Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus.

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca2+) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis.

Imaging signs for preoperative diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum: a blind, randomized diagnostic accuracy study.

Background: Dural ossification (DO) is the leading cause of surgery-related dural tear in patients with ossification of the ligamentum flavum (OLF). An accurate preoperative diagnosis of DO is conducive to the selection of appropriate surgical methods. Although several imaging signs, such as Banner cloud sign (BCs), tram-track sign (TTs), and comma sign (Cs) have been proposed for the preoperative diagnosis of DO, their diagnostic value has not been well studied. The aim of this study was to explore the diagnostic value of BCs, TTs, and Cs, and provide evidence-based data for their clinical application. Methods: This is a blind, randomized diagnostic study using retrospectively collected data from 102 consecutive patients who were diagnosed with OLF and underwent decompression surgery between January 2018 and June 2019. A total of 8 surgeons with different qualifications were recruited to read these imaging signs to identify the presence of DO. Surgical records were used as the reference standard. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the diagnostic accuracy of each imaging sign and their different combinations. Results: Of the 102 patients, 21 were diagnosed with DO. BCs had a significantly higher diagnostic accuracy than TTs and Cs, with the AUC of 0.704, 0.607, and 0.593, respectively. The specificity of BCs, Cs, TTs, and their combination in diagnosing DO was 91.5%, 92.1%, 68.3%, and 62.2%, respectively. In the combined diagnostic test, the results showed that the combined diagnosis accuracy of BCs and Cs was the highest, and the AUC was 0.738. The combination of BCs, Cs, and TTs increased the sensitivity of diagnosing DO (77.5%), but did not improve the diagnostic accuracy, and the AUC was 0.699. Conclusions: BCs had higher diagnostic accuracy than TTs and Cs. BCs and Cs were highly specific for DO, whereas TTs could be confusing due to their non-specific presentations. The combination of BCs, TTs, and Cs improved the sensitivity of DO diagnosis, but not the specificity and accuracy.

Interleukin-17A Promotes Proliferation and Osteogenic Differentiation of Human Ligamentum Flavum Cells Through Regulation of ß-Catenin Signaling.

STUDY DESIGN: A basic experimental study. OBJECTIVE: To elucidate the role and mechanism of interleukin (IL)-17A in thoracic ossification of the ligamentum flavum (TOLF). SUMMARY OF BACKGROUND DATA: TOLF is characterized by the replacement of the thoracic ligamentum flavum with ossified tissue and is one of the leading causes of thoracic spinal stenosis. IL-17A is an important member of the IL-17 family that has received widespread attention for its key contributions to the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF. MATERIALS AND METHODS: Cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine staining were performed to assess the proliferation of ligamentum flavum cells (LFCs). Alkaline phosphatase activity assay, Alizarin red staining, and protein level expression of osteogenic-related genes were used to evaluate the osteogenic differentiation potential of LFCs. The effect of IL-17A on the proliferation and osteogenic differentiation of LFCs was further assessed after silencing ß-catenin by transfection with small interfering RNA. In addition, the possible source of IL-17A was further demonstrated by coculture assays of T helper 17 (Th17) cells with LFCs. Student t test was used for comparisons between groups, and the one-way analysis of variance, followed by the Tukey post hoc test, was used for comparison of more than two groups. RESULTS: IL-17A was elevated in TOLF tissue compared with normal ligamentum flavum. IL-17A stimulation promoted the proliferation and osteogenic differentiation of LFCs derived from patients with TOLF. We found that IL-17A promoted the proliferation and osteogenic differentiation of LFCs by regulating the ß-catenin signaling. Coculture of Th17 cells with LFCs enhanced ß-catenin signaling-mediated proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A. CONCLUSIONS: This is the first work we are aware of to highlight the importance of IL-17A in TOLF. IL-17A secreted by Th17 cells in the ligamentum flavum may be involved in the ossification of the microenvironment by regulating ß-catenin signaling to promote the proliferation and osteogenic differentiation of LFCs.

Learning Curve and Clinical Outcomes of Ultrasonic Osteotome-based En Bloc Laminectomy for Thoracic Ossification of the Ligamentum Flavum.

OBJECTIVE: Despite rapid advances in minimally invasive surgery, en bloc laminectomy remains the most common surgical approach for treating thoracic ossification of the ligamentum flavum (TOLF). However, the learning curve of this risky operation is rarely reported. Therefore, we aimed to describe and analyze the learning curve of ultrasonic osteotome-based en bloc laminectomy for TOLF. METHODS: Among 151 consecutive patients with TOLF who underwent en bloc laminectomy performed by one surgeon between January 2012 and December 2017, we retrospectively analyzed their demographic data, surgical parameters, and neurological function. Neurological outcome was evaluated with the modified Japanese Orthopaedic Association (mJOA) scale, and the Hirabayashi method was used to calculate the neurological recovery rate. The learning curve was assessed with logarithmic curve-fitting regression analysis. Univariate analysis methods were used for statistical analysis, including t-test, rank sum test, and chi-square test. RESULTS: A total of 50% of learning milestones could be reached in approximately 14 cases, and the asymptote in 76 cases. Therefore, 76 of the 151 enrolled patients were defined as the "early group," and the remaining 75 were delimitated as the "late group" for comparison. There was a significant intergroup difference in the corrected operative time (94.80 ± 27.77 vs 65.93 ± 15.67 min, P < 0.001) and the estimated blood loss (median 240 vs 400 mL, P < 0.001). The overall follow-up was 83.1 ± 18.5 months. The mJOA significantly increased from a median of 5 (IQR: 4-5) before the surgery to 10 (IQR: 9-10) at the last follow-up (P < 0.001). The overall complication rate was 37.1%, and no significant intergroup difference was found, except for the incidence of dural tears (31.6% vs 17.3%, p = 0.042). CONCLUSION: Initially, mastering the en bloc laminectomy technique using ultrasonic osteotome for TOLF treatment can be challenging, but the surgeon's experience improves as the operative time and blood loss decrease. Improved surgical experience reduced the risk of dural tears but was not associated with the overall complication rate or long-term neurological function. Despite the relatively long learning curve, en bloc laminectomy is a secure and valid technique for TOLF treatment.

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.

Factors Affecting the Surgical Outcomes of Patients Treated With "de-tension" Surgical Strategy for Multilevel Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine: A Minimum 2-year Follow-Up Study of 83 Patients in a Single Center.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the clinical characteristics and surgical outcomes of patients with multilevel-ossification of the posterior longitudinal ligament (mT-OPLL), and to identify risk factors for unfavorable outcomes. METHODS: Patients who were diagnosed with mT-OPLL and underwent one-stage thoracic posterior laminectomy combined with selective OPLL resection, spinal cord de-tension, and fusion surgery between August 2012 and October 2020 were recruited. Patients' demographic-, surgical- and radiological-related parameters were collected and analyzed. Neurological status was evaluated with mJOA score, and recovery rate (RR) was calculated using the Hirabayashi formula. According to RR, patients were divided into a favorable outcome group (FOG, RR ≥50%) and an unfavorable outcome group (UOG, RR <50%). Univariate and multivariate analyses were used to compare the difference between the 2 groups and to identify risk factors for unfavorable outcomes. RESULTS: A total of 83 patients were included, with an average age of 50.6 ± 8.3 years. Cerebrospinal fluid leakage (60.2%) and transient neurological deterioration (9.6%) were the most common complications. The average mJOA score improved from preoperative 4.3 ± 2.2 to 9.0 ± 2.4 at the last follow-up, and the mean RR was 74.9 ± 26.3%. Disease duration, preoperative nonambulatory status, and the number of decompressed levels were identified as potential risk factors by Univariate analysis (all P < .05). Multivariate analysis showed that the preoperative disease duration and nonambulatory status were independent risk factors for unfavorable outcomes. CONCLUSIONS: Long disease duration and nonambulatory status before surgery were independent risk factors for unfavorable outcomes.

Incidence and cost of vertebral fracture in urban China: a 5-year population-based cohort study.

BACKGROUND: Osteoporotic vertebral fractures cause pain and disability, which result in a heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. MATERIALS AND METHODS: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e. International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. RESULTS: A total of 271 981 vertebral fractures (186 428, 68.5% females and 85 553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased ~1.79-fold during the 5 years, from 85.21 per 100 000 person-years in 2013 to 152.13 per 100 000 person-years in 2017. Medical costs for vertebral fractures increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. CONCLUSION: The dramatic increase in the incidence and cost of clinically recognized vertebral fractures among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.

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.

Development and validation of a novel thoracic spinal stenosis surgical invasiveness index: a single-center study based on 989 patients.

BACKGROUND CONTEXT: Surgical invasiveness indices have been established for general spine surgery (surgical invasiveness index [SII]), spine deformity, and metastatic spine tumors; however, a specific index for thoracic spinal stenosis (TSS) has not been developed. PURPOSE: To develop and validate a novel invasiveness index, incorporating TSS-specific factors for open posterior TSS surgery, which may facilitate the prediction of operative duration and intraoperative blood loss, and the stratification of surgical risk. STUDY DESIGN: A retrospective observational study. PATIENT SAMPLE: Overall, 989 patients who underwent open posterior TSS surgeries at our institution during the past 5 years were included. OUTCOME MEASURES: The operation duration, estimated blood loss, transfusion status, major surgical complications, length of hospital stay, and medical expenses. METHODS: We retrospectively analyzed the data of 989 consecutive patients who underwent posterior surgery for TSS between March 2017 and February 2022. Among them, 70% (n=692) were randomly placed in a training cohort, and the remaining 30% (n=297) automatically constituted the validation cohort. Multivariate linear regression models of operative time and log-transformed estimated blood loss were created using TSS-specific factors. Beta coefficients derived from these models were used to construct a TSS invasiveness index (TII). The ability of the TII to predict surgical invasiveness was compared with that of the SII and assessed in a validation cohort. RESULTS: The TII was more strongly correlated with operative time and estimated blood loss (p<.05) and explained more variability in operative time and estimated blood loss than the SII (p<.05). The TII explained 64.2% of operative time and 34.6% of estimated blood loss variation, whereas the SII explained 38.7% and 22.5%, respectively. In further verification, the TII was more strongly associated with transfusion rate, drainage time, and length of hospital stay than SII (p<.05). CONCLUSIONS: By incorporating TSS-specific components, the newly developed TII more accurately predicts the invasiveness of open posterior TSS surgery than the previous index.

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.

Thirty-day unplanned reoperations of thoracic spine surgery: 10 years of data from a single center with 3242 patients.

BACKGROUND CONTEXT: Unplanned reoperation is a useful quality indicator for spine surgery. However, the rates of a 30-day unplanned reoperation in patients undergoing thoracic spinal surgery are not well established. PURPOSE: To assess the rates, reasons, and risk factors of 30-day unplanned reoperations for thoracic spine surgeries in a single center study. STUDY DESIGN: A retrospective observational study. PATIENT SAMPLE: A total of 3242 patients who underwent thoracic spinal surgery at our institution in the past decade were included. OUTCOME MEASURES: The incidence, chief reasons, and risk factors for unplanned reoperations within 30 days after thoracic spinal surgery. METHODS: We retrospectively analyzed the data of all patients who underwent thoracic spinal surgery between January 2012 and December 2021. Statistical methods, including univariate and multivariate analyses, were performed to assess the incidence, reasons, and risk factors for thoracic degenerative diseases, spinal tumors, kyphosis deformity, and spinal trauma. RESULTS: Of the 3242 patients who underwent thoracic spinal surgery, 107 (3.30%) required unplanned reoperations within 30 days due to epidural hematoma (1.17%), wound complications (0.80%), implant complications (0.43%), inadequate decompression (0.25%), and other causes (0.65%). Patients with degenerative disease (3.88%), spinal tumor (2.98%), and kyphosis deformity (3.33%) had significantly higher incidences of reoperation than those with spinal trauma (1.47%). Unplanned reoperations were classified as hyperacute (30.84%), acute (31.76%), and subacute (37.38%). After univariate analysis, several factors were associated with unplanned reoperation in the 4 cohorts of thoracic spine diseases (p<.05). Multivariate logistic regression analysis revealed that upper thoracic spine surgery (p=.001), concomitant dekyphosis (p=.027), and longer activated partial thromboplastin time (p=.025) were risk factors of unplanned reoperation for thoracic degenerative disease. Whereas American Society of Anesthesiologists (ASA) grade III (p=.015), combined approach (p=.016), and operation time longer than 420 min (p=.042) for spinal tumor, and similar ankylosing spondylitis (p=.023) and operation time longer than 340 min (p=.041) were risk factors of unplanned reoperation for kyphosis deformity. CONCLUSIONS: The unplanned reoperation rate for thoracic spine surgery was 3.30%, with epidural hematoma and wound complications being the most common reasons. However, upper thoracic spine surgery, concomitant dekyphosis, underlying coagulation disorder, longer operation time, higher ASA grade, and comorbidities of ankylosing spondylitis led to an increased risk of unplanned reoperation within 30 days of thoracic spine surgery.

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.

Risk Factors and Three Radiological Predictor Models for the Progression of Proximal Junctional Kyphosis in Adult Degenerative Scoliosis Following Posterior Corrective Surgery: 113 Cases With 2-years Minimum Follow-Up.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To identify risk factors and predictive models for proximal junctional kyphosis (PJK) in a long-term follow-up of patients with adult degenerative scoliosis (ADS) following posterior corrective surgeries. MATERIALS AND METHODS: A consecutive 113 ADS patients undergoing posterior corrective surgery between January 2008 and April 2019 with minimum 2-year follow-up were included. All patients underwent preoperative, postoperative, and final follow-up by X-ray imaging. Multivariate logistic analysis was performed on various risk factors and radiological predictor models. RESULTS: PJK was identified radiographically in 46.9% of patients. Potential risk factors for PJK included postoperative thoracic kyphosis (TK) (P < .05), final follow-up Pelvic Tilt (PT) (P < .05), PT changes at final follow-up (P < .05), age over 55 years old at the surgery (P < .05), theoretical thoracic kyphosis-actual thoracic kyphosis mismatch (TK mismatch) (P < .05) and theoretical lumbar lordosis-acutal lumbar lordosis mismatch (LL mismatch) (P < .05). As for the predictive models, PJK was predictive by the following indicators: preoperative global sagittal alignment ≥45° (Model 1), postoperative pelvic incidence-lumbar lordosis mismatch (PI-LL)≤10° and postoperative PI-LL overcorrection (Model 2), and TK+LL≥0° (Model 3) (P < .05). Postoperative TK mismatch (OR = 1.064) was independent as risk factors for PJK, with the cut-off values respectively set at -28.56° to predict occurrence of PJK. CONCLUSION: The risk of radiographic PJK increases with an age over 55 years old and higher postoperative TK. In addition, postoperative TK mismatch is an independent risk factor for developing PJK. All three predictive models could effectively indicate the occurrence of PJK.

Comparison of Anterior Approach and Posterior Circumspinal Decompression in the Treatment of Giant Thoracic Discs.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The treatment of giant thoracic disc herniation (gTDH)remains challenging for surgeons worldwide because of its large volume and calcified or ossified nature and the limitations of the prior small-sample-size, single-center studies reporting comparative effectiveness. We aim to compare the anterior decompression and spinal fusion (ASF) and posterior circumspinal decompression and spinal fusion (PCDF) for patients with myelopathy due to gTDH in the largest study to date by sample size. METHODS: Preoperative and postoperative functional status, surgical details, and complication rates were compared between the 2 groups. RESULTS: A total of 186 patients were included: 63 (33.9%) ASF and 123(66.1%) PCDF. The PCDF group had significantly shorter operation duration (163.06 ± 53.49 min vs. 180.78 ± 52.06 min, P = 0.032) and a significant decrease in intraoperative blood loss(716.83 mL vs. 947.94 mL, P = 0.045), and also a shorter hospital length of stay (LOS) and postoperative LOS (6 vs. 7, P = 0.011). The perioperative complication rate (13.8% vs. 28.6%, P = 0.015) and surgery-associated complication rate(13.0% vs. 27.0%, P = 0.018) were significantly higher in the ASF group. A higher rate of complete decompression was achieved in the PCDF group. There were no observed significant differences in changes in functional status between the 2 groups. CONCLUSION: PCDF for central or paracentral gTDHs is a highly effective and reliable technique. It can be performed safely with a low complication rate. If either procedure can adequately excise a central or paracentral gTDH, a PCDF approach may be a better option.

Incidence and risk factors of dural ossification in patients with thoracic ossification of the ligamentum flavum.

OBJECTIVE: Dural ossification (DO) is a common clinical feature in patients with thoracic ossification of the ligamentum flavum (OLF) and associated with the increased risk of perioperative complications. However, few studies have been conducted to determine the incidence and independent risk factors of DO in patients with thoracic OLF. The aim of this retrospective study was to determine the incidence and independent risk factors of DO in patients with thoracic OLF. METHODS: A total of 107 patients with thoracic OLF who were admitted to the authors' hospital from December 2020 to December 2021 were included in this study. The independent risk factors of DO in patients with thoracic OLF were determined through univariate analysis followed by multivariate logistic regression analysis with p < 0.05. The diagnostic efficacy of the DO in OLF (DO-OLF) risk classification model was determined on the basis of independent risk factors and evaluated on the basis of sensitivity, specificity, and agreement rate. RESULTS: The incidence of DO in patients with thoracic OLF was 35% (37/107 patients). The tuberous type according to the Sato classification (OR 9.75, p < 0.01) and larger (≥ 9°) supine local kyphosis angle (LKA) (OR 8.13, p < 0.01) were two independent risk factors of DO in thoracic OLF. The DO-OLF risk classification, a novel approach for the diagnosis of DO in patients with thoracic OLF, was established on the basis of the combination of the tuberous type according to the Sato classification and larger supine LKA. The sensitivity, specificity, and agreement rate of this approach for distinguishing between patients with thoracic OLF at high and low risk of DO were 87%, 93%, and 91%, respectively. CONCLUSIONS: The incidence of DO in patients with thoracic OLF was 35%. The tuberous type according to the Sato classification and larger supine LKA (≥ 9°) were independent risk factors of DO in patients with thoracic OLF. The novel DO-OLF risk classification approach could serve as an efficient method for predicting DO in patients with thoracic OLF.

Thirty-day Unplanned Reoperations After Posterior Surgery for Thoracic Spinal Stenosis: A Single-center Study Based on 1948 Patients.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study is to identify the incidences, causes, and risk factors of 30-day unplanned reoperation of posterior surgery for thoracic spinal stenosis (TSS) based on 1948 patients in a single center. SUMMARY OF BACKGROUND DATA: Unplanned reoperation is suggested to be a useful quality indicator for spine surgery. However, the incidences, causes, and risk factors of 30-day unplanned reoperation in patients who underwent posterior spinal surgery for TSS have not been well-established. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of patients who underwent posterior spinal surgery for TSS from January 2011 to December 2021. Statistical methods including univariate and multivariate analyses were performed to assess the incidences, causes, and risk factors. RESULTS: A total of 1948 patients who underwent posterior spinal surgery for TSS in our institution were reviewed, and 77 (3.95%) required unplanned reoperations within 30 days because of epidural hematoma (1.64%), wound-related complications (1.02%), inadequate decompression (0.41%), and implant malposition or failure (0.36%), neurological deficit (0.26%), and other causes (0.26%). After univariate analysis, seven clinical factors were associated with unplanned reoperation ( P <0.05). Multivariate logistic regression analysis showed that upper thoracic spine surgery ( P =0.010), thoracic kyphosis ≥45° ( P =0.039), and intraoperative dural injury ( P =0.047) were independent risk factors for 30-day unplanned reoperation of posterior surgery for TSS. CONCLUSIONS: The incidence of 30-day unplanned reoperations after posterior surgical treatment for TSS was 3.95%. The most common causes were epidural hematoma, wound-related complications, inadequate decompression, and implant malposition or failure. Upper thoracic spine surgery, thoracic kyphosis ≥45°, and intraoperative dural injury led to an increased risk of unplanned reoperation within 30 days after posterior spinal surgery for TSS. LEVEL OF EVIDENCE: 4.

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.

Impact of Diffuse Idiopathic Skeletal Hyperostosis on Clinico-Radiological Profiles and Prognosis for Thoracic Ossification of Ligamentum Flavum-Myelopathy: A Propensity-Matched Monocentric Analysis.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) has been evaluated as a potential risk factor of poor surgical outcomes for lumbar spinal stenosis, whereas the influence of DISH on neuroimaging characteristics and postoperative prognosis of patients with thoracic myelopathy has not been established. Therefore, this study aimed to shed light on this issue. Methods: A monocentric study enrolled 167 eligible patients with thoracic ossification of ligamentum flavum (TOLF), who were followed up for at least 2 years. Clinico-radiological parameters and surgical outcomes were compared between the DISH+ and DISH− groups before and after propensity matching. Subgroup analysis was conducted to compare the functional outcomes between mild DISH (M-DISH) and moderately severe DISH (MS-DISH) groups. Results: Fifty-eight patients were diagnosed as DISH, and its prevalence was 34.7%. Patients with DISH presented with older age, more males, taller stature, heavier weight, more commonly diffuse-type TOLF (p < 0.05). The DISH group showed significantly worse recovery rate (RR) at the final follow-up before and after propensity matching (p < 0.01), and slightly lower preoperative VAS, higher postoperative VAS and lower VAS reduction, despite not reaching the significant differences. Subgroup analysis demonstrated that the M-DISH group was associated with the lower mJOA score (p = 0.01) and RR at the final follow-up (p = 0.001), and tended to present higher preoperative VAS than the MS-DISH group. Conclusions: DISH has a significant predisposition to the elderly males with diffuse-type TOLF. Although the presence of M-DISH might bring about a suboptimal surgical outcome, both DISH and non-DISH patients experienced good neurological function improvements and pain relief through thoracic posterior decompression.

Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis.

Background: Ossification of ligamentum flavum (OLF) is an insidious and debilitating heterotopic ossifying disease with etiological heterogeneity and undefined pathogenesis. Obese individuals predispose to OLF, whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood. Therefore, this study aims to explore distinct obesity-related genes and their functional signatures in OLF. Methods: The transcriptome sequencing data related to OLF were downloaded from the GSE106253 in the Gene Expression Omnibus (GEO) database. The obesity-related differentially expressed genes (ORDEGs) in OLF were screened, and functional and pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI), module analysis, transcription factor enrichment analysis (TFEA), and experiment validation were used to identify hub ORDEGs. The immune infiltration landscape in OLF was depicted, and correlation analysis between core gene SOCS3 and OLF-related infiltrating immune cells (OIICs) as well as 5mC/m6A modifiers in OLF was constructed. Results: Ninety-nine ORDEGs were preliminarily identified, and functional annotations showed these genes were mainly involved in metabolism, inflammation, and immune-related biological functions and pathways. Integrative bioinformatic algorithms determined a crucial gene cluster associated with inflammatory/immune responses, such as TNF signaling pathway, JAK-STAT signaling pathway, and regulation of interferon-gamma-mediated signaling. Eight hub ORDEGs were validated, including 6 down-regulated genes (SOCS3, PPARG, ICAM-1, CCL2, MYC, and NT5E) and 2 up-regulated genes (PTGS2 and VEGFA). Furthermore, 14 differential OIICs were identified by ssGSEA and xCell, and SOCS3 was overlapped to be the core gene, which was associated with multiple immune infiltrates (dendritic cells, macrophage, and T cells) and six m6A modifiers as well as four 5mC regulators in OLF. Reduced SOCS3 and FTO expression and up-regulated DNMT1 level in OLF were validated by Western blotting. Conclusion: This study deciphered immune/inflammatory signatures of obesity-related gene clusters for the first time, and defined SOCS3 as one core gene. The crosstalk between 5mC/m6A methylation may be a key mediator of SOCS3 expression and immune infiltration. These findings will provide more insights into molecular mechanisms and therapeutic targets of obesity-related OLF.

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.