JOR Spine最新文献_第5页

Automated magnetic resonance imaging-based grading of the lumbar intervertebral disc and facet joints 基于磁共振成像的腰椎间盘和关节面自动分级。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-15 DOI: 10.1002/jsp2.1353

Maryam Nikpasand, Jill M. Middendorf, Vincent A. Ella, Kristen E. Jones, Bryan Ladd, Takashi Takahashi, Victor H. Barocas, Arin M. Ellingson

Background

Degeneration of both intervertebral discs (IVDs) and facet joints in the lumbar spine has been associated with low back pain, but whether and how IVD/joint degeneration contributes to pain remains an open question. Joint degeneration can be identified by pairing T1 and T2 magnetic resonance imaging (MRI) with analysis techniques such as Pfirrmann grades (IVD degeneration) and Fujiwara scores (facet degeneration). However, these grades are subjective, prompting the need to develop an automated technique to enhance inter-rater reliability. This study introduces an automated convolutional neural network (CNN) technique trained on clinical MRI images of IVD and facet joints obtained from public-access Lumbar Spine MRI Dataset. The primary goal of the automated system is to classify health of lumbar discs and facet joints according to Pfirrmann and Fujiwara grading systems and to enhance inter-rater reliability associated with these grading systems.

Methods

Performance of the CNN on both the Pfirrmann and Fujiwara scales was measured by comparing the percent agreement, Pearson's correlation and Fleiss kappa value for results from the classifier to the grades assigned by an expert grader.

Results

The CNN demonstrates comparable performance to human graders for both Pfirrmann and Fujiwara grading systems, but with larger errors in Fujiwara grading. The CNN improves the reliability of the Pfirrmann system, aligning with previous findings for IVD assessment.

Conclusion

The study highlights the potential of using deep learning in classifying the IVD and facet joint health, and due to the high variability in the Fujiwara scoring system, highlights the need for improved imaging and scoring techniques to evaluate facet joint health. All codes required to use the automatic grading routines described herein are available in the Data Repository for University of Minnesota (DRUM).

背景：腰椎间盘（IVD）和面关节退化与腰背痛有关，但 IVD/关节退化是否以及如何导致疼痛仍是一个未决问题。关节退变可通过配对 T1 和 T2 磁共振成像（MRI）与分析技术（如普菲尔曼分级（IVD 退变）和藤原评分（面关节退变））来识别。然而，这些分级都是主观的，因此需要开发一种自动技术来提高评分者之间的可靠性。本研究介绍了一种自动卷积神经网络（CNN）技术，该技术是在从公开访问的腰椎 MRI 数据集中获取的 IVD 和关节面临床 MRI 图像上进行训练的。该自动系统的主要目标是根据 Pfirrmann 和藤原分级系统对腰椎间盘和关节面的健康状况进行分级，并提高与这些分级系统相关的评分者之间的可靠性：方法：通过比较分类器结果与专家分级员分级结果的一致性百分比、皮尔逊相关性和弗莱斯卡帕值，衡量 CNN 在 Pfirrmann 和藤原量表上的性能：在普菲尔曼和藤原分级系统中，CNN 的表现与人类分级员相当，但藤原分级的误差更大。CNN 提高了 Pfirrmann 系统的可靠性，这与之前的 IVD 评估结果一致：该研究强调了使用深度学习对 IVD 和面关节健康状况进行分类的潜力，由于藤原评分系统的高变异性，强调了需要改进成像和评分技术来评估面关节健康状况。使用本文所述自动分级例程所需的所有代码均可在明尼苏达大学数据存储库（DRUM）中找到。

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引用次数: 0

Revealing the novel metabolism-related genes in the ossification of the ligamentum flavum based on whole transcriptomic data 基于全转录组数据揭示黄韧带骨化过程中与代谢相关的新基因

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-15 DOI: 10.1002/jsp2.1357

Yongzhao Zhao, Qian Xiang, Shuai Jiang, Jialiang Lin, Weishi Li

Backgrounds

The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation.

Methods

A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells.

Results

There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells.

Conclusions

This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.

背景：黄韧带骨化（OLF）是胸椎脊髓病的主要原因之一。以往的研究表明，代谢紊乱与黄韧带骨化症的发病机制之间可能存在潜在联系。本研究旨在通过严格的代谢相关基因生物信息学工作流程和实验验证，确定代谢紊乱在OLF发病机制中的潜在作用：方法：基于代谢相关基因的一系列生物信息学方法，利用单样本基因组富集分析比较了OLF组织和正常黄韧带（LF）组织的代谢得分。通过基因本体富集分析、京都基因和基因组百科全书富集分析以及蛋白-蛋白相互作用等方法，筛选出了与OLF相关和与代谢相关的差异表达基因（OMDEGs），并探讨了OMDEGs的生物学功能。根据成对的 miRNA 中枢 OMDEGs 构建了竞争性内源性 RNA（ceRNA）网络。进行了相关性分析，以探讨 OLF 代谢紊乱与免疫异常之间的潜在关系。最后，通过细胞实验验证了GBE1和TNF-α在LF细胞成骨分化中的作用：结果：OLF组织与正常LF组织的代谢评分存在明显差异。筛选出49个OMDEGs，并确定了它们的生物学功能。建立了包含三个中心 OMDEGs 和五个差异表达 miRNAs（DEmiRNAs）的 ceRNA 网络。中枢 OMDEG 与 OLF 相关浸润免疫细胞之间的相关性分析表明，代谢紊乱可能通过改变 LF 组织的局部免疫状态而导致 OLF。细胞实验确定了 GBE1 表达和 TNF-α 在 LF 细胞成骨分化中的重要作用：该研究首次通过严格的生物信息学算法和实验验证，初步阐明了代谢紊乱在OLF发病机制中的重要作用，为今后研究OLF的发病机制和筛选有效的治疗靶点提供了新的思路。

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引用次数: 0

Prediction of adolescent idiopathic scoliosis with machine learning algorithms using brain volumetric measurements 利用脑容量测量的机器学习算法预测青少年特发性脊柱侧凸。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-15 DOI: 10.1002/jsp2.1355

Ahmet Payas, Hikmet Kocaman, Hasan Yıldırım, Sabri Batın

Background

It is known that neuroanatomical and neurofunctional changes observed in the brain, brainstem and cerebellum play a role in the etiology of adolescent idiopathic scoliosis (AIS). This study aimed to investigate whether volumetric measurements of brain regions can be used as predictive indicators for AIS through machine learning techniques.

Methods

Patients with a severe degree of curvature in AIS (n = 32) and healthy individuals (n = 31) were enrolled in the study. Volumetric data from 169 brain regions, acquired from magnetic resonance imaging (MRI) of these individuals, were utilized as predictive factors. A comprehensive analysis was conducted using the twelve most prevalent machine learning algorithms, encompassing thorough parameter adjustments and cross-validation processes. Furthermore, the findings related to variable significance are presented.

Results

Among all the algorithms evaluated, the random forest algorithm produced the most favorable results in terms of various classification metrics, including accuracy (0.9083), AUC (0.993), f1-score (0.970), and Brier score (0.1256). Additionally, the most critical variables were identified as the volumetric measurements of the right corticospinal tract, right corpus callosum body, right corpus callosum splenium, right cerebellum, and right pons, respectively.

Conclusion

The outcomes of this study indicate that volumetric measurements of specific brain regions can serve as reliable indicators of AIS. In conclusion, the developed model and the significant variables discovered hold promise for predicting scoliosis development, particularly in high-risk individuals.

背景：众所周知，在大脑、脑干和小脑中观察到的神经解剖和神经功能变化在青少年特发性脊柱侧弯症（AIS）的病因学中起着一定的作用。本研究旨在探讨是否可通过机器学习技术将脑部区域的体积测量结果用作 AIS 的预测指标：方法：研究对象包括有严重脊柱侧弯的 AIS 患者（32 人）和健康人（31 人）。通过磁共振成像（MRI）获得的 169 个大脑区域的体积数据被用作预测因素。研究人员使用最流行的十二种机器学习算法进行了全面分析，包括彻底的参数调整和交叉验证过程。此外，还介绍了与变量显著性相关的研究结果：在所有接受评估的算法中，随机森林算法在各种分类指标方面都取得了最理想的结果，包括准确率（0.9083）、AUC（0.993）、f1 分数（0.970）和 Brier 分数（0.1256）。此外，最关键的变量分别是右侧皮质脊髓束、右侧胼胝体体、右侧胼胝体脾、右侧小脑和右侧脑桥的体积测量值：本研究结果表明，对特定脑区的体积测量可作为 AIS 的可靠指标。总之，建立的模型和发现的重要变量有望预测脊柱侧弯的发展，尤其是高危人群。

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引用次数: 0

Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes 对基于人群的队列中的血清进行蛋白质组学分析，并未发现 Modic 变化的生物标志物。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-15 DOI: 10.1002/jsp2.1337

Friederike Schulze, Juhani Määttä, Sybille Grad, Irina Heggli, Florian Brunner, Mazda Farshad, Oliver Distler, Jaro Karppinen, Jeffrey Lotz, Stefan Dudli

Introduction

Modic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value.

Methods

We used a highly sensitive and reproducible proteomics approach: DIA/SWATH-MS to find serum biomarkers in a subset of the Northern Finland Birth Cohort 1966. Separately, we measured a panel of factors involved in inflammation and angiogenesis to confirm some potential biomarkers published before with an ELISA-based method called V-Plex.

Results

We found neither an association between the serum concentrations of the proteins detected with DIA/SWATH-MS with the presence of MC, nor a correlation with the size of the MC lesions. We did not find any association between the factors measured with the V-Plex and the presence of MC or their size.

Conclusion

Altogether, our study suggests that a robust and generally usable biomarker to facilitate the diagnosis of MC cannot readily be found in serum.

简介莫迪氏病变（MC）是脊椎骨的骨髓病变，可通过磁共振成像（MRI）在退化的椎间盘附近发现。根据其在 T1 和 T2 加权图像上的表现，可定义为三种可相互转换的类型：MC1、MC2 和 MC3。核磁共振成像诊断的观察者间变异性很高，因此，诊断性血清生物标志物与核磁共振成像相辅相成，有助于诊断和随访，具有重要价值：方法：我们采用了一种高灵敏度和可重复性的蛋白质组学方法：DIA/SWATH-MS方法，在1966年北芬兰出生队列的一个子集中寻找血清生物标志物。另外，我们还测量了一组涉及炎症和血管生成的因子，以确认之前用一种名为 V-Plex 的 ELISA 方法公布的一些潜在生物标志物：结果：我们发现，DIA/SWATH-MS 检测到的蛋白质的血清浓度与 MC 的存在之间没有关联，与 MC 病变的大小也没有关联。我们也没有发现用 V-Plex 检测到的因素与 MC 的存在或其大小有任何关联：总之，我们的研究表明，在血清中无法轻易找到一种可靠且普遍可用的生物标志物来帮助诊断 MC。

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引用次数: 0

Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: A Mendelian randomization 探索炎性细胞因子与椎间盘退变之间的因果关系：孟德尔随机试验

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-10 DOI: 10.1002/jsp2.1349

Tao Xu, Guangzi Chen, Jian Li, Yingchi Zhang

Background

Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD.

Method

We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results.

Result

We found interferon-gamma (IFN-γ, p = 2.14 × 10–6, OR = 0.870, 95% CI = 0.821–0.921), interleukin-1 beta (IL-1b, p = 0.012, OR = 0.951, 95% CI = 0.914–0.989), interleukin-4 (IL-4, p = 0.034, OR = 0.946, 95% CI = 0.899–0.996), interleukin-18 (IL-18, p = 0.028, OR = 0.964, 95% CI = 0.934–0.996), granulocyte colony-stimulating factor (GCSF, p = 0.010, OR = 0.919, 95% CI = 0.861–0.980), and Stromal cell-derived factor 1a (SDF1a, p = 0.014, OR = 1.072, 95% CI = 1.014–1.134) were causally associated with risk of IVDD.

Conclusion

Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.

背景：以前的一些研究报告称，炎性细胞因子与椎间盘退变（IVDD）有关。然而，炎性细胞因子与 IVDD 之间的因果关系仍不明确。本研究采用孟德尔随机法（MR）分析炎性细胞因子与 IVDD 风险之间的因果关系：我们使用了对8293名芬兰人进行的全基因组关联研究（GWAS）荟萃分析中与炎性细胞因子相关的基因变异作为工具变量，IVDD数据来自FinnGen联盟。主要分析方法是利用带有随机效应的逆方差加权法（IVW）来评估因果关系。此外，还采用了 MR-Egger、加权中位数、简单模式、加权模式、MR 多变量残差和离群值等补充方法，以增强最终结果的稳健性：我们发现干扰素-γ（IFN-γ，p = 2.14 × 10-6，OR = 0.870，95% CI = 0.821-0.921）、白细胞介素-1 beta（IL-1b，p = 0.012，OR = 0.951，95% CI = 0.914-0.989）、白细胞介素-4（IL-4，p = 0.034，OR = 0.946，95% CI = 0.899-0.996）、白细胞介素-18（IL-18，p = 0.028，OR = 0.964，95% CI = 0.934-0.996）、粒细胞集落刺激因子（GCSF，p = 0.010，OR = 0.919，95% CI = 0.861-0.980）和基质细胞衍生因子 1a（SDF1a，p = 0.014，OR = 1.072，95% CI = 1.014-1.134）与 IVDD 风险存在因果关系：我们的磁共振分析发现，六种炎症细胞因子（IFN-γ、IL-1b、IL-4、IL-18、SDF1a 和 GCSF）与 IVDD 风险改变之间存在潜在的因果关系。

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引用次数: 0

Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes 慢性腹侧脊髓压迫小鼠模型的开发：神经行为、放射学和病理学变化

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-10 DOI: 10.1002/jsp2.1350

Zhongyuan He, Tao Tang, Zhengya Zhu, Fuan Wang, Jianfeng Li, Fu Zhang, Nguyen Tran Canh Tung, Shaoyu Liu, Xizhe Liu, Zhiyu Zhou

Objectives

The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes.

Methods

In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1^flox/flox/EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study.

Results

The results demonstrated a gradual deterioration of compression in the Enpp1^flox/flox/EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05).

Conclusions

The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.

研究目的本研究的主要目的是建立脊柱韧带骨化小鼠模型，以模拟后纵韧带骨化（OPLL）患者的慢性脊髓压迫症状。研究还旨在检测小鼠的神经生物学、放射学和病理学变化：在之前的研究中，我们利用 Crispr-Cas9 技术创建了一个转基因小鼠品系，即 Enpp1 flox/flox /EIIa-Cre （C57/B6 背景），以建立 OPLL 模型。无压迫的野生型（WT）小鼠作为对照组。通过运动评分评估、倾斜板测试和步态分析评估功能障碍。通过 CT 成像确定压迫程度。研究中进行了血红素和伊红染色、鲁索快蓝染色、TUNEL检测、免疫荧光染色、qPCR和Western印迹，以评估细胞凋亡、炎症、血管化和脱髓鞘的水平：结果表明，随着年龄的增长，Enpp1 flox/flox /EIIa-Cre 小鼠组的压迫症状逐渐恶化。在12周至20周期间，恶化速度更快，随后在20周至28周期间逐渐趋于稳定。使用巴索小鼠量表和斜板试验评估的脊髓功能和力量评分显示出明显的下降。步态分析显示，前后步长、步幅和脚趾张开度明显下降。慢性脊髓压迫导致神经元损伤，激活了灰质和前角的星形胶质细胞和小胶质细胞。颈椎后部的逐渐压迫阻碍了血液供应，导致炎症和 Fas 介导的神经细胞凋亡。Bcl2 和 Caspase 3 的激活与进行性神经功能缺损的发展有关（p 结论）：该研究提出了一种经过验证的慢性脊髓压迫模型，使研究人员能够探索与临床相关的 OPLL 治疗方法。

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引用次数: 0

Silibinin promotes healing in spinal cord injury through anti-ferroptotic mechanisms Silibinin 通过抗发炎机制促进脊髓损伤的愈合。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-07-01 DOI: 10.1002/jsp2.1344

Arman Vahabi, Anıl Murat Öztürk, Bünyamin Kılıçlı, Derviş Birim, Gizem Kaftan Öcal, Taner Dağcı, Güliz Armağan

Study Design

Pre-clinical animal experiment.

Objective

In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI.

Methods

The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso–Beattie–Bresnahan test.

Results

Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05).

Conclusion

Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.

研究设计临床前动物实验：本研究调查了西利宾在脊髓损伤（SCI）模型中的治疗效果。在脊髓损伤（SCI）中，继发性损伤机制造成的细胞损失超过了原发性损伤造成的细胞损失。铁凋亡是一种铁依赖性非凋亡性细胞死亡，在 SCI 的发病机制中具有重要影响：研究以体内实验的形式进行，共使用 78 只成年雄性/雌性 Sprague Dawley 大鼠。分组如下SCI、去氧胺（DFO）治疗和西利宾治疗。所有组别均设有随访期为 24 小时、72 小时和 6 周的子组。用分光光度法测量丙二醛（MDA）、谷胱甘肽（GSH）和 Fe2+ 的水平。谷胱甘肽过氧化物酶-4（GPX4）、铁蛋白（FPN）、转铁蛋白受体（TfR1）和 4-羟基壬烯醛（4-HNE）修饰蛋白水平通过 Western 印迹法进行评估。采用巴索-巴蒂-布雷斯纳汉试验评估功能恢复情况：结果：与 SCI 相比，西利宾在 72 小时组和 6 周组的 MDA 和 4-HNE 水平都有明显的抑制作用（p p p p DFO > SCI（p 结论：西利宾在 72 小时组和 6 周组的 MDA 和 4-HNE 水平都有明显的抑制作用（p p p DFO > SCI）：西利宾对铁代谢和脂质过氧化的影响（两者都是铁变态反应的特征）可能有助于治疗活动。在这种情况下，我们的研究结果表明，西利宾是一种潜在的候选治疗药物，在 SCI 模型中具有抗铁细胞减少的特性。能够有效、安全地减轻铁变态反应细胞死亡的治疗药物有可能成为未来临床研究的关键点。

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引用次数: 0

Efficacy of using autologous cells with graft substitutes for spinal fusion surgery: A systematic review and meta-analysis of clinical outcomes and imaging features 在脊柱融合手术中使用自体细胞和移植物替代物的疗效：临床结果和成像特征的系统回顾和荟萃分析。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-06-28 DOI: 10.1002/jsp2.1347

F. Salamanna, D. Contartese, G. Tedesco, A. Ruffilli, M. Manzetti, G. Viroli, M. Traversari, C. Faldini, G. Giavaresi

Over the past several decades, there has been a notable increase in the total number of spinal fusion procedures worldwide. Advanced spinal fusion techniques, surgical approaches, and new alternatives in grafting materials and implants, as well as autologous cellular therapies, have been widely employed for treating spinal diseases. While the potential of cellular therapies to yield better clinical results is appealing, supportive data are needed to confirm this claim. This meta-analysis aims to compare the radiographic and clinical outcomes between graft substitutes with autologous cell therapies and graft substitutes alone. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched for studies comparing graft substitutes with autologous cell therapies and graft substitutes alone up to February 2024. The risk of bias of the included studies was evaluated using the Downs and Black checklist. The following outcomes were extracted for comparison: fusion success, complications/adverse events, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score. Thirteen studies involving 836 patients were included, with 7 studies considered for the meta-analysis. Results indicated that the use of graft substitutes with autologous cell therapies demonstrated higher fusion success rates at 3, 6, and 12 months, lower VAS score at 6 months, and lower ODI score at 3, 6, and 12 months. The complication rate was similar between graft substitutes with autologous cell therapies and graft substitutes alone. Although the current literature remains limited, this meta-analysis suggests that the incorporation of cellular therapies such as bone marrow and platelet derivatives with graft substitutes is associated with a higher fusion rate and significant improvements in functional status and pain following spinal fusion. Future well-designed randomized clinical trials are needed to definitively assess the clinical effectiveness of cellular therapies in spinal fusion.

过去几十年来，全球脊柱融合手术的总数显著增加。先进的脊柱融合技术、手术方法、新的移植材料和植入物以及自体细胞疗法已被广泛用于治疗脊柱疾病。虽然细胞疗法有可能产生更好的临床效果，但这一说法需要支持性数据来证实。本荟萃分析旨在比较移植物替代物与自体细胞疗法和单纯移植物替代物之间的放射学和临床效果。截至 2024 年 2 月，我们在 PubMed、Scopus、Web of Science、ClinicalTrials.gov 和 Cochrane 对照试验中央注册中心检索了比较移植物替代物与自体细胞疗法和单纯移植物替代物的研究。采用Downs和Black核对表对纳入研究的偏倚风险进行了评估。提取了以下结果进行比较：融合成功率、并发症/不良事件、视觉模拟量表（VAS）评分和Oswestry残疾指数（ODI）评分。共纳入 13 项研究，涉及 836 名患者，其中 7 项研究被纳入荟萃分析。结果表明，使用移植物替代物与自体细胞疗法在3、6和12个月时的融合成功率更高，6个月时的VAS评分更低，3、6和12个月时的ODI评分更低。伴有自体细胞疗法的移植物替代物与单纯移植物替代物的并发症发生率相似。尽管目前的文献仍然有限，但这项荟萃分析表明，在移植物替代物中加入骨髓和血小板衍生物等细胞疗法与更高的融合率以及脊柱融合术后功能状态和疼痛的显著改善有关。未来还需要进行精心设计的随机临床试验，以明确评估细胞疗法在脊柱融合术中的临床效果。

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引用次数: 0

A comprehensive review of cell transplantation and platelet-rich plasma therapy for the treatment of disc degeneration-related back and neck pain: A systematic evidence-based analysis 细胞移植和富血小板血浆疗法治疗椎间盘退变相关背痛和颈痛的综合综述：基于证据的系统分析。

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-06-24 DOI: 10.1002/jsp2.1348

Jordy Schol, Shota Tamagawa, Tibo Nico Emmie Volleman, Muneaki Ishijima, Daisuke Sakai

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell- and platelet-rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in-human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2-year follow-up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell- and PRP-treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost-effectiveness assessments to determine the benefits of cell/PRP treatments.

腰痛（LBP）和颈痛是导致残疾的主要原因。细胞和富血小板血浆（PRP）产品是一种潜在的疗法，临床试验和评论都在宣传其疗效。然而，这些临床试验和综述往往忽视了所报道的改善效果的临床意义。在这篇系统性综述中，对疼痛、残疾、生活质量（QoL）和放射影像的有效改善进行了全面描述，并对其临床意义进行了评分。2023 年 7 月，我们在电子数据库中搜索了有关细胞或 PRP 产品缓解椎间盘源性疼痛的人体评估文献。筛选的论文涉及定量疼痛、残疾、QoL、放射学改善和安全性结果。通过 MINORS 和 Cochrane 偏倚来源工具评估偏倚风险。对报告的结果进行了获取、计算和评估，以符合最小临床重要性差异 (MCID) 标准。从筛选出的 7623 篇论文中，共有 80 篇符合资格标准，其中 68 篇为具体研究。其中至少有 1974 名患者接受了治疗。总体而言，细胞/PRP注射可减轻疼痛和残疾，在长达2年的随访中，疼痛和残疾的MCID与接受脊柱融合术的患者所观察到的相似。所纳入的试验主要存在高度偏倚，研究设计不尽相同，只有极少量的随机对照试验。尽管如此，我们还是观察到细胞和 PRP 治疗组群具有明显的临床效果，而且总体安全性良好。这些结果凸显了强大的治疗潜力，但也强调了未来进行成本效益评估的必要性，以确定细胞/PRP疗法的益处。

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引用次数: 0

Static study and numerical simulation of the influence of cement distribution in the upper and lower adjacent vertebrae on sandwich vertebrae in osteoporotic patients: Finite element analysis 骨质疏松症患者上下相邻椎体骨水泥分布对三明治椎体影响的静态研究和数值模拟：有限元分析

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2024-06-21 DOI: 10.1002/jsp2.1343

Shaolong Huang, Xue Wu, Chengqiang Zhou, Xu Zhang, Zhongjian Tang, Xiangyu Qi, Shuai Zhao

Objective

We analyzed the influence of the location of the upper and lower cement on the sandwich vertebrae (SV) by computer finite element analysis.

Materials and Methods

A finite element model of the spinal segment of T11-L1 was constructed and 6 mL of cement was built into T11 and L1 simultaneously. According to the various distributions of bone cement at T11 and L1, the following four groups were formed: (i) Group B-B: bilateral bone cement reinforcement in both T11 and L1 vertebral bodies; (ii) Group L-B: left unilateral reinforcement in T11 and bilateral reinforcement in L1; (iii) Group L-R: unilateral cement reinforcement in both T11 and L1 (cross); (iv) Group L-L: unilateral cement reinforcement in both T11 and L1 (ipsilateral side). The maximum von Mises stress (VMS) and maximum displacement of the SV and intervertebral discs were compared and analyzed.

Results

The maximum VMS of T12 was in the order of size: group B-B < L-B < L-R < L-L. Group B-B showed the lowest maximum VMS values for T12: 19.13, 18.86, 25.17, 25.01, 19.24, and 20.08 MPa in six directions of load flexion, extension, left and right lateral bending, and left and right rotation, respectively, while group L-L was the largest VMS in each group, with the maximum VMS in six directions of 21.55, 21.54, 30.17, 28.33, 19.88, and 25.27 MPa, respectively.

Conclusion

Compared with the uneven distribution of bone cement in the upper and lower adjacent vertebrae (ULAV), the uniform distribution of bone cement in the ULAV reduced and uniformed the stress load on the SV and intervertebral disc. Theoretically, it can lead to the lowest incidence of sandwich vertebral fracture and the slowest rate of intervertebral disc degeneration.

目的通过计算机有限元分析，分析上下骨水泥位置对夹层椎体（SV）的影响。材料与方法建立 T11-L1 脊柱的有限元模型，在 T11 和 L1 中同时植入 6 mL 骨水泥。根据骨水泥在 T11 和 L1 的不同分布，分为以下四组：(i) B-B 组：T11 和 L1 椎体双侧骨水泥加固；(ii) L-B 组：T11 左侧单侧加固，L1 双侧加固；(iii) L-R 组：T11 和 L1 单侧骨水泥加固（交叉）；(iv) L-L 组：T11 和 L1 单侧骨水泥加固（同侧）。对 SV 和椎间盘的最大 von Mises 应力（VMS）和最大位移进行了比较和分析。结果 T12 的最大 VMS 依次为：B-B 组；L-B 组；L-R 组；L-L 组。B-B 组 T12 的最大 VMS 值最低，在负荷屈曲、伸展、左右侧弯、左右旋转六个方向的最大 VMS 值分别为 19.13、18.86、25.17、25.01、19.24 和 20.08 MPa，而 L-L 组是各组中 VMS 值最大的，六个方向的最大 VMS 值分别为 21.55、21.54、30.17、28.33、19.88 和 25.27 MPa。结论与骨水泥在上下相邻椎体（ULAV）的不均匀分布相比，骨水泥在 ULAV 的均匀分布降低并均匀了 SV 和椎间盘的应力负荷。从理论上讲，它可以使夹层椎体骨折的发生率最低，椎间盘退变的速度最慢。

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引用次数: 0