Megan Co, Brian Raterman, Brett Klamer, Arunark Kolipaka, Benjamin Walter
Background
In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI.
Method
MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters.
Results
MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content.
Conclusion
This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue.
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Seth S. Leopold, Robert N. Hensinger, Andrew J. Schoenfeld, Marc Swiontkowski, Michael J. Rossi, Kimberly J. Templeton, Sex and Gender Research in Orthopaedic Journals Group
<p>Sex-based differences in cell biology, tissue function, and anatomy impact disease risk, presentation, and treatment outcomes,<span><sup>1</sup></span> including in musculoskeletal care.<span><sup>2-4</sup></span> As such, these differences should influence how orthopedic surgeons and other healthcare professionals conduct research and provide care for patients who have musculoskeletal disease and injury. In addition, gender roles influence interactions with people who conduct research and healthcare professionals, as well as the likelihood that patients will seek care and how they will respond to treatment.<span><sup>1, 5, 6</sup></span></p><p>Musculoskeletal research, similar to research in other areas of healthcare, does not always disaggregate results based on a patient's sex or gender.<span><sup>7</sup></span> Although some orthopedic surgery journals have explicit editorial standards on the topic of sex and gender in scientific reporting, and although international entities have published sensible guidelines about it,<span><sup>8</sup></span> we have observed that these standards are inconsistently applied.<span><sup>7</sup></span></p><p>Inattention to high-quality standards of scientific reporting can harm patients.<span><sup>9, 10</sup></span> Women have been underrepresented in medical research,<span><sup>11</sup></span> and this trend continues to varying degrees even today, despite mandates to remedy this disparity, at least in federally funded research.<span><sup>12, 13</sup></span> However, these mandates include no guidance about how data should be analyzed or reported, thereby limiting the impact of including more women in clinical studies. The care of women has been substantially compromised as a result<span><sup>14-18</sup></span>; not getting this right has sometimes harmed men with certain diagnoses as well.<span><sup>19</sup></span> As such, it is no stretch to say that doing better research—and improving how that research is reported in journals—would benefit our patients regardless of their sex or gender.</p><p>With this background in mind, leaders of the editorial boards of six orthopedic journals, along with leaders of funding agencies, as well as National Institutes of Health officials, met in November 2023 to discuss these issues. Following that meeting, those editors reached out to the Editors-in-Chief of all indexed orthopedic surgery journals, seeking concurrence on a few key themes pertaining to the reporting of sex and gender in musculoskeletal research.</p><p>We hope that by sharing these resolutions with readers, many of whom are also researchers and representatives on institutional review boards, institutional animal care and use committees, and/or funding agencies and organizations, the orthopedic research of the future will be both better designed and better reported.</p><p>Funding for this conference was made possible (in part) by (1R13AR082710–01) from the National Institute of Arthritis and Musculoskeleta
细胞生物学、组织功能和解剖学方面的性别差异会影响疾病的风险、表现和治疗效果，1 包括肌肉骨骼方面的治疗效果。2-4 因此，这些差异会影响骨科医生和其他医疗保健专业人员如何开展研究以及如何为患有肌肉骨骼疾病和损伤的患者提供治疗。此外，性别角色还会影响与研究人员和医护人员之间的互动，以及患者寻求治疗的可能性和他们对治疗的反应。1, 5, 6 肌肉骨骼研究与其他医疗保健领域的研究类似，并不总是根据患者的性别对研究结果进行分类。9, 10 女性在医学研究中的代表性一直不足，11 而且这种趋势至今仍在不同程度上持续，尽管有规定要求弥补这种差距，至少在联邦政府资助的研究中是如此。12, 13 然而，这些规定并不包括关于如何分析或报告数据的指导，从而限制了将更多女性纳入临床研究的影响。有鉴于此，六家骨科期刊编辑部的领导、资助机构的领导以及美国国立卫生研究院的官员于 2023 年 11 月召开会议，讨论这些问题。我们希望，通过与读者分享这些决议，未来的骨科研究将得到更好的设计和更好的报告，而读者中的许多人也是研究人员以及机构审查委员会、机构动物护理和使用委员会和/或资助机构和组织的代表。临床骨科及相关研究》、《小儿骨科杂志》和《脊柱》主编；《关节镜》助理主编的所有 ICMJE 潜在利益冲突披露表：The Journal of Arthroscopic & Related Surgery》杂志的副主编、《JBJS Case Connector》杂志的副主编和《JBJS Case Connector》杂志的副主编的申请表已在各刊物存档，可应要求查看。骨与关节外科杂志》主编的 "潜在利益冲突披露表 "随文章在线版（http://links.lww.com/XXXXXXX）一起提供。会议书面材料或出版物以及演讲者和主持人所表达的观点不一定反映美国卫生与公众服务部的官方政策，提及的商品名称、商业行为或组织也不意味着美国政府的认可。
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The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer-induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms.
Methods
Using the database from the First Affiliated Hospital of Sun Yat-sen University, the whole spinal x-rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key-point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed.
Results
In the study, a total of 2082 spinal x-ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1-score of 0.809 for curve type evaluation and an F1-score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1-score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1-score for ultimate Lenke type classifier was 0.885.
Conclusions
This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future.
目的 Lenke分类系统被广泛用作青少年特发性脊柱侧凸（AIS）的术前评估方案。然而，人工测量容易受到观察者引起的变异的影响，从而影响对进展的评估。本研究的目标是利用创新的深度学习算法开发一种自动伦克分类系统。 方法 使用中山大学附属第一医院的数据库，回顾性地收集整个脊柱的 X 光图像。具体来说，图像收集分为 AIS 组和对照组。对照组由接受常规健康检查且没有脊柱侧弯的人组成。之后，对所有图像的相对特征进行注释。利用基于关键点的检测方法实现深度学习，从而实现脊椎检测，并根据相关标准进行 Cobb 角度测量和脊柱侧弯分类。此外，还采用分割方法实现了腰椎椎弓根的识别，以确定腰椎改建者的类型。最后，进一步对模型性能进行了定量分析。 结果 研究共收集了 407 名 AIS 患者和 227 名对照组患者的 2082 张脊柱 X 光图像。脊椎检测模型在曲线类型评估方面的 F1 分数为 0.809，在胸椎矢状剖面方面的 F1 分数为 0.901。Cobb角测量的类内相关效率（ICC）为0.925。在椎体椎弓根分割模型的性能分析中，腰椎修正剖面的 F1 分数为 0.942，目标像素的交点大于结合点（IOU）为 0.827，豪斯多夫距离（HD）为 6.565 ± 2.583 毫米。具体来说，终极伦克类型分类器的 F1 分数为 0.885。 结论 本研究通过采用深度学习网络来实现识别模式和特征提取，构建了一个自动化的伦克分类系统。我们的模型还需要在未来的更多案例中进一步验证。
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Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott
Background
Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc.
Methods
We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition.
Results
We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species.
Conclusion
To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.
{"title":"Can axial loading restore in vivo disc geometry, opening pressure, and T2 relaxation time?","authors":"Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott","doi":"10.1002/jsp2.1322","DOIUrl":"https://doi.org/10.1002/jsp2.1322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648159","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}
Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell
Background
Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.
Methods
Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.
Results
NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.
Conclusions
Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.
{"title":"Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk","authors":"Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell","doi":"10.1002/jsp2.1332","DOIUrl":"https://doi.org/10.1002/jsp2.1332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639615","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}
Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur
Background
Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.
Methods
Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.
Results
CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.
Conclusion
There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.
{"title":"Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk","authors":"Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur","doi":"10.1002/jsp2.1333","DOIUrl":"https://doi.org/10.1002/jsp2.1333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639616","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}
Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu
Background
Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.
Methods
In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.
Results
In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.
Conclusions
API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.
{"title":"Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy","authors":"Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu","doi":"10.1002/jsp2.1325","DOIUrl":"https://doi.org/10.1002/jsp2.1325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559650","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}
Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke
Background
Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.
Methods
MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.
Results
The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.
Conclusions
The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.
{"title":"Automatic grading of intervertebral disc degeneration in lumbar dog spines","authors":"Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke","doi":"10.1002/jsp2.1326","DOIUrl":"https://doi.org/10.1002/jsp2.1326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559649","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}
Hans-Joachim Wilke, Maresa Großkinsky, Michael Ruf, Benedikt Schlager
Background
Surgical treatment of adolescent idiopathic scoliosis (AIS) is very complex and modern instrumentation techniques offer multiple possibilities. Despite numerous publications, there is no clear consensus on the optimal strategy for the correction of scoliotic deformities. The goal of this study was to summarize the current surgical strategies for specific AIS cases within various countries.
Method
Thirty-two experienced scoliosis surgeons from 15 countries were asked to plan surgeries on 12 representative AIS cases. All AIS cases had an indication for surgery. A questionnaire was provided to document surgical planning. The surgeons were provided with the patients' age and sex, together with radiographs in the lateral and sagittal planes during upright standing and in lateral bending to the left and right, as well as with clinical images. The angles of the main spinal curvatures were specified in the questionnaire. The surgeons were asked to specify their preferred classification system, their surgical approach, the planned fusion length, the type of implants, the rod type, and the resection steps. The data were analyzed with respect to the inter-rater variability, which was quantified using the Fleiss-Kappa Method.
Results
There was a good agreement (k = 0.61) between the surgeons in choosing the Lenke curve type, and a moderate agreement for the lumbar (0.41) and sagittal (0.56) modifiers. The most frequently planned resection procedure was complete facetectomy (67%). The posterior approach was the most commonly (91%) selected strategy to treat AIS. Anterior approaches were chosen most for Lenke 5 type with a rate of 20%. The upper instrumented vertebra (UIV) varied most for Lenke 1, 5, and 6 cases, with a vertebral level discrepancy of up to 10 levels at Lenke 6. The lowest instrumented vertebra varied most for Lenke 1 and 4 by up to five levels. Polyaxial screws were chosen most (56%), followed by monoaxial (20%) and uniplanar (19%) screws and hooks (5%).
Conclusions
The results highlight the commonalities and discrepancy in the surgical treatment of AIS in between surgeons. The selected LIV and UIV can vary depending on the curve type and surgeon. Hook constructs appear to be generally replaced by transpedicular screws. The survey indicates open questions in the AIS treatment and in the understanding of scoliosis biomechanics.
{"title":"Range of international surgical strategies for adolescent idiopathic scoliosis: Evaluation of a multi-center survey","authors":"Hans-Joachim Wilke, Maresa Großkinsky, Michael Ruf, Benedikt Schlager","doi":"10.1002/jsp2.1324","DOIUrl":"https://doi.org/10.1002/jsp2.1324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Surgical treatment of adolescent idiopathic scoliosis (AIS) is very complex and modern instrumentation techniques offer multiple possibilities. Despite numerous publications, there is no clear consensus on the optimal strategy for the correction of scoliotic deformities. The goal of this study was to summarize the current surgical strategies for specific AIS cases within various countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Thirty-two experienced scoliosis surgeons from 15 countries were asked to plan surgeries on 12 representative AIS cases. All AIS cases had an indication for surgery. A questionnaire was provided to document surgical planning. The surgeons were provided with the patients' age and sex, together with radiographs in the lateral and sagittal planes during upright standing and in lateral bending to the left and right, as well as with clinical images. The angles of the main spinal curvatures were specified in the questionnaire. The surgeons were asked to specify their preferred classification system, their surgical approach, the planned fusion length, the type of implants, the rod type, and the resection steps. The data were analyzed with respect to the inter-rater variability, which was quantified using the Fleiss-Kappa Method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a good agreement (<i>k</i> = 0.61) between the surgeons in choosing the Lenke curve type, and a moderate agreement for the lumbar (0.41) and sagittal (0.56) modifiers. The most frequently planned resection procedure was complete facetectomy (67%). The posterior approach was the most commonly (91%) selected strategy to treat AIS. Anterior approaches were chosen most for Lenke 5 type with a rate of 20%. The upper instrumented vertebra (UIV) varied most for Lenke 1, 5, and 6 cases, with a vertebral level discrepancy of up to 10 levels at Lenke 6. The lowest instrumented vertebra varied most for Lenke 1 and 4 by up to five levels. Polyaxial screws were chosen most (56%), followed by monoaxial (20%) and uniplanar (19%) screws and hooks (5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results highlight the commonalities and discrepancy in the surgical treatment of AIS in between surgeons. The selected LIV and UIV can vary depending on the curve type and surgeon. Hook constructs appear to be generally replaced by transpedicular screws. The survey indicates open questions in the AIS treatment and in the understanding of scoliosis biomechanics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559651","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}
Zhibo Ren, Jinke Ji, Caili Lou, Yuxin Gao, Xueyan Feng, Qiang Ye, Wei Jia, Xu Zhang, Ningkui Niu
<div> <section> <h3> Objectives</h3> <p>The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).</p> </section> <section> <h3> Methods</h3> <p>The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of <i>Mycobacterium tuberculosis</i> infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.</p> </section> <section> <h3> Results</h3> <p>S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, <i>p</i> < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (<i>p</i> < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (<i>p</i> < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (<i>p</i> < 0.05), 0.754 (<i>p</i> < 0.01), 0.716 (<i>p</i> < 0.01), 0.656 (<i>p</i> < 0.05), and 0.681 (<i>p</i> < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.</p> </section> <section> <h3> Conclusion</h3> <p>S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.</p> </se
{"title":"Analysis of the value of potential biomarker S100-A8 protein in the diagnosis and pathogenesis of spinal tuberculosis","authors":"Zhibo Ren, Jinke Ji, Caili Lou, Yuxin Gao, Xueyan Feng, Qiang Ye, Wei Jia, Xu Zhang, Ningkui Niu","doi":"10.1002/jsp2.1331","DOIUrl":"https://doi.org/10.1002/jsp2.1331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of <i>Mycobacterium tuberculosis</i> infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, <i>p</i> < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (<i>p</i> < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (<i>p</i> < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (<i>p</i> < 0.05), 0.754 (<i>p</i> < 0.01), 0.716 (<i>p</i> < 0.01), 0.656 (<i>p</i> < 0.05), and 0.681 (<i>p</i> < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.</p>\u0000 </se","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140544432","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}
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