Comparison of the efficacy of ROI-C cage with Zero-P device in anterior cervical discectomy and fusion of cervical degenerative disc disease: a two-year follow-up study.

Background: This study aimed to compare the clinical outcomes of Zero-P and ROI-C devices applied to anterior cervical discectomy and fusion (ACDF) surgery of cervical degenerative disc disease (CDDD). Methods: From January 2020 and December 2020, 56 patients with CDDD who underwent ACDF using Zero-P or ROI-C were included in this retrospective study. The outcomes included visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI) score, Cobb angle, dysphagia, and bone fusion rate. Dysphagia was assessed using the Bazaz grading system. The comparison of outcomes between the two groups was based on the 2-year follow-up time point, which was defined as the last follow-up visit. Results: The Zero-P group included 16 males and 14 females, with a mean age of 56.2 (range, 35-65) years. The ROI-C group included 11 males and 15 females, with a mean age of 57.4 (range, 36-67) years. There was no significant difference in gender and mean age between the two groups. There were no significant differences in VAS score, JOA score, NDI score, Cobb angle, dysphagia, and bone fusion rate between two groups at the last follow up visit. In the Zero-P group, the duration of surgeries involving C3-4 or C6-7 segments was significantly longer than those including C4-5 or C5-6 segments (135.0 ± 19.0 vs. 105.6 ± 17.5 min, P < 0.05). In surgeries involving C3-4 or C6-7 segments, the operation time of ROI-C was significantly shorter than that of Zero-P (106.5 ± 19.5 vs.112.2 ± 20.5 min, P < 0.05). There were no significant differences in the dysphagia or cage subsidence rates between the Zero-P and ROI-C groups (P > 0.05). The Cobb angle in the last follow-up visit in the Zero-P group (24.4 ± 4.5°) was significantly higher than that in the ROI-C group (18.1 ± 2.3°) (P < 0.05). Conclusions: ACDF using ROI-C device showed an efficacy similar to the Zero-P device, as well as a shorter operation time for surgeries involving C3-4 or C6-7 segments. However, ROI-C could cause more loss of Cobb angle over time, which could lead to uncomfortable symptoms.

Proximal tibial osteotomy with absorbable spacer combined with fibular osteotomy has similar clinical outcomes to high tibial osteotomy in the treatment of knee osteoarthritis.

PURPOSE: Proximal tibia osteotomy with absorbable spacer combined with fibular osteotomy (TPOASI) is an emerging surgical technique for treating knee osteoarthritis (KOA); however, the efficacy of this procedure remains unknown. We hypothesize that TPOASI can achieve similar clinical outcomes to opening-wedge high tibial osteotomy (OW-HTO). The objective of this study is to compare the clinical results between these two procedures. METHODS: Patients who underwent TPOASI or OW-HTO from July 2016 to September 2020 were included. The following outcome parameters were determined before and after the surgery: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale of pain, the Intermittent and Persistent Osteoarthritis Pain Scale, femorotibial angle, and post-operative complications. RESULTS: In total, 209 cases were analyzed (102 in TPOASI group; 107 in OW-HTO group) with 3.1 years average follow-up. Both procedures achieved significant improvement in KOOS (62.0 to 24.4 in the TPOASI and 62.8 to 26.2 in the OW-HTO group, p < 0.001) and WOMAC score (68.9 to 24.1 in the TPOASI versus 69.9 to 26.1 in the OW-HTO group, p < 0.001). There were no significant differences in complications or femorotibial angle between the two groups but the only significant difference in the outcome parameters was the WOMAC stiffness score (19.6 in the TPOASI versus 26.5 in the OW-HTO group). CONCLUSION: TPOASI achieves comparable results to OW-HTO in terms of clinical scores, radiographic results, and complications, but has the advantage of avoiding internal fixation removal.

Preoperative quantitative diffusion tensor imaging on the spinal nerve root is a predictor for the surgical outcome of lumbar disc herniation: a prospective study of 117 patients.

BACKGROUND: The diffusion tensor imaging (DTI) parameters (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) are commonly used to provide quantitative information on tissues. This study aimed to evaluate the predictive value of preoperative DTI of the spinal nerve roots in the surgical outcome of lumbar disc herniation (LDH). METHODS: A total of 117 LDH patients were included. According to the postoperative improvement rate, the patients were dichotomized into the unfavorable group (N.=35) and favorable group (N.=82). RESULTS: The favorable group had a younger age (P=0.005) and a shorter disease course (P<0.001) than the unfavorable group. The favorable group had higher affected side FA and ADC and lower healthy/affected FA and ADC ratio than the unfavorable group (all P<0.05). Logistic regression analysis showed that younger age, shorter disease course, higher affected side FA and ADC, lower healthy/affected FA and ADC ratio, and lower healthy side ADC were the independent factors associated with positive surgical outcome. ROC analysis showed that the affected side FA had an excellent predictive performance for the surgical outcome (AUC=0.900). The Healthy/affected FA ratio had a good predictive performance (AUC=0.846). The overall predictive accuracy ranged from 0.91 to 0.92. However, ADC had poor predictive performance (AUC ranged from 0.626 to 0.663). CONCLUSIONS: These results suggested the preoperative affected side FA value had an excellent predictive performance for the surgical outcome of LDH patients. The LDH patients with a higher preoperative affected side FA value were more likely to have a positive surgical outcome.

Comparison of region-of-interest delineation methods for diffusion tensor imaging in patients with cervical spondylotic radiculopathy.

BACKGROUND: Diffusion tensor imaging is a promising technique for determining the responsible lesion of cervical radiculopathy, but the selection and delineation of the region of interest (ROI) affect the results. This study explored the impact of different ROI sketching methods on the repeatability and consistency of DTI measurement values in patients with cervical spondylotic radiculopathy (CSR). METHODS: This retrospective study included CSR patients who underwent DTI imaging. The images were analyzed independently by two radiologists. Four delineation methods were used: freehand method, maximum roundness, quadrilateral method, and multi-point averaging method. They re-examined the images 6 weeks later. The intra-class correlation coefficient (ICC) was used to investigate the consistency between the two measurements and the reproducibility between two radiologists. RESULTS: Forty-two CSR patients were included in this study. The distribution of the compressed nerve roots was five C4, eight C5, sixteen C6, eleven C7, and two C8. No differences were found among the four methods in fractional anisotropy (FA) or apparent diffusion coefficient (ADC), irrespective of radiologists (all P>0.05). Similar results were observed between the first and second measurements (all P>0.05), but some significant differences were observed for radiologist 2 for the four-small rounds method (P=0.033). The freehand and single largest circle methods were the two methods with the highest ICC between the two measurements and the two radiologists (all ICC >0.90). CONCLUSION: The freehand and single largest circle methods were the most consistent methods for delineating DTI ROI in patients with CSR.

Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis.

OBJECTIVE: This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. METHODS: The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1ß (IL-1ß) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays. RESULTS: OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1ß-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends. CONCLUSIONS: Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage.

Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma.

PURPOSE: Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. MATERIALS AND METHODS: Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. RESULTS: A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. CONCLUSION: Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Application of Magnetic Resonance Diffusion Tensor Imaging in the Clinical Diagnosis of Disc Herniation after Lumbar Spine Injury.

Magnetic resonance diffusion-weighted imaging (DTI) provides a unique perspective on the pathophysiological and microstructural changes during spinal cord injury, with high spatial specificity; meanwhile, NM reflects the conduction and integrity of neuroelectrical signals in spinal cord fiber tracts, with time-specific and dynamic evaluation effects. The fractional anisotropy (FA) value, SEP amplitude, and neurological function score or improvement rate are correlated. The combination of DTI and NM can more reliably quantify the spinal cord function, evaluate the effectiveness of treatment, and determine the patient's prognosis, which can provide reference for clinical decision making and future research for SCI patients. That is, the lower the preoperative FA value and the lower the SEP amplitude, the worse the preoperative and postoperative neurological function, the lower the improvement rate, and the worse the prognosis of patients. Therefore, we believe that spinal cord function can be graded according to JOA scores to find the corresponding FA and SEP amplitude ranges and that, by measuring FA and SEP amplitude in the future, we can reverse the assessment of spinal cord function, expected postoperative improvement, and long-term prognosis. At the same time, FA values can also help determine the nature of the lesion to some extent.

Structure of Lumbar Intervertebral Foraminal Ligaments Based on 3-Dimensional Reconstruction Through Ultrathin Cryomilling of a Human Cadaver.

BACKGROUND: This study aimed to assess the feasibility of using the 3-dimensional (3-D) reconstruction technique based on ultrathin cryomilling to show the lumbar intervertebral foraminal ligaments in situ. METHODS: Cryomilling was performed on an embalmed human cadaver to acquire successive cross-sectional images. In each of the images, the boundaries of lumbar intervertebral foraminal ligaments and their adjacent structures were outlined, labeled, and reconstructed for 3-D modeling. The morphology, attachments, and spatial orientation of ligaments were described. RESULTS: A total of 9 ligaments in 10 lumbar intervertebral foramina (IVFs) were identified and reconstructed. These ligaments can be divided into 5 types. The IVFs were divided into 2 or 3 main portions by the first 4 types of ligaments (transforaminal ligaments, corporotransverse ligaments, "reticular" ligaments, and "Y-shaped" ligaments). The radiating ligaments (the fifth type of ligaments) attached to the surrounding structures of the IVF and were connected directly to the nerve root sleeves. Although there was no indication of neurovascular compromise in this normal specimen, these ligaments limit the space within the bony IVF such that under certain pathologic conditions (e.g., inflammation), their presence would make neurovascular compression more likely than if they were absent. CONCLUSIONS: The 3-D reconstruction technique based on ultrathin cryomilling can effectively show the lumbar intervertebral foraminal ligaments and their anatomical characteristics in situ, providing a new way to clarify the relationships between these ligaments and their adjacent structures.

Biomechanical study of the C5-C8 cervical extraforaminal ligaments.

BACKGROUND: The anatomical distribution of the extraforaminal ligaments in the cervical intervertebral foramina has been well studied. However, detailed descriptions of the biomechanical characteristics of these ligaments are lacking. METHODS: The paravertebral muscles were dissected, and the extraforaminal ligaments and nerve roots were identified. The C5 and C7 or C6 and C8 cervical nerve roots on both sides were randomly selected, and a window was opened on the vertebral lamina to expose the posterior spinal nerve root segments. Five needles were placed on the nerve root and the bone structure around the intervertebral foramen; the distal end of the nerve root was then tied with silk thread, and the weights were connected across the pulley. A weight load was gradually applied to the nerve root (50 g/time, 60 times in total). At the end of the experiment, segments of the extraforaminal ligaments were selectively cut off to compare the changes in nerve root displacement. RESULTS: The displacement of the C5, C6, C7, and C8 nerve roots increases with an increasing traction load, and the rate of change of nerve root displacement in the intervertebral foramen is smaller than that in the nerve root on the outside area (p < 0.05). Extraforaminal ligaments can absorb part of the pulling load of the nerve root; the C5 nerve root has the largest load range. CONCLUSIONS: Cervical extraforaminal ligaments can disperse the tension load on the nerve root and play a role in protecting the nerve root. The protective effect of the C5 nerve root was the strongest, and this may anatomically explain why the C5 nerve roots are less prone to simple avulsion.

PLK2 modulation of enriched TAp73 affects osteogenic differentiation and prognosis in human osteosarcoma.

There are three subtypes of undifferentiated human conventional osteosarcoma (HCOS): osteoblastic osteosarcoma (OOS), chondroblastic osteosarcoma (COS), and fibroblastic osteosarcoma (FOS). HCOS also exhibits heterogeneous pathological maldifferentiation in individual patients. Currently, the mechanism regulating HCOS differentiation remains unclear, and therapies are ineffective. Osteopontin (OPN) and osteocalcin (OCN) are markers of osteoblast maturation, and their expression is inhibited in HCOS. A previous study found that PLK2 inhibited TAp73 phosphorylation and consequent anti-OS function of TAp73 in OS cells with enriched TAp73. TAp73 was also reported to regulate bone cell calcification. Here, OOS was found to have higher TAp73 levels and PLK2 expression than those in COS, which is correlated with HCOS maldifferentiation according to Spearman analysis and affects patient prognosis according to Kaplan-Meier survival analysis. In the conventional OS cell-line Saos2 and in patient-derived xenograft OS (PDX-OS) cells, increased PLK2 expression owing to abundant TAp73 levels affected OPN and OCN content as measured by RT-PCR and Western blotting, and alizarin red staining showed that PLK2 affected calcium deposition in OS cells. In addition, PLK2 inhibition in PDX-OS cells prohibited clone formation, as indicated by a clonogenic assay, and sensitized OS cells to cisplatin (CDDP) (which consequently limited proliferation), as shown by the CCK-8 assay. In an established PDX animal model with abundant TAp73 levels, PLK2 inhibition or CDDP treatment prevented tumor growth and prolonged median survival. The combined therapeutic effect of PLK2 inhibition with CDDP treatment was better than that of either monotherapy. These results indicate that increased PLK2 levels due to enriched TAp73 affect osteogenic differentiation and maturation and OS prognosis. In conclusion, PLK2 is a potential target for differentiation therapy of OS with enriched TAp73.