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Patient-Reported Outcomes Among an Observational Cohort of Individuals With Chronic Low Back Pain 慢性腰痛患者报告的观察性队列结果
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-13 DOI: 10.1002/jsp2.70097
Carol M. Greco, Nathan E. Dodds, Amanda M. Acevedo, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Michael J. Schneider, Nam V. Vo, Ajay D. Wasan, Lan Yu, Gwendolyn A. Sowa

Background

Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient-reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB3P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in-person LB3P study enrollment visit.

Methods

The LB3P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain-related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed.

Results

PRO measures were collected from 1007 LB3P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in-person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self-efficacy, and positive outlook were within normal limits, as indicated by PROMIS T-scores. However, PROMIS Physical function was below normal, with T-scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfacti

慢性腰痛(cLBP)是一种复杂的、致残的、对患者和社会都昂贵的疾病。患者的社会环境、信仰和行为以动态的方式与生物医学因素相互作用,并有可能放大或减少痛苦。通过患者报告的结果(PROs)来评估疼痛体验是很重要的。匹兹堡大学机械研究中心,题为“腰痛:生物学,生物力学,行为表型(LB3P)”,是美国国立卫生研究院帮助结束成瘾长期倡议的一部分。LB3P进行了一项前瞻性、观察性队列研究,以确定1000多名cLBP患者的表型。本文报告了在LB3P研究登记访问中获得的PROs和选定的人口统计变量的关键信息。LB3P研究的参与者完成了许多PROs,包括NIH背痛研究工作组的最低数据集评估和NIH HEAL倡议的公共数据元素。研究将疼痛因素分为5个概念域:(1)疼痛特征和质量;(2)疼痛相关心理社会因素;(3)一般心理社会因素;(4)一般健康和生活方式因素;(5)健康社会决定因素。还评估了患者对症状状态的接受程度,包括对10个问题中的每一个症状的水平是否令人满意的回答是/否。结果收集1007例LB3P患者cLBP PRO测量数据。在亲自入组访问中收集的PRO变量的均值和标准差,或中位数和四分位数范围,以及百分比被呈现在整个组中,并按出生性别(女性和男性)和年龄(60岁和≥60岁)分层。对于所有参与者来说,不分性别和年龄,疼痛强度和干扰的平均程度是中等的。通过PainDETECT评估的神经性疼痛在整个样本中占18%,在60岁以下的人中占22.5%。平均而言,疲劳、抑郁和焦虑症状、记忆和注意力、自我效能感和积极前景在正常范围内,如PROMIS t评分所示。然而,PROMIS的身体功能低于正常,t评分在轻度到中度的损害范围内。当参与者被要求对10个功能领域的症状状态的可接受程度进行评分时,最常报告的不满意领域是:疼痛强度和干扰、身体功能、睡眠和疲劳。在SDoH领域,近一半(44%)的参与者报告有过创伤经历。在整个群体中,36%的人表示难以支付食物、医疗和取暖等基本需求,而60岁以上人群中有51%的人表示存在这种程度的经济压力。结论LB3P cLBP观察队列表现出中等水平的疼痛强度,疼痛干扰生活活动和疼痛相关残疾。参与者报告了轻度至中度与疼痛相关的社会心理因素,而抑郁和焦虑等一般心理健康挑战相对较少。许多参与者报告了创伤经历的历史,并面临着当前的经济挑战。LB3P PRO结果为社区cLBP患者样本提供了参考价值。
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引用次数: 0
Feasibility of Physical Exam and Performance-Based Tests in Individuals With Chronic Low Back Pain: A Descriptive Study 慢性腰痛患者体格检查和性能测试的可行性:一项描述性研究
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-12 DOI: 10.1002/jsp2.70096
Sara R. Piva, Zakiy Alfikri, William Anderst, Kevin M. Bell, Cristiane Carlesso, Jessa Darwin, Anthony Delitto, Carol M. Greco, Marit E. Johnson, Gina P. McKernan, Rachel McLoughlin, Charity G. Patterson, Rachel E. Roos, Michael J. Schneider, Clair Smith, Gwendolyn A. Sowa, Nam V. Vo, Leming Zhou
<div> <section> <h3> Background</h3> <p>Despite the wide utilization of physical tests and pain assessments to evaluate individuals with chronic low back pain (cLBP), there is limited information about their feasibility in terms of test duration, the ability of individuals with cLBP to perform these tests, and associated adverse events. The literature also lacks reports on comprehensive characterization of physical tests to serve as a reference for clinicians and researchers. The objectives of the present work are to assess the feasibility of a comprehensive battery of physical tests and pain assessments germane to individuals with cLBP and characterize the tests' values in the context of a large cohort.</p> </section> <section> <h3> Methods</h3> <p>This cross-sectional analysis uses enrollment data from a large observational study conducted by the University of Pittsburgh Mechanistic Research Center—“Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P).” LB<sup>3</sup>P is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. Individuals with cLBP were screened by trained clinicians who assessed their safety to partake in up to 37 physical tests based on pre-existing medical conditions. Testers could elect not to administer tests based on their clinical judgment and participants could refuse to partake in tests. The reasons for not performing tests were recorded. The feasibility of the tests was assessed by the time to complete each test, percentages and reasons for tests not done, and adverse events related to test performance. Descriptive statistics for the physical tests were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60) to serve as reference values for individuals with cLBP.</p> </section> <section> <h3> Results</h3> <p>The testing protocol took on average 130 min. In total, 8.9% of tests were not done. About one third of tests not done were screened out due to medical conditions identified during the safety screening, and two-thirds due to the tester's clinical judgment or participant refusal. Only four adverse events occurred, and they resolved without sequelae. The tests most often omitted were those requiring maximal and submaximal physical effort or could elevate blood pressure in those with hypertension, such as muscle strength testing of the hip, abdomen, and thigh, or hand immersion in cold water. From the 1007 participants enrolled in the study, those who did not complete one or more tests tended to be older, obese, less educated, and experienced more disability and back pain for a longer time. The descriptive statistics of th
背景:尽管身体检查和疼痛评估被广泛用于评估慢性腰痛(cLBP)患者,但在测试持续时间、cLBP患者执行这些检查的能力以及相关不良事件方面,关于其可行性的信息有限。文献也缺乏全面表征的物理测试的报告,以作为临床医生和研究人员的参考。本研究的目的是评估与cLBP患者相关的一系列全面的身体测试和疼痛评估的可行性,并在一个大队列的背景下描述这些测试的价值。方法横断面分析使用匹兹堡大学机械研究中心进行的一项大型观察性研究的登记数据-“腰痛:生物学,生物力学,行为表型(LB3P)”。LB3P是美国国立卫生研究院帮助结束成瘾长期倡议的一部分。cLBP患者由训练有素的临床医生筛选,他们根据已有的医疗状况评估他们参加多达37项身体检查的安全性。测试人员可以根据他们的临床判断选择不进行测试,参与者可以拒绝参加测试。记录了不执行测试的原因。通过完成每项测试的时间、未完成测试的百分比和原因以及与测试性能相关的不良事件来评估测试的可行性。计算总体样本和亚组(男性/女性和年龄60岁/≥60岁)体格检查的描述性统计数据,作为cLBP患者的参考值。结果检测方案平均耗时130 min。总共有8.9%的测试没有完成。约三分之一未完成的测试是由于在安全筛选期间确定的医疗条件而被筛选掉的,三分之二是由于测试人员的临床判断或参与者的拒绝。仅发生4次不良事件,且均无后遗症。最常被忽略的测试是那些需要最大和次最大的体力努力或可能升高高血压患者血压的测试,如臀部、腹部和大腿的肌肉力量测试,或手浸在冷水中。从参与研究的1007名参与者中,那些没有完成一项或多项测试的人往往年龄更大,肥胖,受教育程度更低,经历更多残疾和背部疼痛的时间更长。37项试验的描述性统计数据按性别和年龄分层。结论:本研究结果支持对cLBP患者进行全面的身体检查和疼痛评估的安全性和可行性。本研究还提供了有关cLBP患者测试表现频率、未完成原因、持续时间和描述性结果的新信息。这一综合表征为今后的研究规划和临床实践提供了比较参考价值。
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引用次数: 0
Comments on “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” 《探讨葛根素通过调节髓核细胞凋亡治疗椎间盘退变的潜力》一文评论
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-12 DOI: 10.1002/jsp2.70099
Ji Jin, Miao Liu, Jiajie Guo, Hong Sun

We read with interest the article by Xiaoqiang Wang et al. [1] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.

First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.

Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [2, 3]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [4].

We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.

我们饶有兴趣地阅读了2024年12月11日发表在《JOR Spine》杂志上的王晓强等人的文章《通过调节髓核细胞凋亡探索葛根素对椎间盘退变的治疗潜力》。该研究提出了葛根素在减轻椎间盘退变(IDD)中的作用的令人信服的发现。然而,关于数据分析和解释,我们想提出两个关键点,这可能会影响结论的有效性。首先,在图1E中,给出了四个不同数据集的交集大小。然而,结果似乎是违反直觉的:交集大小随着数据集的增加而增加,而随着数据集的减少而减少。这种观察结果与数学原理相矛盾,因为由于可变性增加和公共元素减少,多个数据集的交集通常会随着更多数据集的增加而减少。我们建议作者重新审视用于计算这些交叉点的方法,并验证数据处理步骤以确保准确性。澄清交点大小是如何推导出来的,将大大提高这一分析的可靠性。其次,作者没有明确说明差异分析中使用的log2FoldChange阈值。根据图2A,绝对值的范围在0.2到0.3之间。如此低的阈值可能导致差异表达基因的范围过宽,从而可能降低研究结果的生物学意义[2,3]。我们建议作者证明他们选择阈值的合理性,并考虑采用更严格的截止值来提高结果的稳健性。此外,通过功能富集分析探索鉴定基因的生物学相关性可以加强研究结论[4]。我们认为,解决这些问题将大大提高研究的清晰度和影响。我们感谢作者对该领域的贡献,并希望我们的评论将鼓励进一步完善这一重要工作。谢谢你考虑我们的意见。我们期待作者的回复和任何可能的后续研究。
{"title":"Comments on “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells”","authors":"Ji Jin,&nbsp;Miao Liu,&nbsp;Jiajie Guo,&nbsp;Hong Sun","doi":"10.1002/jsp2.70099","DOIUrl":"https://doi.org/10.1002/jsp2.70099","url":null,"abstract":"<p>We read with interest the article by Xiaoqiang Wang et al. [<span>1</span>] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.</p><p>First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.</p><p>Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [<span>2, 3</span>]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [<span>4</span>].</p><p>We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814983","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
Central Pattern Generators in Spinal Cord Injury: Mechanisms, Modulation, and Therapeutic Strategies for Motor Recovery 脊髓损伤的中枢模式产生:机制、调节和运动恢复的治疗策略
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-11 DOI: 10.1002/jsp2.70100
Hao Su, Longfei Jing, Dongmei Lv, Zhendong Huan, Wenqiang Xu

Background

Spinal cord injury (SCI) compromises the communication between the brain and spinal circuits involved in locomotion, resulting in severe motor dysfunction. However, currently available therapies have limited effectiveness in restoring motor function after SCI.

Objective

Recent research has highlighted the importance of the central pattern generator (CPG), a spinal circuitry responsible for generating coordinated patterns of leg motor activity in the absence of brain-derived inputs, in locomotor recovery. Therefore, a highly promising approach for restorative treatment after SCI involves reactivating the CPG network to harness its rhythmic activity-generating capabilities. Various forms of neuromodulation, such as pharmacological agents, electrical stimulation, and light-based regulatory strategies, have been utilized for this purpose.

Results

This review summarizes the organizational structure and functional characteristics of CPG networks, examines CPG alterations following SCI, and evaluates recent advances in neuromodulation strategies aimed at restoring motor function through CPG reactivation.

Conclusions

This review also highlights existing challenges and outlines prospective directions for future research in the field.

脊髓损伤(SCI)损害了参与运动的大脑和脊髓回路之间的通信,导致严重的运动功能障碍。然而,目前可用的治疗方法在恢复脊髓损伤后的运动功能方面效果有限。最近的研究强调了中枢模式发生器(CPG)在运动恢复中的重要性,CPG是一种在没有脑源性输入时负责产生腿部运动活动协调模式的脊髓回路。因此,对于脊髓损伤后的恢复性治疗,一个非常有希望的方法是重新激活CPG网络,以利用其节律性活动产生能力。各种形式的神经调节,如药理学,电刺激和基于光的调节策略,已被用于这一目的。结果总结了CPG网络的组织结构和功能特征,研究了脊髓损伤后CPG的变化,并评估了通过CPG再激活恢复运动功能的神经调节策略的最新进展。本综述还强调了该领域存在的挑战,并概述了未来研究的展望方向。
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引用次数: 0
Gait Analysis During Paralysis Recovery in a Rat Incomplete Spinal Cord Injury Model 大鼠不完全性脊髓损伤模型瘫痪恢复过程中的步态分析
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-06 DOI: 10.1002/jsp2.70102
Misa Toyota, Shion Masuda, Daiki Nohara, Satoru Oba, Mayu Tomomitsu, Momoko Nagai-Tanima, Tomoki Aoyama

Background

In this study, we aimed to create a rat model of incomplete spinal cord injury and to determine the relationship between muscle tone and gait characteristics during recovery from paralysis. This necessity stems from the need for animal models with motor function dynamics in rehabilitation development for spinal cord injury.

Methods

Thirty-eight-week-old male Sprague-Dawley rats were divided randomly into two groups: Sham and spinal cord injury groups. Three-dimensional gait analysis, Hoffman reflex, Basso-Beatie-Bresnahan score, muscle wet weight, and histological assessment were performed on postoperative days 3, 7, and 14, respectively.

Results

The incomplete spinal cord injury model showed paralysis recovery over time at postoperative day 14. At ground contact, the ankle plantar flexion angle was higher in the spinal cord injury group than in the Sham group on postoperative day 3; however, it reduced on postoperative day 14. Nevertheless, the ankle plantar flexion angle on the foot-off phase was significantly higher on postoperative days 3 and 14. The ankle abduction angle in the spinal cord injury group significantly increased over time and was higher than in the Sham group at all time points. Hoffmann reflex results showed that muscle tone was significantly higher in the spinal cord injury group on postoperative day 3 and increased over time. The model's gait was significantly affected by muscle tone changes.

Conclusion

The model provides a valuable tool for studying spastic gait and gait changes associated with improvement in paralysis.

在本研究中,我们旨在建立不完全脊髓损伤大鼠模型,并确定瘫痪恢复过程中肌肉张力与步态特征之间的关系。这种必要性源于对脊髓损伤康复发展中运动功能动力学动物模型的需求。方法38周龄雄性Sprague-Dawley大鼠随机分为假手术组和脊髓损伤组。分别于术后第3、7、14天进行三维步态分析、Hoffman反射、Basso-Beatie-Bresnahan评分、肌肉湿重和组织学评估。结果不完全脊髓损伤模型术后第14天出现麻痹恢复。与地面接触时,脊髓损伤组术后第3天踝关节底屈曲角度高于Sham组;然而,术后第14天减少。然而,在术后第3天和第14天,足离期的踝关节跖屈曲角度明显升高。脊髓损伤组大鼠踝关节外展角随时间明显增高,各时间点均高于Sham组。Hoffmann反射结果显示脊髓损伤组术后第3天肌肉张力明显增高,且随时间延长而增高。肌张力变化对模型的步态有显著影响。结论该模型为研究痉挛性步态和步态变化与麻痹改善的关系提供了有价值的工具。
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引用次数: 0
Spatial and Diurnal Variations in Sodium Content Within Intervertebral Disc Tissue 椎间盘组织内钠含量的空间和日变化
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-08-05 DOI: 10.1002/jsp2.70079
Jordin T. Marshall, Anthony D. Lutton, Mark W. Grinstaff, John W. Olesik, Benjamin A. Walter

Background

Daily cycles in tissue osmolarity within the intervertebral disc (IVD) are a biophysical signal that regulates cellular metabolism and arise from deformation of the charged and hydrated extracellular matrix (ECM). However, the magnitude of these osmotic cycles remains unclear due to spatial variations in ECM composition and fixed charge density (FCD) between the regions of the IVD and between the pericellular matrix (PCM) and surrounding ECM. This study aimed to (1) validate the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to assess intra-tissue sodium content and (2) apply this method to assess temporal and spatial changes in intra-tissue sodium content during a diurnal loading cycle.

Methods

The FCD of nucleus pulposus (NP) tissue was modified via equilibrium dialysis, and intra-tissue sodium was assessed via inductively coupled plasma-optical emission spectroscopy (ICP-OES) and LA-ICP-MS. In addition, tissue was stained with a cationic iodine-based contrast agent, and iodine was assessed via LA-ICP-MS. Diurnal changes in sodium were measured via LA-ICP-MS and ICP-OES in bovine caudal motion segments loaded under simulated physiologic loading for 40 (n = 4) or 48 (n = 4) hours, representing end-of-day and end-of-night deformations, respectively.

Results

Intra-tissue sodium content assessed via LA-ICP-MS strongly correlated (r ≥ 0.95) with ICP-OES sodium content, theoretical FCD values, and LA-ICP-MS iodine content in equilibrated tissue. Diurnal sodium results demonstrate that at the macroscale the NP region possessed a greater sodium content than the annulus fibrosus (AF) and experienced greater diurnal changes (“end-of-day-NP” sodium [0.52 ± 0.18 mEq Na/g wet wt], “end of night-NP” sodium [0.34 ± 0.13 mEq Na/g wet wt]) than the AF which did not experience a diurnal change. At the microscale, average PCM sodium normalized to adjacent ECM sodium at the end-of-day (2.3 ± 0.96) was greater than at the end-of-night (1.5 ± 0.38), indicating cells embedded within their specialized PCM likely experience elevated osmotic fluctuations.

椎间盘内组织渗透压(IVD)的每日循环是一种生物物理信号,它调节细胞代谢,产生于带电和水合的细胞外基质(ECM)的变形。然而,由于细胞外基质组成和固定电荷密度(FCD)在IVD区域之间以及细胞周基质(PCM)与周围细胞外基质之间的空间差异,这些渗透循环的大小仍不清楚。本研究旨在(1)验证激光烧蚀-电感耦合等离子体质谱法(LA-ICP-MS)评估组织内钠含量的有效性;(2)应用该方法评估组织内钠含量在日加载周期内的时空变化。方法采用平衡透析法修饰髓核组织的FCD,采用电感耦合等离子体发射光谱(ICP-OES)和LA-ICP-MS测定组织内钠含量。此外,用阳离子碘造影剂对组织进行染色,并通过LA-ICP-MS评估碘含量。通过LA-ICP-MS和ICP-OES测量了在模拟生理负荷下加载40 (n = 4)或48 (n = 4)小时的牛尾端运动节段的钠的日变化,分别代表白天结束和晚上结束的变形。结果LA-ICP-MS测定的组织内钠含量与ICP-OES测定的组织内钠含量、理论FCD值和LA-ICP-MS测定的平衡组织内碘含量呈显著正相关(r≥0.95)。钠的日变化结果表明,在宏观尺度上,NP区比纤维环区(AF)具有更高的钠含量,并且比AF区有更大的日变化(“日末NP”钠[0.52±0.18 mEq Na/g wet wt],“夜末NP”钠[0.34±0.13 mEq Na/g wet wt]),而AF区没有发生日变化。在微观尺度上,在白天结束时,平均PCM钠归一化到邻近ECM钠(2.3±0.96)大于在晚上结束时(1.5±0.38),表明嵌入其专门PCM的细胞可能经历了更高的渗透波动。
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引用次数: 0
Comparative Performance of Calcium Phosphate Grafts and Iliac Crest Autograft in Posterolateral Spinal Fusion in Rabbits 磷酸钙移植物与自体髂骨移植物在兔后外侧脊柱融合术中的性能比较
IF 3.9 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-07-30 DOI: 10.1002/jsp2.70101
William R. Walsh, Rema A. Oliver, Matthew H. Pelletier, Tian Wang, Chris Christou, Emma R. Walsh, Jonathan M. Page, Chase T. Davis, Gregory M. Williams

Background

Calcium phosphate (CaP) biomaterials are widely used in surgical applications such as spinal fusion to substitute for or extend autogenous bone graft. Preclinical testing in standardized animal models is useful for evaluating the relative performance of materials differing in composition and structure, including a newer generation of submicron-structured CaP (sCaP) with surface features uniformly smaller than 1 μm. The purpose of this study was to compare three clinically available CaP-based materials and iliac crest autograft in the rabbit posterolateral fusion (PLF) model.

Methods

A novel sCaP with bovine collagen type I (sCaP/Col I) and two clinically established materials, sCaP with alkylene oxide copolymer (sCaP/AOC) and microstructured CaP with bovine collagen type I (mCaP/Col I), were evaluated in a skeletally mature, single-level, non-instrumented, bilateral rabbit PLF model. Iliac crest autograft served as a control. Endpoints included radiographic, mechanical, and histological evaluation at postoperative 6, 9, and 12 weeks.

Results

Fusion progressed with postoperative time with all grafts, and the CaP materials yielded fusion rates by micro-CT and manual palpation similar to those of the autograft control at each time point. When tested as autograft extenders, sCaP/Col I and sCaP/AOC demonstrated equivalent results for all endpoints. When hydrated with bone marrow aspirate and used as bone graft substitutes, sCaP/Col I supported earlier fusion than mCaP/Col I with an increased radiographic fusion rate at 9 weeks (p = 0.032) and increased bone tissue content by histomorphometry at 12 weeks (p = 0.006). New bone was observed to form with all materials, and no adverse local biological reactions were seen.

Conclusions

Differences in the composition and structure of clinically available CaP-based materials influenced the achievement of spinal fusion in a standardized rabbit PLF model. These results may help guide the selection and use of materials in clinical applications and the future development of biomaterials with improved performance.

磷酸钙(CaP)生物材料广泛应用于外科手术,如脊柱融合,以替代或延长自体骨移植。标准化动物模型的临床前测试有助于评估不同成分和结构材料的相对性能,包括表面特征均匀小于1 μm的新一代亚微米结构CaP (sCaP)。本研究的目的是比较三种临床可用的cap基材料和髂骨自体移植物在兔后外侧融合(PLF)模型中的应用。方法采用一种新型牛I型胶原蛋白sCaP (sCaP/Col I)和两种临床建立的材料,氧化亚烯共聚物sCaP (sCaP/AOC)和牛I型胶原微结构CaP (mCaP/Col I),在骨骼成熟、单水平、无固定的双侧兔PLF模型中进行评估。自体髂骨移植作为对照。终点包括术后6、9和12周的放射学、力学和组织学评估。结果所有移植物的融合均随术后时间的推移而进展,micro-CT和手工触诊显示,CaP材料在每个时间点的融合率与自体移植物对照组相似。当作为自体接枝扩展剂进行测试时,sCaP/Col I和sCaP/AOC在所有端点上都显示出相同的结果。当用骨髓抽液水化并用作骨移植替代品时,sCaP/Col I比mCaP/Col I支持更早的融合,在9周时放射学融合率增加(p = 0.032),在12周时组织形态学测量增加骨组织含量(p = 0.006)。所有材料均可形成新骨,未见局部不良生物反应。结论临床上可用的cap基材料的组成和结构的差异影响了标准化兔PLF模型脊柱融合的实现。这些结果可能有助于指导临床应用中材料的选择和使用,以及未来性能更好的生物材料的开发。
{"title":"Comparative Performance of Calcium Phosphate Grafts and Iliac Crest Autograft in Posterolateral Spinal Fusion in Rabbits","authors":"William R. Walsh,&nbsp;Rema A. Oliver,&nbsp;Matthew H. Pelletier,&nbsp;Tian Wang,&nbsp;Chris Christou,&nbsp;Emma R. Walsh,&nbsp;Jonathan M. Page,&nbsp;Chase T. Davis,&nbsp;Gregory M. Williams","doi":"10.1002/jsp2.70101","DOIUrl":"https://doi.org/10.1002/jsp2.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Calcium phosphate (CaP) biomaterials are widely used in surgical applications such as spinal fusion to substitute for or extend autogenous bone graft. Preclinical testing in standardized animal models is useful for evaluating the relative performance of materials differing in composition and structure, including a newer generation of submicron-structured CaP (sCaP) with surface features uniformly smaller than 1 μm. The purpose of this study was to compare three clinically available CaP-based materials and iliac crest autograft in the rabbit posterolateral fusion (PLF) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A novel sCaP with bovine collagen type I (sCaP/Col I) and two clinically established materials, sCaP with alkylene oxide copolymer (sCaP/AOC) and microstructured CaP with bovine collagen type I (mCaP/Col I), were evaluated in a skeletally mature, single-level, non-instrumented, bilateral rabbit PLF model. Iliac crest autograft served as a control. Endpoints included radiographic, mechanical, and histological evaluation at postoperative 6, 9, and 12 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fusion progressed with postoperative time with all grafts, and the CaP materials yielded fusion rates by micro-CT and manual palpation similar to those of the autograft control at each time point. When tested as autograft extenders, sCaP/Col I and sCaP/AOC demonstrated equivalent results for all endpoints. When hydrated with bone marrow aspirate and used as bone graft substitutes, sCaP/Col I supported earlier fusion than mCaP/Col I with an increased radiographic fusion rate at 9 weeks (<i>p</i> = 0.032) and increased bone tissue content by histomorphometry at 12 weeks (<i>p</i> = 0.006). New bone was observed to form with all materials, and no adverse local biological reactions were seen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Differences in the composition and structure of clinically available CaP-based materials influenced the achievement of spinal fusion in a standardized rabbit PLF model. These results may help guide the selection and use of materials in clinical applications and the future development of biomaterials with improved performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740353","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
Animal Models of Disc Degeneration Using Puncture Injury: A 20 Year Perspective 穿刺损伤椎间盘退变的动物模型:20年的观察
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-07-28 DOI: 10.1002/jsp2.70093
Charu Jain, Jonathan J. Huang, Yunsoo Lee, Saad Chaudhary, Andrew C. Hecht, Alon Lai, Koichi Masuda, James Kang, James C. Iatridis

Background

Intervertebral disc (IVD) degeneration (IVDD) is a major cause of global disability. Three papers on puncture models of IVDD were published 20 years ago, transforming the application of preclinical animal models for pathophysiology and therapeutic screening studies.

Methods

Narrative review describing historic and current usage of preclinical puncture models of IVDD, documenting their introduction to induce slow, progressive IVDD and evolution to include many injury types broadly called “puncture models.” IVDD puncture models were reviewed for variability in species, needle gauge, puncture depth, IVD compartment, injectates, angle of puncture, motion of needle, and IVDD phenotype mimicked.

Results

IVD puncture models gained prominence following seminal 2005 publications describing needle puncture to induce slow, progressive IVDD for screening therapies. Specific details of puncture methods were described for controlling injury severity to induce IVDD phenotypes, including slow progressive IVDD, severe IVDD, chronic IVDD, disc herniation, and Modic-like changes. Common measurements for characterizing IVDD were also described.

Conclusions

Surgically induced IVD puncture injury animal models have evolved over decades to include many variations simulating distinct clinical phenotypes of IVDD. To facilitate cross-study comparisons, we recommend reporting a common set of injury features including needle gauge, puncture depth, injectates, puncture angle changes, needle motion, involvement of endplate and surrounding tissues, and phenotypes of IVDD mimicked. Surgically induced “outside-in” puncture injury models are valuable tools to test specific hypotheses and screening therapies.

背景椎间盘退变(IVDD)是全球致残的主要原因之一。20年前发表了三篇关于IVDD穿刺模型的论文,改变了临床前动物模型在病理生理和治疗筛选研究中的应用。方法对IVDD临床前穿刺模型的历史和当前使用情况进行叙述性回顾,记录其引入诱发缓慢、进行性IVDD的过程,并演变为包括许多被广泛称为“穿刺模型”的损伤类型。回顾了IVDD穿刺模型在物种、针距、穿刺深度、IVD室、注射剂、穿刺角度、针的运动和IVDD表型模拟方面的可变性。结果:IVD穿刺模型在2005年的开创性出版物中获得了突出的地位,这些出版物描述了针穿刺诱导缓慢,进行性IVDD的筛查治疗。我们描述了针刺方法的具体细节,以控制损伤严重程度,诱导IVDD表型,包括缓慢进行性IVDD、严重IVDD、慢性IVDD、椎间盘突出和modic样改变。描述了IVDD的常见测量方法。手术诱导的IVD穿刺损伤动物模型已经发展了几十年,包括许多模拟IVDD不同临床表型的变异。为了便于交叉研究比较,我们建议报告一组常见的损伤特征,包括针规、穿刺深度、注射剂、穿刺角度变化、针的运动、终板和周围组织的累及以及模拟IVDD的表型。手术诱导的“由外而内”穿刺损伤模型是检验特定假设和筛选疗法的宝贵工具。
{"title":"Animal Models of Disc Degeneration Using Puncture Injury: A 20 Year Perspective","authors":"Charu Jain,&nbsp;Jonathan J. Huang,&nbsp;Yunsoo Lee,&nbsp;Saad Chaudhary,&nbsp;Andrew C. Hecht,&nbsp;Alon Lai,&nbsp;Koichi Masuda,&nbsp;James Kang,&nbsp;James C. Iatridis","doi":"10.1002/jsp2.70093","DOIUrl":"https://doi.org/10.1002/jsp2.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration (IVDD) is a major cause of global disability. Three papers on puncture models of IVDD were published 20 years ago, transforming the application of preclinical animal models for pathophysiology and therapeutic screening studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Narrative review describing historic and current usage of preclinical puncture models of IVDD, documenting their introduction to induce slow, progressive IVDD and evolution to include many injury types broadly called “puncture models.” IVDD puncture models were reviewed for variability in species, needle gauge, puncture depth, IVD compartment, injectates, angle of puncture, motion of needle, and IVDD phenotype mimicked.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IVD puncture models gained prominence following seminal 2005 publications describing needle puncture to induce slow, progressive IVDD for screening therapies. Specific details of puncture methods were described for controlling injury severity to induce IVDD phenotypes, including slow progressive IVDD, severe IVDD, chronic IVDD, disc herniation, and Modic-like changes. Common measurements for characterizing IVDD were also described.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Surgically induced IVD puncture injury animal models have evolved over decades to include many variations simulating distinct clinical phenotypes of IVDD. To facilitate cross-study comparisons, we recommend reporting a common set of injury features including needle gauge, puncture depth, injectates, puncture angle changes, needle motion, involvement of endplate and surrounding tissues, and phenotypes of IVDD mimicked. Surgically induced “outside-in” puncture injury models are valuable tools to test specific hypotheses and screening therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714908","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
Development and Validation of a Machine Learning-Based Online Prognostic Model for Cervical Spondylosis Patients After Anterior Cervical Discectomy and Fusion: A Multicenter Study 基于机器学习的颈椎病患者前路椎间盘切除术和融合后在线预后模型的开发和验证:一项多中心研究
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-07-28 DOI: 10.1002/jsp2.70090
Sitan Feng, Shengsheng Huang, Zhongxian Zhou, Bin Zhang, Chengqian Huang, Tianyou Chen, Chenxing Zhou, Shaofeng Wu, Jichong Zhu, Jiarui Chen, Jiang Xue, Xinli Zhan, Chong Liu

Background

Cervical spondylosis (CS) is a degenerative condition often requiring surgical intervention, such as anterior cervical discectomy and fusion (ACDF), to alleviate symptoms. However, postoperative outcomes can vary significantly. This study aimed to develop and validate a predictive model for 1-year outcomes in CS patients after ACDF using multiple machine learning algorithms.

Methods

Data from 973 patients across three clinical centers, including 872 patients in the retrospective cohort and 101 patients in the prospective cohort, were utilized. A variety of clinical and laboratory features were identified using LASSO regression. Various machine learning algorithms were employed to develop predictive models. The models' performance was assessed and compared using metrics such as receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration analysis, and decision curve analysis (DCA). Model interpretation and feature importance analysis were carried out using the SHapley Additive exPlanations (SHAP) method. Finally, the model was deployed on the web by using the Shiny app.

Results

The model was constructed using 10 essential predictors. Ten machine learning models were evaluated, with the stacking ensemble learning model demonstrating superior predictive performance (AUC = 0.81 in the internal validation set, 0.80 in the external validation set, and 0.82 in the prospective cohort). Furthermore, CRP, MONO, ESR, and age were highlighted as critical predictors.

Conclusions

This predictive tool offers a robust framework for personalized postoperative management in CS patients, potentially improving clinical outcomes.

背景颈椎病(CS)是一种退行性疾病,通常需要手术干预,如前路颈椎椎间盘切除术和融合(ACDF),以缓解症状。然而,术后结果可能有很大差异。本研究旨在利用多种机器学习算法开发并验证ACDF后CS患者1年预后的预测模型。方法采用来自三个临床中心的973例患者的数据,其中回顾性队列872例,前瞻性队列101例。使用LASSO回归识别各种临床和实验室特征。使用各种机器学习算法来开发预测模型。采用受试者工作特征(ROC)曲线、曲线下面积(AUC)、校准分析和决策曲线分析(DCA)等指标对模型的性能进行评估和比较。采用SHapley加性解释(SHAP)方法进行模型解释和特征重要性分析。最后,使用Shiny应用程序将模型部署到web上。结果使用10个基本预测因子构建模型。对10种机器学习模型进行了评估,其中堆叠集成学习模型表现出更优越的预测性能(内部验证集的AUC = 0.81,外部验证集的AUC = 0.80,前瞻性队列的AUC = 0.82)。此外,CRP、MONO、ESR和年龄被强调为关键预测因子。该预测工具为CS患者的个性化术后管理提供了一个强有力的框架,有可能改善临床结果。
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引用次数: 0
Evaluation of a Force-Control Experimental Method to Perform Unconstrained Load-Induced Subsidence Testing of Spinal Interbody Implants 脊柱椎体间植入物无约束载荷诱导沉降试验的力控制实验方法评价
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-07-25 DOI: 10.1002/jsp2.70087
Rémy Benais, Richard Barina, Stewart McLachlin

Introduction

Intervertebral body fusion devices (“interbody cages”) used in spinal surgeries are susceptible to axial and/or rotational subsidence into the underlying vertebral bone. Experimental testing standards to examine implant subsidence, such as ASTM F2267, simplify the implant loading conditions and vertebral bone materials for ease of use and repeatability. Yet, the ability to assess clinically relevant risk of rotational subsidence with these methods is limited.

Methods

The present work aimed to develop and evaluate a novel force-control (FC) test method for performing unconstrained load-induced implant subsidence into a heterogeneous material interface. The developed method was compared to the ASTM F2267 method, which uses a lubricated ball-and-socket joint, using the AMTI VIVO joint motion simulator to apply unconstrained loading up to 4 kN. Subsidence testing was performed on two different polyurethane (PU) foam densities (rigid 20 and 30 PCF) sandwiched together providing a heterogeneous boundary interface to induce implant rotation into the less dense foam.

Results

Axial and rotational subsidence values varied significantly between the two test methods (p < 0.05). Unconstrained axial compression up to 4 kN yielded, on average, 2.5 ± 0.4 mm of axial subsidence for ASTM-based setup compared to 4.8 ± 0.6 mm for the FC setup. The ASTM-based setup had an average implant rotation of 2.8° ± 0.5°, in contrast to the FC setup, with an average of 18.0° ± 0.9°. Additionally, the experimental FC results had good agreement with a computational finite element model of the same FC setup and PU foam materials.

Conclusions

This new FC method for unconstrained load-induced subsidence testing demonstrates potential improvements in consideration for rotational implant subsidence and the associated clinical burden in spinal surgery.

脊柱手术中使用的椎体间融合装置(“椎体间固定器”)容易轴向和/或旋转沉降到下面的椎骨。用于检查植入物下沉的实验测试标准,如ASTM F2267,简化了植入物加载条件和椎体骨材料,便于使用和可重复性。然而,用这些方法评估旋转沉陷的临床相关风险的能力是有限的。方法本工作旨在开发和评估一种新的力控制(FC)测试方法,用于在非均质材料界面中进行无约束载荷诱导的植入物沉降。将开发的方法与ASTM F2267方法进行了比较,该方法使用润滑球窝关节,使用AMTI VIVO关节运动模拟器施加高达4 kN的无约束载荷。研究人员将两种不同密度的聚氨酯(PU)泡沫(刚性20pcf和30pcf)夹在一起进行沉降测试,以形成非均质边界界面,诱导植入物旋转进入密度较低的泡沫中。结果两种试验方法的轴向和旋转沉降值差异显著(p < 0.05)。在高达4kn的无约束轴向压缩条件下,astm装置的轴向沉降平均为2.5±0.4 mm,而FC装置的轴向沉降平均为4.8±0.6 mm。基于astm的装置平均种植体旋转2.8°±0.5°,而FC装置平均为18.0°±0.9°。此外,实验结果与相同FC设置和PU泡沫材料的计算有限元模型吻合较好。结论:这种用于无约束载荷诱导沉降试验的新型FC方法在考虑脊柱手术中旋转植入物沉降和相关临床负担方面具有潜在的改进潜力。
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引用次数: 0
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JOR Spine
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