pelvic reconstruction.

The effects of punctured nucleus pulposus on lumbar radicular pain in rats: a behavioral and immunohistochemical study.

OBJECT: Application of the nucleus pulposus (NP) to the nerve root has been developed as a model of lumbar radicular pain. The relationship between disc degeneration and the induction of radicular pain, however, has not yet been fully explored. The authors of this study investigated pain-related behaviors and expression of tumor necrosis factor-alpha (TNF-alpha) in the dorsal root ganglion (DRG) to evaluate the effects of punctured NP on lumbar radiculopathy. METHODS: An anular needle puncture model of intervertebral disc degeneration in a rat tail was established. Normal and previously punctured NP tissues were obtained and placed on the L-5 nerve root following a hemilaminectomy. Behavioral tests including assessment of motor function, mechanical threshold, and thermal withdrawal latency were performed before and after surgery. The TNF-alpha immunoreactivity in L-5 DRG specimens was examined through immunohistochemical study. RESULTS: The punctured discs showed significant degeneration 2 weeks after intervention. Application of both normal and punctured NP induced mechanical hyperalgesia in the ipsilateral paw for 10 days after surgery, but hyperalgesia was more severe in the punctured NP group. No statistically significant within-group changes in thermal withdrawal latency over time were found. A significant increase in the expression of TNF-alpha-positive neurons in DRG specimens was observed in both NP graft groups. CONCLUSIONS: Needle puncture led to degenerative changes in the rat tail disc, and the degenerated NP enhanced mechanical hyperalgesia induced by application of the NP to the lumbar nerve root. This model of disc degeneration and lumbar radicular pain is appropriate for evaluating the efficacy of biological treatments for degenerative disc diseases.

Effect of iliac screw insertion depth on the stability and strength of lumbo-iliac fixation constructs: an anatomical and biomechanical study.

STUDY DESIGN: Comparison of feasibility and safety of the placement of short and long iliac screws by anatomic and biomechanical evaluations as they apply to lumbo-iliac fixation construct. OBJECTIVE: To compare the stability of the short and long iliac screw fixations for lumbo-iliac reconstruction by anatomic and biomechanical evaluations. SUMMARY OF BACKGROUND DATA: Spinopelvic reconstruction remains a challenge to spine surgeons. Despite the advent of many fixation methods, the use of iliac screws seems most favorable so far. Various lengths of iliac screws are applied in surgical treatments; however, no biomechanical comparison has been reported based on the screw length. METHODS: For anatomic observation, CT scan data of 60 Chinese adults were used to measure the details of the iliac spine structures. For biomechanical evaluation, 7 adult human cadavers (L3-pelvis) were observed. L4-S1 pedicle screw fixation was performed with posterior spinal fixation system. On the basis of the lengths of iliac screws, 2 groups were tested (short screw group using 70 mm screws and long screw group using 138 mm screws). In this study, short and long iliac screws were placed in the same specimen. Biomechanical testing was performed on a material testing machine under 800 N compression and 7 Nm torsion loading modes for stiffness evaluations. Finally, pullout testing was performed for all the iliac screws to measure the maximum pullout force. RESULTS: The length of the line between posterior superior iliac spine and anterior inferior iliac spine was 140.6 +/- 1.1 mm, and the distance between this line and the greater sciatic notch was 18.3 +/- 0.8 mm. The length of the line between posterior superior iliac spine and the second narrowest point was 67.1 +/- 0.62 mm in men and 70.1 +/- 1.4 mm in women. Insertion lengths of the short and long iliac screws were 70 +/- 2 mm and 138 +/- 4 mm, respectively. The lumbo-pelvic reconstruction using short and long iliac screws restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing respectively. In torsion testing, the use of short and long iliac screws harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial stiffness, respectively. No significant difference was detected between the 2 reconstructions in terms of compressive and torsional stiffness (P > 0.05). However, the maximum pullout strength of long iliac screw group was significantly higher than the short screw group (P < 0.05). CONCLUSION: The local stability is rather difficult to be restored to the original levels regardless the length of iliac screws. Obviously, long iliac screws resisted significantly greater axial pullout force. However, under physiologic, torsional, and compressive loading conditions, the mechanical stability of lumbo-pelvic fixation construct with short iliac screws was comparable with that of the long ones. Therefore, the use of short iliac screws, which are only about half the length of the long iliac screws, could reduce the implantation risk without significantly compromising on the stability of the construct.

[Experimental study on spinal fusion induced by hBMP-4 gene modified tissue engineered bone].

OBJECTIVE: To evaluate the efficacy of hBMP-4 gene modified tissue engineered bone graft in the enhancement of rabbit spinal fusion and find an ideal kind of substitute for the autograft bone. METHODS: Rabbit BMSCs were cultured and transfected with AAV-hBMP-4 using different MOI value. The optimal MOI value were determined by observing cell's morphology change. BMSCs were then transfected with AAV-hBMP4 and AAV-EGFP respectively, following which the transfected cells were evenly suspended in a collagen sponge I, and implanted to either side of the L5,6 intertransverse spaces posterolateral in the New Zealand rabbits to induce spinal fusion. Fourteen rabbits were randomly divided into 2 groups. Group 1: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and autograft bone in the left side. Group 2: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and AAV-EGFP transfected BMSCs in the left side (EGFP side). Radiographs and three-dimensional CT of the spine, manual palpation, gross and histological examination of the fusion masses for all the animals were performed subsequent to animals having been sacrificed at 12 weeks after surgery. RESULTS: Evaluation has been taken in 12 New Zealand rabbits delivered into 2 groups which meet the criterion after operation. Eleven in 12 implemented sides involved hBMP-4 achieved bony fusion, to which 5 in 6 autografted sides was similar. But only 2 in 6 sides in EGFP-group achieved bony fusion meanwhile. Three-dimensional CT scan and palpation also evidenced the results. Bone formation was observed obviously on specimen both in hBMP4 sides and autografted ones. EGFP-group also got bony integration, but the quantity was small. CONCLUSION: Tissue-engineered bone graft constructed from application of hBMP4 is a fine substitute for autograft. Effective enhancement of bony integration in spinal fusion surgery has been evidenced in vivo.