Case report: A complete lower cervical fracture dislocation without permanent neurological impairment.

BACKGROUND: Complete fractures and dislocations of the lower cervical spine are usually associated with severe spinal cord injury. However, a very small number of patients do not have severe spinal cord injury symptoms, patients with normal muscle strength or only partial nerve root symptoms, known as "lucky fracture dislocation". The diagnosis and treatment of such patients is very difficult. Recently, we successfully treated one such patient. CASE PRESENTATION: A 73-year-old male patient had multiple neck and body aches after trauma, but there was sensory movement in his limbs. However, preoperative cervical radiographs showed no significant abnormalities, and computed tomography (CT) and magnetic resonance imaging (MRI) confirmed complete fracture and dislocation of C7. Before operation, the halo frame was fixed traction, but the reduction was not successful. Finally, the fracture reduction and internal fixation were successfully performed by surgery. The postoperative pain of the patient was significantly relieved, and the sensory movement of the limbs was the same as before. Two years after surgery, the patient's left little finger and ulnar forearm shallow sensation recovered, and the right flexion muscle strength basically returned to normal. CONCLUSION: This case suggests that when patients with trauma are encountered in the clinic, they should be carefully examined, and the presence of cervical fracture and dislocation should not be ignored because of the absence of neurological symptoms or mild symptoms. In addition, positioning during handling and surgery should be particularly avoided to increase the risk of paralysis.

Upregulated estrogen receptors impairs myogenesis and elevates adipogenesis related factor levels in the paravertebral muscles of patients with idiopathic scoliosis.

The prevalence of idiopathic scoliosis (IS) is 2-3% worldwide and is more common in girls. Estrogen receptors (ERs) is supposed to be related to sex differences and development of IS. Meanwhile, paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of IS. But the changes of ERs between the PVMs from IS patients and controls, and the mechanism by which ERs may affect IS patients remain unclear. Thus, the expression levels of ERs, myogenesis regulator (MYOG) and adipogenesis related factors (CEBPA, PPARγ, FABP4), as well as morphological changes in the PVMs and primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs) of IS patients and controls were investigated. Increased expression levels of ERs and CEBPA, PPARγ, FABP4, together with severe myofiber necrosis and fat infiltration, were found in the PVMs of IS patients. Meanwhile, upregulated ERs, FABP4 and CEBPA, downregulated MYOG and impaired myogenesis were also revealed in the hSM-MPCs of IS patients compared with those of controls. Upregulation of ERs inhibited myogenesis but increased expression of CEBPA and FABP4 in C2C12 myoblasts. Nevertheless, treatment of ER antagonist increased expression of MYOG, enhanced myogenesis and decreased expression of CEBPA and FABP4 in skeletal muscle cells of IS patients. Therefore, our study suggested that PVMs specific upregulation of ERs could impair myogenesis and increase the expression of adipogenesis related factors, further leading to PVMs abnormalities in IS patients.

The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity characterized by changes in the three-dimensional structure of the spine. It usually initiates during puberty, the peak period of human growth when the secretion of numerous hormones is changing, and it is more common in females than in males. Accumulating evidence shows that the abnormal levels of many hormones including estrogen, melatonin, growth hormone, leptin, adiponectin and ghrelin, may be related to the occurrence and development of AIS. The purpose of this review is to provide a summary and critique of the research published on each hormone over the past 20 years, and to highlight areas for future study. It is hoped that the presentation will help provide a better understanding of the role of endocrine hormones in the pathogenesis of AIS.

Retrospective analysis of deformed complex vertebral osteotomy in children with severe thoracic post-tubercular angular kyphosis.

BACKGROUND: Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. METHODS: Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. RESULTS: The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P < 0.001) with a mean kyphosis correction of 63.41°; at the final follow up, it was 18.4° ± 2.29° (P < 0.001) without obvious loss of correction. The postoperative mean TK, LL, and SVA were reduced to 24.05° ± 3.84°, 46.9° ± 3.53°, and 0.6 cm ± 0.34 cm, respectively (P < 0.001 for all); and there was no obvious loss of sagittal alignment and balance at the final follow up (p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P < 0.001); and ODI score reduced from 22.21 ± 6.93 to 5.02 ± 2.6 (P < 0.001) at the final follow up. CONCLUSIONS: DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Treatment of ankylosing spondylitis complicated with a thoracolumbar Andersson lesion by posterior closed osteotomy, debridement and fusion through the fracture line.

BACKGROUND: An Andersson lesion (AL) is a fatigue fracture occurring across three columns in ankylosing spondylitis (AS), resulting in spinal pseudarthrosis (SP) formation, most commonly in the thoracolumbar segment. However, there is still great controversy and few reports on the best surgical method for the treatment of AS combined with thoracolumbar AL. The purpose of this study was to investigate the efficacy of posterior closed osteotomy, debridement and fusion through the fracture line for the treatment of this disease. METHODS: The clinical data of 13 patients (male 8, female 5, mean age 50.6 years) with AS combined with thoracolumbar AL treated with posterior closed osteotomy, debridement and fusion through the fracture line were retrospectively analysed. The following parameters of the full-length lateral spine radiographs were measured preoperatively and at the last follow-up: cervical 7 tilt (C7T), global kyphosis (GK), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), local kyphosis (LK), angle of the fusion levels (AFL), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and sagittal vertical axis (SVA). The visual analog scale (VAS), Oswestry disability index (ODI) and Scoliosis Research Society-22 (SRS-22) scores were recorded preoperatively and at the last follow-up. RESULTS: The mean operation time was 345 min, the mean blood loss was 673 mL, and the mean follow-up time was 21.9 months. Compared with the preoperative values, the C7T, GK, TK, TLK, LK, AFL, PT, SS and SVA values of all patients were significantly improved at the last follow-up (P < 0.05); GK improved from 81.62 ± 16.11 to 50.15 ± 8.55, with an average of 31° of correction (F = 75.945, P<0.001). The VAS, ODI and SRS-22 scores also significantly improved (P < 0.05). At the last follow-up, bone fusion was found in all fracture ends. One patient developed numbness in the lower limbs after surgery and recovered after 3 months of rehabilitation; none of the remaining patients experienced postoperative complications. CONCLUSIONS: Posterior closed osteotomy, debridement and fusion through the fracture line completely removes the necrotic tissue around the SP, relieves symptoms, and corrects kyphosis simultaneously. It reduces the tension behind the fracture line or changes the tension into compressive stress, enabling stable repair of the fracture and avoiding anterior surgery. It is a safe and effective operation.

Abnormal TNS3 gene methylation in patients with congenital scoliosis.

BACKGROUND: Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. METHODS: Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. RESULTS: A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 < 0.01). There was no significant difference in the degree of methylation of SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 < 0.01). CONCLUSION: Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (> 130°).

INTRODUCTION: The treatment of extremely severe and rigid spinal deformities was a great surgical challenge. Pulmonary impairment often occurred, which increased the challenges to already daunting surgical approaches. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction (HFT) for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (AIS) of more than 130°. MATERIALS AND METHODS: From 2010 to 2017, 11 patients suffered from extremely severe and rigid AIS of more than 130° underwent posterior-only surgical correction with HFT. The preoperative mean coronal Cobb angle of major curve was 139.01° ± 5.83°, and the mean flexibility was 17.21% ± 3.33%; the mean angle of thoracic kyphosis (TK) and lumbar lordosis (LL) were 65.02° ± 7.21° and 39.05° ± 4.08°, respectively; the mean trunk shift (TS) and sagittal vertical axis (SVA) were 3.3 ± 0.97 cm and 3.97 ± 1.16 cm, respectively; moreover, the percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV1%) were 50.08% ± 6.07% and 53.46% ± 5.96%, respectively; the mean body height and weight were 140.09 ± 4.95 cm and 37 ± 4.34 kg, respectively. RESULTS: The mean duration of surgery was 335.91 ± 48.31 min and blood loss was 1590 ± 520.1 ml. The average period of follow-up was 32.18 ± 8.17 months. After heavy HFT, the mean coronal Cobb angle of major curve was reduced to 82.98° ± 6.91° with correction rate of 40.39%. After posterior-only surgical correction, the mean coronal Cobb angle was further reduced to 51.17° ± 5.4° with correction rate of 63.27%. The postoperative mean TK, LL, TS and SVA were improved to 23.85° ± 5.14°, 44.95° ± 2.26°, 1.32 ± 0.72 cm and 1.42 ± 0.83 cm, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.72%; moreover, the mean FVC% and FEV1% were increased to 65.45% ± 5.29% and 69.08% ± 5.32% with improvement of 15.36% and 15.62%, respectively; the mean body height and weight were increased to 154.45 ± 5.32 cm and 45 ± 4.02 kg with improvement of 14.36 cm and 8 kg, respectively. The spinal cord function was stable, and there were no new neurological symptoms after correction. CONCLUSIONS: Posterior-only surgical correction with heavy HFT could be safe and effective for the treatment of extremely severe and rigid AIS of more than 130° in reducing the incidence of complications and greatly improving curve correction.

Minimum 5-year follow-up outcomes for one-stage posterior instrumentation without neurosurgery intervention for correction of scoliosis associated with Chiari I malformation and syringomyelia.

INTRODUCTION: Traditionally, the common belief has been that, all patients with Chiari I malformation (CM-1) and syringomyelia (SM) undergoing a neurosurgical procedure even if they are neurologically asymptomatic. As the pathology of CM-1 and SM has become better understood, the traditional concepts have been challenged. The objective of this study was to investigate the minimum 5-year follow-up clinical outcomes of surgical treatment of patients with scoliosis associated with CM-1 and SM and to evaluate the necessity of neurosurgical intervention before corrective surgery. METHODS: This retrospective study was performed from May 2009 to September 2014. We enrolled 35 patients with scoliosis associated with CM-1 and SM who were undergoing spinal correction surgery without neurosurgical intervention. During the surgery, spinal cord monitor and wake-up test were used. Preoperative, postoperative, and final follow-up major curve coronary Cobb angle, correction rate, apical vertebral rotation (AVR), apical vertebral translation (AVT), thoracic kyphosis angle (T5-T12), lumbar lordosis angle (L1-S1) were analyzed on radiographs. RESULTS: The mean follow-up period was 82.5 months. The preoperative and postoperative mean curve coronary Cobb angle was from 55.7 ± 7.5° to 20.1 ± 5.8°, correction rate was 63.9%, AVR from 2.8 ± 0.6° to 1.3 ± 0.5°, AVT from 5.1 ± 1.4 to 1.7 ± 0.7 cm, thoracic kyphosis angle from 18.7 ± 4.0° to 32.2 ± 2.7°, lumbar lordosis angle from 36.3 ± 4.1° to 43.8 ± 3.2°. No neurological deficits occurred during the operation and follow-up. CONCLUSIONS: Our minimum 5-year follow-up outcomes showed that in a distinct patient population of neurologically asymptomatic individuals with CM-1, SM and progressive scoliosis, posterior instrumented spinal deformity surgery can be safely done without neurosurgical interverventions with the help of preoperative flexibility evaluation and intraoperative neuromonitoring.

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OBJECTIVES: Spinal infection is a rare infectious disease that is difficult to treat. The incidence of spinal infection is on the rise with the experiential use of antibiotics, the increasing incidence of drug-resistant bacteria, and the improvement of detection techniques. Traditional detection methods have limitations such as low sensitivity and long time-consuming in the diagnosis of spinal infection. In the clinical diagnosis and treatment of spinal infection, it has always been the focus and difficulty to determine the type of pathogens and to use antibiotics in a targeted manner. Many patients in the early stage of spinal infection due to the limitations of traditional detection methods cannot be quickly and accurately diagnosed, resulting in diagnosis delay, missed the best treatment time, bringing disastrous consequences to patients. There is an urgent need for a high-specificity, high-sensitivity, and time-saving test technique in clinical practice, which can simultaneously distinguish and identify the pathogen of spinal infection. Metagenomic next-generation sequencing (mNGS) is a new frontier technology emerging in recent years. It can detect all known pathogens in samples and has been used to diagnose clinically atypical and rare infectious diseases. This study aims to analyze the sensitivity of mNGS technique in diagnosing pathogens after spinal infection and its effect on prognosis. METHODS: Clinical data of 82 patients with spinal infection admitted to Xiangya Hospital of Central South University from January 2019 to December 2021 were retrospectively analyzed. Peripheral blood erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) were routinely performed before surgery, and focal tissue specimens were obtained during surgery. Microbial culture, histopathological examination, and mNGS detection were performed. All patients were assigned into a targeted medication group (n=71) and an experienced treatment group (n=1) based on the results of mNGS. After regular follow-up, the sensitivity of mNGS to detect pathogens of spinal infection and its effect on prognosis were evaluated. RESULTS: The positive rate of mNGS (86.59%, 71/82) was significantly higher than that of microbial culture (18.99%, 15/79) and PCT (30.23%, 13/43). There were no significant differences in preoperative temperature, white blood cell count, neutrophil ratio, and scores of Visual Analogue Scale between the targeted medication group and the experienced treatment group. Preoperative use of antibiotics had no significant effect on the positive rate of mNGS and microbial culture (P=0.681). According to the targeted medication group, postoperative CRP and ESR showed a decreasing trend, and the ESR was significantly lower than that of the experienced treatment group at 30 days follow-up (P=0.044). CONCLUSIONS: Compared with the microbial culture or PCT, mNGS has a higher sensitivity rate to detect pathogens of spinal infection. Patients receiving targeted antibiotics based on the results of mNGS have better outcomes than those receiving the experienced medicine.

Nontargeted Metabolomic Analysis of Plasma Metabolite Changes in Patients with Adolescent Idiopathic Scoliosis.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a relatively common spinal rotation deformity, and the pathogenesis of AIS is accompanied by metabolic dysfunction and changes in biochemical factors. In this study, plasma metabolite changes in AIS patients were analyzed based on nontargeted metabolomics to provide new insights for clarifying functional metabolic abnormalities in AIS patients. METHODS: Clinical indexes and blood samples were collected from 12 healthy subjects and 16 AIS patients. Metabolomics was used to analyze the changes in metabolites in plasma samples. The correlation between plasma metabolites and clinical indexes was analyzed by the Spearman rank correlation coefficient. RESULTS: Analysis of clinical data showed that the body weight, body mass index (BMI), and bone mineral density (BMD) index of the AIS group significantly decreased, while the blood phosphorus and Cobb angles increased significantly. Metabolomic analysis showed significant changes in 72 differential metabolites in the plasma of the AIS group, mainly including organooxygen compounds, carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, and keto acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that arginine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle (TCA cycle) were significantly enriched in the AIS and healthy groups. Spearman rank correlation coefficient analysis showed that the plasma metabolites C00026 (oxoglutarate), C00062 (L-arginine, arginine), C01042 (N-acetylaspartate), and C00158 (citrate) were significantly correlated with clinical indexes in AIS patients. In the healthy group, the plasma metabolites C00122 (fumarate), C00025 (glutamate and L-glutamic acid) and C00149 (malate, L-malic acid) were significantly correlated with clinical indexes, while C00624 (N-acetylglutamate) was not significantly correlated with the clinical indexes. CONCLUSION: The occurrence of AIS led to changes in clinical indexes and plasma metabolites. Plasma biomarkers and functional metabolic pathways were correlated with clinical indexes, which might provide new insights for the diagnosis and treatment of AIS.

Halo traction combined with posterior-only approach correction for cervical kyphosis with Neurofibromatosis-1: minimum 2 years follow-up.

BACKGROUND: Surgical management of cervical kyphosis in patients with NF-1 is a challenging task. Presently, anterior-only (AO), posterior-only (PO) and combined anterior-posterior (AP) spinal fusion are common surgical strategies. However, the choice of surgical strategy and application of Halo traction remain controversial. Few studies have shown and recommended posterior-only approach for cervical kyphosis correction in patients with NF-1. The aim of this study is to evaluate the safety and the effectiveness of halo Traction combined with posterior-only approach correction for treatment of cervical kyphosis with NF-1. METHODS: Twenty-six patients with severe cervical kyphosis due to NF-1 were reviewed retrospectively between January 2010 and April 2018. All the cases underwent halo traction combined with posterior instrumentation and fusion surgery. Correction result, neurologic status and complications were analyzed. RESULTS: In this study, cervical kyphosis Cobb angle decreased from initial 61.3 ± 19.7 degrees to postoperative 10.6 ± 3.7 degrees (P<0.01), with total correction rate of 82.7%, which consist of 45.8% from halo traction and 36.9% from surgical correction. JOA scores were improved from preoperative 13.3 ± 1.6 to postoperative 16.2 ± 0.7 (P<0.01). Neurological status was also improved. There was no correction loss and the neurological status was stable in mean 43 months follow-up. Three patients experienced minor complications and one patient underwent a second surgery. CONCLUSION: Halo traction combined with PO approach surgery is safe and effective method for cervical kyphosis correction in patients with NF-1. A satisfied correction result, and successful bone fusion can be achieved via this procedure, even improvement of neurological deficits can also be obtained. Our study suggested that halo traction combined with PO approach surgery is another consideration for cervical kyphosis correction in patients with NF-1.

Posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis with spinal epidural abscess: a minimum 5-year follow-up.

OBJECTIVE: To investigate the clinical efficacy and feasibility of posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis (TB) with spinal epidural abscess. METHODS: From January 2008 to January 2014, a total of 45 patients (27 male and 18 female) were reviewed. The patients were diagnosed with thoracolumbar TB with spinal epidural abscess. The patients underwent posterior-only debridement, internal fixation, and interbody fusion using titanium mesh. Hence, we assessed the intraoperative and postoperative complications, disease recurrences, kyphosis deformity correction, and neurological improvement following the American Spinal Injury Association (ASIA). We used SPSS 22.0 for the statistical analyses. An independent Student's t-test was used for the analysis of preoperative and postoperative continuous variables. The value of P (P < 0.05) was considered statistically significant. RESULTS: The mean age of patients was 37.76 ± 10.94 years (17-59 years). The mean follow-up time was 82.76 ± 12.56 months (60-128 months). The mean kyphosis Cobb angle preoperative was 29.36 ± 13.29° (5-55°) and postoperative was 3.58 ± 5.44° (- 6-13°), given the value of P (P < 0.001). According to the neurological score by the ASIA scale, there were 3 cases of grade B, 11 cases of grade C, 16 cases of grade D, and 15 cases of grade E preoperatively. The neurological score improved by 1 ~ 2 grades. All patients achieved pain relief and the VAS score significantly reduced at the last follow-up (P<0.05). While 1 patient had cerebrospinal fluid leakage, 1 had a neurological complication, 1 had delayed surgical wound healing, and 1 had a disease recurrence. No pseudoarthrosis or implant failure occurred in our patients. All patients achieved solid bone graft fusion. CONCLUSION: For thoracolumbar TB patients with spinal epidural abscess, posterior-only debridement, internal fixation, and interbody fusion using titanium mesh are safe and effective surgical treatments.

High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis.

BACKGROUND: The etiology of congenital scoliosis (CS) is complex and uncertain. Abnormal DNA methylation affects the growth and development of spinal development. In this study, we investigated the role of DNA methylation in CS. METHODS: The target region DNA methylation level in the peripheral blood of patients with CS was analyzed. Through in-depth analysis, genes closely related to the growth and development of the vertebra were identified. EdU staining was performed to verify the role of differentially expressed genes in chondrocyte proliferation. RESULTS: The hypermethylated KAT6B gene was observed in patients with CS, and was positively correlated with the Cobb angle. KAT6B was primarily expressed on chondrocytes. The promoter of KAT6B in CS patients was hypermethylated, and its expression was significantly reduced. Further mechanistic studies revealed that EZH2 mediated trimethylation of lysine 27 on histone H3 of the KAT6B promoter. Overexpression of KAT6B in CS-derived primary chondrocytes can significantly promote chondrocyte proliferation, which may be related to activation of the RUNX2/Wnt/ß-catenin signaling pathway. CONCLUSION: Epigenetic modification of KAT6B may be a cause of CS. If similar epigenetic modification abnormalities can be detected through maternal liquid biopsy screening, they may provide useful biomarkers for early screening and diagnosis of CS.

Changes in circulating cell-free nuclear DNA and mitochondrial DNA of patients with adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed. METHODS: The plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. RESULTS: The plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type. CONCLUSION: Although with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.

Association of IFNG gene polymorphisms with pulmonary tuberculosis but not with spinal tuberculosis in a Chinese Han population.

Spinal tuberculosis (STB) is an extrapulmonary form of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), which accounts for around 2% of all TB cases and can lead to spine degeneration. It is widely accepted that host genetic factors participate in the pathogenesis of active TB, but the factors controlling which TB form will manifest after Mtb infection remain unknown. We hypothesized that a genetic difference may exist between the development of STB and pulmonary tuberculosis (PTB). Here, three single nucleotide polymorphisms (SNPs) in the IFNG gene (rs2069718), IRGM gene (rs10065172), and MBL2 gene (rs11003125) were genotyped among 183 PTB patients, 177 STB patients, and 360 healthy controls from the Chinese Han population. We found that rs2069718 genotypes were significantly associated with PTB (TT, p = 0.007; CT, p = 0.008) but not STB, and the TT genotype (p = 0.046) of rs2069718 were less common in PTB than in STB. In contrast, neither PTB nor STB were found to be associated with rs10065172 and rs11003125. Overall, we found a difference in the rs2069718 genetic distribution between the STB and PTB patients in a Chinese Han population. The rs2069718 TT genotype was associated with a protective role in PTB but not STB development during active Mtb infection.

Matrix metalloproteinase-1 promoter -1607 bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population.

BACKGROUND: Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase-1 (MMP-1) is increased in cells with Mycobacterium tuberculosis infection. MMP-1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP-1-1607 influences its transcription, its role in spinal tuberculosis remains unknown. METHODS: Healthy controls and patients with spinal tuberculosis of Han ethnicity were recruited between January 2010 and May 2016. The MMP-1-1607 1G/2G polymorphism was genotyped using the Sequenom mass Array polymorphism analysis system. RESULTS: The genotypes of 1G/1G, 1G/2G, and 2G/2G were found in 13.7%, 53.6%, and 32.8% of patients, and 12.2%, 37.4%, and 50.4% of controls, respectively. The 1G/2G genotype were more common in cases than in controls (P=2.05E-04). The 1G allele showed an association with an increased risk for spinal tuberculosis when compared to 2G allele (P=.004). 1G genotypes, having at least one 1G allele, were associated with the risk of developing spinal tuberculosis (1G/1G+1G/2G vs 2G/2G: OR=2.084, 95%CI=1.401-3.100, P=2.65E-04). CONCLUSION: 1G genotypes of the MMP-1-1607 may be associated with susceptibility to spinal tuberculosis in Southern Chinese Han population.

Management of eosinophilic granuloma in pediatric patients: surgical intervention and surgery combined with postoperative radiotherapy and/or chemotherapy.

BACKGROUND: Eosinophilic granuloma (EG) of spine in pediatric patients presents kinds of clinical manifestation and a difficult management scenario. The choice of treatment, issues of surgical intervention versus conservative treatment, combination therapy or single treatment, all these factors, including neurological deficits, spinal stability, long-term complications, and continued skeletal growth, must be considered. METHODS: From 2008 to the 2015, 31 pediatric patients of spinal EG were retrospectively reviewed. They were 17 males and 14 females, with a mean age 8.89 ± 2.84 years old (range, 3.5-14 years old). All the cases were divided into two groups. Twenty-three cases (Group S) accepted surgical interventions and surgery combined with local low-dose radiotherapy and/or chemotherapy. Eight patients (Group C) accepted radiotherapy and/or chemotherapy. All the patients had imaging studies of the lesion including standard radiography, three-dimensional computed tomography (CT) scan, and magnetic resonance imaging (MRI) prior to and after treatment. Cases in group S underwent surgery-related treatment, which include six patients accepted surgery only, nine patients accepted postoperative low-dose radiotherapy, four patients accepted additional chemotherapy, and four patients accepted both. Cases in group C accepted radiotherapy and/or chemotherapy, which include five patients accepted radiotherapy, one patient accepted chemotherapy, and two patients accepted both radiotherapy and chemotherapy. Clinical symptoms, neurologic status, radiologic manifestations, treatment, outcome, and/or complications were recorded and analyzed. RESULTS: All the 31 patients had pain relief (both in group S and group C) but the patients in group S obtained more prompt pain relief. All the patients in group S obtained local kyphosis correction, reconstruction of stability of spine, and recovery of neurological deficit after treatment. They have no surgery-related complications after treatment and in follow-up. Seventeen patients who received additional postoperative radiotherapy and/or chemotherapy also had good outcomes. There were no severe radiation and chemotherapy complications in procedure. The patients (group C) who accepted non-surgical treatment also have no severe complications, and a new femur lesion was found in one patient in follow-up. CONCLUSION: Surgical intervention, including anterior and/or posterior approach with bone graft or surgery combined with postoperative low-dose radiotherapy and/or chemotherapy is a safe and effective way for treatment of the spinal EG. Compared with radiotherapy and/or chemotherapy, more prompt pain relief can be achieved via surgical intervention or surgery combined radiotherapy and/or chemotherapy.

More preoperative flexibility implies adequate neural pliability for curve correction without prophylactic untethering in scoliosis patients with asymptomatic tethered spinal cord, a retrospective study.

BACKGROUND: Tethered spinal cord is frequently associated with scoliosis. It is still controversial whether a prophylactic untethering is necessary before correction procedure in scoliosis patients with tethered spinal cord. In this study we determined the clinical outcome of a one-stage posterior scoliosis correction without a prophylactic untethering for treating scoliosis with an asymptomatic tethered spinal cord. METHODS: Seventeen (5 males and 12 females) scoliosis patients with tethered spinal cords were retrospectively reviewed. All patients underwent a one-stage posterior scoliosis correction without preventive untethering. Parameters of radiograph were used to assess correction result. The Scoliosis Research Society (SRS)-22 questionnaire was analyzed pre- and post-operatively to evaluate the clinical outcomes. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the pre- and post-operative spinal cord function. RESULTS: The post-operative coronal Cobb angle was significantly decreased compared with preoperative. (23.8 ± 6.4° vs. 58.4 ± 12.6°, P < 0.01). The coronal Cobb angle was 22.4 ± 6.8° at the final follow-up evaluation. The apical vertebral translation (AVT) was also decreased significantly. (27.5 mm vs. 60.9 mm, P < 0.01). The SRS-22 total score was improved at the 1-year follow-up evaluation compared with the pre-operative SRS-22 total score (87 ± 4 vs. 70 ± 5, p < 0.05). The functional activities, pain, self-image, mental health, and surgery satisfactory scores at the final follow-up evaluation were all improved compared with the corresponding pre-operative scores, especially the self-image and mental health scores (p < 0.05). The spinal cord function was stable and there was no new neurological symptoms after scoliosis correction. No difference existed between the pre- and post-operative total mJOA score (26 ± 2 vs. 27 ± 2, p = 0.39), which including subjective symptom (p = 0.07), clinical symptom (p = 0.33), daily activities (p = 0.44) and bladder function (p = 0.67). CONCLUSION: One-stage posterior scoliosis correction is a safe and effective surgical procedure for scoliosis patients combined with asymptomatic tethered spinal cord who have adequate spinal cord function reserve.

One-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion in the surgical treatment of thoracolumbar spinal tuberculosis with kyphosis in children: a preliminary report.

PURPOSE: The purpose of this study was to determine the efficacy and feasibility of surgical management of children with thoracolumbar spine tuberculosis with kyphosis by using one-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion. METHODS: From October 2010 to September 2013, 21 children with thoracolumbar spinal tuberculosis accompanied by kyphosis were treated with one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion. There were 13 males and 8 females, aged from 7 to 13 years old (average age 9.9 years). The mean follow-up was 34 months (range26-48 months). Patients were evaluated before and after surgery in terms of ESR, neurologic status, pain, and kyphotic angle. RESULTS: Spinal tuberculosis was completely cured, and the grafted bones were fused in all 21 patients. There was no recurrent tuberculous infection. ESR got normal within 3 months in all patients. The ASIA neurologic classification improved in all cases. Pain relief was obtained in all patients. The average preoperative kyphosis was 29.7° (range 12-42°) and decreased to 5.5° (range 2-10°), postoperatively. There was no significant loss of the correction at the latest follow-up. CONCLUSIONS: Our results show that one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion were an effective treatment for children with thoracolumbar spinal tuberculosis. It is characterized as minimum surgical trauma, good neurologic recovery, good correction of kyphosis, and prevention of progressive kyphosis.

One-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion in the surgical treatment of lumbo-sacral spinal tuberculosis in the aged.

PURPOSE: Aged patients represent a high risk group for acquiring spinal tuberculosis, and it still remains a leading cause of kyphosis and paraplegia in developing nations. Aged patients often combined with cardiovascular and respiratory disease and single lung ventilation via anterior approach surgery could result in more post-operative complications. We aimed to analyze the efficacy and feasibility of surgical management of aged patients with lumbo-sacral spine tuberculosis using one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion. METHODS: From March 2009 and July 2012, 17 aged patients with lumbo-sacral spinal tuberculosis were treated with one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion. There were eight male and nine female with a mean age of 63.3 years (range: 60-71 years). The mean follow-up was 46.5 months (range 38-70 months). Patients were evaluated before and after surgery in terms of ESR, neurological status, visual analog scale (VAS), and lumbosacral angle. RESULTS: Spinal tuberculosis was completely cured and the grafted bones were fused in all 17 patients. There were no recurrent tuberculous infections. ESR became normal within three months in all patients. The ASIA neurological classification and VAS scores improved in all cases. The average preoperative lumbosacral angle was 20.6° (range 18.1°-22.5°) and became 29.4° (range 27.1°-32.5°) at final follow-up. CONCLUSIONS: Our results showed that one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion was an effective treatment for aged patients with lumbo-sacral spinal tuberculosis. It is characterized with minimum surgical trauma, good pain relief, good neurological recovery, and good reconstruction of the spinal stability.