DJ-1-mediated p62 degradation delays intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is the most important pathological basis of degenerative spinal diseases, for which effective interventions are still lacking. Oxidative stress is considered to be one of the leading pathological mechanisms contributing to IDD. However, the exact role of DJ-1 as an essential member of the antioxidant defense system in IDD is still unclear. Therefore, the aim of this study was to investigate the role played by DJ-1 in IDD and to reveal its potential molecular mechanisms. Western blot and immunohistochemical staining assays were performed to detect the expression of DJ-1 in degenerative nucleus pulposus cells (NPCs). After overexpression of DJ-1 in NPCs by lentiviral transfection, DCFH-DA and MitoSOX fluorescent probes were used to evaluate the levels of reactive oxygen species (ROS); while western blot, TUNEL staining, and Caspase-3 activity were used to assess apoptosis. Immunofluorescence staining was used to demonstrate the relationship between DJ-1 and p62. After inhibition of lysosomal degradation function with chloroquine, p62 degradation and apoptosis in DJ-1 overexpressing NPCs were further examined. In vivo, we assessed the therapeutic effect of upregulated DJ-1 on IDD by X-ray, MRI and Safranin O-Fast green staining. The protein expression of DJ-1 was significantly decreased in degenerated NPCs, accompanied by increased apoptosis. However, overexpression of DJ-1 significantly inhibited the elevated ROS levels and apoptosis in NPCs under oxidative stress. Mechanistically, our results showed that upregulation of DJ-1 promoted p62 degradation via the autophagic lysosomal pathway and that the protective effect of DJ-1 on NPCs under oxidative stress was partially mediated by promoting lysosomal pathway degradation of p62. Moreover, intradiscal injection of adeno-associated virus for overexpression of DJ-1 mitigated the progression of IDD in rats. This study reveals that DJ-1 maintains the homeostasis of NPCs by promoting the degradation of p62 through the autophagic lysosomal pathway, suggesting that DJ-1 is a promising new target for IDD intervention.

Clinical progression of ossification of the ligamentum flavum in thoracic spine: a 10- to 11-year follow-up study.

BACKGROUND: Thoracic ossification of ligamentum flavum (TOLF) can be asymptomatic and progress insidiously. But, long-term follow-up results of clinical progression of TOLF are still unknown. METHODS: The clinical progression of 81 patients with TOLF at our center, followed for 10 to 11 (mean, 10.3) years from May 2010 to November 2021, were analyzed. Among them, 51 patients with thoracic myelopathy were caused by single- or multi-segment TOLF, and received partial TOLF resection (30 patients) or total TOLF resection (21 patients). The remaining 30 patients showed TOLF on imaging examinations, but TOLF was not the responsible compressing factor causing myelopathy and with no TOLF resection. The mJOA score (total 11 scores) and spinal operation were used to evaluate the clinical progression at follow-up. RESULTS: During the 10- to 11-year follow-up of 81 TOLF patients, 71 (87.7%) had no deterioration of neurological function, and 10 (12.3%) patients had deterioration of neurological function and had another spinal operation, including only 4 (4.9%) suffered thoracic myelopathy caused by the progression of TOLF; 6 (7.4%) for other spinal diseases: 2 (2.5%) had fall damage and acute spinal cord injury at the TOLF level; 2 (2.5%) had thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL); 2 (2.5%) had cervical spondylosis and received cervical operation. CONCLUSIONS: Most TOLF (87.7%) patients had no clinical progression and received no reoperations for TOLF in the ten-year dimension (mean, 10.3 years). Narrow spinal canal for TOLF increases the risk of traumatic paraplegia.

Clinical and radiographic features of adult calcified thoracic disc herniation: a retrospective analysis of 31 cases.

PURPOSE: To analyze the clinical and radiographic characteristics of calcified thoracic disc herniation (CTDH) and explore the possible pathogeneses. METHODS: This is a retrospective clinical review of prospectively collected imaging data based at a single institute from 2004 to 2021. Clinical and radiographic parameters of CTDH patients were retrospectively collected and analyzed. RESULTS: All 31 patients included presented thoracic myelopathy with a 17.05-month preoperative disease duration. Three (9.7%) patients had a history of trauma, and the rest had insidious onset. The average spinal canal ventral-occupying ratio was 74.90 ± 15.16%. The most prominent radiographic feature was the calcification of the nucleus pulposus in the intervertebral disc and the calcified lesion contiguous with the disc space protruding into the spinal canal. Three main imaging forms of CTDH were found: calcium-ringed lesion (5), heterogeneous calcification lesion (19), and homogeneous calcification lesion (7). The radiographic manifestations, intraoperative findings, and postoperative pathologies of the three subtypes were different. The calcium-ringed lesion type was younger and had a shorter preoperative duration and significantly lower mJOA score. A special case was observed conservatively for five years, which suggested that a heterogeneous lesion could progress to a homogeneous lesion. CONCLUSIONS: Adult CTDH is a special thoracic disc disease with insidious onset, a long course, and a high spinal canal-occupying ratio. Calcium deposits in the spinal canal originate from the nucleus pulposus. The intraoperative findings and postoperative pathology of subtypes are different, which might indicate different pathological mechanisms.

Prevalence, diagnosis, and impact on clinical outcomes of dural ossification in the thoracic ossification of the ligamentum flavum: a systematic review.

STUDY DESIGN: Systematic review. BACKGROUND CONTEXT: Thoracic ossification of the ligamentum flavum (TOLF) has become the principal cause of thoracic spinal stenosis. Dural ossification (DO) was a common clinical feature accompanying with TOLF. However, on account of the rarity, we know little about the DO in TOLF so far. PURPOSE: This study was conducted to elucidate the prevalence, diagnostic measures, and impact on the clinical outcomes of DO in TOLF by integrating the existing evidence. METHODS: PubMed, Embase, and Cochrane Database were comprehensively searched for studies relevant to the prevalence, diagnostic measures, or impact on the clinical outcomes of DO in TOLF. All retrieved studies meeting the inclusion and criterion were included into this systematic review. RESULTS: The prevalence of DO in TOLF treated surgically was 27% (281/1046), ranging from 11 to 67%. Eight diagnostic measures have been put forward to predict the DO in TOLF using the CT or MRI modalities, including "tram track sign", "comma sign", "bridge sign", "banner cloud sign", "T2 ring sign", TOLF-DO grading system, CSAOR grading system, and CCAR grading system. DO did not affect the neurological recovery of TOLF patients treated with the laminectomy. The rate of dural tear or CSF leakage in TOLF patients with DO was approximately 83% (149/180). CONCLUSION: The prevalence of DO in TOLF treated surgically was 27%. Eight diagnostic measures have been put forward to predict the DO in TOLF. DO did not affect the neurological recovery of TOLF treated with laminectomy but was associated with high risk of complications.

LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.

Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine-rich repeat-containing G-protein-coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF.

Banner cloud sign: a novel method for the diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum.

PURPOSE: Dural ossification (DO) is common in patients with ossification of the ligamentum flavum (OLF) and is the leading cause of dural tears. However, the methods used for DO diagnosis are limited. The purpose of this study was to propose a novel CT-based imaging sign, Banner cloud sign (BCs), and clarify its clinical characteristics and correlations with DO. METHODS: 57 OLF patients who underwent thoracic spine decompression surgery in our single-center between January- and October-2018 were recruited and divided into two groups based on the presence of DO. Patient demographics and radiographic data were analyzed. Hematoxylin-eosin staining and micro-CT were used to detect the micro-morphological changes of DO. The diagnostic value of BCs for DO was assessed by sensitivity and specificity. RESULTS: 12 patients with a total of 19 segments were diagnosed as DO. The incidence of DO was 21.1% (12/57) in OLF patients and 9.5% (19/200) in OLF segments. Patients with DO had a shorter disease duration and a higher incidence of cerebrospinal fluid leakage than those without DO. Hematoxylin-eosin staining and micro-CT showed that the dura mater was ossified and fused with ossified ligamentum flavum, and diffusion along the dura mater, like a banner cloud flying on the mountain. The sensitivity and specificity of BCs in DO diagnosis were 78.9 and 90.6%, respectively. CONCLUSION: BCs can vividly and intuitively describe the imaging features of DO and has high diagnostic accuracy. It could be a promising and valuable method for the diagnosis of DO.

Significance of body mass index on thoracic ossification of the ligamentum flavum in Chinese population.

PURPOSE: To investigate the risk factors for thoracic ossification of the ligamentum flavum (TOLF), especially the relationship between BMI and TOLF. METHODS: A total of 856 individuals consisting of 326 controls without ossification of spinal ligaments and 530 TOLF inpatients who underwent thoracic spine decompression surgery at our hospital between January 2013 and September 2020 were included. All subjects were classified into 4 grades: Grade 0) control; Grade 1) single-segment TOLF; Grade 2) multi-segment TOLF; and Grade 3) TOLF combined thoracic ossification of the posterior longitudinal ligament (T-OPLL). Logistic regression analysis was performed to identify the risk factors for TOLF. The TOLF index was calculated to assess the severity of TOLF, and its relationship with BMI was investigated by correlation analysis. RESULTS: Overall, TOLF patients are most numerous in the 50-59 age group. Age and gender were considered as independent risk factors for Grades 1 and 2. BMI was identified as an independent risk factor for TOLF. Furthermore, BMI was significantly higher in Grade 1 (26.1 VS 24.5 kg/m2, P = 0.0001), Grade 2 (28.2 VS 24.5 kg/m2, P < 0.0001), and Grade 3 (29.1 VS 24.5 kg/m2, P < 0.0001) than Grade 0. Notably, in TOLF patients without combined T-OPLL, BMI was positively correlated with TOLF index, while BMI was negatively correlated with age in younger individuals. CONCLUSION: BMI is a crucial risk factor for TOLF. It highlights the necessity of close follow-up of asymptomatic TOLF patients with high BMI to detect and treat their TOLF progression promptly.

Radiographic and clinical features of thoracic disk disease associated with myelopathy: a retrospective analysis of 257 cases.

PURPOSE: To analyze the clinical and radiographic characteristics of thoracic disk disease associated with myelopathy (TDM). METHODS: This is a retrospective clinical review of prospectively collected imaging data based at a single institute. Based on preoperative CT and MRI, we classified TDM as thoracic disk herniation (TDH), THD with ossification (THDO), TDH with posterior bony avulsions of the vertebrae (TDH with PBA), TDH with posterior vertebral osteophytes (TDH with PVO), giant thoracic osteophyte and calcific discitis with herniation (CDH). Patient characteristics and radiographic data were compared between different types of TDM. RESULTS: Among the 257 patients included, 12.06% of patients presented with symptoms after traumatic events. The most frequent complaint at onset and preoperative was back pain (29.2%) and subjective lower limb weakness (75.5%), respectively. All TDH with PBA is distributed at the lower thoracic segments, while CDH predominantly in the middle and lower thoracic segments. TDH with PBA was more frequent in men than TDH and CDH. Compared with TDH, TDHO, and TDH with PVO, TDH with PBA was younger in surgery age, and TDH and CDH had lower preoperative JOA scores than TDH with PBA. CDH had a larger ventral occupying ratio than TDH, TDHO, and TDH with PBA. CONCLUSIONS: The onset of TDM was generally insidious but may be triggered acutely by apparently trivial events. With a low prevalence, TDM varied clinical symptoms. Different types of TDM had various clinical features, which might indicate different pathological mechanisms.

Surgical strategy for non-continuous thoracic spinal stenosis: one- or two-stage surgery?

PURPOSE: Non-continuous thoracic spinal stenosis (NTSS) is a rare disease, but it is a challenging clinical entity for spine surgeons. However, few studies have focused on its treatment. Therefore, the purpose of this study was to provide surgical treatment guidelines for it by comparing the clinical outcomes of different surgical approaches. METHODS: Patients who underwent thoracic decompression surgery for two diseased segments with two incisions (normal segments ≥ 3) between January 2010 and December 2018 were included. Among these patients, nine were treated with posterior decompression (PD) and circumferential decompression (CD) procedures in one-stage surgery (group A), 14 with PD and CD procedures in two-stage surgery (group B), 36 patients with PD procedures in one-stage surgery and 15 with PD procedures in two-stage surgery (group D). Medical records, operative time, blood loss and complications were reviewed. Neurologic status was assessed by the modified Japanese Orthopaedic Association scale for thoracic myelopathy. RESULTS: Groups A, B, C and D were followed for 54.11 ± 20.51 months, 49.36 ± 29.30 months, 49.94 ± 31.94 months and 39.93 ± 26.18 months, respectively. When comparing groups A and B, operative time, blood loss and length of stay in hospital were significantly less in group A. However, the average recovery rate in group B was significantly higher than that in group A. In regard to groups C and D, group C showed a significantly shorter length of stay in hospital and lower rate of post-operative neurological deterioration. At final follow-up, groups C and D showed similar average recovery rates. CONCLUSION: Different surgical procedures are suitable for different types of NTSS. For patients with NTSS mainly caused by posterior compression, PD via laminectomy in one-stage with two incisions can achieve satisfying clinical outcomes. Staged surgery, including CD and PD procedures, is recommended for patients with NTSS mainly caused by anterior compression.

Pseudomeningocele-a rare complication following thoracic spinal decompression surgery: clinical features, treatment guidelines, technical notes, and evaluation of results.

PURPOSE: Pseudomeningocele (PMC) is a rare complication following thoracic spinal decompression surgery. The aim of this study is to assess the clinical features and treatment of PMC and provide the technical notes with revision surgery. METHODS: Between January 2010 and December 2019, patients who developed PMC after posterior thoracic surgery were enrolled. An additional 25 patients who suffered cerebrospinal fluid leakage (CSFL) but did not develop PMC in the same period were randomly selected. General data, intra-operative factors, CSFL position, cost, modified Japanese Orthopaedic Association (mJOA) scores, patient satisfaction, and clinical features were recorded and compared between the two groups. RESULTS: Eighteen patients were diagnosed with PMC after thoracic spinal surgery. The average length, width, and depth were 16.25 ± 5.73 cm, 6.96 ± 3.61 cm and 4.39 ± 2.2 cm, respectively. The most common symptom was neurological deficits following incision problems and headache. Compared with the control group, the PMC group showed a longer duration of initial surgery, greater estimated blood loss, an increased rate of CSFL on the ventral side, reduced mJOA scores, and lower patient satisfaction at the final follow-up. CONCLUSION: PMC is a rare complication of thoracic surgery with an incidence of 1.12%. PMC typically occurs at the upper and lower thoracic spine, resulting in increased health care costs, poorer neurological recovery, and a lower rate of patient satisfaction. The management of PMC should be individualized depending on diagnosis time and symptoms.

Risk factors associated with post-operative neurological deterioration in patients with thoracic disc disorders with myelopathy.

PURPOSE: Post-operative neurological deterioration (ND) is a severe complication. However, limited literature exists on the ND in thoracic disc disorders with myelopathy (TDM). This study describes the risk factors of neurological deterioration in TDM with instrumentation and fusion. METHODS: A single-centre review of TDM with instrumentation and fusion during 2006-2019 was performed. Post-operative neurological deterioration was defined as the deterioration of pre-existing neurological function or the appearance of new neurological symptoms. Patients were then grouped into two groups depending on neurological deterioration (ND group) or not (non-ND group). Demographics, radiographic parameters, and surgical characteristics were compared between the two groups. RESULTS: A total of 257 cases were included, and neurological deterioration occurred in 16 (6.23%) cases. Multivariate analysis revealed spinal canal occupancy ratio > 75%, U-shaped compressed spinal cord in axial MRI, calcified herniated disc, anterior approach, and intra-operative blood loss > 1500 mL were associated with ND. Ten patients (62.5%) had complete neurological recovery within six months, and four patients (25%) had progressive neurological function improvement and equal or better than pre-operation within nine months. CONCLUSIONS: The rate of neurological deterioration is 6.23%, and a higher spinal canal occupancy ratio, U-shaped compressed spinal cord, calcified herniated disc, anterior approach, and massive intra-operative blood loss were associated with neurological deterioration. Long-term outcomes of neurological deterioration are favourable, and 62.5% of patients experienced complete neurological recovery within six months. Patients with TMD who undergo surgery should be properly informed of the potential risks of neurological deterioration, despite its usually transient nature in most patients.

Genome-wide DNA methylation profile analysis in thoracic ossification of the ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) causes serious spinal canal stenosis. The underlying aetiology may relate to genetic and inflammatory factors. DNA methylation plays a critical role in osteogenesis and inflammation, whereas there is no genome-wide DNA methylation analysis about TOLF. The two subtypes of TOLF (single-level and multiple-level) have distinct clinical features. Using micro-computed tomography (micro-CT), we showed the ossification arose from the joint between two vertebrae at one/both sides of ligament flavum. With Illumina Infinium Human Methylation 850 BeadChip arrays, genome-wide DNA methylation profile was measured in ligament flavum of eight healthy and eight TOLF samples. Only 65 of the differentially methylated cytosine-phosphate-guanine dinucleotides were found in both subtype groups. Principal component analysis and heat map analysis showed a different methylation pattern in TOLF samples, and methylation patterns of two subtypes are also distinct. The Gene Ontology enrichment analysis was significantly enriched in differentiation and inflammation. Pyrosequencing analysis and quantitative real-time polymerase chain reaction were performed to validate the arrays results and expression levels, to test six differentially methylated genes (SLC7A11, HOXA10, HOXA11AS, TNIK, homeobox transcript antisense RNA, IFITM1), using another independent samples (P < 0.05). Our findings first demonstrated an altered Genome-wide DNA methylation profile in TOLF, and implied distinct methylated features in two subtypes.

The prevalence and clinical characteristics of thoracic spinal stenosis: a systematic review.

PURPOSE: Thoracic spinal stenosis (TSS) is a rare disease secondary to multiple pathological changes that differ in prevalence and clinical characteristics. The epidemiological characteristics of these pathologies are largely unknown due to the limited case samples and regional differences. Therefore, a systematic review was conducted to elucidate the prevalence and clinical characteristics of TSS. METHODS: Case series and case reports on the ossification of the posterior longitudinal ligaments (OPLL), ossification of the ligamentum flavum (OLF) and thoracic disk herniation (TDH) were screened from PubMed, Embase and Web of Science databases and systematically reviewed. Epidemiological, demographic and segmental distribution data were extracted and analyzed. RESULTS: A total of 129 studies including 1935 subjects were selected, of which 361 (18.7%) were diagnosed with OPLL, 804 (41.5%) with OLF, 143 (7.4%) with OPLL + OLF and 627 (32.4%) with TDH. Most reports were from China, Japan and USA. Thoracic OPLL occurred mostly at the middle-thoracic spine (43.4%), while OLF predominately occurred at the lower-thoracic spine (63.1%). TDH was mainly localized in the middle (46.0%) and lower-thoracic (50.3%) spine. Thirty-two studies involving 524 patients described tandem spinal stenosis, of which 52.1% had accompanying cervical diseases and 35.9% lumbar diseases. CONCLUSIONS: There are significant differences in the age, sex and segment distribution characteristics of different pathologies leading to TSS. Tandem spinal stenosis is not uncommon and should be considered when diagnosing TSS. Our findings provide new insights into the prevalence and clinical characteristics of TSS and can help reduce misdiagnosis.

A systematic review of complications in thoracic spine surgery for ossification of ligamentum flavum.

STUDY DESIGN: Systematic review. OBJECTIVES: The aim of this systematic review is to summarize the incidence of complications, to relate complication incidence to procedures performed, to assess the impact of the year of study publication and follow-up duration on complication incidence. METHODS: The authors conducted the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE searches for relevant literatures. The incidence of complications was summarized. Correlation of the incidence with year of study publications, follow-up duration, and the surgical outcome was statistically evaluated. RESULTS: A total of 16 studies met our inclusion criteria, including 475 patients. All of these studies were retrospective case series. The mean age of patients ranged from 55 to 64 years. Average follow-up duration ranged from 26 to 65 months. Partial patients in four studies underwent surgeries and reserved posterior structure of the spinal canal. The others underwent operations removing posterior structure of spinal canal. The mean recovery rate from each individual study varied between 31 and 68% and the pooled neurologic function recovery rate was 53% (95% CI: 43-62%). The mean complication rate was 24%. Cerebrospinal fluid leakage was the most reported postoperative complication (19%), then neurologic deterioration (5%). Other complications included local infections, wound dehiscence, increased kyphotic deformity, an hematoma. CONCLUSIONS: Operations removing posterior structure of spinal canal are the main technique to decompress spinal cord. Cerebrospinal fluid leakage and postoperative neurologic deterioration were the most reported complications.

MiR-199b-5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway.

Ossification of the ligamentum flavum (OLF) is a pathology almost only reported in East Asian countries. The leading cause of OLF is thoracic spinal canal stenosis and myelopathy. In this study, the role of miR-199b-5p and jagged 1 (JAG1) in primary ligamentum flavum cell osteogenesis was examined. MiR-199b-5p was found to be down-regulated during osteogenic differentiation in ligamentum flavum cells, while miR-199b-5p overexpression inhibited osteogenic differentiation. In addition, JAG1 was found to be up-regulated during osteogenic differentiation in ligamentum flavum cells, while JAG1 knockdown via RNA interference caused an inhibition of Notch signalling and osteogenic differentiation. Moreover, target prediction analysis and dual luciferase reporter assays supported the notion that JAG1 was a direct target of miR-199b-5p, with miR-199b-5p found to down-regulate both JAG1 and Notch. Further, JAG1 knockdown was demonstrated to block the effect of miR-199b-5p inhibition. These findings imply that miR-199b-5p performs an inhibitory role in osteogenic differentiation in ligamentum flavum cells by potentially targeting JAG1 and influencing the Notch signalling pathway.

A systematic review of complications in thoracic spine surgery for ossification of the posterior longitudinal ligament.

PURPOSE: To answer two questions: (1) what are the common complications associated with surgery for thoracic myelopathy caused by ossification of the posterior longitudinal ligament, and (2) which surgical approach is safer with regard to the incidence of post-operative complications. METHODS: Relevant literature searches were performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, KoreaMed, and the Japan CentraRevuoMedicina. RESULTS: 15 studies met the inclusion criteria and were retrieved. They included a total of 595 patients, 39 % of whom were male and 61 % female. The mean patient age ranged from 52.6 to 60.9 years. The mean recovery rate from each individual study varied between 24.7 and 77.6 % and the pooled neurologic function recovery rate was 50.4 %. From these 15 studies, the mean complication rate was 39.4 %. By far, two complications were more common than the others: cerebrospinal fluid leakage (incidence rate 22.5 %) and post-operative neurologic deficit (incidence rate 13.9 %). 7.7 % of patients from the indirect decompression group experienced cerebrospinal fluid leakage, while it was reported in 25.6 % of those in the direct decompression group. Neurologic deficit was reported in 8.4 % of patients undergoing indirect decompression and 19.8 % of those undergoing direct decompression. CONCLUSIONS: Cerebrospinal fluid leakage and neurologic deficit were the two most common complications following surgical decompression of the thoracic spine with ossification of the posterior longitudinal ligament. Patients undergoing indirect decompression surgeries had significantly lower complication rates compared with those undergoing direct decompression surgeries.

Posterior corrective surgery for moderate to severe focal kyphosis in the thoracolumbar spine: 57 cases with minimum 3 years follow-up.

PURPOSE: To evaluate the radiological and clinical outcomes of the corrective surgery for patients with moderate to severe focal kyphosis in thoracolumbar spine. METHODS: Fifty-seven patients with moderate to severe focal kyphosis of the thoracolumbar spine underwent apical segmental resection osteotomy with dual axial rotation correction at our hospital. There were 30 male and 27 female patients. The mean age was 34.3 years. The kyphosis level radiographs were obtained from each patient before surgery, immediately after surgery and at follow-up. Local kyphosis and scoliosis Cobb angles were measured. Full-spine standing radiographs were obtained before surgery and at follow-up, and the spine sagittal and coronal balance were evaluated. The height of patients, the Frankel grading system for neurological functions, the Oswestry disability index for life quality, the visual analogue score for back pain and the patient satisfactory index for satisfaction to surgery were applied before surgery and at follow-up. The radiological and clinical outcomes were further analyzed in different sub-groups of patients according to etiology, severity of kyphosis, age, level of kyphosis apex, Frankel grade before surgery, and complications. RESULTS: The average follow-up time of patients was 46.1 months. The average kyphosis angle reduced from 94.6° before surgery to 31.0° immediately after surgery, and remained at 34.4° at follow-up. The sagittal balance of the spine, height of patients, Frankel grading, Oswestry disability index and visual analogue score were improved. The patient satisfactory index (PSI) showed a satisfied rate of 91.2%. The correction rate was significantly higher in patients with kyphosis angle less than 95° and age less than 35 years. The clinical improvement rate was significantly higher in patient with kyphosis apex at lower thoracic spine or thoracolumbar segment, Frankel grade E before surgery and no complication group. The incidence of intra-operative and early stage complications was 38.6%, and the incidence of instrumentation failure was 10.5%. The most severe complication was transient spinal cord injury, and the incidence was 7.0%. All complications got good relief after appropriate intervention. CONCLUSIONS: Apical segmental resection osteotomy with dual axial rotation correction is an effective procedure to treat moderate to severe focal kyphosis, the prevention of serious neurological complications is fundamental to achieve the ideal clinical results.

MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes.

Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 (FOXO1), growth differentiation factor 5 (GDF5) and SRY-box 6 (SOX6) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1, GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1, GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1, GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1, GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1, GDF5 and SOX6.

A diagnostic study of thoracic myelopathy due to ossification of ligamentum flavum.

PURPOSE: We set out to establish a magnetic resonance imaging (MRI) and computed tomography (CT)-based diagnostic method for determining the responsible segments in thoracic myelopathy due to ossification of the ligamentum flavum (OLF). METHODS: Forty-four patients who underwent surgery for treatment of myelopathy due to OLF between June 2005 and May 2013 were enrolled in this study as the myelopathy group. Forty-four patients who were identified through CT and MRI scans to have OLF but had no definite neurologic deficits prior to the examination were included as the control group. MRI and CT examination were reviewed, and the degree of spinal canal compromise was graded on axial T2-weighted MRI. Anteroposterior spinal canal diameter was measured at the maximally stenosed level on axial and sagittal CT. The canal grade and the cross-section area-occupying ratio were measured and calculated on the CT scans. The diagnostic coincidence rates for the indices were then compared. RESULTS: Cases of Grade IV were all in the myelopathy group while cases of Grade II were all in the control group. The canal grade (paramedian) was the most relevant continuous variable with the largest JOA score (r = 0.685, P < 0.005). A canal grade (paramedian) of <60% can be used as a critical value for determining OLF-induced myelopathy (sensitivity and specificity, 95.5%). CONCLUSION: Spinal canal compromise is relevant to spinal cord deficits in patients with OLF, and a canal grade (paramedian) can be used to quantify spinal cord deficits. Additionally, a canal grade (paramedian) of <60% on axial CT scan can serve as a critical value for diagnosing OLF-induced myelopathy, especially for Grade III compression on T2-weighted MRI.

[Analysis of risk factors for deep surgical site infection after posterior thoracic and lumbar surgery].

OBJECTIVE: To study the risk factors for deep surgical site infection after posterior thoracic and lumbar surgery. METHODS: The medical data of the patients with deep surgical site infection after posterior thoracic and lumbar surgery from January 2008 to December 2013 were reviewed.For each case patient, 3 non-infected controls were randomly selected from the same database of all patients who underwent posterior thoracic and lumbar surgery.Patients who had diagnosis of spinal fractures, infection, tuberculosis, and tumor were excluded. The microbiology and related factors were collected and analyzed. T-test, χ2 test and Logistic analysis were used to analyze the data, respectively. RESULTS: Ninety-nine cases were identified (infection group), 57 men and 42 women, average 54.5 years old, average body mass index 26.4 kg/m2. Fifty-five (55.6%) patients were identified with organisms, and the most common identified organism was Staphylococcus Aureus. Compared with the cases in the control group (44.4 g/L), the cases in the infection group (43.1 g/L) had a significant low albumin preoperatively (P=0.001). Multivariate Logistic analysis showed that obesity (OR=2.102, 95% CI=1.259-3.508), diabetes (OR=1.926, 95% CI=1.041-3.563), number of surgical levels≥3 (OR=1.985, 95% CI=1.130-3.486) were risk factors for this complication (P<0.05). CONCLUSION: For deep surgical site infection after posterior thoracic and lumbar surgery, obesity, diabetes, preoperative low albumin and number of surgical levels≥3 are risk factors.