Dynesys治疗腰椎退变和不稳(附13例报告)

[目的]探讨动力性固定器Dynesys治疗腰椎退变和不稳的固定原理、适应证和初步疗效。[方法]作者于2004年在瑞士Basel大学骨科进修学习期间,随访Dynesys治疗12个月以上的13例患者,平均随访16个月(范围12～25个月);年龄58～78岁,平均65岁;所有患者均有保守治疗难以治愈的腰痛或腰腿痛6个月以上,术前Oswestry评分50～69分,平均58分;Ⅰ度退变性腰椎滑脱1例,腰椎管狭窄症6例,腰椎间盘突出症或伴节段性不稳3例,退变性脊椎关节病3例。[结果]Oswestry评分至最后随访改善到24～53分,平均31.3分;参照Nakai标准,优5例,良5例,可2例,差1例;无螺钉弯曲或断裂。差者1例术后1年再次行椎管探查、改行强直性固定融合。[结论]Dynesys是治疗腰椎退变和轻度不稳的一种有效的非融合性、动力性固定系统。

Metallic debris from metal-on-metal total hip arthroplasty regulates periprosthetic tissues

The era of metal-on-metal(MoM) total hip arthroplasty has left the orthopaedic community with valuable insights and lessons on periprosthetic tissue reactions to metallic debris. Various terms have been used to describe the tissue reactions. Sometimes the nomenclature can be confusing. We present a review of the concepts introduced by Willert and Semlitsch in 1977,along with further developments made in the understanding of periprosthetic tissue reactions to metallic debris. We propose that periprosthetic tissue reactions be thought of as(1) gross(metallosis, necrosis, cyst formation and pseudotumour);(2) histological(macrophage-dominated, lymphocyte-dominated or mixed);and(3) molecular(expression of inflammatory mediators and cytokines such as interleukin-6 and tumor necrosis factor-alpha). Taper corrosion and modularity are discussed, along with future research directions to elucidate the antigen-presenting pathways and materi-al-specific biomarkers which may allow early detection and intervention in a patient with adverse periprosthetic tissue reactions to metal wear debris.

Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP,TGFβ,and Wnt signaling in articular cartilage formation and osteoarthritis

Runt-related transcription factor 1(Runx1)plays a key role in cartilage formation,but its function in articular cartilage formation is unclear.We generated non-inducible and inducible Runx1-deficient mice(Runx1^(f/f)Col2α1-Cre and Runx1^(f/f)Col2α1-CreER mice)and found that chondrocyte-specific Runx1-deficient mice developed a spontaneous osteoarthritis(OA)-like phenotype and showed exacerbated articular cartilage destruction under OA,characterized by articular cartilage degradation and cartilage ossification,with decreased Col2α1 expression and increased Mmp13 and Adamts5 expression.RNA-sequencing analysis of hip articular cartilage from the Runx1^(f/f)Col2α1-Cre mice compared to that from wild-type mice and subsequent validation analyses demonstrated that Runx1 is a central regulator in multiple signaling pathways,converging signals of the Hippo/Yap,TGFβ/Smad,and Wnt/β-catenin pathways into a complex network to regulate the expression of downstream genes,thereby controlling a series of osteoarthritic pathological processes.RNA-sequencing analysis of mutant knee joints showed that Runx1’s role in signaling pathways in articular cartilage is different from that in whole knee joints,indicating that Runx1 regulation is tissue-specific.Histopathologic analysis confirmed that Runx1 deficiency decreased the levels of YAP and p-Smad2/3 and increased the levels of activeβ-catenin.Overexpression of Runx1 dramatically increased YAP expression in chondrocytes.Adeno-associated virus-mediated Runx1 overexpression in the knee joints of osteoarthritic mice showed the protective effect of Runx1 on articular cartilage damaged in OA.Our results notably showed that Runx1 is a central regulator of articular cartilage homeostasis by orchestrating the YAP,TGFβ,and Wnt signaling pathways in the formation of articular cartilage and OA,and targeting Runx1 and its downstream genes may facilitate the design of novel therapeutic approaches for OA.

Reprogramming macrophages via immune cell mobilized hydrogel microspheres for osteoarthritis treatments

Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis(OA).However,the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment.In this study,inspired by the innate immune,immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines,macrophage antibodies and engineered cell membrane vesicles(sEVs)via covalent and non-covalent junctions.The immune cell mobilized hydrogel microspheres,based on a mixture of streptavidin grafted hyaluronic acid methacrylate(HAMA-SA)and Chondroitin sulfate methacrylate(ChSMA)microspheres(HCM),can recruit,capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment.In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment,capture,and reprogramming abilities.Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5%.Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA.Therefore,the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.

“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

Learning curve of computer-assisted navigation system in spine surgery

Background Spine surgery using computer-assisted navigation （CAN） has been proven to result in low screw misplacement rates, low incidence of radiation exposure and excellent operative field viewing versus the conventional intraoperative image intensifier （CⅢ）. However, as we know, few previous studies have described the learning curve of CAN in spine surgery.Methods We performed two consecutive case cohort studies on pedicel screw accuracy and operative time of two spine surgeons with different experience backgrounds, A and B, in one institution during the same period. Lumbar pedicel screw cortical perforation rate and operative time of the same kind of operation using CAN were analyzed and compared using CⅢ for the two surgeons at initial, 6 months and 12 months of CAN usage.Results CAN spine surgery had an overall lower cortical perforation rate and less mean operative time compared with CⅢ for both surgeon A and B cohorts when total cases of four years were included. It missed being statistically significant,with 3.3% versus 4.7% （P=0.191） and 125.7 versus 132.3 minutes （P=0.428） for surgeon A and 3.6% versus 6.4%（P=0.058）, and 183.2 versus 213.2 minutes （P=0.070） for surgeon B. in an attempt to demonstrate the learning curve,the cases after 6 months of the CAN system in each surgeon＇s cohort were compared. The perforation rate decreased by 2.4% （P=0.039） and 4.3% （P=0.003） and the operative time was reduced by 31.8 minutes （P=0.002） and 14.4 minutes （P=0.026） for the CAN groups of surgeons A and B, respectively. When only the cases performed after 12 months using the CAN system were considered, the perforation rate decreased by 3.9% （P=0.006） and 5.6% （P 〈0.001） and the operative time was reduced by 20.9 minutes （P 〈0.001） and 40.3 minutes （P 〈0.001） for the CAN groups of surgeon A and B, respectively.Conclusions In the long run, CAN spine surgery decreased the lumbar screw cortical perforation rate and operative time. The learning curve showed a sharp drop after 6 months of using CAN that plateaued after 12 months; which was demonstrated by both perforation rate and operative time data. Careful analysis of the data showed CAN is especially useful for less experienced surgeon to reduce perforation rate and intraoperative time, although further comparative studies are anticipated.

Correlation between magnetic resonance T2 image signal intensity ratio and cell apoptosis in a rabbit spinal cord cervical myelopathy model

Background Cervical spondylotic myelopathy （CSM） is a common cause of disability in elderly patients.Previous studies have shown that spinal cord cell apoptosis due to spinal cord compression plays an important role in the pathology of myelopathy.Although changes in magnetic resonance imaging （MRI） T2 signal intensity ratio （SIR） are considered to be an indicator of CSM,little information is published supporting the correlation between changes in MRI signal and pathological changes.This study aims to testify the correlation between MRI T2 SIR changes and cell apoptosis using a CSM animal model.Methods Forty-eight rabbits were randomly assigned to four groups：one control group and three experimental chronic compression groups,with each group containing 12 animals.Chronic compression of the cervical spinal cord was implemented in the experimental groups by implanting a screw in the C3 vertebra.The control group underwent sham surgery.Experimental groups were observed for 3,6,or 9 months after surgery.MRI T2-weighted SIR Tarlov motor scores and cortical somatosensory-evoked potentials （CSEPs） were periodically monitored.At each time point,rabbits from one group were sacrificed to determine the level of apoptosis by histology （n=6） and Western blotting （n=6）.Results Tarlov motor scores in the compression groups were lower at all time points than the control group scores,with the lowest score at 9 months （P ＜0.001）.Electrophysiological testing showed a significantly prolonged latency in CSEP in the compression groups compared with the control group.All rabbits in the compression groups showed higher MRI T2 SIR in the injury epicenter compared with controls,and higher SIR was also found at 9 months compared with 3 or 6 months.Histological analysis showed significant apoptosis in the spinal cord tissue in the compression groups,but not in the control group.There were significant differences in apoptosis degree over time （P ＜0.001）,with the 9-month group displaying the most severe spinal cord apoptosis.Spearman＇s rank correlation test showed that there was close relation between MRI SIR and degree of caspase-3 expression in Western blotting （r=0.824.P ＜0.001）.Conclusions Clear apoptosis of spinal cord tissue was observed during chronic focal spinal compression.Changes in MRI T2 SIR mav be related to the severity of the apoptosis in cervical spinal cord.

Role of Diffusion-weighted and Contrast-enhanced Magnetic Resonance Imaging in Differentiating Activity of Ankylosing Spondylitis

Background： Previous studies showed that combining apparent diffusion coefficient （ADC） value with the Spondyloarthritis Research Consortium of Canada （SPARCC） index value might provide a reliable evaluation of the activity of ankylosing spondylitis （AS）, and that contrast-enhanced （CE） magnetic resonance imaging （MRI） is unnecessary. However, the results were based on confirming only a small random sample. This study aimed to assess the role of CE-MRI in differentiating the disease activity of AS by comparingADC value with a large sample. Methods： A total of l 15 patients with AS were enrolled in accordance with Bath AS Disease Activity Index and laboratory indices, and 115 patients were divided into two groups, including active group （n = 69） and inactive group （n 46）. SPARCC, ASI, and ADC values were obtained from the short tau inversion recovery （STIR）, diffusion-weighted imaging （DWI）, and CE-MRI, respectively. One-way analysis of variance and receiver operating characteristic analysis were performed for all parameters. Results： The optimal cutoff values （with sensitivity, specificity, respective area under the curve, positive likelihood ratio, and negative likelihood ratio） for the differentiation between active and inactive groups are as follows： SPARCC = 6 （72.06%, 82.61%, 0.836, 4.14, 0.34）; ASI （%） 153 （80.6%, 84.78%, 0.819, 5.3, 0.23）; ADC value - 1.15 × 10 3 mm2/s （72.73% 81.82%, 0.786, 4, 0.33）. No statistical differences were found among the predictive values of SPARCC, △SI, and ADC. Multivariate analysis showed no significant difference between the combination of SPARCC and ADC values with and without ASI. Conclusions： Using large sample, we concluded that the combination of STIR and DWI would play significant roles in assessing the disease activity, and CE-MRI sequence is not routinely used in imaging of AS to avoid renal fibrosis and aggravation of kidney disease.

Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine

Traumatic spinal cord injury(SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold(LOCS) and human placenta-derived mesenchymal stem cells(hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment(control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans(CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin(Tuj-1)-and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending(CGRP-positive) sensory fibers and descending(5-HT-and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.

Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation

Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.