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Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs’ stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP. [ABSTRACT FROM AUTHOR]

This study sought to investigate and evaluate a modified axial translaminar screw fixation for treating odontoid fractures. We performed a retrospective study at Wenzhou Medical University Affiliated Second Hospital between March 2016 and June 2018. We retrospectively collected and analyzed the medical records of 23 cases with odontoid fractures. All patients were identified as type II odontoid fractures without neurological deficiency and serious diseases following the classification of Anderson. The average age, gender ratio, and body mass index (BMI) were 54.3 ± 11.1 years, 12 men to 11 women, and 22.6 ± 2.4 kg/m2, respectively. Patients in this study accepted screw fixation using our modified axial translaminar screw fixation combined with atlas pedicle or lateral mass screw fixation. Within the technique, a small cortical "window" was dug in the middle of the axial contralateral lamina, such that the screws in the lamina were visualized to prevent incorrectly implanting the posterior spinal canal through the visualized "window." A total of 46 bone screws were accurately inserted into the axial lamina without using fluoroscopy. The length of all translaminar screws ranged between 26 and 30 mm, while the diameter was 3.5 mm. During the follow‐up survey, the visual analog scale (VAS) and neck disability index (NDI) were measured. We provide a simple modification of Wright's elegant technique with the addition of "visualized windows" at the middle of the axial lamina. In all patients, screws were inserted accurately without bony breach and the screw angle was 56.1 ± 3.0°. Mean operative time was 102 ± 28 min with an average blood loss of 50 ± 25 mL. Postoperative hemoglobin and mean length of hospital stay were 12.0 ± 1.4 g/dL and 10.4 ± 3.4 days, respectively. The average follow‐up time of all cases was 14.7 months and no internal fixation displacement, loosening, or breakage was found. All patients with odontoid fractures reported being satisfied with the treatment during the recheck period and good clinical outcomes were observed. At 1, 6, and 12 months, NDI and VAS showed that the symptoms of neck pain and limitations of functional disability improved significantly during follow‐up. Our results suggest that the modified translaminar screw fixation technique can efficiently treat Anderson type II odontoid fracture, followed by the benefits of less soft tissue dissection, simple operation, no fluoroscopy, and accurate placement of screws. [ABSTRACT FROM AUTHOR]

The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis. [ABSTRACT FROM AUTHOR]

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Apoptosis has been regarded to mediate intervertebral disc degeneration ( IDD); however, the basic question of how the apoptotic bodies are cleared in the avascular intervertebral disc without phagocytes, which are essential to apoptosis, remains to be elucidated. Our goals were to investigate the ultrastructure of nucleus pulposus ( NP) cells undergoing chondroptosis, a variant of apoptotic cell death, in a rabbit annular needle-puncture model of IDD. Experimental IDD was induced by puncturing discs with a 16-G needle in New Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was demonstrated by X-ray, magnetic resonance imaging and histological staining. TUNEL staining suggested a significant increase in the apoptosis index in the degenerated NP. However, the percentage of apoptotic cells with the classic ultrastructure morphology was much less than that with chondroptotic ultrastructure morphology under transmission electron microscopy ( TEM). The chondroptotic cells from the early to late stage were visualized under TEM. In addition, the percentage of chondroptotic cells was significantly enhanced in the degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated tissue. Western blotting revealed an increase in caspase3 expression in the degenerated NP. The expression of the Golgi protein (58K) was increased by the fourth week after puncture but decreased later. These findings indicate that chondroptosis is a major type of programmed cell death in the degenerated rabbit NP that may be related to the progressive development of IDD. [ABSTRACT FROM AUTHOR]

The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1. [ABSTRACT FROM AUTHOR]

Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2. [ABSTRACT FROM AUTHOR]

Background Context: Animals are commonly used to model the human spine for in vitro and in vivo experiments. Many studies have investigated similarities and differences between animals and humans in the lumbar and thoracic vertebrae. However, a quantitative anatomic comparison of calf, pig, and human cervical spines has not been reported. Purpose: To compare fundamental structural similarities and differences in vertebral bodies from the cervical spines of commonly used experimental animal models and humans. Study Design: Anatomical morphometric analysis was performed on cervical vertebra specimens harvested from humans and two common large animals (i.e., calves and pigs). Methods: Multiple morphometric parameters were directly measured from cervical spine specimens of twelve pigs, twelve calves and twelve human adult cadavers. The following anatomical parameters were measured: vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), spinal canal width (SCW), spinal canal depth (SCD), pedicle width (PW), pedicle depth (PD), pedicle inclination (PI), dens width (DW), dens depth (DD), total vertebral width (TVW), and total vertebral depth (TVD). Results: The atlantoaxial (C1–2) joint in pigs is similar to that in humans and could serve as a human substitute. The pig cervical spine is highly similar to the human cervical spine, except for two large transverse processes in the anterior regions ofC4–C6. The width and depth of the calf odontoid process were larger than those in humans. VBW and VBD of calf cervical vertebrae were larger than those in humans, but the spinal canal was smaller. Calf C7 was relatively similar to human C7, thus, it may be a good substitute. Conclusion: Pig cervical vertebrae were more suitable human substitutions than calf cervical vertebrae, especially with respect to C1, C2, and C7. The biomechanical properties of nerve vascular anatomy and various segment functions in pig and calf cervical vertebrae must be considered when selecting an animal model for research on the spine. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship between height ratio of the iliac crest to L4 (HR), width ratio of the iliac crest to L4 (WR) and L5-S1 disc degeneration.Methods: On T2-weighted sagittal images of the 50 randomly selected patients, two observers graded L5-S1 discs and some other parameters were measured. Then, relative signal intensity (RSI) of the L5-S1 nucleus pulposus was calculated. On anteroposterior and lateral radiographs of the same 50 patients' lumbar spine, the parameters such as the height of the iliac crest were measured and then HR and WR were calculated. Finally, HR, WR and the percentage of the sROM of L5-S1 in L1-S1 segments of the other 51 randomly selected patients were calculated.Results: Positive correlations were found between HR, WR and RSI of the L5-S1 disc. Negative correlations were found between HR, WR and modified Pfirrmann scores of L5-S1 nucleus pulposus. A statistically significant negative correlation was found between HR and the percentage of sROM of L5-S1 in L1-S1 segments.Conclusions: Low HR and (or) WR were the risk factors for L5-S1 disc degeneration. High HR could reduce the percentage of sROM of L5-S1 in L1-S1 segments and high HR and (or) WR could reduce the incidence of L5-S1 disc degeneration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To design and investigate a novel technique of percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion. Methods: CT scans of 45 patients were collected and imported into Mimics software for three-dimensional (3D) reconstruction. Cylinders were drawn to simulate the trajectory of the oblique screw. Six measurements were obtained for each unit to design a right size cage: a the distance between the intersection of the simulated trajectory of the screw with the inferior border of the upper vertebra and its anteroinferior corner; b the distance between the intersection of the simulated trajectory of the screw with the superior border of the inferior vertebra and its anterosuperior corner; h the height of the intervertebral space; θ the angle between simulated trajectory of screw and the upper endplate of inferior vertebra; uw: the width of the inferior endplate of upper vertebra; iw: the width of upper endplate of inferior vertebra. Three intact adult fresh-frozen cadaveric specimens were obtained, percutaneous posterior transdiscal oblique screw fixation was performed under X-ray apparatus, and interbody cage was implanted by assistance with special self-retaining retractor system and endoscope. Results: According to the results of data measured from 3D images, trapezoid shape interbody cages with suitable size were designed. Percutaneous posterior oblique screw fixation with lateral interbody fusion was performed on three cadaveric specimens successfully. Conclusion: Using specially designed trapezoid shape interbody cages, assisted by intra-operative image intensification and endoscope, it is feasible to perform percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion technique. [ABSTRACT FROM AUTHOR]

ABSTRACT 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 Egger's 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. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective clinical study. Objective: To evaluate the efficacy and safety of transforaminal decompression and interbody fusion in the treatment of thoracolumbar fracture and dislocation with spinal cord injury. Methods: Twenty-six spinal cord injured patients with thoracolumbar fracture and dislocation were treated by transforaminal decompression and interbody fusion. The operation time, intraoperative blood loss, and complications were recorded; the Cobb angle and compressive rate (CR) of the anterior height of two adjacent vertebrae were measured; and the nerve injury was assessed according to sensory scores and motor scores of the American Spinal Injury Association (ASIA) standards for neurological classification of spinal cord injury. Results: The operative time was 250±57 min, and intraoperative blood loss was 440±168 ml. Cerebrospinal leakage was detected and repaired during the operation in two patients. A total of 24 of 26 patients were followed up for more than 2 years. ASIA sensory scores and motor scores were improved significantly at 3 months and 6 months after operation; the Cobb angle and CR of the anterior height of two adjacent vertebrae were corrected and showed a significant difference at post-operation; and the values were maintained at 3 months after operation and the last follow-up. Conclusion: We showed that transforaminal decompression together with interbody fusion is an alternative method to treat thoracolumbar fracture and dislocation. [ABSTRACT FROM AUTHOR]

Phosphoserine has potential effectiveness as a simple substrate in preparing bone replacement materials, which could enhance bone forming ability. However, there is a need to investigate the independent effect of phosphoserine on osteogenic differentiation of human adipose stem cells (hADSCs). hADSCs were cultured in an osteogenic medium with phosphoserine. Cell proliferation was analysed by CCK8 and osteogenic differentiation was measured by alkaline phosphatase (ALP) activity, von Kossa staining and real time-polymerase chain reaction (RT-PCR). No stimulatory effect of phosphoserine on cell proliferation was noted at Days 1, 4 and 7. Deposition of calcium increased after the addition of phosphoserine. mRNA expression of type I collagen (COL-I), alkaline phosphatase (ALP), osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and RUNX2 increased markedly with phosphoserine treatment. The BMP-2 antagonist, noggin, and its receptor kinase inhibitors, dorsomorphin and LDN-193189, attenuated phosphoserine-promoted ALP activity. BMP-responsive and Runx2-responsive reporters were activated by phosphoserine treatment. Thus phosphoserine can promote osteogenic differentiation of hADSCs, probably by activating BMP and Runx2 pathways, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Purpose: To establish reference data on the dimensions of C2 lamina to guide the use of translaminar screws with Wright's technique and a modified technique for pediatric patients in different age groups.Methods: 113 pediatric patients were divided into six age groups, and their cervical vertebrae were studied on CT scans. Laminar height, width, length and screw angle were measured. Statistical analysis was performed using Student t tests, Pearson's correlation and linear regression analysis.Results: Mean laminar height was 10.95 ± 2.81 mm, and mean width was 6.01 ± 0.90 mm. For Wright's technique, mean laminar length was 30.65 ± 3 mm, and the screw angle was 56.02° ± 3.62°. For the modified technique, mean laminar length was 22.07 ± 2.38 mm, and the screw angle was 67.40° ± 3.39°. 95.6% (108/113) of the children could insert a screw into the lamina (laminar width ≥ 4.5 mm), 72.6% (82/113) could accept bilateral translaminar screws (laminar width ≥ 4.5 mm and laminar height ≥ 9 mm).Conclusion: Our investigation provides insight into the anatomy of C2 lamina in six pediatric age groups. Compared to adults, the benefits of C2 translaminar screws fixation are more obvious in the pediatric spine which has a large C2 lamina. Compared to Wright's technique, the modified technique should insert a screw with bigger insert angle and shorter screw length. [ABSTRACT FROM AUTHOR]

Purpose: To establish reference data on the dimensions of C2 lamina to guide the use of translaminar screws with Wright's technique and a modified technique for pediatric patients in different age groups. Methods: 113 pediatric patients were divided into six age groups, and their cervical vertebrae were studied on CT scans. Laminar height, width, length and screw angle were measured. Statistical analysis was performed using Student t tests, Pearson's correlation and linear regression analysis. Results: Mean laminar height was 10.95 ± 2.81 mm, and mean width was 6.01 ± 0.90 mm. For Wright's technique, mean laminar length was 30.65 ± 3 mm, and the screw angle was 56.02° ± 3.62°. For the modified technique, mean laminar length was 22.07 ± 2.38 mm, and the screw angle was 67.40° ± 3.39°. 95.6 % (108/113) of the children could insert a screw into the lamina (laminar width ≥4.5 mm), 72.6 % (82/113) could accept bilateral translaminar screws (laminar width ≥4.5 mm and laminar height ≥9 mm). Conclusion: Our investigation provides insight into the anatomy of C2 lamina in six pediatric age groups. Compared to adults, the benefits of C2 translaminar screws fixation are more obvious in the pediatric spine which has a large C2 lamina. Compared to Wright's technique, the modified technique should insert a screw with bigger insert angle and shorter screw length. [ABSTRACT FROM AUTHOR]

Background: Transforaminal lumbar interbody fusion (TLIF) has become one of the most widely used procedures for lumbar spinal disorders. However, it is still unclear whether TLIF with unilateral pedicle screw (PS) fixation is as effective as that with bilateral PS fixation. We performed a meta-analysis of the literatures and aimed to gain a better understanding of whether TLIF with unilateral PS fixation was safe and effective for lumbar diseases. Methodology/Principal Findings: We systematically searched Ovid, Springer, and Medline databases for relevant randomized controlled trials (RCTs) that compared the clinical and radiological outcomes of unilateral versus bilateral PS fixation in TLIF. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. We generated pooled risk ratios or weighted mean differences across studies. According to our predefined inclusion criteria, seven RCTs with a total of 441 patients were included in this study. Baseline characteristics were similar between the unilateral and bilateral groups. Our meta-analysis showed that no significant difference was detected between the two groups in terms of postoperative clinical function, fusion status, reoperation rate, complication rate, and hospital stay (p>0.05). Pooled estimates revealed that the unilateral group was associated with significantly reduced implant cost, operative time and blood loss (p<0.05). Conclusions/Significances: Our meta-analysis suggested TLIF with unilateral PS fixation was as safe and effective as that with bilateral PS fixation for lumbar diseases in selected patients. Despite these findings, our meta-analysis was based on studies with small sample size and different study characteristics that might lead to the inconsistent results such as various functional outcomes among the included studies. Therefore, high-quality randomized controlled trials with larger sample size are also needed to further clarify these issues and to provide the long-term outcomes. [ABSTRACT FROM AUTHOR]

The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to quantify the intra- and postoperative complications of an interspinous process device (Coflex) in managing degenerative lumbar diseases and to investigate corresponding therapeutic strategies. Methods: Between January 2008 and December 2012, we retrospectively analysed a total of 131 patients who underwent decompressive surgery along with the Coflex system for the treatment of degenerative lumbar diseases. The related complications were reported, and appropriate measures were taken. Clinical outcomes and radiological data were collected and analysed, and clinical outcomes were evaluated with paired-samples T test. Results: Related complications occurred in 11 patients. Among them, six cases were found with surgical technique-related complications, including device-related complications in three cases: spinal process fracture ( n = 1), Coflex loosening ( n = 1), fixed-wing breakage ( n = 1), dura mater tear in two cases and superficial wound infection in one case. All of them received corresponding conservative treatment and obtained a good result. The other five cases had non-device-related complications and required additional spinal surgery. The conservative therapy group had apparent improvement of VAS score and ODI, and remained well to final follow-up ( P < 0.05). The second operation group also improved postoperatively (each P < 0.05). Conclusion: The Coflex dynamic interspinous process device shows a low complication and re-operation rate. Standard operation and strict follow-up observation can effectively avoid surgical technique-related complications. The key points to ensure surgical effect and to reduce non-device-related complications are mastering surgical indications and thorough intra-operative decompression. [ABSTRACT FROM AUTHOR]

Purpose: This is a meta-analysis of randomized and non-randomized studies comparing the clinical and radiological efficacy of minimally invasive (MI) and conventional open transforaminal lumbar interbody fusion (open-TLIF) for degenerative lumbar diseases. Methods: A literature search of the MEDLINE database identified 11 studies that met our inclusion criteria. A total of 785 patients were examined. Pooled estimates of clinical and radiological outcomes, and corresponding 95 % confidence intervals were calculated. Results: The pooled data revealed that MI-TLIF was associated with less blood loss, shorter hospital stay, and a trend of better functional outcomes when compared with open-TLIF. However, MI-TLIF significantly increased the intraoperative X-ray exposure. Both techniques had similar operative time, complication rate, and re-operation rate. Conclusions: Based on the available evidence, MI-TLIF for degenerative lumbar diseases might lead to better patient-based outcomes. MI-TLIF would be a promising procedure, but extra efforts are needed to reduce its intraoperative radiation exposure. More randomized controlled trials are needed to compare these two surgical options. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of mini-open anterior approach to the cervicothoracic junction (CTJ) in cadaveric specimens. Methods: Four adult fresh-frozen cadaveric specimens were used for this study. On the cadaveric specimen, an osteotomy window was made in manubrium sterni to remove the bony obstacle. To bypass the vital vascular and neural structures over the operative field, we used the surgical corridor which was located medially by the brachiocephalic artery and laterally by the right brachiocephalic vein, or in combination with another surgical corridor between the ascending aorta and the superior vena cava. And we used a special self-retaining retractor system and an endoscope to facilitate the procedures. Results: Surgical procedures performed on the four fresh-frozen cadaveric specimens to expose the CTJ through mini-open anterior approach were successful. The anterior surface of C6-T5 could be exposed, allowing complete decompression and application of locking plate and screws. The most caudal accessible vertebral body was T5 vertebral body in our study. Conclusion: It is feasible to expose the CTJ through this mini-open anterior approach. [ABSTRACT FROM AUTHOR]

Purpose: This study describes a percutaneous technique for C2 transpedicular screw fixation and evaluates its safety and efficacy in the treatment of patients with hangman's fracture. Methods: Ten patients with hangman's fracture were treated by percutaneous C2 transpedicular screw fixation. There are six males and four females, who were, based on the classification of Levine and Edwards, sorted as follows: type I fracture, three cases; type II, five cases; type IIa, two cases. The causes of injury were road traffic accident in six patients and falling injury in four patients. Other associated lesions included rib fractures (7 patients), head injuries (4 patients), and fractures of extremities (6 patients). Results: The new technique was performed successfully in all cases. The average operation time was 98 min (range 60-130 min) and the estimated blood loss was 25 ml (range 15-40 ml). No complications such as vascular or neural structures injuries were found intraoperatively. Postoperative CT scans demonstrated that 17 (85 %) of 20 screws were placed satisfactorily, and 3 (15 %) screws showed perforations of the pedicle wall (<2 mm). These patients were asymptomatic and no further intervention was required postoperatively. After 8-25 months follow-up (mean 15.3 months), solid fusion was demonstrated by computed tomography. All cases got well-sagittal alignment and no angulation or dislocation was found at the segment of C2-C3. There was no loss of fixation. Clinical examination showed a full range of motion in the neck in all patients. Conclusions: The fluoroscopically assisted percutaneous C2 transpedicular screw fixation method is a technically feasible and minimally invasive technique for hangman's fracture. [ABSTRACT FROM AUTHOR]

Full article available online at Healio.com/Orthopedics. Search: 20121120-33 Lumbar interspinous devices are intended to unload the facet joints, restore foraminal height, lower intradisk pressure, and provide motion-preserving stabilization. They are an alternative treatment for patients with spinal degeneration and have increased in popularity in recent years. To the authors' knowledge, heterotopic ossification has not been previously reported around an interspinous device, and this is the first reported case of interspinous fusion after interspinous device placement. A 66-year-old man presented with a 3-year history of low back pain and a 4-month history of radiating pain down his left leg. A diagnosis was made of lumbar spinal stenosis and left disk herniation at L4-L5 after physical and imaging examinations. A dynamic interspinous device was implanted after the decompressive surgery. The patient's symptoms were relieved postoperatively. Thirty-two months later, he returned with back pain after being in a traffic accident. Lumbar radiographs showed a massive bony formation around the implant. Radiographs and a computed tomography scan 4.5 years later revealed that the implanted device segments were fused. No implant motion was seen on dynamic radiographs. Because the patient was symptom free, no interventions were performed. Heterotopic bone formation around a dynamic interspinous device may hamper motion preservation, and heterotopic ossification is a potential mid- and long-term complication. [ABSTRACT FROM AUTHOR]

Purpose: To study the anatomic parameters related to clival screw and establish reference data concerning the craniovertebral fixation technique.Methods: Morphometric measurement of the clivus and the surrounding anatomic structures were obtained on 41 dry bone specimens. Then, 2-D CT reconstruction of the craniovertebral region of 30 patients (19 men and 11 women, ranging in age from 20-64 years with an average age of 38.8 years) were performed to measure the safety range for a 3.5-mm screw placement. Nine entry points were evaluated. Finally, one male fresh cadaver specimen (age 46 years) was dissected to observe the craniovertebral region.Results: The clivus faces the basilar artery, the V ~ XII cranial nerves, the pons, and ventral medulla oblongata at its intracranial surface. The longitudinal diameter of extracranial clivus was 25.87 ± 2.64 mm. The narrowest diameter of the clivus was 12.84 ± 1.08 mm, the distance between the left and right hypoglossal canal was 32.70 ± 2.09 mm at its widest part. The distance between the left and right structures, the maximum value was 49.31 ± 4.16 mm at carotid canal, the minimum value was 16.54 ± 2.04 mm at the occipital condyle. The measurement of clival screws placement simulation via 2-D CT reconstruction images shows the maximum upper insertion angle of three components the optimal entry points, the candidate points, the limit entry points was 130.19°, 125.23° and 85.72°, and the total mean screw length was 7.57, 10.13 and 15.6 mm at the vertical entry angle, respectively.Conclusions: Clival screw placement is a viable option for craniovertebral fixation. There is a safe scope for the screw length and angle of the screw placement. And, these parameters obtained in the present study will be helpful for anyone contemplating the use of clival screw fixation. [ABSTRACT FROM AUTHOR]

Purpose: To study the anatomic parameters related to clival screw and establish reference data concerning the craniovertebral fixation technique. Methods: Morphometric measurement of the clivus and the surrounding anatomic structures were obtained on 41 dry bone specimens. Then, 2-D CT reconstruction of the craniovertebral region of 30 patients (19 men and 11 women, ranging in age from 20-64 years with an average age of 38.8 years) were performed to measure the safety range for a 3.5-mm screw placement. Nine entry points were evaluated. Finally, one male fresh cadaver specimen (age 46 years) was dissected to observe the craniovertebral region. Results: The clivus faces the basilar artery, the V ~ XII cranial nerves, the pons, and ventral medulla oblongata at its intracranial surface. The longitudinal diameter of extracranial clivus was 25.87 ± 2.64 mm. The narrowest diameter of the clivus was 12.84 ± 1.08 mm, the distance between the left and right hypoglossal canal was 32.70 ± 2.09 mm at its widest part. The distance between the left and right structures, the maximum value was 49.31 ± 4.16 mm at carotid canal, the minimum value was 16.54 ± 2.04 mm at the occipital condyle. The measurement of clival screws placement simulation via 2-D CT reconstruction images shows the maximum upper insertion angle of three components the optimal entry points, the candidate points, the limit entry points was 130.19°, 125.23° and 85.72°, and the total mean screw length was 7.57, 10.13 and 15.6 mm at the vertical entry angle, respectively. Conclusions: Clival screw placement is a viable option for craniovertebral fixation. There is a safe scope for the screw length and angle of the screw placement. And, these parameters obtained in the present study will be helpful for anyone contemplating the use of clival screw fixation. [ABSTRACT FROM AUTHOR]

Improved pedicle screw insertion accuracy has been reported with the assistance of computer tomography-based navigation. Studies also indicated that fluoroscopy-based navigation offers high accuracy and is comparable to CT-based assistance. However, different population characteristics and assessment methods resulted in inconsistent conclusions. We searched OVID, Springer, and MEDLINE databases to conduct a meta-analysis of the published literature specifically looking at accuracy of pedicle screw placement with different navigation methods. Subgroups and descriptive statistics were determined based on the subject type (in vivo or cadaveric), navigational method, and spinal level. A total number of 7,533 pedicle screws were summarised in our database with 6,721 screws accurately inserted into the pedicles (89.22%). Overall, the median placement accuracy for the in vivo CT-based navigation subgroup (90.76%) was higher than that with the use of two-dimensional (2D) fluoroscopy-based navigation (85.48%). We concluded that CT-based navigation could provide a higher accuracy in the placement of pedicle screws for all subgroups presented. In the lumbar level, 2D fluoroscopy-based navigation was comparable with CT-based navigation. Discrepancy between the two navigation types increased in the thoracic level for the in vivo populations, where there was less potential in the use of 2D fluoroscopy-based navigation than CT-based navigation. [ABSTRACT FROM AUTHOR]

The most common pattern among thoracolumbar burst fractures involves failure of the superior vertebra end-plate. There have been many biomechanical studies of thoracolumbar burst fractures, but the biomechanics related to the internal architecture of thoracolumbar vertebrae has been rarely documented. The objective of this study was to test the hypotheses that distribution of the bone mineral density (BMD) of the thoracolumbar spine is related to the stress concentration in this region and therefore, supports the pattern of burst fractures that occur most commonly. We measured spinal BMD of the first lumbar vertebra in 22 individuals using quantitative computed tomography (QCT) in three levels. At each level, the BMD for the trabecular compartment was determined from each of six sites and from one site within each pedicle. Thus the trabecular density was measured at a total of 20 sites for each person. The highest average QCT BMD was in the pedicle (sites 13 and 14), whereas the BMD was abruptly decreased at the posterior part of the vertebral body near the pedicles. The results of the study indicate that stress concentration of the spine related to the regional variation in vertebral bone density may be implicated in the biomechanical mechanism underlying thoracolumbar burst fractures. This finding may be correlated with the injury mechanism of thoracolumbar burst fractures and of clinical significance. [ABSTRACT FROM AUTHOR]