Circular RNA hsa_circ_0083756 promotes intervertebral disc degeneration by sponging miR-558 and regulating TREM1 expression.

OBJECTIVES: Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. Circular RNAs (circRNAs) have been demonstrated to exert vital functions in IVDD. However, the role and mechanism of hsa_circ_0083756 in the development of IVDD remain unclear. MATERIALS AND METHODS: RT-qPCR was performed to detect expressions of hsa_circ_0083756, miR-558 and TREM1 in nucleus pulposus (NP) tissues and cells. CCK8 assay, flow cytometry, TUNEL assay, RT-qPCR and WB were used to clarify the roles of hsa_circ_0083756 in NP cells proliferation and extracellular matrix (ECM) formation. Bioinformatics analyses, dual-luciferase reporter gene experiment, RNA immunoprecipitation (RIP) assay and FISH assay were performed to predict and verify the targeting relationship between hsa_circ_0083756 and miR-558, as well as that between miR-558 and TREM1. Ultimately, the effect of hsa_circ_0083756 on IVDD was tested through anterior disc-puncture IVDD animal model in rats. RESULTS: hsa_circ_0083756 was upregulated in degenerative NP tissues and cells. In vitro loss-of-function and gain-of-function studies suggested that hsa_circ_0083756 knockdown promoted, whereas hsa_circ_0083756 overexpression inhibited NP cells proliferation and ECM formation. Mechanistically, hsa_circ_0083756 acted as a sponge of miR-558 and subsequently promoted the expression of TREM1. Furthermore, in vivo study indicated that silencing of hsa_circ_0083756 could alleviate IVDD in rats. CONCLUSIONS: hsa_circ_0083756 promoted IVDD via targeting the miR-558/TREM1 axis, and hsa_circ_0083756 may serve as a potential therapeutic target for the treatment of IVDD.

Surgical outcome of thoracic myelopathy caused by ossification of ligamentum flavum.

Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy (TM) because of the spinal canal narrowing. The aim of this study was to investigate clinical outcomes of symptomatic thoracic OLF treated using posterior decompressive laminectomy. We made a retrospective review of patients who underwent posterior decompressive laminectomy from 2007 through 2016 for symptomatic TM caused by OLF. Thirty-three patients who had surgery for TM caused by OLF that was diagnosed based on clinical, radiologic, and pathologic evaluations. All patients had undergone decompressive laminectomy and excision of the OLF. The clinical course was evaluated according to modified JOA scores. Magnetic resonance imaging was used to determine the number of vertebral segments demonstrating OLF, the level of thoracic cord involvement, and spine lesions coexisting with OLF. Results showed the neurological status improved at follow up (70.82±32.22months) from a preoperative mean Japanese Orthopaedic Association score of 7.03±1.29 points to 9.52±0.83 points at the last follow up (p<0.01). Recovery outcomes were excellent in 8 patients, good in 22 patients, fair in 2 patients and poor in 1 patient. Surgical complications, which resolved after appropriate and prompt treatment, including cerebrospinal fluid leakage in 4 patient, immediate postoperative neurologic deterioration in 2 patient, and wound infection in 4 patient. Our findings suggest that posterior decompressive laminectomy with or without instrumented fusion is an effective treatment for symptomatic thoracic OLF, which provides satisfactory clinical improvement.

Comparison of pullout strength of the thoracic pedicle screw between intrapedicular and extrapedicular technique: a meta-analysis and literature review.

BACKGROUND: Intrapedicular fixation in thoracic spine is often limited, because of high risk of complication, especially in scoliosis patients. Extrapedicular screws fixation techniques provide an alternate solution for extremely small or abnormal thoracic pedicles deformity. However, the pullout resistance of extrapedicular screws has not been clearly defined. The aim of our study was to systematically review the existing evidence regarding the pullout resistance of thoracic extrapedicular screws compared with intrapedicular screws. METHODS: A systematic search of all studies published through Nov 2014 was performed using Medline, EMBASE, OVID and other databases. All studies that compared the pullout resistance of thoracic extrapedicular screws with intrapedicular screws were selected. The data from the included studies were extracted and analyzed regarding pullout resistance force. Forest plots were constructed to summarize the data and compare the biomechanical stability achieved. RESULTS: Five studies were included, with a total of 27 cadaveric specimens and 313 screws. The vertebral levels of the cadavers potted were T1-T8, T2-T12, T7-T9, T6-T11 and T4-T12 respectively. Overall, the results demonstrated that there was no significant difference in ultimate pullout strength between intrapedicular screws and extrapedicular screws (95% CI=-63.73 to 27.74; P=0.44); extrapedicular screws significantly increased the length of placements by a mean of 6.24 mm (95% CI=5.38 to 7.10; P<0.001); while the stiffness in intrapedicular screws was significantly stronger by a mean of 45.82 N/mm compared with extrapedicular screws (95% CI=-70.09 to -21.56; P<0.001). CONCLUSIONS: Meta-analysis of the existing literature showed that thoracic extrapedicular screws provided comparable but slightly lower pullout strength compared with intrapedicular screws, extrapedicular screws placement is much safer than intrapedicular screws. So thoracic extrapedicular screws offer a good alternative when it is hard to insert by intrapedicular approach, especially in scoliosis patients with severe vertebral deformities.

[Comparative study of Kurokawa's double door laminoplasty and modified Kurokawa's double door laminoplasty for the treatment of cervical disorders].

OBJECTIVE: To observe and compare the medium-long-term efficacy of Kurokawa's and modified Kurokawa's double door laminoplasty for the treatment of cervical disorders. METHODS: A retrospective analysis was performed to compare the outcomes and complications between two kinds of operations on 172 cases from January 2002 to December 2010, including 106 cases of cervical spondylotic myelopathy, 52 cases of cervical stenosis, 21 cases of cervical ossification of the posterior longitudinal ligament. Patients were divided into two groups according to two surgical methods: traditional group, including 51 male and 18 female patients, with mean age of (56 ± 18) years (35-76 years); modified group, including 75 male and 28 female patients, with mean age of (58 ± 20)years (35-80 years). The two groups were comparable and compared according to different data using t test, χ(2) test and rank sum test. RESULTS: All patients were followed up continuously for (52 ± 33)months, 123 patients were followed up ≥ 2 years, 71 patients ≥ 5 years. All patients' Japanese Orthopaedic Association (JOA) score improved significantly at the latest follow-up(t = 3.420, P < 0.01); no significant difference between the patients' JOA score improvement rate of two groups. The postoperative incidence rate of axial symptoms in patients of modified group (3.9%) was significantly lower than the traditional group (14.5%) (χ(2) = 7.548, P < 0.05), and cervical intervertebral activity decreased in the modified group was better than the traditional group in the first 3 months postoperatively (27% ± 6% vs. 19% ± 4%,Z = 6.34, P < 0.05), but during the medium-long-term follow-up, no significant difference in the cervical intervertebral activity decreased between two groups. CONCLUSIONS: Medium-long-term efficacy of Kurokawa's and modified Kurokawa's double door laminoplasty is satisfied and reliable. Avoiding damaging of semispinalis cervicis insertion in spinous process of C2, the modified operation method can protect the extensor group of the neck muscle and reduce the incidence of postoperative axial symptoms better.

Serum levels of IL-33 is increased in patients with ankylosing spondylitis.

Interleukin-33 (IL-33) is implicated in rheumatoid arthritis with effects of promoting tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) productions, which have been demonstrated to play a pivotal role in ankylosing spondylitis (AS). However, changes of IL-33 levels and its effects in AS have not been investigated. Eighty-nine and 178 healthy controls were included in the current study. Erythrocyte sedimentation rate, serum levels of C-reactive protein, IL-17, and IL-33 were determined. Effects of IL-33 on TNF-α and IL-6 productions were investigated. Effects of IL-33 on neutrophil migration were also evaluated. Serum levels of IL-33 were elevated in AS patients. Moreover, IL-33 was significantly higher in active AS patients according to Bath Ankylosing Spondylitis Disease Activity Index. IL-33 concentrations in serum were positively correlated with TNF-α and IL-17 levels (IL-33 and TNF-α, r = 0.54, P < 0.01; IL-33 and IL-17, r = 0.47, P < 0.01). IL-33 dose-dependently enhanced TNF-α and IL-6 productions by peripheral blood mononuclear cells (PBMCs) responding to lipopolysaccharide. IL-33 induced neutrophil migration only in higher doses (≥10 ng/ml). Serum levels of IL-33 were elevated in AS patients. IL-33 may play a role in AS development via enhancing TNF-α production by PBMCs and inducing neutrophil migration.

Transpedicular fixation in management of thoracolumbar burst fractures: monosegmental fixation versus short-segment instrumentation.

STUDY DESIGN: A prospective clinical trial was conducted. OBJECTIVE: To compare the clinical and radiologic late results of monosegmental transpedicular fixation versus short-segment pedicle instrumentation (SSPI) in management of thoracolumbar burst fractures and evaluate the efficacy of monosegmental transpedicular fixation. SUMMARY OF BACKGROUND DATA: SSPI (1 level above and 1 below the fracture level) are accepted by many surgeons as an accepted technique for the treatment of thoracolumbar burst fractures. To preserve more motion segments, some authors have advocated monosegmental pedicle instrumentation (MSPI). The recent developments showed that MSPI yielded good clinical results; however, there were no report about comparison of clinical outcome between monosegmental and biosegmental transpedicular fixation in management of thoracolumbar burst fractures. METHODS: Eighty-five patients with thoracolumbar burst fractures fulfilling the inclusion criteria were included in the study. The patients were randomized by a simple method into 2 groups. Group 1 were treated with monosegmental transpedicular fixation (n = 47), and group 2 were treated with biosegmental transpedicular fixation (n = 38). Clinical (Low Back Outcome Score and Oswestry Disability Index) and radiologic (load-sharing classification index, sagittal index, and percentage of anterior body height compression) outcomes were analyzed. RESULTS: The 2 groups were similar in age, follow-up period, and severity of the deformity and fracture. The postoperative and follow-up sagittal index, local kyphosis, percentage of anterior body height compression, and average correction loss in local kyphosis in both groups were not significantly different. The failure rate between the 2 surgical approaches was also not significantly different (group 1 = 6.38% and group 2 = 5.26%). Oswestry Disability Index improved in both groups by >25 points in a similar amount (P = 0.23). The average follow-up Low Back Outcome Score was 74.9 and 60.2 for group 1 and group 2, respectively (P = 0.033). CONCLUSION: In conclusion, radiologic parameters demonstrated that both MSPI and SSPI are the effective and reliable operative techniques for selected thoracolumbar burst fractures. MSPI shortened the operative time and decreased the amount of blood loss significantly and, thus, offered better clinical results. Nevertheless, long-term studies are supposed to be performed to support the outcomes.

[Biomechanical effects of sacrectomy extents on stability of lumbo-iliac fixation using iliac screw techniques].

OBJECTIVE: To evaluate the effects of sacrectomy extent on the stability of lumbo-iliac fixation using single or dual iliac screw technique, and to determine which conditions require the dual iliac screw technique. METHODS: Nine fresh L2 to pelvic specimens were harvested from donated adult cadavers. After testing the intact state simulated by L3-5 pedicle screw fixation, sequential partial sacrectomies and L3 to iliac fixation using bilateral single iliac screw (Single) were conducted on the same specimen as follows: in group A, under S1 partial sacrectomy and Single; in group B, under 1/2 S1 partial sacrectomy and Single; in group C, one-side (left) sacroiliac joint resection and Single; in group D, total sacrectomy and Single; and in group E, the single iliac screw was replaced by dual iliac screws based on group D. Biomechanical testing was performed on a material testing machine under 0-800 N compression and 7-7 N x m torsion loading modes for construct stiffness evaluation. RESULTS: The compressive stiffness of intact condition was (392 +/- 119) N/mm, groups A, B, C, D, and E obtained 106.4% +/- 9.5%, 102.7% +/- 8.0%, 92.2% +/- 10.1%, 72.7% +/- 8.0%, and 107.7% +/- 10.7% of intact condition, respectively. No significant differences were found among groups A, B, C, and the intact state (P > 0.05), however, the four groups showed significantly higher compressive stiffness than group D (P < 0.05). Although group E exhibited a comparable compressive stiffness with groups A, B, and intact state (P > 0.05), it displayed markedly higher compressive stiffness than groups C and D (P < 0.05). The torsional stiffness of intact state was (3.22 +/- 1.23) N x m/deg. Groups A, B, C, D, and E acquired 105.4% +/- 10.1%, 89.8% +/- 12.3%, 75.9% +/- 10.6%, 71.2% +/- 10.2%, and 109.1% +/- 16.9% of intact state, respectively. No significant differences were detected among groups A, B, E, and the intact state (P > 0.05). However, groups C and D showed remarkably lower torsional stiffness than groups A, E, and the intact state (P < 0.05). Importantly, group E offered remarkably higher torsional stiffness than group B (P < 0.05). CONCLUSION: After under 1/2 S1 partial sacrectomy, single iliac screw technique could effectively restore local stability; whereas it could hardly provide adequate stability for further resection of one-side sacroiliac joint or total sacrectomy; in such situation, the use of dual iliac screw technique could obtain sufficient construct stability. Therefore, in the surgical treatment of sacral tumor, the dual iliac screw technique should be considered for the unstable conditions of total sacrectomy or under 1/2 S1 sacrectomy with one-side sacroiliac joint resection.

[Biomechanical effects of insertion location and bone cement augmentation on fixation strength of iliac screw].

OBJECTIVE: To compare the maximum pull-out strength of the upper iliac screw and lower iliac screw with and without polymethylmethacrylate (PMMA) augmentation, and to provide the experimental evidences for the rational use of iliac screws. METHODS: Ten intact human ilium from 5 donated cadavers with formalin embalmed were selected. The bone mineral density (BMD) of L1-4 of each cadaver was measured with a dual energy X-ray absorptiometry. The screws placed in the upper and lower iliac column were named as the upper and lower iliac screw, respectively. Using 70 mm length and 7.5 mm diameter screws with and without PMMA augmentation, 4 iliac screw technique models were sequentially established and tested as follows: upper iliac screw (group A), upper iliac screw with PMMA augmentation (group B), lower iliac screw (group C), and lower iliac screw with PMMA augmentation (group D). Each ilium was mounted on a material testing machine with its position similar to standing. Under 2 000 cyclic compressive loadings of 100-300 N to the screw, the maximum pull-out strength of iliac screw was measured. RESULTS: The BMD value of the 5 human cadavers was (0.88 +/- 0.06) g/cm2. All the iliac screws were inserted into the screw tracts accurately as expected. No screw penetrations of acetabulum or cortex was not observed through visual inspection. There was no "halo" ring sign surrounding any screw after the 2 000 cycle loading. The maximum pull-out strengths of groups A, B, C, and D were (964 +/- 250), (1462 +/- 266), (1537 +/- 279), and (1964 +/- 422) N, respectively. Group D exhibited the highest maximum pull-out strength among the 4 groups (P < 0.05). No significant difference was detected between groups B and C (P > 0.05); however, groups B, C showed higher maximum pull-out strength than group A (P < 0.05). CONCLUSION: The lower iliac screw offers significantly higher fixation strength than the upper iliac screw; PMMA augmentation could effectively increase the fixation strength of iliac screws and therefore could be applied in the salvage of iliac screw loosening.

Monosegmental transpedicular fixation for selected patients with thoracolumbar burst fractures.

STUDY DESIGN: A prospective cohort study on selected consecutive patients. OBJECTIVE: To evaluate the efficacy of an innovative operative technique called monosegmental transpedicular fixation for the treatment of some thoracolumbar burst fractures. SUMMARY OF BACKGROUND DATA: Short-segment pedicle screw instrumentation is accepted by many spinal surgeons as an acceptable technique for the treatment of thoracolumbar burst fractures. Preoperative evaluation using the spinal load-sharing makes this technique more reliable. To preserve more motion segments, some authors have advocated using monosegmental pedicle screw instrumentation (MSPI) to treat thoracolumbar fractures. However, up until now this kind of maneuver is only performed in cases of flexion distraction injuries. METHODS: A cohort of 20 patients with thoracolumbar burst fractures fulfilling the inclusion criteria were prospectively submitted to surgical treatment of monosegmental transpedicular fixation plus posterior fusion. All instrumentations were performed with pedicle screws inserted bilaterally into the fractured level and 1 adjacent level, either superior or inferior depending on the locating side of the intact endplate. All patients were followed up. The preoperative radiographs, the postoperative radiographs within 1 week of operation, and the radiographs of the most recent follow-up were evaluated for kyphosis correction recorded in the Sagittal Index and Load-Sharing Classification (LSC) index. The postoperative functional outcomes were evaluated using the Frankel Performance Scale together with the Denis Pain Scale. RESULTS: Eighteen patients were followed up successfully with an average final follow-up of 24.7+/-8.0 months. The focal kyphotic angulations were corrected satisfactorily with the mean Sagittal Index of preoperative 16.5+/-6.6 degrees, initial postoperative 4.0+/-2.4 degrees, and latest follow-up 4.8+/-4.0 degrees. No obvious loss of correction occurred except for 2 patients who both scored 8 points on the LSC Score. Postoperatively, most patients attained both functional neurologic improvement and pain relief, and only a few complications were noted. CONCLUSIONS: For selected thoracolumbar burst fractures, MSPI can provide the same or better fixation and preserve more motion segments than other methods of posterior pedicle instrumentation. With preoperative evaluation using the spinal LSC system, MSPI is effective and reliable for the treatment of thoracolumbar burst fractures when properly indicated.