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Deep learning-based structure segmentation and intramuscular fat annotation on lumbar magnetic resonance imaging 基于深度学习的腰椎磁共振成像结构分割和肌肉内脂肪标注
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-09-17 DOI: 10.1002/jsp2.70003
Yefu Xu, Shijie Zheng, Qingyi Tian, Zhuoyan Kou, Wenqing Li, Xinhui Xie, Xiaotao Wu

Background

Lumbar disc herniation (LDH) is a prevalent cause of low back pain. LDH patients commonly experience paraspinal muscle atrophy and fatty infiltration (FI), which further exacerbates the symptoms of low back pain. Magnetic resonance imaging (MRI) is crucial for assessing paraspinal muscle condition. Our study aims to develop a dual-model for automated muscle segmentation and FI annotation on MRI, assisting clinicians evaluate LDH conditions comprehensively.

Methods

The study retrospectively collected data diagnosed with LDH from December 2020 to May 2022. The dataset was split into a 7:3 ratio for training and testing, with an external test set prepared to validate model generalizability. The model's performance was evaluated using average precision (AP), recall and F1 score. The consistency was assessed using the Dice similarity coefficient (DSC) and Cohen's Kappa. The mean absolute percentage error (MAPE) was calculated to assess the error of the model measurements of relative cross-sectional area (rCSA) and FI. Calculate the MAPE of FI measured by threshold algorithms to compare with the model.

Results

A total of 417 patients being evaluated, comprising 216 males and 201 females, with a mean age of 49 ± 15 years. In the internal test set, the muscle segmentation model achieved an overall DSC of 0.92 ± 0.10, recall of 92.60%, and AP of 0.98. The fat annotation model attained a recall of 91.30%, F1 Score of 0.82, and Cohen's Kappa of 0.76. However, there was a decrease on the external test set. For rCSA measurements, except for longissimus (10.89%), the MAPE of other muscles was less than 10%. When comparing the errors of FI for each paraspinal muscle, the MAPE of the model was lower than that of the threshold algorithm.

Conclusion

The models demonstrate outstanding performance, with lower error in FI measurement compared to thresholding algorithms.

背景腰椎间盘突出症(LDH)是腰痛的常见原因。腰椎间盘突出症患者通常会出现脊柱旁肌肉萎缩和脂肪浸润(FI),从而进一步加重腰痛症状。磁共振成像(MRI)是评估脊柱旁肌肉状况的关键。我们的研究旨在开发一种用于在核磁共振成像上自动进行肌肉分割和 FI 注释的双重模型,以帮助临床医生全面评估 LDH 状况。 方法 研究回顾性收集了 2020 年 12 月至 2022 年 5 月期间诊断为 LDH 的数据。数据集按 7:3 的比例分成训练集和测试集,并准备了一个外部测试集来验证模型的通用性。模型的性能使用平均精确度(AP)、召回率和 F1 分数进行评估。一致性采用骰子相似系数(DSC)和科恩卡帕(Cohen's Kappa)进行评估。计算平均绝对百分比误差(MAPE)以评估模型测量相对横截面积(rCSA)和 FI 的误差。计算阈值算法测量的 FI 的 MAPE,以便与模型进行比较。 结果 共有 417 名患者接受了评估,其中男性 216 人,女性 201 人,平均年龄为 49 ± 15 岁。在内部测试集中,肌肉分割模型的总体 DSC 为 0.92 ± 0.10,召回率为 92.60%,AP 为 0.98。脂肪标注模型的召回率为 91.30%,F1 得分为 0.82,Cohen's Kappa 为 0.76。不过,外部测试集的结果有所下降。在 rCSA 测量中,除了长肌(10.89%)外,其他肌肉的 MAPE 均小于 10%。在比较每块脊柱旁肌肉的 FI 误差时,模型的 MAPE 均低于阈值算法。 结论 与阈值算法相比,模型的 FI 测量误差更小,表现出卓越的性能。
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引用次数: 0
Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs 开发和验证深度学习模型,用于识别脊柱平片上的椎弓根螺钉品牌
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-09-17 DOI: 10.1002/jsp2.70001
Yu-Cheng Yao, Cheng-Li Lin, Hung-Hsun Chen, Hsi-Hsien Lin, Wei Hsiung, Shih-Tien Wang, Ying-Chou Sun, Yu-Hsuan Tang, Po-Hsin Chou

Background

In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images.

Methods

A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models.

Results

The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412).

Conclusion

The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.

背景 在脊柱翻修手术中,以前的椎弓根螺钉(PS)可能需要更换为新的植入物。如果术前不能准确识别椎弓根螺钉的品牌,可能会增加围手术期并发症的风险。本研究旨在开发并验证一种最佳深度学习(DL)模型,该模型可使用前后位(AP)和侧位图像在脊柱平片(PRS)上识别基于 PS 的器械的品牌。 方法 在这项回顾性研究中,共有 529 名患者接受了来自 7 家制造商的 PS 型器械。收集术后 PRS 作为基本事实。训练、验证和测试数据集分别包含 338、85 和 106 名患者。YOLOv5 用于裁剪螺钉轨迹,EfficientNet-b0 模型用于根据不同的 PRS 图像开发单一模型(AP、Lateral、Merge 和 Concatenated)。集合模型是单一模型的不同组合。主要结果是模型在准确度、灵敏度、精确度、F1-分数、卡帕值和曲线下面积(AUC)方面的表现。次要结果是模型与人类读者的相对性能以及 DL 模型的外部验证。 结果 在单一模型中,侧向模型的性能最稳定。集合方法提高了判别性能。AP + Lateral 集合模型的性能最稳定,准确率为 0.9434,F1 得分为 0.9388,AUC 为 0.9834。集合模型的性能与经验丰富的骨科医生相当,优于经验不足的骨科医生。外部验证显示,Lat + Concat 组合模型的准确度最高(0.9412)。 结论 DL 模型在根据 PRS 的 AP 和/或侧位图像识别 PS 型器械的品牌方面表现稳定,可帮助脊柱矫形外科医生在临床实践中制定术前翻修计划。
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引用次数: 0
Neural network segmentation of disc volume from magnetic resonance images and the effect of degeneration and spinal level 神经网络分割磁共振图像中的椎间盘体积以及退化和脊柱水平的影响。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-09-04 DOI: 10.1002/jsp2.70000
Milad I. Markhali, John M. Peloquin, Kyle D. Meadows, Harrah R. Newman, Dawn M. Elliott

Background

Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI.

Methods

Lumbar spine MRIs were acquired from 43 subjects (23–83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades.

Results

Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I–IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate.

Conclusion

This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.

背景:磁共振成像(MRI)可无创量化椎间盘结构,但需要进行既耗时又容易出现人为错误的分割。神经网络的最新进展可以改进人工分割。本研究的目的是建立一种方法,对年龄和椎间盘退化程度不同的受试者的三维椎间盘体积进行自动切片分割。对 U-Net 卷积神经网络进行了训练,以分割三维 T1 加权脊柱 MRI:方法:采集了 43 名受试者(23-83 岁)的腰椎 MRI 图像,并进行手动分割。使用 TensorFlow 框架训练 U-Net 架构。对模型进行了两轮调整。模型的性能是通过一个不与训练集交叉的验证集来测量的。在每一轮调整中,都会选择具有最佳骰子相似系数(DSC)的模型版本。模型开发完成并选出最终的 U-Net 模型后,对该模型在不同椎间盘水平和退变等级之间的性能进行了比较:结果:最终模型的性能与人工分割相当,I-IV 级退变的平均 DSC = 0.935 ± 0.014。人工分割和 U-Net 模型在 V 级椎间盘分割中的表现都不理想。与第一轮开始时的基线模型相比,最佳模型的过滤器/参数较少(75%),仅使用至少有一个椎间盘标记像素的切片进行训练,对输入图像进行对比度拉伸,并且使用了更高的辍学率:这项研究成功地训练了一个 U-Net 模型,该模型可对年龄和椎间盘退变程度不同的人群的三维椎间盘体积进行自动切片分割。最终训练出的模型可用于科学研究。
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引用次数: 0
Protective effects of curcumin against spinal cord injury 姜黄素对脊髓损伤的保护作用
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-14 DOI: 10.1002/jsp2.1364
Seyed Mehrad Razavi, Danial Khayatan, Zahra Najafi Arab, Yasamin Hosseini, Maryam Khanahmadi, Saeideh Momtaz, Tannaz Jamialahmadi, Thomas P. Johnston, Amir Hossein Abdolghaffari, Amirhossein Sahebkar

Background

In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.

Aims

This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.

Materials & Methods

The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.

Results

Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.

Discussion

Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.

Conclusion

Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.

背景 过去几十年来,随着人口老龄化的加剧,神经系统疾病和神经退行性疾病的发病率也急剧上升。神经退行性疾病会降低患者的生活质量,并给医疗系统带来高昂的成本。这些缓慢进展的疾病会导致患者出现功能、知觉和行为障碍。因此,神经退行性损伤一直是科学家和临床医生感兴趣的课题。脊髓损伤(SCI)就是其中一种疾病。脊髓损伤可导致不可逆的损伤,主要分为两种亚型:创伤性和非创伤性,每种亚型的病理生理学特征都截然不同。 目的 本综述旨在收集姜黄素(Cur)有益作用的相关信息,特别强调其对脊髓损伤(SCI)患者的抗炎特性。 材料与amp; 方法 该综述整理了大量体内、体外和临床试验数据,这些数据记录了姜黄素对 SCI 的影响。它研究了服用 CUR 后病理生理途径的调节和炎症级联的调节。 结果 有研究表明,涉及核因子红细胞 2 相关因子 2(Nrf2)、核因子卡巴 B(NF-kB)和转化生长因子 beta(TGF-β)信号通路的各种病理生理过程会加重 SCI 造成的损伤。服用 CUR 可调节这些信号通路,从而减轻 SCI 并发症。 讨论 抗炎化合物,尤其是 CUR,可以调节这些病理生理通路并调节炎症级联。姜黄素是一种著名的天然产品,具有显著的抗炎作用,已在实验和临床试验中得到广泛证实。 结论 姜黄素改变 Nrf2、NF-kB 和 TGF-β 信号通路关键步骤的潜力表明,它可能在减轻 SCI 并发症方面发挥作用。
{"title":"Protective effects of curcumin against spinal cord injury","authors":"Seyed Mehrad Razavi,&nbsp;Danial Khayatan,&nbsp;Zahra Najafi Arab,&nbsp;Yasamin Hosseini,&nbsp;Maryam Khanahmadi,&nbsp;Saeideh Momtaz,&nbsp;Tannaz Jamialahmadi,&nbsp;Thomas P. Johnston,&nbsp;Amir Hossein Abdolghaffari,&nbsp;Amirhossein Sahebkar","doi":"10.1002/jsp2.1364","DOIUrl":"https://doi.org/10.1002/jsp2.1364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical implications of linking microstructure, spatial biochemical, spatial biomechanical, and radiological features in ligamentum flavum degeneration 将黄韧带变性的微观结构、空间生物化学、空间生物力学和放射学特征联系起来的临床意义。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-09 DOI: 10.1002/jsp2.1365
Azril Azril, Kuo-Yuan Huang, Hsin-Yi Liu, Wei-An Liao, Wen-Lung Liu, Jonathan Hobley, Yeau-Ren Jeng
<div> <section> <h3> Background</h3> <p>The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments.</p> </section> <section> <h3> Objective</h3> <p>This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics.</p> </section> <section> <h3> Method</h3> <p>We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions.</p> </section> <section> <h3> Results</h3> <p>Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis.</p> </section> <section> <h3> Discussion</h3> <p>Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.</p> </section> </di
背景:黄韧带(LF)退变是椎管狭窄症的一个关键因素,可导致神经压迫和疼痛。即使有了新的治疗方案,也必须更好地了解黄韧带变性,以确保这些治疗的有效性:本研究旨在通过研究 LF 退化的各个方面(包括组织学、微观结构、化学成分和生物力学)之间的联系来深入了解 LF 退化:我们分析了27名腰椎病患者的30个腰椎间盘突出样本,利用磁共振成像(MRI)将腰椎间盘变性等级与组织中的纤维化水平联系起来。X 射线衍射(XRD)分析评估了腰椎间盘基质成分因退行性变而发生的微观结构变化。仪器纳米压痕与拉曼光谱相结合,探索了腰椎间盘突出症腹侧和背侧区域的空间微生物力学和生物化学特征:结果:我们的研究结果表明,低密度脂蛋白纤维化等级的严重程度与低密度脂蛋白厚度的增加之间存在明显的关联。XRD 分析表明,随着退化程度的加深,结晶成分和羟基磷灰石分子也在增加。拉曼光谱检测到磷酸、蛋白多糖和脯氨酸/羟脯氨酸在酰胺 I 波段上的比例发生了变化,表明细胞外基质成分发生了改变。生物力学测试表明,随着纤维化程度的增加,低密度脂蛋白组织变得更硬,伸展性更差:值得注意的是,微观空间评估显示,与腹侧相比,LF背侧承受着更大的机械应力,以及更明显的生化和生物力学变化。LF 的退化涉及影响组织学、化学成分和生物力学的复杂过程。充分了解这些变化对于开发新的、有效的椎管狭窄治疗方法至关重要。这些发现可以提高诊断的准确性,确定潜在的生物标记物和治疗目标,指导个性化治疗策略,推动组织工程方法的发展,帮助做出明智的临床决策,并对患者进行有关 LF 退化的教育。
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引用次数: 0
Biomolecular therapies for chronic discogenic low back pain: A narrative review 治疗慢性椎间盘源性腰痛的生物分子疗法:叙述性综述。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-06 DOI: 10.1002/jsp2.1345
Imke Rudnik-Jansen, Sanda van Kruining Kodele, Laura Creemers, Bert Joosten

Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.

椎间盘(IVD)退变引起的慢性腰背痛(又称慢性椎间盘源性腰背痛(CD-LBP))是最常见的肌肉骨骼疾病之一。IVD 的退变过程(如炎症和细胞外基质分解)会导致神经营养素的释放。局部神经营养素水平的升高会刺激感觉神经元的萌发和神经支配。此外,与邻近背根神经节直接相连的萌发的感觉神经会增加小胶质细胞的活化,从而导致疼痛的维持和慢性化。目前的疼痛治疗方法不足以或不适合长期使用。此外,大多数针对椎间盘退变潜在发病机制的治疗方法都侧重于修复和再生,而忽视了慢性疼痛。生物分子疗法如何影响退行性 IVD 环境、疼痛信号级联以及感觉神经元的神经支配和兴奋性往往仍不清楚。本综述探讨了 CD-LBP 的慢性疼痛治疗这一相对欠缺探索的领域,总结了针对 CD-LBP 的疗法的效果,并特别强调了慢性疼痛。事实证明,基于阻断促炎介质或神经营养素活性的方法会阻碍神经元向椎间盘的生长。此外,细胞外基质成分或移植间充质干细胞的组织再生和神经抑制特性也是潜在的有趣生物分子方法,不仅能阻止 IVD 退化,还能阻碍痛觉敏感化。目前,大多数生物分子疗法都是基于急性 IVD 退化模型,因此不能反映 CD-LBP 患者临床慢性疼痛的真实情况。未来的研究应着眼于调查治疗干预措施对包含已建立的感觉神经生长的慢性退化椎间盘的影响。深入了解生物分子疗法对 CD-LBP 患者疼痛(慢性化)途径和疼痛缓解的影响,有助于缩小新型 CD-LBP 治疗方法的临床前研究与临床治疗之间的差距,优化疼痛治疗。
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引用次数: 0
The potential effect of romosozumab on perioperative management for instrumentation surgery 罗莫单抗对器械手术围手术期管理的潜在影响。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-05 DOI: 10.1002/jsp2.1356
Koji Ishikawa, Soji Tani, Tomoaki Toyone, Koki Tsuchiya, Tomoko Towatari, Yusuke Oshita, Ryo Yamamura, Kazuki Wada, Takashi Nagai, Toshiyuki Shirahata, Katsunori Inagaki, Kudo Yoshifumi

Background

Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM).

Methods

This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD).

Results

Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group.

Conclusion

Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.

背景:与年龄相关的骨骼健康变化会增加接受骨科手术的老年患者出现并发症的风险。骨质疏松症是确保器械手术成功的关键治疗目标。骨科手术中的药物干预,尤其是新药罗莫司单抗的疗效尚不清楚。我们旨在使用基于定量计算机断层扫描(QCT)的有限元方法(FEM),评估为期 3 个月的罗莫索单抗治疗对脊柱器械手术相关生物力学参数的影响:这项开放标签的前瞻性研究纳入了81名年龄在60至90岁之间、符合骨质疏松症标准并计划接受罗莫索单抗或艾地骨化醇治疗的患者。研究人员使用血液样本、双能量吸收测定法(DXA)和 QCT 对患者进行了评估。在基线和治疗后 3 个月,使用 FEM 对生物力学参数进行评估。主要终点是3个月时的生物力学参数,次要终点包括椎弓根周围(P-vBMD)和椎体(V-vBMD)区域体积骨矿密度的变化:结果:罗莫索单抗治疗3个月后,P-vBMD和V-vBMD均明显高于埃尔德卡西妥。值得注意的是,与埃尔德钙化醇组相比,罗莫索单抗组在3个月时通过FEM估算的所有生物力学参数都有了更大的改善:结论:罗莫索单抗能明显增加区域vBMD和生物力学参数,在减少接受骨科器械手术的骨质疏松症患者的术后并发症方面具有潜在的临床益处。本研究强调了罗莫司单抗治疗的新优势,并提倡进一步研究其在围手术期管理中的有效性。
{"title":"The potential effect of romosozumab on perioperative management for instrumentation surgery","authors":"Koji Ishikawa,&nbsp;Soji Tani,&nbsp;Tomoaki Toyone,&nbsp;Koki Tsuchiya,&nbsp;Tomoko Towatari,&nbsp;Yusuke Oshita,&nbsp;Ryo Yamamura,&nbsp;Kazuki Wada,&nbsp;Takashi Nagai,&nbsp;Toshiyuki Shirahata,&nbsp;Katsunori Inagaki,&nbsp;Kudo Yoshifumi","doi":"10.1002/jsp2.1356","DOIUrl":"10.1002/jsp2.1356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cryopreserving the intact intervertebral disc without compromising viability 冷冻保存完整的椎间盘,同时不影响其存活能力。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-05 DOI: 10.1002/jsp2.1351
Ward Shalash, Ryan Forcier, Adam Z. Higgins, Morgan B. Giers

Background

Tissue cryopreservation requires saturation of the structure with cryoprotectants (CPAs) that are also toxic to cells within a short timeframe unless frozen. The race between CPA delivery and cell death is the main barrier to realizing transplantation banks that can indefinitely preserve tissues and organs. Unrealistic cost and urgency leaves less life-threatening ailments unable to capitalize on traditional organ transplantation systems that immediately match and transport unfrozen organs. For instance, human intervertebral discs (IVD) could be transplanted to treat back pain or used as ex vivo models for studying regenerative therapies, but both face logistical hurdles in organ acquisition and transport. Here we aimed to overcome those challenges by cryopreserving intact IVDs using compressive loading and swelling to accelerate CPA delivery.

Methods

CPAs were tested on bovine nucleus pulposus cells to determine the least cytotoxic solution. Capitalizing on our CPAs Computed Tomography (CT) contrast enhancement, we imaged and quantified saturation time in intact bovine IVDs under different conditions in a bioreactor. Finally, the entire protocol was tested, including 1 week of frozen storage, to confirm tissue viability in multiple IVD regions after thawing.

Results

Results showed cryopreserving medium containing dimethyl sulfoxide and ethylene glycol gave over 7.5 h before cytotoxicity. While non-loaded IVDs required over 3 days to fully saturate, a dynamic loading protocol followed by CPA addition and free-swelling decreased saturation time to <5 h. After cryopreserving IVDs for 1 week with the optimized CPA and permeation method, all IVD regions had 85% cell viability, not significantly different from fresh unfrozen controls.

Conclusions

This study created a novel solution to a roadblock in IVD research and development. Using post-compression swelling CPA can be delivered to an intact IVD over 20× more quickly than previous methods, enabling cryopreservation of the IVD with no detectable loss in cell viability.

背景:组织冷冻保存需要用冷冻保护剂(CPAs)使组织结构达到饱和,除非冷冻,否则这些保护剂在短时间内也会对细胞产生毒性。CPA 给药与细胞死亡之间的竞争是实现可无限期保存组织和器官的移植库的主要障碍。不现实的成本和紧迫性使得生命威胁较小的疾病无法利用传统的器官移植系统,因为传统的器官移植系统可以立即匹配和运输未冷冻的器官。例如,人类椎间盘(IVD)可以通过移植来治疗背痛,或用作研究再生疗法的体外模型,但两者都面临器官获取和运输方面的后勤障碍。在此,我们旨在通过冷冻保存完整的 IVD,利用压缩加载和膨胀来加速 CPA 的输送,从而克服这些挑战:方法:在牛髓核细胞上测试 CPA,以确定细胞毒性最小的解决方案。利用 CPA 的计算机断层扫描(CT)对比增强功能,我们对生物反应器中不同条件下完整牛 IVD 的饱和时间进行了成像和量化。最后,对整个方案进行了测试,包括一周的冷冻储存,以确认解冻后多个 IVD 区域的组织存活率:结果表明,含有二甲亚砜和乙二醇的冷冻保存介质可在 7.5 小时后产生细胞毒性。未加载的 IVD 需要 3 天以上才能完全饱和,而动态加载方案在添加 CPA 和自由膨胀后,饱和时间缩短至结论:这项研究为解决 IVD 研发中的一个难题提供了新的解决方案。利用压缩后溶胀法将 CPA 运送到完整的 IVD 的速度比以前的方法快 20 倍以上,从而实现了 IVD 的冷冻保存,而且细胞活力不会出现可检测到的损失。
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引用次数: 0
Flexible support material maintains disc height and supports the formation of hydrated tissue engineered intervertebral discs in vivo 柔性支撑材料可保持椎间盘高度,并支持体内水合组织工程椎间盘的形成。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-08-05 DOI: 10.1002/jsp2.1363
Alikhan B. Fidai, Byumsu Kim, Marianne Lintz, Sertac Kirnaz, Pravesh Gadjradj, Blake I. Boadi, Maho Koga, Ibrahim Hussain, Roger Härtl, Lawrence J. Bonassar

Background

Mechanical augmentation upon implantation is essential for the long-term success of tissue-engineered intervertebral discs (TE-IVDs). Previous studies utilized stiffer materials to fabricate TE-IVD support structures. However, these materials undergo various failure modes in the mechanically challenging IVD microenvironment. FlexiFil (FPLA) is an elastomeric 3D printing filament that is amenable to the fabrication of support structures. However, no present study has evaluated the efficacy of a flexible support material to preserve disc height and support the formation of hydrated tissues in a large animal model.

Methods

We leveraged results from our previously developed FE model of the minipig spine to design and test TE-IVD support cages comprised of FPLA and PLA. Specifically, we performed indentation to assess implant mechanical response and scanning electron microscopy to visualize microscale damage. We then implanted FPLA and PLA support cages for 6 weeks in the minipig cervical spine and monitored disc height via weekly x-rays. TE-IVDs cultured in FPLA were also implanted for 6 weeks with weekly x-rays and terminal T2 MRIs to quantify tissue hydration at study endpoint.

Results

Results demonstrated that FPLA cages withstood nearly twice the deformation of PLA without detrimental changes in mechanical performance and minimal damage. In vivo, FPLA cages and stably implanted TE-IVDs restored native disc height and supported the formation of hydrated tissues in the minipig spine. Displaced TE-IVDs yielded disc heights that were superior to PLA or discectomy-treated levels.

Conclusions

FPLA holds great promise as a flexible and bioresorbable material for enhancing the long-term success of TE-IVD implants.

背景:植入后的机械增强对组织工程椎间盘(TE-IVDs)的长期成功至关重要。以往的研究利用较硬的材料来制造 TE-IVD 支撑结构。然而,这些材料在具有机械挑战性的 IVD 微环境中会出现各种失效模式。FlexiFil(FPLA)是一种弹性三维打印长丝,可用于制造支撑结构。然而,目前还没有研究评估过柔性支撑材料在大型动物模型中保持椎间盘高度和支持水合组织形成的功效:我们利用之前开发的迷你猪脊柱有限元模型的结果,设计并测试了由 FPLA 和 PLA 组成的 TE-IVD 支撑笼。具体来说,我们采用压痕法评估植入物的机械响应,并用扫描电子显微镜观察微观损伤。然后,我们在小鼠颈椎中植入FPLA和PLA支撑笼6周,并每周通过X光片监测椎间盘高度。在FPLA中培养的TE-IVD也被植入6周,每周进行一次X光检查和终端T2 MRI检查,以量化研究终点时的组织水合情况:结果表明,FPLA保持架可承受近两倍于聚乳酸的变形,而机械性能不会发生有害变化,且损伤极小。在体内,FPLA保持架和稳定植入的TE-IVDs恢复了原生椎间盘高度,并支持水合组织在迷你猪脊柱中的形成。移位的 TE-IVDs 所产生的椎间盘高度优于 PLA 或椎间盘切除术处理过的水平:FPLA作为一种灵活的生物可吸收材料,在提高TE-IVD植入物的长期成功率方面大有可为。
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引用次数: 0
Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide 用胶原杂交肽量化椎间盘退行性病变患者纤维环的胶原完整性。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-07-31 DOI: 10.1002/jsp2.1359
Manmeet S. Dhiman, Taylor J. Bader, Dragana Ponjevic, Paul T. Salo, David A. Hart, Ganesh Swamy, John R. Matyas, Neil A. Duncan

Introduction

Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD.

Methods

Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section.

Results

Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed.

Discussion and Conclusions

These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.

导言:椎间盘退行性疾病(DDD)伴随着椎间盘(IVD)结构的变化。纤维环(AF)细胞外基质的降解与 IVD 的退化有关。胶原蛋白是 IVD 的重要组成部分。胶原杂交肽(CHP)是一种能与降解胶原结合的工程蛋白,我们用它来量化 AF 中的胶原损伤。我们用这种方法比较了从无 DDD 的供体处获得的房颤样本和从因症状性 DDD 而接受手术的患者处获得的房颤样本:方法:将新鲜的心房颤动组织包埋在最佳切割温度的化合物中,然后冷冻切片,厚度为 8 μm。对切片进行苏木精和伊红染色,以进行一般组织形态学评估。用 Cy3 结合的 CHP 对连续切片进行染色,并对每个 CHP 染色切片上的三个感兴趣区(ROI)的平均荧光强度和 Cy3 阳性染色的面积分数进行平均:与非 DDD 样本相比,在 DDD 样本中检测到 CHP 平均荧光强度(p = 0.0004)和阳性染色面积百分比(p = 0.00008)的增加。在非滴滴涕样本(R = 0.98,p = 5E-8)和滴滴涕样本(R = 0.79,p = 0.0012)中,平均荧光强度和阳性染色面积百分比之间存在显著相关性。非DDD 组和 DDDD 组的性别和腰椎间盘水平亚组之间未发现明显差异。只有组织病理学(非腰椎间盘突出症与腰椎间盘突出症)对测量参数有影响。没有观察到组织病理学、性别和腰椎间盘水平之间的三方交互作用:这些研究结果表明,与非DDD样本相比,DDD样本的AF胶原降解程度更高,CHP染色增加就是证明。两个测量参数之间的强正相关性表明,当胶原降解发生时,该技术可以检测到,并且在整个组织中广泛存在。这项研究为我们提供了新的视角,让我们了解在 DDD 过程中发生的与房颤胶原降解相关的结构改变。
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