Xiang-Yang Wang

Percutaneous pedicle screw fixation for neurologic intact thoracolumbar burst fractures.

Study Design Prospective consecutive series. Objective To evaluate the efficacy and safety of percutaneous pedicle screw fixation (PPSF) for thoracolumbar AO type A3 fractures with a specially designed surgical instrument system. Summary of Background Data Minimally invasive surgery including PPSF is becoming increasingly widespread in the spine surgery. The technique of PPSF was mostly used as supplemental fixation combined with minimally invasive posterior or anterior lumbar interbody fusion in management of lumbar degenerative disorders. There are fewer studies available in literature regarding PPSF without additional kyphoplasty or vertebroplasty for management of thoracolumbar burst fractures. Methods Thirty-six adult patients, who had single thoracolumbar AO type A3 fractures and the load-sharing score of 6 or less, underwent application of percutaneous short-segment pedicle screw fixation. Radiologic parameters including kyphotic angle and vertebral height loss were assessed before and after surgery, and functional outcome was evaluated by Prolo questionnaire. Results All patients were successfully managed with percutaneous minimal invasive procedures. The average operative time was 78 minutes (range 62 to 117 min). The average intraoperative blood loss was 75 mL (range 50 to 220 mL). After a mean follow-up of 48.5 months (range 32 to 63 mo), 31 of 36 (86.1%) patients had a satisfactory result (19 excellent and 12 good) and 5 of them fair. Conclusions Our clinical results suggest that PPSF can be an alternative for management of thoracolumbar AO type A3 fractures that have no neurologic deficits. With a specially designed percutaneous instrument and pedicle screw system, the procedure has been proved as relatively safe and a minimally invasive approach for the management of thoracolumbar burst fracture without neurologic deficit.

Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration†‡

This research was aimed to study the mechanisms by which diabetes aggravates intervertebral disc degeneration (IDD) and to discuss the relationship between autophagy and IDD in nucleus pulposus (NP) cells. Sixteen weeks after injecting streptozotocin (STZ), the intervertebral discs (IVDs) were studied by histology, Alcian blue, 1,9‐dimethylmethylene blue (DMMB), immunohistochemistry, and RT‐PCR to explore the IDD. The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). The level of autophagy in NP cells was detected by Western blot, immunohistochemistry, and transmission electron microscopy (TEM). The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases‐9) and extrinsic (caspase‐8) pathways as well as their common executioner (caspase‐3). Cellular senescence was increased about twofold in NP of diabetic rats. In addition, the Western blot, immunohistochemistry, and TEM demonstrated higher level of autophagy in NP cells of diabetic rats than control rats to a statistically significant extent. These findings support that diabetes induced by STZ can cause IDD by accelerating the apoptosis and senescence of NP cells excluding the overweight influence. And the results suggest that the autophagy may be a response mechanism to the change of NP cells in diabetic rats.

Interspinous Spacer versus Traditional Decompressive Surgery for Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis

Background Dynamic interspinous spacers, such as X-stop, Coflex, DIAM, and Aperius, are widely used for the treatment of lumbar spinal stenosis. However, controversy remains as to whether dynamic interspinous spacer use is superior to traditional decompressive surgery. Methods Medline, Embase, Cochrane Library, and the Cochrane Controlled Trials Register were searched during August 2013. A track search was performed on February 27, 2014. Study was included in this review if it was: (1) a randomized controlled trial (RCT) or non-randomized prospective comparison study, (2) comparing the clinical outcomes for interspinous spacer use versus traditional decompressive surgery, (3) in a minimum of 30 patients, (4) with a follow-up duration of at least 12 months. Results Two RCTs and three non-randomized prospective studies were included, with 204 patients in the interspinous spacer (IS) group and 217 patients in the traditional decompressive surgery (TDS) group. Pooled analysis showed no significant difference between the IS and TDS groups for low back pain (WMD: 1.2; 95% CI: −10.12, 12.53; P = 0.03; I2 = 66%), leg pain (WMD: 7.12; 95% CI: −3.88, 18.12; P = 0.02; I2 = 70%), ODI (WMD: 6.88; 95% CI: −14.92, 28.68; P = 0.03; I2 = 79%), RDQ (WMD: −1.30, 95% CI: −3.07, 0.47; P = 0.00; I2 = 0%), or complications (RR: 1.39; 95% CI: 0.61, 3.14; P = 0.23; I2 = 28%). The TDS group had a significantly lower incidence of reoperation (RR: 3.34; 95% CI: 1.77, 6.31; P = 0.60; I2 = 0%). Conclusion Although patients may obtain some benefits from interspinous spacers implanted through a minimally invasive technique, interspinous spacer use is associated with a higher incidence of reoperation and higher cost. The indications, risks, and benefits of using an interspinous process device should be carefully considered before surgery.

The Relationship Between Vitamin A and Risk of Fracture: Meta-Analysis of Prospective Studies

Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta‐carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta‐analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I2 statistic to assess heterogeneity and Eggers test to assess publication bias. Eight vitamin A (or retinol or beta‐carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta‐carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]). Both high or low level of blood retinol was shown to increase the risk of hip fracture (adj.RR [95% CI] = 1.87 [1.31, 2.65] and 1.56 [1.09, 2.22], respectively). The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose‐response meta‐analysis shows a U‐shaped relationship between serum retinol level and hip fracture risk. Our meta‐analysis suggests that blood retinol level is a double‐edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta‐carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake.

The accuracy of a method for printing three-dimensional spinal models.

Background To study the morphology of the human spine and new spinal fixation methods, scientists require cadaveric specimens, which are dependent on donation. However, in most countries, the number of people willing to donate their body is low. A 3D printed model could be an alternative method for morphology research, but the accuracy of the morphology of a 3D printed model has not been determined. Methods Forty-five computed tomography (CT) scans of cervical, thoracic and lumbar spines were obtained, and 44 parameters of the cervical spine, 120 parameters of the thoracic spine, and 50 parameters of the lumbar spine were measured. The CT scan data in DICOM format were imported into Mimics software v10.01 for 3D reconstruction, and the data were saved in .STL format and imported to Cura software. After a 3D digital model was formed, it was saved in Gcode format and exported to a 3D printer for printing. After the 3D printed models were obtained, the above-referenced parameters were measured again. Results Paired t-tests were used to determine the significance, set to P<0.05, of all parameter data from the radiographic images and 3D printed models. Furthermore, 88.6% of all parameters of the cervical spine, 90% of all parameters of the thoracic spine, and 94% of all parameters of the lumbar spine had Intraclass Correlation Coefficient (ICC) values >0.800. The other ICC values were <0.800 and >0.600; none were <0.600. Conclusion In this study, we provide a protocol for printing accurate 3D spinal models for surgeons and researchers. The resulting 3D printed model is inexpensive and easily obtained for spinal fixation research.

Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo

Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose- and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells’ apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD.

Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury

In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells. Treatment with rapamycin, an autophagy activator, partially abolished the adverse effect of diabetes, suggesting that diabetes may enhance neurological damage and suppress locomotor recovery after SCI, in addition to its effects on apoptosis and autophagy. In contrast, further stimulation of autophagy improved neurological function via inhibition of apoptosis. These results explained how diabetes exacerbates SCI in cellular level and suggested autophagy stimulation to be a new therapeutic strategy for diabetic SCI.

Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Spinal cord injury (SCI) is a severe neurological disease with few efficacious drugs. Autophagy is a cellular process to confront with stress after SCI and considered to be a therapeutic target of SCI. In this study, we investigated the therapeutic effect of metformin on functional recovery after SCI and its underlying mechanism of autophagy regulation. Using a rat model of traumatic SCI, we found improved function recovery which was paralleled by a reduction of apoptosis after metformin treatment. We further examined autophagy via detecting autophagosomes by transmission electron microscopy and immunofluorescence, as well as autophagy markers by western blot in each groups. The results showed that the number of autophagosomes and expression of autophagy markers such as LC3 and beclin1 were increased in SCI group, while autophagy substrate protein p62 as well as ubiquitinated proteins were found to accumulate in SCI group, indicating an impaired autophagy flux in SCI. But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and functional recovery effect of metformin on SCI, which suggested that the protective effect of metformin on SCI was through autophagy flux stimulation. Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation. Together, these results illustrated that metformin improved functional recovery effect through autophagy flux stimulation and implied metformin to be a potential drug for SCI therapy.

Microendoscopic anterior approach for irreducible atlantoaxial dislocation: surgical techniques and preliminary results.

Study Design Surgical techniques and preliminary results. Objective To describe and evaluate the safety and efficacy of a new minimal invasive technique for the irreducible atlantoaxial dislocation (IADD). Summary of Background Data Endoscope has been widely used in minimal invasive spinal surgery. However, there are no clinical reports regarding anterior approach for IADD in the literature. Methods Ten consecutive patients with IADD were treated by anterior release with microendoscopic aide and subsequently reduction, anterior transarticular screw fixation and morselized autologous bone grafts. There were 3 cases of odontiod dysplasia, 4, chronic odontiod fracture, 1, odontiod absence, 1 fasilar impression, and 1 malunion of odontoid fracture. According to Symon and Lavenders classification of disability, 6 cases were moderate disability, 3 severe nonbedbound, and 1 severe bedridden. The procedure was performed by the same surgeon (Yong-Long Chi). Results The new technique was performed successfully in all cases. All the patients underwent transarticular screw fixation and anterior morselized autograft fusion. The average operation time was 120 min (range, 90 to 150 min) and the mean estimated blood loss was 150 mL (range, 100 to 250 mL). Postoperative radiographs demonstrated that 9 cases restored anatomic position and 1 had partial reduction. According to the postoperative computed tomography all the screws were appropriately placed. Follow-up after surgery, longest is 16 months and minimal 8 months with a mean of 12 months, neurologic status was improved in all patients. There was no loss of fixation and solid fusion was achieved in all cases. Conclusions Surgical technique of microendoscopic anterior release, reduction, fixation, and fusion is safe and reliable minimally invasive for treating IADD.

Pooled Analysis of Non-Union, Re-Operation, Infection, and Approach Related Complications after Anterior Odontoid Screw Fixation

Background Anterior odontoid screw fixation (AOSF) has been one of the most popular treatments for odontoid fractures. However, the true efficacy of AOSF remains unclear. In this study, we aimed to provide the pooled rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid fractures. Methods We searched studies that discussed complications after AOSF for type II or type III odontoid fractures. A proportion meta-analysis was done and potential sources of heterogeneity were explored by meta-regression analysis. Results Of 972 references initially identified, 63 were eligible for inclusion. 54 studies provided data regarding non-union. The pooled non-union rate was 10% (95% CI: 7%–3%). 48 citations provided re-operation information with a pooled proportion of 5% (95% CI: 3%–7%). Infection was described in 20 studies with an overall rate of 0.2% (95% CI: 0%–1.2%). The main approach related complication is postoperative dysphagia with a pooled rate of 10% (95% CI: 4%–17%). Proportions for the other approach related complications such as postoperative hoarseness (1.2%, 95% CI: 0%–3.7%), esophageal/retropharyngeal injury (0%, 95% CI: 0%–1.1%), wound hematomas (0.2%, 95% CI: 0%–1.8%), and spinal cord injury (0%, 95% CI: 0%–0.2%) were very low. Significant heterogeneities were detected when we combined the rates of non-union, re-operation, and dysphagia. Multivariate meta-regression analysis showed that old age was significantly predictive of non-union. Subgroup comparisons showed significant higher non-union rates in age ≥70 than that in age ≤40 and in age 40 to <50. Meta-regression analysis did not reveal any examined variables influencing the re-operation rate. Meta-regression analysis showed age had a significant effect on the dysphagia rate. Conclusions/Significances This study summarized the rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid factures. Elderly patients were more likely to experience non-union and dysphagia.