Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization.

Background: Ankylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored. Methods: We chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran's Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells. Results: Overall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E-05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E-05, OR: 2.9871, 95%CI: 1.8289-4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E-06, OR: 0.5446, 95%CI: 0.4260-0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E-06, OR: 0.0.5423, 95%CI: 0.4210-0.6983). Our findings were consistently stable and reliable. Conclusions: Our findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.

Development and validation of a nomogram to predict the risk of constipation after lumbar interbody fusion surgery.

INTRODUCTION: To understand the incidence of postoperative constipation and the risk factors of constipation in patients with lumbar interbody fusion, we constructed and verified the constipation risk prediction model, so as to provide reference for the prevention and treatment of postoperative constipation. METHODS: The data of patients undergoing lumbar interbody fusion in our hospital were retrospectively analyzed from December 2021 to December 2022. According to postoperative constipation, the patients were divided into constipation group and non-constipation group. Univariate logistic regression analysis and multivariate logistic regression analysis were used to determine independent risk factors for postoperative constipation. Based on independent risk factors, a nomogram was developed to predict the risk of constipation after lumbar interbody fusion. The prediction performance was assessed using receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA). Finally, bootstrapping method for internal validation was further evaluated the nomogram. RESULTS: A total of 282 patients participated in the study. 176 patients (62.41%) after lumbar interbody occurred constipation, and 106 patients were asymptomatic. Multivariate regression analysis showed independent risk factors, including the use of calcium channel blockers, polypharmacy, postoperative bed time, and constipation history. Multivariate regression analysis was used to establish the model. The C-index of the nomogram was 0.827 (95% CI 0.779-0.875), and the C-index of interval bootstrapping validation was 0.813 (95% CI 0.765-0.861), and the area under the AUC was 0.800. The nomogram showed good discrimination ability. CONCLUSIONS: The use of calcium channel blockers, polypharmacy, postoperative bed time, and history of constipation are independent risk factors for postoperative constipation in patients undergoing lumbar interbody fusion. The constructed risk prediction model has good discriminative ability.

Posterior Lateral Endoscopic Cervical Discectomy Through a Lateral Mass Approach in the Treatment of Cervical Spondylotic Radiculopathy.

OBJECTIVE: The present study outlines the feasibility, safety, and short-term clinical outcomes of posterior lateral endoscopic cervical discectomy (PLECD) through a lateral mass approach for treating cervical spondylotic radiculopathy (CSR). METHODS: This single-center retrospective observational study involved 30 patients with single-level CSR who had failed conservative treatment and presented with clinical symptoms consistent with imaging findings undergoing PLECD via a lateral mass approach. Primary outcomes included the visual analog scale (VAS) for neck and arm pain, the Japanese Orthopedic Association (JOA) score, and the modified MacNab criteria. Radiographic follow-up consisted of static and dynamic cervical radiographs and computed tomographic scans. RESULTS: Thirty patients (13 men and 17 women; mean age 48.8 ± 11.9 years) underwent this procedure, and the mean operative time was 74.90 ± 13.52 minutes. Mean follow-up was 7.37 ± 2.17 months. The VAS scores for the neck and arm decreased significantly at the last follow-up (neck, 26.80 ± 4.75 to 9.87 ± 1.78; arm, 71.30 ± 8.48 to 14.73 ± 4.00) (P < 0.05). The JOA score also decreased from 13.47 ± 1.36 to 15.90 ± 0.92 at the last follow-up (P < 0.05). Twenty-nine patients demonstrated satisfactory outcomes based on the modified MacNab criteria at the last follow-up. All patients exhibited a positive clinical response, experiencing relief from symptoms. Postoperative computed tomography (CT) scans confirmed the complete removal of lesions. CONCLUSIONS: PLECD through a lateral mass approach, as an alternative to conventional "keyhole" approaches, proves to be a novel and viable therapeutic option for CSR, demonstrating both high efficacy and safety.

Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization.

Background: Intervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated. Method: We obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR. Result: In total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD. Conclusion: Our findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.

Posterior unilateral approach with 270° spinal canal decompression and three-column reconstruction using double titanium mesh cage for thoracic and lumbar burst fractures.

Objective: To evaluate the clinical effects of the posterior unilateral approach with 270° spinal canal decompression and three-column reconstruction using double titanium mesh cage (TMC) for thoracic and lumbar burst fractures. Materials and methods: From May 2013 to May 2018, 27 patients with single-level thoracic and lumbar burst fractures were enrolled. Every patient was followed for at least 18 months. Demographic data, neurologic status, back pain, canal compromise, anterior body compression, operative time, estimated blood loss and surgical-related complications were evaluated. Radiographs were reviewed to assess deformity correction, anterior body height correction, bony fusion and TMC subsidence. Results: The average preoperative percentages of canal compromise and anterior body height compression were 58.4% and 50.5%, respectively. All surgeries were successfully completed in one phase, the operative time was 151.5 ± 25.5 min (range: 115-220 min), the estimated blood loss was 590.7 ± 169.9 ml (range: 400-1,000 ml). Neurological function recovery was significantly improved except for 3 grade A patients. The preoperative visual analog scale (VAS) scores for back pain were significantly decreased compared with the values at the last follow-up (P = 0.000). The correct deformity angle was 12.4 ± 4.7° (range: 3.9-23.3°), and the anterior body height recovery was 96.7%. The TMC subsidence at the last follow-up was 1.3 ± 0.7 mm (range: 0.3-3.1 mm). Bony fusion was achieved in all patients. Conclusion: The posterior unilateral approach with 270° spinal canal decompression and three-column reconstruction using double TMC is a clinically feasible, safe and alternative treatment for thoracic and lumbar burst fractures.

[Posterior percutaneous endoscopy via vertical anchor technique combined with trench technique for single-segmental central cervical disc herniation].

OBJECTIVE: To investigate the clinical feasibility, safety, and effectiveness of posterior percutaneous endoscopy via vertical anchor technique combined with trench technique for single-segmental central cervical disc herniation. METHODS: Between July 2017 and August 2019, 13 patients with the single-segmental central cervical disc herniation suffering from various neurologic deficits were treated with posterior percutaneous endoscopy via vertical anchor technique combined with trench technique. There were 6 males and 7 females with an average age of 50.5 years (range, 43-64 years). Disease duration ranged from 3 to 17 months (mean, 9.2 months). The clinical symptoms of 5 cases were mainly neck pain, radiculopathy, and numbness in upper limbs, and the visual analogue scale (VAS) score was 6.60±0.55. The clinical symptoms of 8 cases were myelopathy including upper extremities numbness, weakness, and trouble walking, and the modified Japanese Orthopedic Association (mJOA) score was 12.75±0.71. The surgery-related complications, operation time, and intraoperative blood loss were recorded, and the results of clinical symptoms were measured by VAS scores and mJOA scores. RESULTS: All procedures were completed successfully, no severe complications such as dural tears or cerebrospinal fluid leakage occurred. The operation time ranged from 83 to 164 minutes (mean, 101.2 minutes). The intraoperative blood loss was 25-50 mL (mean, 33.1 mL). After operation, 12 of 13 cases were followed up 10-24 months (mean, 17.6 months). The VAS scores of patients with preoperative pain symptoms were 2.40±0.55 on the first day after operation and 1.80±0.45 at last follow-up, which were significantly lower than those before operation ( P<0.05). The mJOA scores of patients with the symptoms of spinal cord injury were 12.63±0.52 on the first day after operation and 14.29±0.95 at last follow-up, and the score at last follow-up was significantly higher than that before operation ( P<0.05). Acute extremities weakness occurred for the postoperative hematoma formation in 1 case (disc herniation at C 4, 5) presented with myelopathy preoperatively, and muscle strength was recovered after the clearance of hematoma and spinal cord decompression under percutaneous endoscopy. CONCLUSION: Posterior percutaneous endoscopy via vertical anchor technique and trench technique for single-segmental central cervical disc herniation was clinical feasible, safe, and effective, and could be an alternative approach to the treatment of central cervical disc herniation.

Niclosamide: drug repurposing for human chondrosarcoma treatment via the caspase-dependent mitochondrial apoptotic pathway.

Poor sensitivity to chemotherapy drugs and high recurrence rates are the bottlenecks to successful chondrosarcoma treatment. Notably, niclosamide has been identified as a potential anti-cancer agent. To investigate the effects and mechanisms of niclosamide in the context of human chondrosarcoma treatment, SW1353 and CAL78 human chondrosarcoma cells were treated with various concentrations of niclosamide. The CKK-8 assay was performed to quantify cell viability. Cell proliferation was determined with crystal violet staining and colony forming assays. TUNEL and annexin V-FITC flow cytometry assays were performed to detect cell apoptosis. Wound healing and Transwell assays were conducted to evaluate migratory and invasive cell behaviors. The effect of niclosamide on the mitochondria was evaluated with the JC-1 and Seahorse Cell Mito Stress Assays. The expression of caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and ß-tubulin levels were investigated by western blotting. Collectively, the data demonstrated that niclosamide inhibited cell growth and proliferation, attenuated migratory and invasive cell behaviors, and promoted apoptosis. Niclosamide is as a potent chondrosarcoma tumor inhibitor that activates the caspase-dependent mitochondrial apoptotic pathway and could be a novel therapeutic approach to treat chondrosarcoma.

Therapeutic Effectiveness of Percutaneous Endoscopic Spinal Surgery for Intraspinal Cement Leakage Following Percutaneous Vertebroplasty: An Early Clinical Study of 12 Cases.

BACKGROUND: Intraspinal cement leakage is a catastrophic complication of percutaneous vertebroplasty (PVP). Percutaneous endoscopic spinal surgery (PESS) for intraspinal cement leakage has rarely been reported. OBJECTIVES: To evaluate the therapeutic effectiveness of PESS for intraspinal cement leakage following PVP. STUDY DESIGN: This was a retrospective study approved by the ethics committee of our institution. SETTING: Department of Orthopedics from an affiliated hospital. METHODS: Twelve patients with neurologic impairments resulting from intraspinal cement leakage after PVP were treated with PESS for spinal decompression from May 2014 to June 2018. Computed tomography and 3-dimensional reconstruction were used to confirm the vertebral level of cement leakage. The surgical index, neurologic function, and clinical results were recorded in this study. RESULTS: The leaked cement of all patients was successfully removed under PESS, and no severe intraoperative complications were reported in our study. The operation time ranged from 43 to 119 minutes (mean, 65.5 minutes). The amount of intraoperative blood loss was 64.25 ± 9.62 mL. The lengths of postoperative hospital stays were 5.25 ± 2.53 days. The follow-up rate was 83.3% (10/12). The follow-up time ranged from 14 to 30 months (mean, 22 months). The Visual Analog Scale scores of foraminal leaks improved from 6.50 ± 0.93 preoperatively to 1.75 ± 0.71 at the last follow-up (P < 0.05). Neurologic function was evaluated by Japanese Orthopaedic Association 29 scores, which improved from 18.75 ± 1.06 to 22.70 ± 1.64 (P < 0.0001). The good and excellent rates were 80% according to the modified Macnab criteria. LIMITATIONS: This study is limited by the volume of patients and the deep learning curve needed for PESS. CONCLUSIONS: PESS, as a minimally invasive technique, can achieve targeted spinal cord decompression and may be a safe and effective alternative approach to conventional procedures for cement leakage after PVP. KEY WORDS: Endoscopes, cement leakage, minimally invasive surgery, percutaneous vertebroplasty.

Biomechanical Study of Novel Unilateral Fixation Combining Unilateral Pedicle and Contralateral Translaminar Screws in the Subaxial Cervical Spine.

INTRODUCTION: In several situations, the stability of the subaxial cervical spine is damaged and involves the lateral mass of 1 side; in these cases, a pedicle screw (PS) or lateral mass screw (LMS) may not be suitable for placement on the affected side. Therefore, salvage short-segment fixation with satisfactory stability is needed when bilateral fixation is not feasible. METHODS: Seven fresh-frozen human cervical spine specimens were used to test the 3-plane range of motion (ROM) of the C4-C5 segment. Quasistatic 2-Nm flexibility testing was performed in the following sequence: 1) intact; 2) destabilization (using 3-column injury models) treated with bilateral mass screws (BMSs); 3) destabilization treated with a unilateral PS combined with a contralateral translaminar screw (UPS+CTLS); and 4) destabilization treated with bilateral PSs (BPSs). Then, a pullout strength test was performed for the PSs, LMSs, and translaminar screws (TLSs) using 7 isolated C4 and C5 vertebrae. RESULTS: The UPS+CTLS group showed no significant difference from the BMS group in the 3-plane ROM or from the BPS group in the axial rotation or flexion-extension ROM but showed a significantly greater lateral bending ROM than did the BPS group. The pullout strength test showed that both C4 and C5 TLSs had strength similar to that of LMSs but poorer than that of PSs. CONCLUSIONS: Fixation with the hybrid UPS+CTLS construct performed as well as BMS fixation in our biomechanical tests and may play a clinical role when BPS or BMS placement is not feasible for short-segment fixation.

Modified posterior percutaneous endoscopic cervical discectomy for lateral cervical disc herniation: the vertical anchoring technique.

PURPOSE: During the long-term practice of percutaneous endoscopic cervical discectomy (PECD) at our institution, we have modified the protocol to include the vertical anchoring technique (VAT), which we will describe in detail in this article. The objective of this study was to compare the clinical outcomes associated with the conventional posterior PECD technique with that associated with the modified technique to determine the safety and efficacy of the latter technique. METHODS: From December 2014 to January 2016, a total of 44 patients with single cervical disc herniation were randomly divided into two groups. One group underwent conventional posterior PECD, and the other group underwent posterior PECD combined with VAT. The operative time, fluoroscopy times and perioperative complications were recorded. The visual analog scale (VAS) for neck and arm pain and the modified MacNab criteria at 1 day, 3, 6, and 12 months after surgery were used to evaluate the postoperative outcomes. RESULTS: All patients underwent surgery successfully without severe complications. The operative time and intraoperative fluoroscopy times were significantly less in patients treated with VAT than in those who underwent conventional posterior PECD (P < 0.05). Both types of surgery significantly improved the symptoms of patients. According to the results of the follow-up period, there were no significant differences in VAS scores for neck and arm pain or the modified MacNab criteria between the two groups (P > 0.05). There was no recurrence in either group during the follow-up period. CONCLUSIONS: Although the clinical outcomes of the two surgical techniques were similar, the VAT decreased the operative time and intraoperative fluoroscopy times in posterior PECD surgery. The learning curve for posterior PECD could be shortened by using the VAT. These slides can be retrieved under Electronic Supplementary Material.

[Effectiveness of percutaneous endoscopic technique in treatment of intraspinal cement leakage after percutaneous vertebroplasty].

Objective: To evaluate the feasibility and safety of percutaneous endoscopic technique in the treatment of intraspinal cement leakage after percutaneous vertebroplasty (PVP). Methods: Between May 2014 and March 2016, 5 patients with lower limb pain and spinal cord injury caused by intraspinal cement leakage after PVP, were treated with percutaneous endoscopic spinal decompression. Of 5 cases, 3 were male and 2 were female, aged from 65 to 83 years (mean, 74.4 years). The course of disease was 10-30 days (mean, 16.2 days). Imageological examinations confirmed the levels of cement leakage at T 12, L 1 in 3 cases, and at L 1, 2 in 2 cases; bilateral sides were involved in 1 case and unilateral side in 4 cases. Two patients had lower limb pain, whose visual analogue scale (VAS) were 8 and 7; 3 patients had lower extremities weakness, whose Japanese Orthopedic Association (JOA) 29 scores were 18, 20, and 19. According to American Spinal Injury Association (ASIA) impairment scale, neural function was rated as grade E in 2 cases and grade D in 3 cases. Results: The operation time was 55-119 minutes (mean, 85.6 minutes), and the blood loss was 30-80 mL (mean, 48 mL). CT scan and three-dimensional (3D) reconstruction at 1 day after operation showed that cement leakage was removed in all patients. Five cases were followed up 6-21 months (mean, 12 months). In 2 patients with lower limb pain, and VAS score was significantly decreased to 2 at last follow-up. In 3 patients with lower extremities weakness, the muscle strength was improved progressively, and the JOA29 scores at last follow-up were 21, 23, and 22. Conclusion: Percutaneous endoscopic technique for intraspinal cement leakage after PVP is safe, effective, and feasible.