Radiologic Evaluation of Uncinate Processes of the Cervical Spine and the Relationship Between the Uncinate Process and Vertebral Artery: Implication in Anterior Cervical Spine Surgery.

OBJECTIVE: To determine the relationship between the uncinate process (UP) and vertebral artery (VA) from a radiologic view and to confirm the surgical safety margin to minimize the risk of VA injury during anterior cervical approaches. METHODS: We retrospectively reviewed computed tomography angiography of 205 patients by using a contrast-enhanced computed tomography angiography protocol of the VA. Four kinds of images were simultaneously reconstructed to measure all the parameters associated with VA and UP of cervical spine. RESULTS: The shortest distance from the UP's tip to the VA's medial border (P < 0.001) was at the C-6 level (2.9 ± 0.9 mm on the left and 3.2 ± 1.3 mm on the right), and the longest distance (P < 0.001) was at the C-3 level on both sides. The distance between UP's tip and the medial border of the ipsilateral VA was statistically significantly different at each cervical level, and the right distance was larger than the left (P < 0.05). We found the height of UP gradually increased from C-3 to C5-level and then decreased from C-5 to C-7 level for both sides. The mean distance between the medial borders of left UP and left VA was on average 7.5 ± 1.4 mm. The diameter of VA was on average 3.4 ± 0.6 mm on the left side and 3.2 ± 0.7 mm on the right. The diameter of the VA was statistically significantly different on both sides, and the left side was larger than the right (P < 0.05). CONCLUSIONS: Detailed radiologic anatomy of VA and UP was reviewed in this study. A deep understanding of the correlation between the UP and VA is essential to perform anterior cervical spine surgery safely and ensure adequate spinal canal decompression.

Comparison of clinical outcomes between sequestered cervical disk herniation and non-sequestered cervical disk herniation after anterior cervical decompression and fusion: a cohort study.

BACKGROUND: The advantages of anterior cervical decompression and fusion (ACDF) were well published, while research on postoperative results in different subtypes of cervical disk herniation (CDH) still remains blank. This study aimed to explore the surgical outcome between sequestration and other types in CDH. METHODS: This retrospective cohort study enrolled 108 patients treated with ACDF in our hospital. The participants were divided into two groups according to the existence of a sequestered disk. The Visual analog scale score, the Japanese Orthopedics Association (JOA) score and the Neck disability index score were used to evaluate postoperative outcome. RESULTS: Significant improvements were observed in both groups at every viewpoint (P < 0.001). The mean JOA was 15.04 ± 1.26 in the sequestered disk group and 14.45 ± 1.43 in the non-sequestered disk group two months after the operation (P = 0.026 < 0.05). The improvement in JOA at two months after ACDF showed a significant difference: 46.58% ± 39.17% in the sequestered disk group and 33.39% ± 28.82% in the non-sequestered disk group (P = 0.047 < 0.05). Thirty-two patients in the sequestered disk group (64%) and 19 patients in the non-sequestered disk group (32.76%) presented with high signal intensity of the spinal cord on preoperative cervical T2-weighted MRI (P < 0.001). CONCLUSIONS: Patients with sequestered cervical disks seemed to have a higher degree of symptom improvement two months after ACDF. CDH with a sequestered disk appears to be more likely to cause high signal intensity changes in the compressed cervical spine on T2-weighted MRI. We prefer early positive surgery in patients with sequestered cervical disks from the clinical point of view.

Predictive value of vertebral Hounsfiled Unit for titanium mesh cage subsidence following ACCF surgery.

OBJECTIVE: To investigate the predictive value of cervical Hounsfiled Unit (HU) values for postoperative titanium mesh cage (TMC) subsidence. METHODS: Clinical data of patients who underwent ACCF surgery for degenerative cervical myelopathy between January 2016 and August 2018 were analyzed. Among the 126 patients included, 74 were male and 52 were female, with a mean age of 61.0 ± 9.9 years. The mean follow-up was 37.1 ± 11.2 months. Preoperative vertebral HU values were measured and the degree of TMC subsidence during follow-up was assessed. Patients were divided into two groups according to the presence or absence of subsidence: the subsidence group and the control group. Vertebral HU values were compared between the two groups, and correlation analysis was performed between HU values and TMC subsidence values. In addition, the predictive value and threshold of HU were analyzed by using ROC. RESULTS: There were 22 patients (14 males and 8 females) who developed TMC subsidence (subsidence group), while 104 patients (60 males and 44 females) did not develop TMC subsidence (control group) during follow-up. Comparative analysis of demographic characteristics between the two groups showed no significant differences in gender, age, BMI, diagnosis, surgical levels, and follow-up duration (all P values > 0.05). There was a significant difference in mean HU between the subsidence group (287.6 ± 49.6) and the control group (342.4 ± 61.4) (t = -3.92, P < 0.01). In the subsidence group, there was a significant correlation between subsidence values and HU values (r = -0.52, P = 0.01), whereas no such correlation was observed in the control group (r = - 0.07, P = 0.51). ROC analysis indicated that vertebral HU values could potentially be used to predict subsidence after ACCF, with an area under the ROC curve of 0.77 (95% CI 0.66-0.87; P < 0.01). The optimal HU threshold was found to be 298, with a sensitivity of 76.9% and specificity of 68.2%. CONCLUSION: Preoperative vertebral HU values were associated with postoperative TMC subsidence. Vertebral HU may be a valuable predictor of postoperative subsidence.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFß) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFß/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

Evaluation of Haplo-Paraspinal-Muscle-Preserving Technique to Prevent Postoperative Axial Pain in Cervical Laminoplasty.

BACKGROUND: The present study aimed to assess the efficacy of a new haplo-paraspinal-muscle-preserving (HMP) laminoplasty technique in the treatment of cervical myelopathy. METHODS: The medical records of 68 patients diagnosed with multisegmental cervical myelopathy were retrospectively reviewed. Of these, 22 patients who underwent HMP laminoplasty were defined as the muscle-preserved group (MP), and 46 patients who underwent traditional open-door laminoplasty were enrolled and defined as the traditional open-door laminoplasty group (LP). Patient demographic data and surgical parameters like clinical and radiological parameters, operation duration, blood loss, and spinal canal expansion distance were compared. RESULTS: Average surgical time and blood loss were significantly reduced in the MP group when compared with the LP group (P < 0.05). Both groups demonstrated significant improvements in neurological function and spinal canal expansion (P > 0.05). However, the visual analog scale score in the MP group was significantly lower compared with the LP group at the 6-month follow-up (P < 0.05), but no differences were found at the 1-year follow-up. The loss of lordosis was more prominent in the LP group when compared with the MP group at 1-year follow-up (P < 0.05). Lower events of persistent axial pain were found in the MP group but with no statistical significance. More hinge side laminae fractures could be found in the MP group, but more hinge side displacements were found in the LP group. CONCLUSIONS: The HMP laminoplasty technique is relatively safe, effective, easier to perform, and better for lordosis maintenance and complication control compared with the traditional open-door technique. CLINICAL RELEVANCE: Although traditional open-door laminoplasty is an efficient approach in treating multisegmental cervical myelopathy, the complications could significantly affect the clinical outcome. Our new HMP laminoplasty technique has a lower complication rate and a better lordosis maintenance ability; therefore, it could be a better choice in treating multisegmental cervical myelopathy.

Continuous release of mefloquine featured in electrospun fiber membranes alleviates epidural fibrosis and aids in sensory neurological function after lumbar laminectomy.

Recurrent low back pain after spinal surgeries, such as lumbar laminectomy, is a major complication of excessive epidural fibrosis. Although multiple preclinical and clinical methods have been aimed at ameliorating epidural fibrosis, their safety and efficacy remain largely unclear. Single implanted electrospun fibrous membranes provide physical barriers that can decrease tissue fibrosis after surgery; however, they also trigger local inflammation due to the implantation of a foreign body, thus subsequently attenuating their anti-fibrosis properties. Here, we designed a strategy that permits easy incorporation of mefloquine into polylactic acid membranes, and stable long-term mefloquine release, to potentially improve anti-fibrosis effects and relieve or prevent low back pain. The electrospun fibrous membranes grafted with mefloquine showed a well-controlled early temporary peak release, and secondary drug release occurred smoothly over several weeks. Histopathological and histomorphometric results indicated that the drug-loaded membranes had excellent anti-fibrosis effects after laminectomy in rats. Inflammation and neovascularization at the surgical site indicated that the mefloquine-grafted electrospun fibrous membranes provided sustained anti-inflammatory outcomes while effectively alleviating associated neuropathic pain hypersensitivity. In summary, our study indicated that polylactic acid-mefloquine grafted electrospun fibrous membranes may be a potential local agent to mitigate epidural fibrosis and support sensory neurological function after laminectomy, thereby potentially improving patients' postoperative outcomes.

Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis.

Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio-synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene-related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity-modifying protein 1 (RAMP1) and cyclic AMP response element-binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

Bi-Needle PELD with Intra-Discal Irrigation Technique for the Management of Lumbar Disc Herniation.

BACKGROUND: Lumbar disc herniation (LDH) is the most common cause of sciatica. Percutaneous endoscopic discectomy (PELD) is indicated when conservative treatments fail, which has been proved effective. During conventional PELD, ruptured discs and loose fragments inside discs are removed as much as possible to guarantee a lower reherniation rate, but it inevitably would lead to deterioration of disc degeneration and loss of disc height after PELD. Ensuring sufficient decompression while alleviating the post-operation disc degeneration process is still a clinical problem. OBJECTIVE: To evaluate the imaging and clinical outcomes of bi-needle PELD with intradiscal irrigation technique for the treatment of lumbar disc herniation (LDH). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China. METHODS: A total of 48 patients who underwent bi-needle PELD (B-PELD) or conventional-PELD (C-PELD) for LDH in our 2 spine centers were included in this study. There were 26 cases in the C-PELD group (male 12 cases, female 14 cases) with an average age of 34.6 ± 6.8 years. And there were 22 patients in the B-PELD group (male 10 cases, female 12 cases) with an average age of 35.1 ± 6.4 years. The difference in postoperative disc degeneration (Pfirrmann grades, disc-vertebra height ratios [D-V H ratios]), visual analog scale (VAS) of low back pain, and reoperation rates were compared between the 2 groups. RESULTS: There was no significant difference in gender, age, disease duration, and surgical level between the 2 groups (P > 0.05). The postoperative VAS of back pain was 2.31 ± 0.53 for the C-PELD group and 0.63 ± 0.74 for the B-PELD group; the difference was significant (P = 0.013). The difference between the preoperative and postoperative D-V H ratios in the C-PELD group was significant (P < 0.0001), while it was not significant in the B-PELD group (P = 0.6708). The difference between the loss of D-V H ratios after surgery was significant between the 2 groups (P = 0.0003). The loss of D-V H ratios was higher in the C-PELD group. The difference between the preoperative and postoperative Pfirrmann grades in the B-PELD group was not significant (P = 0.7261); however, it was significant in the C-PELD group (P = 0.0012). The reoperation rate in the C-PELD group was 7.7%, and the reoperation rate in the B-PELD group was 4.5%; the difference was not significant (P = 1). LIMITATIONS: This study employed a retrospective design, and its inherent selection bias and limited statistical power should be considered. CONCLUSIONS: Bi-needle technique with saline irrigation maneuver showed a significant advantage of restoration of disc height and amelioration of disc degeneration compared to conventional PELD surgery.

Intervertebral-spreader-assisted anterior cervical discectomy and fusion prevents postoperative axial pain by alleviating facet joint pressure.

OBJECTIVE: To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. METHODS: Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. RESULTS: Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P < 0.05). The biomechanical study in cervical cadavers also showed significantly and continuously decreased facet joint pressure in the spreader assisted vertebral distraction group (P < 0.01). CONCLUSIONS: Spreader-assisted vertebral distraction method effectively alleviates postoperative neck pain in degenerative cervical spondylosis patients treated with ACDF. The mechanism may be related to the transient relief of facet joint pressure during the vertebral distraction procedure in ACDF.

Application of a new integrated low-profile anterior plate and cage system in single-level cervical spondylosis: a preliminary retrospective study.

BACKGROUND: Although ACDF has been widely used in treating cervical spondylosis and related diseases, the complications along with this anterior surgical technique have hindered its application and affected the postoperative outcome of the patients. Here, we investigated the clinical and radiological outcomes of a new integrated low-profile anterior plate and cage system for anterior cervical discectomy and fusion (ACDF) in treating cervical spondylosis. METHODS: A total of 96 cervical spondylosis patients who underwent single-level ACDF between 2018 to 2020 in our institute were enrolled. There were 28 patients using the new implants and 68 patients using the zero-profile (Zero-P) implants. The Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) were used to evaluate the clinical outcomes. The cervical and segmental Cobb angle and range of motion (ROM) were used to assessed the radiological outcomes. Incidence of complications were also recorded. All data were recorded at pre-operation, 6-month and 12-month post-operation. RESULTS: All patients were followed-up for at least 1-year, the mean follow-up time was over one year. The fusion rate was similar in the two groups. There was no significant difference in the postoperative JOA score recovery rate, postoperative VAS score of neck and arm pain, postoperative ROM, and incidence of complications between two groups (P > 0.05). However, postoperative cervical and segmental Cobb angle were better maintained in the new low-profile implant group compared to Zero-P group. CONCLUSIONS: The clinical outcomes of the new low-profile implant were satisfactory and comparable to that of zero-profile system. It may have advantages in improving and maintaining the cervical lordosis, and can be an alternative device for single-level cervical spondylosis treated with ACDF.

Anterior cervical discectomy and fusion, open-door laminoplasty, or laminectomy with fusion: Which is the better treatment for four-level cervical spondylotic myelopathy?

Four-level cervical spondylotic myelopathy (CSM) is a common disease affecting a large number of people, with the optimal surgical strategy remaining controversial. This study compared the clinical outcomes, radiological parameters, and postoperative complications of primarily performed surgical procedures such as anterior cervical discectomy and fusion (ACDF), open-door laminoplasty (LAMP), and laminectomy with fusion (LF) in treating four-level CSM. A total of 116 patients who received ACDF (38 cases), LAMP (45 cases), and LF (33 cases) were followed up for a minimum of 24 months were enrolled in this study and retrospectively analyzed. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) scoring system, the Neck Disability Index (NDI), and the Visual Analogue Scale (VAS). Changes in the curvature of the cervical spine were determined using the cervical curvature index (CCI) and the C2-C7 Cobb angle. Cervical mobility was evaluated using the C2-C7 range of motion (ROM) and active cervical ROM (aROM). Complications were recorded and compared among the three groups. All patients achieved significant improvement in JOA, NDI, and VAS scores at the final follow-up (P < 0.05), whereas no remarkable difference was found among the groups (P > 0.05). In addition, both C2-7 ROM and aROM were significantly reduced in the three groups and LAMP showed the least reduction relatively. As for complications, LAMP showed the lowest overall incidence of postoperative complications, and patients in the ACDF group were more susceptible to dysphagia, pseudoarthrosis than LAMP and LF. Considering improvements in clinical symptoms and neurological function, no remarkable difference was found among the groups. Nevertheless, LAMP had advantages over the other two surgical procedures in terms of preserving cervical mobility and reducing postoperative complications.

[Application of aided three-dimension CT navigation system in craniocervical junction malformation disease surgery].

OBJECTIVE: To investigate the related problems of three-dimension CT navigation system applied to craniocervical junction malformation diseases surgery. METHODS: The clinical data of 61 patients with craniocervical junction malformation disease who underwent surgical treatment from July 2015 to March 2018 was retrospectively analyzed. There were 39 males and 22 females aged from 25 to 73 years old with a mean of (46.20±12.09) years. According to the different ways of screw placements, these patients were divided into navigation group (30 cases) and non navigation group (31 cases). The screws insertion in the navigation group were guided under three-dimension CT computer-aided navigation system, while the screws insertion were guided by C-arm fluoroscopy and intraoperative anatomical landmarks in non-navigation group. All surgeries were performed by the same group of surgeons. All cases were scanned by CT after operation to assess the accuracy of the screw insertion. RESULTS: A total of 122 screws were inserted in the study, including 60 screws in navigation group and 62 screws in non-navigation group. The screw positions in navigation group were all satisfactory, and there were no screw-related complications. The position of 3 screws (4.83%) in non-navigation group was not satisfactory, and there was no obvious neurological symptoms after operation. The operation time of navigation group was from 87.5 to 112.5 min with a mean of (99.6± 12.0) min;and non-navigation group was from 87.5 to 107.5 min, with a mean of (97.5±10.5) min. There was no statistically significant difference in the operation time between two groups (P>0.05). The screw insertion time in navigation group was from 1.50 to 4.20 min, with a mean of (2.51±1.02) min;and non navigation group was from 1.80 to 5.10 min, with a mean of (3.25±1.05) min. The screw insertion time in navigation group was shorter than that in non-navigation group (P<0.05). The intraoperative blood loss in navigation group was from 122 to 153 ml, with a mean of (137.57±9.48) ml, which in non-navigation group wasfrom 121 to 158 ml, with a mean of (138.75±8.56) ml, there was no statistically significant difference between two groups (P>0.05). CONCLUSION: The three-dimensional CT computer-aided navigation system has the characteristics of clear imaging and accurate positioning, which can help improve the accuracy and safety of the screw insertion in craniocervical junction malformation disease surgery.

The Heterogeneity of Infiltrating Macrophages in Metastatic Osteosarcoma and Its Correlation with Immunotherapy.

BACKGROUND: Metastatic osteosarcoma is a common and fatal bone tumor. Several studies have found that tumor-infiltrating immune cells play pivotal roles in the progression of metastatic osteosarcoma. However, the heterogeneity of infiltrating immune cells across metastatic and primary osteosarcoma remains unclear. METHODS: Immune infiltration analysis was carried out via the "ESTIMATE" and "xCell" algorithms in primary and metastatic osteosarcoma. Then, we evaluated the prognostic value of infiltrating immune cells in 85 osteosarcomas through the Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve. Infiltrations of macrophage M1 and M2 were evaluated in metastatic osteosarcoma, as well as their correlation with immune checkpoints. Macrophage-related prognostic genes were identified through Weighted Gene Coexpression Network Analysis (WGCNA), Lasso analysis, and Random Forest algorithm. Finally, a macrophage-related risk model had been constructed and validated. RESULTS: Macrophages, especially the macrophage M1, sparingly infiltrated in metastatic compared with the primary osteosarcoma and predicted the worse overall survival (OS) and disease-free survival (DFS). Macrophage M1 was positively correlated with immune checkpoints PDCD1, CD274 (PD-L1), PDCD1LG2, CTLA4, and TIGIT. In addition, four macrophage-related prognostic genes (IL10, VAV1, CD14, and CCL2) had been identified, and the macrophage-related risk model had been validated to be reliable for evaluating prognosis in osteosarcoma. Simultaneously, the risk score showed a strong correlation with several immune checkpoints. CONCLUSION: Macrophages potentially contribute to the regulation of osteosarcoma metastasis. It can be used as a candidate marker for metastatic osteosarcoma' prognosis and immune checkpoints blockades (ICBs) therapy. We constructed a macrophage-related risk model through machine-learning, which might help us evaluate patients' prognosis and response to ICBs therapy.

Celecoxib-Loaded Electrospun Fibrous Antiadhesion Membranes Reduce COX-2/PGE2 Induced Inflammation and Epidural Fibrosis in a Rat Failed Back Surgery Syndrome Model.

To date, failed back surgery syndrome (FBSS) remains a therapy-refractory clinical condition after spinal surgery. The antiadhesion membrane is applied to prevent FBSS by isolating fibrosis; however, the inflammation stimulated by the foreign body and surgical trauma needs to be further resolved simultaneously. Therefore, we developed new electrospun polycaprolactone (PCL) fibrous membranes loaded with celecoxib (CEL) to prevent fibrosis and inflammation associated with FBSS. The CEL-loaded PCL fibers were randomly distributed, and the drug was released over two weeks. Fluorescence micrographs revealed that the fibroblasts proliferated less on the PCL-CEL fibrous membranes than in the PCL group and the blank control. In the rat laminectomy model after 4 weeks, magnetic resonance imaging of epidural fibrosis was least in the PCL-CEL group. Expression of COX-2 and PGE2 was lower in the PCL-CEL group. It concluded that the CEL-loaded PCL membrane could reduce fibrosis and inflammation in a rat model of FBSS via COX-2/PGE2 signaling pathways.

Bi-needle technique versus transforaminal endoscopic spine system technique for percutaneous endoscopic lumbar discectomy in treating intervertebral disc calcification: a propensity score matched cohort analysis.

OBJECTIVE: The aim of this study was to evaluate the clinical results of a Bi-needle technique and conventional transforaminal endoscopic spine system (TESSYS) technique for percutaneous endoscopic lumbar discectomy (PELD) in treating patients with intervertebral disc calcification (IDC). BACKGROUND: PELD has gained acceptance for treating patients with IDC. The Bi-needle technique was designed to improve the efficiency and safety of PELD. METHOD: Bi-needle and TESSYS group within each cohort were balanced using 1:1 propensity score matching. Finally, 32 patients with IDC treated by Bi-needle technique from December 2015 to September 2017 were enrolled and 25 patients treated by TESSYS technique from the same spine surgery center between January 2013 and October 2017 were enrolled as controls. RESULTS: Propensity score matching generated 22 Bi-needle and 22 TESSYS patients. There were no significant differences in visual analog scale and lumbar Japanese Orthopaedic Association scores between Bi-needle and TESSYS group. Operative time and rate of complications in the Bi-needle was significantly better than the TESSYS group (p < 0.01). CONCLUSIONS: Both surgical methods achieved good clinical outcomes. However, compared with the TESSSY technique, operative time of the Bi-needle technique is shorter, and rate of complications is lower.

The relationship between preoperative cervical sagittal balance and clinical outcome of laminoplasty treated cervical ossification of the posterior longitudinal ligament patients.

BACKGROUND CONTEXT: Laminoplasty is a common surgical method used to treat patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although laminoplasty is preferred over traditional laminectomy, the factors affecting the complications and outcomes are unclear. Recently, sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical degenerative diseases, but their relationships with laminoplasty-treated OPLL outcomes remains unknown. PURPOSE: The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcome in laminoplasty treated OPLL patients. STUDY DESIGN: This is a retrospective case study. PATIENT POPULATION: Between January 2015 and January 2017, 181 consecutively included patients who underwent cervical laminoplasty for OPLL were enrolled (male:female ratio=126:75; mean age=60.2 years). Cervical spine lateral radiographs in neutral, flexion, and extension positions were taken before and 2 years after the surgery. OUTCOME MEASURES: The C2-C7 Cobb angle, T1 slope, C1-C7 sagittal vertical axis (SVA), C2-C7 SVA, CGH (center of gravity of the head)-C7 SVA, cervical JOA (Japanese Orthopedic Association) score, and neck VAS (visual analogue scale) score were measured preoperatively and postoperatively at the 2-year follow-up. METHODS: The patients were divided into two groups according to changes in the lordotic angle or the recovery rate of the JOA score. The relationships between the postoperative lordosis loss or the clinical outcome and the preoperative variables, including the patient's age, JOA score, C2-C7 Cobb angle, T1 slope, C1-C7 SVA, C2-C7 SVA, and CGH-C7 SVA, were investigated. RESULTS: The patients were divided into two groups according to the postoperative change in the C2-C7 Cobb angle. There were no differences in the age, preoperative C2-C7 Cobb angle, C1-C7 SVA, or C2-C7 SVA; there was only a difference in the preoperative CGH-C7 SVA and T1 slope level (p=.038, p=.042). The postoperative JOA and JOA recovery rate were related to the postoperative lordosis loss in cervical alignment (p=.048, p=.031). We again divided the patients into two groups according to the JOA recovery rate and found that only the preoperative CGH-C7 SVA and C1-C7 SVA were related to the neurological outcome (p=.011, p=.047). According to the multivariate logistic regression analysis, higher preoperative CGH-C7 SVA levels were significantly associated with decreases in the lordosis angle postoperatively and the clinical outcome (p=.018, OR=1.225; p=.034, OR=1.654). The ROC (receiver operating characteristic) analysis revealed that the proper cutoff value of preoperative CGH-C7 SVA for predicting the postoperative loss of lordosis and clinical outcomes is 3.8 cm. CONCLUSION: Preoperative cervical sagittal balance indexes are related to the outcomes of OPLL patients after laminoplasty. Patients with high preoperative CGH-C7 SVA levels have a high probability of developing sagittal imbalances and neurological symptoms of the cervical spine, and this measurement can be used as a predictor of outcomes in laminoplasty-treated cervical OPLL patients.

Sensory nerves regulate mesenchymal stromal cell lineage commitment by tuning sympathetic tones.

The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E2 (PGE2) secreted by osteoblasts could activate sensory nerve EP4 receptor to promote bone formation by inhibiting sympathetic activity. However, the fundamental units of bone formation are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of COX-2 in osteoblasts, could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases the PGE2 level) or propranolol (a beta blocker) significantly promoted osteogenesis and inhibited adipogenesis. This effect of SW033291, but not propranolol, was abolished in conditional EP4-KO mice under normal conditions or in the bone repair process. We conclude that the PGE2/EP4 sensory nerve axis could regulate MSC differentiation in bone marrow of adult mice.

Does Obesity Affect Outcomes of Multilevel ACDF as a Treatment for Multilevel Cervical Spondylosis?: A Retrospective Study.

STUDY DESIGN: This was a retrospective study of the clinical and radiologic outcomes of multilevel anterior cervical discectomy and fusion (ACDF) surgery for multilevel cervical spondylosis patients. OBJECTIVE: In this retrospective study, we intended to determine the relationship of neck circumference, neck length, and body mass index (BMI) with the outcomes of multilevel ACDF surgeries for patients with multilevel cervical spondylosis. SUMMARY OF BACKGROUND DATA: Obesity has become a worldwide epidemic problem since the beginning of the 21st century. However, no study has focused on how local or whole-body obesity indexes (neck circumference, length of neck, and BMI) are related to the outcome of anterior cervical surgery. METHODS: A total of 156 consecutive patients with multilevel cervical spondylosis who underwent anterior cervical surgery in our department from 2010 to 2016 were enrolled in our study. Preoperative parameters of patients such as the neck circumference, length of neck, height and weight were measured, and the BMI was also calculated. Neck circumference and length of neck in neutral position ratio was determined as an index for evaluated the neck situation. Preoperative and postoperative neurological functions were evaluated using the neck disability index (NDI) and Japan Orthopedic Association (JOA) scores. Postoperative complications during the follow-up period were also recorded. Correlations between the obesity indexes and the various factors were analyzed. RESULTS: The mean follow-up duration was 3.9±1.4 years (2.0-7.3 y). Compared with the preoperative score, the NDI and JOA score had significantly improved. There were 46 patients (29.49%) developed complications after surgery. Patients in the obese group had the highest rate of complications. Neck circumference and length of neck in neutral position ratio, BMI, and number of operation levels were significant risk factors for the occurrence of dysphagia after multilevel ACDF. CONCLUSIONS: Patients with a higher BMI, larger neck circumference, and shorter neck length may have a longer operation duration, more blood loss, and more postoperative complications. The authors recommended that the presence of obesity and neck circumference and length should be carefully considered in the perioperative risk assessment for a multilevel ACDF surgery.

Inflammatory-sensitive CHI3L1 protects nucleus pulposus via AKT3 signaling during intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the main cause of low back pain and the mechanism of which is far from fully revealed. Although inflammation directed nucleus pulposus (NP) extracellular matrix metabolism dysregulation is known to be the main cause of the degeneration process, few is known about the protective factors. Using high-throughput label-free proteomics, we found that inflammation-related autocrine factor Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is highly expressed in the NP cells during degeneration. Immunohistochemical analysis show that the expression of CHI3L1 is NP tissue specific, and increase significantly during degeneration. Overexpression of CHI3L1 significantly decrease the catabolism, and increase the anabolism of extracellular matrix. Knockdown of CHI3L1 using siRNAs show the opposite results, which imply that the protective role of CHI3L1 in IDD. Using high-throughput RNA sequencing and functional analyses, we find that AKT3 expression and its phosphorylation is mainly regulated by CHI3L1. And lastly, the mechanism of which is also validated using human and mouse degenerated NP tissues. In summary, our findings show that the inflammation-related autocrine factor CHI3L1 is NP specific, and it protects IDD by promoting the AKT3 signaling, which may serve as a potential therapeutic target in intervertebral disc degeneration.

Effect of sIL-13Rα2-Fc on the progression of rat tail intervertebral disc degeneration.

BACKGROUND: The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition. METHODS: A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting. RESULTS: Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen. CONCLUSION: These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.