Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function.

Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although >70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119 715 individuals combined with precomputed gene expression weights of six panels from four tissue types. The candidate genes identified by TWAS were further validated by TWAS replication and gene expression profiles. We identified 74 conditionally independent genes significantly associated with thyroid function, such as PDE8B (P = 1.67 × 10-282), PDE10A (P = 7.61 × 10-119), NR3C2 (P = 1.50 × 10-92) and CAPZB (P = 3.13 × 10-79). After TWAS replication using UKBB datasets, 26 genes were replicated for significant associations with thyroid-relevant diseases/traits. Among them, 16 genes were causal for their associations to thyroid-relevant diseases/traits and further validated in differential expression analyses, including two novel genes (MFSD6 and RBM47) that did not implicate in previous GWASs. Enrichment analyses detected several pathways associated with thyroid function, such as the cAMP signaling pathway (P = 7.27 × 10-4), hemostasis (P = 3.74 × 10-4), and platelet activation, signaling and aggregation (P = 9.98 × 10-4). Our study identified multiple candidate genes and pathways associated with thyroid function, providing novel clues for revealing the genetic mechanisms of thyroid function and disease.

Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

Correlation of R2* with fat fraction and bone mineral density and its role in quantitative assessment of osteoporosis.

OBJECTIVES: To investigate the correlation of R2* with vertebral fat fraction (FF) and bone mineral density (BMD), and to explore its role in the quantitative assessment of osteoporosis (OP). METHODS: A total of 83 patients with low back pain (59.77 ± 7.46 years, 30 males) were enrolled, which underwent lumbar MRI in IDEAL-IQ sequences and quantitative computed tomography (QCT) scanning within 48h. The FF, R2*, and BMD of all 415 lumbar vertebrae were respectively measured. According to BMD, all vertebrae were divided into BMD normal, osteopenia, and OP groups, and the difference of FF and R2* among groups was analyzed by one-way ANOVA. The correlation between R2*, FF, and BMD was analyzed by Pearson's test. Taking BMD as the gold standard, the efficacies for FF and R2* in diagnosis of OP and osteopenia were assessed by receiver operating characteristic curve, and their area under the curve (AUC) was compared with DeLong's test. RESULTS: The FF and R2* were statistically different among groups (F values of 102.521 and 11.323, both p < 0.05), and R2* were significantly correlated with FF and BMD, respectively (r values of -0.219 and 0.290, both p < 0.05). In diagnosis of OP and osteopenia, the AUCs were 0.776 and 0.778 for FF and 0.638 and 0.560 for R2*, and the AUCs of R2* were lower than those of FF, with Z values of 4.030 and 4.087, both p < 0.001. CONCLUSION: R2* is significantly correlated with FF and BMD and can be used as a complement to FF and BMD for quantitative assessment of OP. KEY POINTS: • R2* based on IDEAL-IQ sequences has a definite but weak linear relationship with FF and BMD. • FF is significantly correlated with BMD and can effectively evaluate BMAT. • R2* can be used as a complement to FF and BMD for fine quantification of bone mineral loss and bone marrow fat conversion.

Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density.

OBJECTIVES: This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis. METHODS: A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis. RESULTS: Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD - 1.018 × VFF - 0.726 × ESFF (R2 = 0.860, F = 125.979, P < 0.001). CONCLUSIONS: Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.

Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis.

Osteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.

Feature selection approaches identify potential plasma metabolites in postmenopausal osteoporosis patients.

INTRODUCTION: Postmenopausal women with osteoporosis (PMOP) are prone to fragility fractures. Osteoporosis is associated with alterations in the levels of specific circulating metabolites. OBJECTIVES: To analyze the metabolic profile of individuals with PMOP and identify novel metabolites associated with bone mineral density (BMD). METHODS: We performed an unsupervised metabolomics analysis of plasma samples from participants with PMOP and of normal controls (NC) with normal bone mass. BMD values for the lumber spine and the proximal femur were determined using dual-energy X-ray absorptiometry. Principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) were performed for metabolomic profile analyses. Metabolites with P < 0.05 in the t-test, VIP > 1 in the PLS-DA model, and SNR > 0.3 between the PMOP and NC groups were defined as differential abundant metabolites (DAMs). The SHapley additive explanations (SHAP) method was utilized to determine the importance of permutation of each DAM in the predictive model between the two groups. ROC analysis and correlation analysis of metabolite relative abundance and BMD/T-scores were conducted. KEGG pathway analysis was used for functional annotation of the candidate metabolites. RESULTS: Overall, 527 annotated molecular markers were extracted in the positive and negative total ion chromatogram (TIC) of each sample. The PMOP and NC groups could be differentiated using the PLS-DA model. Sixty-eight DAMs were identified, with most relative abundances decreasing in the PMOP samples. SHAP was used to identify 9 DAM metabolites as factors distinguishing PMOP from NC. The logistic regression model including Triethanolamine, Linoleic acid, and PC(18:1(9Z)/18:1(9Z)) metabolites demonstrated excellent discrimination performance (sensitivity = 97.0, specificity = 96.6, AUC = 0.993). The correlation analysis revealed that the abundances of Triethanolamine, PC(18:1(9Z)/18:1(9Z)), 16-Hydroxypalmitic acid, and Palmitic acid were significantly positively correlated with the BMD/T score (Pearson correlation coefficients > 0.5, P < 0.05). Most candidate metabolites were involved in lipid metabolism based on KEGG functional annotations. CONCLUSION: The plasma metabolomic signature of PMOP patients differed from that of healthy controls. Marker metabolites may help provide information for the diagnosis, therapy, and prevention of PMOP. We highlight the application of feature selection approaches in the analysis of high-dimensional biological data.

Plasma lipidomics analysis reveals altered lipids signature in patients with osteonecrosis of the femoral head.

INTRODUCTION: Although studies have established a link between lipid metabolism disorder and osteonecrosis of the femoral head (ONFH), the characteristics of the circulating lipidome signature of ONFH have not yet been investigated and need to be explored. OBJECTIVES: We aimed to explore the plasma lipidome signatures in patients with ONFH, and to identify specific lipid biomarkers of ONFH. METHODS: In this study, a comprehensive detection and analysis of plasma lipidomics was conducted in clinical human cohort, including 32 healthy normal control (NC) subjects and 91 ONFH patients in different subgroups [alcohol-induced ONFH (AONFH), steroid-induced ONFH (SONFH), and traumatic-induced ONFH (TONFH)] or at different disease stages (stage I, II, III and IV of ONFH) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Overall, the plasma lipidome profile differs between ONFH and NC samples. Lipidome signature including 22 common differentially expressed lipids (DELs) in all three subgroups (variable importance in projection > 1, P < 0.05, fold change > 1.5 or < 0.67, compared to the NC group) was identified. Besides, the subtype-specific lipidome profiles for each ONFH subgroup were also analyzed. Generally, the AONFH subgroup has the largest number of DELs, and the plasma levels of triacylglycerol lipid compounds increased obviously in the AONFH samples. In the subgroup of SONFH, the relative abundance of lipid 4-Aminobenzoic acid increased significantly with changes in the expression of several of its interactive genes. We have identified that 9 stage-positive and 2 stage-negative lipids may function as novel biomarkers predicting the progression of ONFH. CONCLUSION: Our study presents an overview of the phenotype-related plasma lipidome signature of patients with ONFH. The results will provide insight into the mechanisms underlying the metabolism of lipids in the pathogenesis and progression of ONFH and help identify novel lipids biomarkers or disease diagnosis and treatment targets.

Dual-Energy Computed Tomography Virtual Noncalcium Technique in Diagnosing Osteoporosis: Correlation With Quantitative Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate dual-energy computed tomography (CT) virtual noncalcium (VNCa) technique as a means of quantifying osteoporosis. METHODS: Dual-energy CT scans were obtained prospectively, targeting lumbar regions of 55 patients with chronic low back pain. A standard quantitative CT (QCT) phantom was positioned at the waist during each procedure, using proprietary software (QCT Pro; Mindways, Tex) to measure bone mineral density (BMD) in each vertebral body. Vendor dual-energy analytic software was altered with a specially modified configuration file to produce a "Virtual Non Calcium" or "VNCa" output, as such output variables were remapped to produce the following calcium values rather than iodine, yielding the following QCT parameters: CT value of calcium (originally "contrast media" [CM]), CT value of mixed energy imaging (regular CT value [rCT]), calcium density (originally "contrast agent density" [CaD]), and fat fraction (FF). Pearson test served to assess correlations between BMD and these parameters. Multiple linear regression analysis was applied to construct an equation for generating regressive BMD (rBMD) values. In gauging diagnostic accuracies, the criterion-standard BMD cutoff point (<80 mg/cm3) was adopted for QCT, whereas the rBMD threshold was defined by receiver operating characteristic curve. RESULTS: Contrast media, rCT, CaD, and FF values (reflecting CT value of calcium, regular CT value, calcium density, and fat fraction, respectively) significantly correlated with BMD (r values: 0.885, 0.947, 0.877, and 0.492, respectively; all P < 0.01). Contrast media, CaD, and FF showed independent associations with BMD; the regressive equation was formulated as follows: rBMD = 54.82 - 0.19 × CM + 20.03 × CaD - 1.24 × FF. The area under the curve of rBMD in diagnosing osteoporosis was 0.966 ± 0.009 (P < 0.01). At an rBMD threshold of less than 81.94 mg/cm3, sensitivity and specificity were 90.0% and 92.0%, respectively. CONCLUSIONS: Dual-energy CT VNCa technique may constitute a valid alternative method for quantifying the mineral content and marrow fat composition of bone in diagnostic assessments of osteoporosis.

Radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking.

OBJECTIVE: To study radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking. METHODS: Patients who underwent lumbar internal fixation in our hospital from June 2017 to February 2020 were divided into Tinavi group (with optical tracking) and Renaissance group (without optical tracking) according to assisted technology. The imaging data of the patients were collected, and the accuracy of screw implantation was measured according to Rampersaud A-D grade. Clinical outcomes such as operative time, fluoroscopic time and radiations dose were also collected. RESULTS: A total of 376 patients were included, including 201 patients in the Tinavi group with 968 screws implanted and 175 patients in the Renaissance group with 822 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation in the Tinavi group was 94.9%-98.7%, respectively, while in the Renaissance group was 91.2%-94.5%, respectively. There was significant difference between the two groups (P < 0.05). The operative time and operative time per screw in the Tinavi group were lower than those in the Renaissance group. However, fluoroscopic time per screw and radiations dose of the Tinavi group were significantly higher than those of the Renaissance group. CONCLUSION: Optical tracking in robotic system appears to increase accuracy because of the ability to detect the real-time position of the patient. Although there are still many problems to be solved, robot with optical tracking system shows its great potential in clinical application.

Trends of epidemiological characteristics of traumatic spinal cord injury in China, 2009-2018.

OBJECTIVE: We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. METHODS: A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. RESULTS: There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0-46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2-67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7-8.8%). The elderly population (aged 65-74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8-134.3]). CONCLUSIONS: The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Sonic Hedgehog Effectively Improves Oct4-Mediated Reprogramming of Astrocytes into Neural Stem Cells.

Irreversible neuron loss following spinal cord injury (SCI) usually results in persistent neurological dysfunction. The generation of autologous neural stem cells (NSCs) holds great potential for neural replenishment therapies and drug screening in SCI. Our recent studies demonstrated that mature astrocytes from the spinal cord can directly revert back to a pluripotent state under appropriate signals. However, in previous attempts, the reprogramming of astrocytes into induced NSCs (iNSCs) was unstable, inefficient, and frequently accompanied by generation of intermediate precursors. It remained unknown how to further increase the efficiency of astrocyte reprogramming into iNSCs. Here, we show that mature astrocytes could be directly converted into iNSCs by a single transcription factor, Oct4, and that the iNSCs displayed typical neurosphere morphology, authentic NSC gene expression, self-renewal capacity, and multipotency. Strikingly, Oct4-driven reprogramming of astrocytes into iNSCs was potentiated with continuous sonic hedgehog (Shh) stimulation, as demonstrated by a sped-up reprogramming and increased conversion efficiency. Moreover, the iNSC-derived neurons possessed functionality as neurons. Importantly, crosstalk between Sox2/Shh-targeted downstream signals and phosphatidylinositol 3-kinase/cyclin-dependent kinase 2/Smad ubiquitin regulatory factor 2 (PI3K/Cdk2/Smurf2) signaling is likely involved in the mechanisms underlying this cellular event. The highly efficient reprogramming of astrocytes to generate iNSCs will provide an alternative therapeutic approach for SCI using autologous cells.

Radiological and Clinical Differences between Tinavi Orthopedic Robot and O-Arm Navigation System in Thoracolumbar Screw Implantation for Reconstruction of Spinal Stability.

BACKGROUND Pedicle screw fixation is one of the most commonly used methods in spine surgery. We introduce a surgical robot system from China based on 3-dimensional fluoroscopy imaging and compare it with the commonly used O-arm navigation system. We study the differences in accuracy, safety, and clinical effect in auxiliary pedicle screw fixation. MATERIAL AND METHODS Patients who underwent thoracolumbar internal fixation in our hospital from 2017 to 2019 were divided into a robot and navigation group according to whether surgery was assisted by the Tinavi orthopedic robot or O-arm navigation system. Imaging data of patients were searched from the image system and accuracy of screw implantation was measured by Rampersaud A to D grade classification. Deviation sagittal, deviation transversal, and facet joint violation were also measured and calculated. RESULTS In total, 306 patients were included: 136 patients in the robot group with 760 screws implanted; 166 patients in the navigation group with 908 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation was 96.2% and 99.6%, respectively, in the robot group and 90.5% and 96.7%, respectively, in the navigation group, with a significant difference between the 2 groups (P<0.05). The sagittal and transversal deviations in the robot group were significantly less than those in the navigation group (P<0.05). CONCLUSIONS The Tinavi orthopedic robot can significantly improve surgical accuracy and safety of pedicle screw fixation, as compared with that of O-arm navigation technology, without increasing complications. It shows great potential in clinical application.

Percentage fat fraction in magnetic resonance imaging: upgrading the osteoporosis-detecting parameter.

BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disorder identified as an essential health issue worldwide. Orthopedic imaging approaches were commonly used with some limitations. Thus, our study aimed to investigate the diagnostic value of magnetic resonance spectroscopy (1-H MRS) and m-Dixon-Quant in OP. METHODS: A total of 76 subjects were enrolled in the study and bone mineral density (BMD) was measured using quantitative computed tomography (QCT). Then, the subjects were divided into three groups according to BMD: normal control group, osteopenia group and OP group. The following parameters were recorded for each patient: gender, age, height, body weight, waist circumference, and hip circumference. Further, the fat fraction percentage (FF%) values were determined by 1-H MRS and m-Dixon-Quant methods. RESULTS: In both 1-H MRS and magnetic resonance Imaging (MRI) m-Dixon-Quant, the FF% exhibited a negative correlation with BMD (P < 0.05). The FF% value of the OP group was significantly higher than that of the control group (P < 0.05). In addition, the FF% value in the m-Dixon scans was positively related to age, while BMD showed a negative linear relationship with age (P < 0.0001). Further, females had a significantly higher FF% value compared to males (P < 0.01), and height was correlated with BMD (P < 0.05) but not with FF% (P > 0.05). CONCLUSIONS: MRI investigations especially FF% value in the m-Dixon-Quant imaging system is correlated with OP. Its diagnostic value remains to be demonstrated on a large prospective cohort of patients. Besides, parameters such as age, gender, and height are important factors for predicting and diagnosing OP.

Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats.

BACKGROUND: Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism. METHODS: In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5'-bromo-2'-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting. RESULTS: We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. CONCLUSIONS: Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.

The feasibility of inserting a C1 pedicle screw in patients with ponticulus posticus: a retrospective analysis of eleven patients.

BACKGROUND: Ponticulus posticus is a common anatomic variation that can be mistaken for a broad posterior arch during C1 pedicle screw placement. When the atlas lateral mass screws are placed via the posterior arch, injury to the vertebral artery may result. To our knowledge, there are few clinical studies that have analyzed the feasibility of C1 pedicle screw fixation in patients with ponticulus posticus, in clinical practice. PURPOSE: To evaluate the feasibility of inserting a C1 pedicle screw in patients with ponticulus posticus. METHODS: Between January 2008 and January 2012, 11 consecutive patients with atlantoaxial instability, and with a ponticulus posticus at C1, underwent posterior fusion surgery in our institution. According to preoperative computed tomography (CT) reconstruction, a complete ponticulus posticus was found unilaterally in nine patients and bilaterally in two. Postoperative CT reconstructive imaging was performed to assess whether C1 pedicle screw placement was successful. Patients were followed up at regular intervals and evaluated for symptoms of ponticulus posticus syndrome. RESULTS: Thirteen C1 pedicles (atlas vertebral artery groove), each with a complete ponticulus posticus, were successfully inserted with thirteen 3.5- or 4.0-mm diameter pedicle screws, without resection of the bony anomaly. No intraoperative complications (venous plexus, vertebral artery, or spinal cord injury) occurred. The mean follow-up period was 21 (range 14-30) months. Postoperative CT reconstructive images showed that all 13 pedicle screws were inserted in the C1 pedicles without destruction of the atlas pedicle cortical bone. In the follow-up period, none of the patients demonstrated clinical symptoms of ponticulus posticus syndrome or developed bone fusion. CONCLUSION: Three-dimensional CT imaging should be considered prior to C1 pedicle screw fixation in patients with ponticulus posticus, to avoid mistaking the ponticulus posticus for a widened dorsal arch of the atlas. If there is no ponticulus posticus syndrome preoperatively, C1 pedicle screw fixation can be successfully performed without removing the bony anomaly.

The Role of Posterior Longitudinal Ligament in Cervical Disc Replacement: An Ovine Cadaveric Biomechanical Analysis.

BACKGROUND Cervical disc replacement (CDR) has been widely used to restore and maintain mobility and function of the treated and adjacent motion segments. Posterior longitudinal ligament (PLL) resection has been shown to be efficient in anterior cervical decompression and fusion. However, less is known about the biomechanical effect of PLL removal versus preservation in cervical disc arthroplasty. MATERIAL AND METHODS Three motion segments of 24 ovine cervical spines (C2-C5) were evaluated in a robotic spine system with axial compressive loads of 50 N. These cervical spines were divided in three groups according to the following conditions: (1) intact spine, (2) C3/C4 CDR with the Prestige LP prosthesis and PLL preservation, and (3) C3/C4 CDR with the Prestige LP prosthesis and PLL removal. The ranges of motion (ROMs) were recorded and analyzed in each group. RESULTS The C3/C4 ROM in group 3 (CDR with PLL removed) increased significantly in flexion-extension and axial rotation compared with group 1 (intact spine). Moreover, in flexion-extension, the mean total ROM was significantly larger in group 3 than in group 1. All the ROM observed in group 2 (CDR with PLL preserved) did not significantly differ from the ROM observed in group 1. CONCLUSIONS Compared with intact spines, CDR with PLL removal partly increased ROM. Moreover, the ROM in CDR with PLL preservation did not significantly differ from the ROM observed in intact spines. The PLL appears to contribute to the balance and stability of the cervical spine and should thus be preserved in cervical disc replacement provided that the posterior longitudinal ligament is not degenerative and the compression can be removed without PLL takedown.

A prospective randomized controlled study comparing the pain relief in patients with osteoporotic vertebral compression fractures with the use of vertebroplasty or facet blocking.

PURPOSE: To compare the clinical and radiological outcomes of patients undergoing percutaneous vertebroplasty (PVP) versus those undergoing facet blocking (FB) for severe pain due to osteoporotic vertebral compression fractures (OVCFs). METHODS: Two hundred and six patients who had OVCFs on spine radiography and intractable back pain for ≤8 weeks were recruited between January 2009 and January 2013 (165 females and 41 males, age ≥55 years). Patients were randomly assigned to the PVP group (100 patients) or the FB group (106 patients). VAS, ODI, Roland Morris disability (RMD) scores, scores on the Standardized Physical Component of the SF-36 form (SPC) and scores on the Standardized Mental Component of the SF-36 form (SMC) were determined preoperatively and at each follow-up time (1 day, 1 week, 1, 3, 6, and 12 months). In addition, plain radiographs were obtained at 3, 6, and 12 months postoperatively to detect new fractures. RESULTS: Significantly lower VAS, ODI, and RMD scores for patients in the PVP group compared to those in the FB group were observed at follow-up of 1 day and 1 week (p < 0.05). However, differences in the VAS, ODI, RMD and SPC/MCS (SF-36) scores between the two groups at follow-ups of more than 1 month were statistically insignificant (p > 0.05). Difference in numbers of new fractures in the two groups at the follow-up of 12 months was also statistically insignificant. CONCLUSIONS: PVP produced better pain relief than FB in the short term (≤1 week). However, the difference in pain-relief between these two techniques was insignificant in the long term (follow-up between 1 month and 12 months).

Morphological studies of cartilage endplates in subaxial cervical region.

PURPOSE: The aim of this study was to provide morphological data of endplates for the redesign of cervical artificial disc for use in the middle and lower cervical spine (C3-C7). METHODS: Reformatted CT scans of 73 individuals were analysed. The shapes of superior endplates (SEPs) and inferior endplates (IEPs) were classified as either flat or arced. The curvature radius of the IEP and sagittal disc angle were measured in the mid-sagittal plane. The maximum transverse diameter (MTD) of the SEPs and IEP was measured in the coronal plane. RESULTS: The majority of SEPs were flat (79.5 % at C7 and 91.8-95.9 % at C3-C6). Almost all (98.6-100 %) IEPs were arced. The curvature radius has a gradually increasing trend from C3 to C6 (P < 0.05, mean 29.26 mm). There were significant differences at C3-C7 in the average sagittal disc angles (5.80°, 6.92°, 7.51°, and 8.82°, respectively; P < 0.05; mean 7.26°), the average MTDs of the SEPs (13.64, 14.42, 15.03, and 16.74 mm, respectively, P < 0.05; mean 14.96 mm) and the average MTD of the IEPs (16.77, 17.67, 19.15, and 21.66 mm, respectively; P < 0.05; mean 18.81 mm). CONCLUSION: The majority of SEPs were flat, while almost all IEPs were curved. The curvature radius of IEPs has a gradually increasing trend from C3 to C6. The average sagittal disc angles, MTDs of the SEPs and IEPs significantly increased from C3 to C7. Based on the above, the current cervical artificial disc design does not sufficiently match the morphology of cervical endplates (CEPs). This mismatch may lead to some postoperative complications of cervical disc arthroplasty.

The impact of posterior temporary internal distraction on stepwise corrective surgery for extremely severe and rigid scoliosis greater than 130°.

AIM: To investigate the efficacy and safety of temporary internal distraction corrective surgery for extremely severe scoliosis. METHODS: Eleven scoliosis patients (3 males and 8 females) with curves ≥130° (mean 148.8°; range 130°-157°) who underwent a two-stage surgery, including a posterior temporary internal distraction correction and definitive posterior spinal correction with posterior pedicle screw instrumentation from 2008 to 2011 were retrospectively reviewed. Minimum follow-up was 2-years (mean 41.8 months; range 27.0-63.0 months). The analysis focused on the impact of temporary internal distraction on curve correction, pulmonary function tests (PFTs), complications and surgical outcomes. Neurosurveillance of sensory (somatosensory-evoked potentials) and motor (motor-evoked potentials) potential was performed in all cases. Posterior instrumentation was used in all patients. RESULTS: After the use of internal distraction, the preoperative major curve (mean 148.8°; range 130°-157°) was corrected to a mean of 79° (range 63°-87°), the T5-T12 kyphosis Cobb angle (mean 79°; range 30°-97°) was corrected to a mean of 59° (range 20°-75°), the coronal imbalance (mean 0.8 cm; range -3.6 to 2.8 cm) was improved to a mean of 0.6 cm (range -1.5 to 2.0 cm), the forced vital capacity percentage (FVC%) was improved from 59.3 ± 11.6 to 68.7 ± 13.7, and the forced expiratory volume in 1 s (FEV1%) was improved from 61.4 ± 13.6 to 71.3 ± 9.3. The average increase in body height was 6.7 cm, and the dorsum razor was corrected to 3-5 cm. During definitive surgery, the final major curves were corrected to a mean of 55° (range 32°-72°), the T5-T12 kyphosis Cobb was corrected to 35° (range 15°-68°), the coronal imbalance was improved to 0.5 cm (range -1.2 to 1.8 cm), the FVC% was improved to 71.2 ± 8.3, the FEV1% was improved to 76.3 ± 16.7, the increase in body height was 3.1 cm, and the dorsum razor was corrected to 1-3 cm. The mean interval time between the two surgeries was 3.5 months. None of the patients exhibited postoperative neurologic deficits or infections. No instrument complications were found during the final follow-up. CONCLUSIONS: Temporary internal distraction in a two-stage corrective surgery provided patients who had extremely severe and rigid scoliosis, an effective and safe solution for scoliosis without significant complications.

The beneficial effect of Batroxobin on blood loss reduction in spinal fusion surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: Our objective was to evaluate the efficacy and safety of Batroxobin on blood loss during spinal operations. METHODS: After obtaining approval from the ethics committee at the hospital along with informed written consent, we performed a double-blind, randomized, placebo-controlled study with 100 patients who were randomized equally into 2 groups (Batroxobin and placebo). Patients received either 2 ku IV 15 min before surgery and followed 1 ku IM of Batroxobin following surgery, or an equivalent volume of placebo (normal saline). Cost of Batroxobin treatment is amounted to 84.75 euros. The primary outcomes were intraoperative, 24 h postoperative, and total perioperative blood loss. Secondary outcomes were hemoglobin (Hb), red blood cell count (RBC), the volume of blood/fluid transfusion intraoperatively, and 24 h postoperatively. Safety evaluation parameters were the incidence of venous thrombosis in the lower extremities, active partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen. The data were analyzed using the Statistical Package for the Social Science Version 12.0. The results were presented as mean ± SEM. The Mann-Whitney test and Independent Student t test, when appropriate, were used to compare the 2 groups, and differences were considered significant if the P value was <0.05. RESULTS: 88 patients were included in the analysis while 12 patients were withdrawn from the study due to extended surgical duration, change of surgical procedure, or after the patients' request. The total perioperative blood loss was approximately 31% lower in patients given Batroxobin versus placebo (700.5 ± 45.81 vs 485.7 ± 30.01 mL, P = 0.001). The Batroxobin group had significantly less intraoperative blood loss (326.1 ± 24.16) compared to the placebo group (556.0 ± 43.58), but there was no difference in the amount of blood/fluid transfused, postoperatively Hb, or RBC between the two groups. After the operation, coagulation parameters were not significantly different between the 2 groups at the days 1 or 3 postoperatively. No adverse events related to the use of Batroxobin were recorded. There were no cases of superficial wound infection. None of the subjects died during the study. CONCLUSIONS: In this study, prophylactic use of Batroxobin provided an effective and cheap method for reducing blood loss without coagulopathy during or after operations. The use of Batroxobin for patients undergoing one-level PLIF surgery safely and effectively reduced the total amount of perioperative blood loss.