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Clinical efficacy and biomechanical analysis of a novel hollow pedicle screw combined with kyphoplasty for the treatment of Kümmell disease 新型空心椎弓根螺钉联合后凸成形术治疗k<s:1> mmell病的临床疗效及生物力学分析。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-12-06 DOI: 10.1002/jsp2.70017
Shixiao Zhong, Hui Zhong, Kun Huang, Yayu Zhao, Wen Lei, Weichao Li

Background

Vertebral augmentation is the preferred treatment for Kümmell disease (KD), but there exists a risk of cement displacement resulting in severe back pain and exacerbation of kyphosis. The study aimed to investigate the efficacy and safety of a novel hollow pedicle screw combined with kyphoplasty (HPS-KP) for treating KD, effectively preventing postoperative bone cement displacement.

Methods

The prospective study included 50 KD patients with no neurological deficit detected during clinical and radiological evaluation who underwent HPS-KP (n = 25) and PKP (n = 25) surgeries. The visual analogue scale (VAS) score, Oswestry dysfunction index (ODI), anterior vertebral height (AVH), wedge-shape affected vertebral Cobb angle (WCA), bisegmental Cobb angle (BCA), and complications were evaluated and compared in both groups. Besides, a finite element (FE) model of T11-L2 was constructed. The stress distributions, maximum von Mises stresses of vertebrae and bone cement, and maximum displacement of bone cement were compared and analyzed.

Results

The VAS and ODI scores at 3 days, 3 and 6 months, and 1 year after surgery significantly improved in both groups (p < 0.05). The AVH, BCA, and WCA significantly improved initially after the surgery in both groups (p < 0.05). The displacement of M2 was larger than other models, especially in flexion, right bending, and left and right rotation, while that of M6 was the lowest under all conditions.

Conclusion

HPS-KP was a safe and effective treatment for KD, effectively relieving pain, restoring vertebral height, and correcting local kyphosis, and it had better biomechanical stability and safety than ordinary single PKP and PKP combined with pediculoplasty in avoiding cement loosening and displacement.

背景:椎体增量术是治疗Kümmell病(KD)的首选方法,但存在骨水泥移位的风险,导致严重背痛和脊柱后凸加重。该研究旨在探讨新型空心椎弓根螺钉联合椎体成形术(HPS-KP)治疗KD的有效性和安全性,有效防止术后骨水泥移位:这项前瞻性研究纳入了50名在临床和放射学评估中未发现神经功能缺损的KD患者,他们分别接受了HPS-KP(25人)和PKP(25人)手术。对两组患者的视觉模拟量表(VAS)评分、Oswestry 功能障碍指数(ODI)、椎体前高度(AVH)、楔形受累椎体 Cobb 角(WCA)、双节段 Cobb 角(BCA)和并发症进行了评估和比较。此外,还构建了 T11-L2 的有限元(FE)模型。对应力分布、椎体和骨水泥的最大 von Mises 应力以及骨水泥的最大位移进行了比较和分析:结果:两组患者术后 3 天、3 个月、6 个月和 1 年的 VAS 和 ODI 评分均明显改善(p p 结论:HPS-KP 是一种安全、有效的治疗方法:HPS-KP是一种安全有效的KD治疗方法,能有效缓解疼痛、恢复椎体高度、矫正局部椎体后凸,在避免骨水泥松动和移位方面,其生物力学稳定性和安全性优于普通单一PKP和PKP联合椎弓根成形术。
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引用次数: 0
Distinct clinical characteristics of adolescent idiopathic scoliosis with asymmetrical ESR1 expression in paraspinal muscle progenitor cells 脊柱旁肌肉祖细胞中ESR1表达不对称的青少年特发性脊柱侧弯症具有不同的临床特征
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-26 DOI: 10.1002/jsp2.70018
Hanlong Xin, Wenyuan Sui, Wenhua Mao, Junlin Yang, Xiexiang Shao

Background

Previous studies found decreased ESR1 expression of concave paraspinal muscle progenitor cells could contribute to the initiation and progression of adolescent idiopathic scoliosis (AIS). The current study investigated the clinical characteristics of AIS with asymmetrical ESR1 expression in paraspinal muscle progenitor cells.

Materials and Methods

Bilateral deep paraspinal muscle progenitor cells were obtained from 25 consecutive eligible female patients with AIS. RT-qPCR was performed to evaluate the expression of ESR1. The demographic data (the age at surgery, height, weight, BMI, and age at initiation), posteroanterior and lateral radiographs data (Risser sign, Cobb angle, apical vertebral rotation, and location of apical vertebra), and MR imaging data (bilateral paraspinal muscle CSA ratio and bilateral fatty component ratio) were collected. The correlation between asymmetrical ESR1 expression of paraspinal muscle progenitor cells and the aforementioned clinical characteristics were analyzed.

Results

Twelve out of twenty-five patients (48%) showed bilateral ESR1 expression ratio (convex/concave) more than 1.5 folds, and they were divided into the ESR1 asymmetry group. When compared with the ESR1 symmetry group, patients in the ESR1 asymmetry group showed significantly more severe scoliosis (p = 0.041), more hypoplastic concave paraspinal muscle (p = 0.015), and more muscular fatty infiltration in the concave side (p = 0.034). The bilateral ESR1 expression ratio was significantly correlated with Cobb angle (r2 = 0.282, p = 0.006), bilateral paraspinal muscle CSA ratio (r2 = 0.253, p = 0.011), and bilateral fatty component ratio (r2 = 0.248, p = 0.011).

Conclusion

There were 48% of AIS patients with significantly decreased ESR1 expression in concave paraspinal muscle progenitor cells (convex/concave>1.5 folds), while patients with more asymmetrical ESR1 expression showed more hypoplastic paraspinal muscle and fatty infiltration on the concave side, and more severe scoliotic deformity.

背景 以前的研究发现,脊柱旁凹肌祖细胞中ESR1表达的减少可能会导致青少年特发性脊柱侧弯症(AIS)的发生和发展。本研究探讨了脊柱旁肌祖细胞ESR1表达不对称的AIS的临床特征。 材料与方法 从连续 25 例符合条件的女性 AIS 患者中获取双侧深脊柱旁肌肉祖细胞。采用 RT-qPCR 评估 ESR1 的表达。收集了人口统计学数据(手术年龄、身高、体重、体重指数和发病年龄)、后正位和侧位X光片数据(Risser征、Cobb角、椎尖旋转和椎尖位置)以及磁共振成像数据(双侧脊柱旁肌肉CSA比值和双侧脂肪成分比值)。分析了脊柱旁肌肉祖细胞不对称 ESR1 表达与上述临床特征之间的相关性。 结果 25例患者中有12例(48%)的双侧ESR1表达比(凸/凹)超过1.5倍,被分为ESR1不对称组。与 ESR1 对称组相比,ESR1 不对称组的患者脊柱侧凸明显更严重(p = 0.041),脊柱旁肌肉凹陷更严重(p = 0.015),凹侧肌肉脂肪浸润更严重(p = 0.034)。双侧 ESR1 表达比值与 Cobb 角(r2 = 0.282,p = 0.006)、双侧脊柱旁肌肉 CSA 比值(r2 = 0.253,p = 0.011)和双侧脂肪成分比值(r2 = 0.248,p = 0.011)显著相关。 结论 有48%的AIS患者脊柱旁肌祖细胞凹面(凸/凹>1.5折)ESR1表达明显减少,而ESR1表达更不对称的患者表现出更多的脊柱旁肌发育不良和脂肪浸润在凹面一侧,脊柱侧弯畸形更严重。
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引用次数: 0
Correction to “Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs” 对 "用于识别脊柱X光平片上椎弓根螺钉品牌的深度学习模型的开发与验证 "的更正。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-26 DOI: 10.1002/jsp2.70013

Yao YC, Lin CL, Chen HH, et al. Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs. JOR Spine. 2024;7(3):e70001.

The affiliation of one of the authors (Yu-Hsuan Tang) should be verified in the first page (1 of 13).

Incorrect affiliation was investigated for the author “Yu-Hsuan Tang8”:

8Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.

Correct affiliation for the author “Yu-Hsuan Tang9” should be verified as following in the page 1:

9Department of Life Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.

We apologize for this error.

[此处更正了文章 DOI:10.1002/jsp2.70001]。
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引用次数: 0
The effects of extracellular matrix-degrading enzymes polymorphisms on intervertebral disc degeneration 细胞外基质降解酶多态性对椎间盘退变的影响
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-20 DOI: 10.1002/jsp2.70012
Di Zhao, Yao-xing Dou, Ling-feng Zeng, Yan-hong Han, Fang-zheng Lin, Nan-jun Xu, Jun Liu, Yu-ping Zeng

Objective

The objective of the current study was to investigate the correlation between polymorphisms in extracellular matrix-degrading enzymes and the risk of intervertebral disc degeneration (IDD) diseases.

Methods

The databases PubMed, Embase, and Cochrane Database were systematically queried from the inception until March 2023 to ascertain studies that meet the eligibility criteria. Utilizing a standardized data collection form to extract data from individual studies. The data were quantified using odds ratio (OR) along with its corresponding 95% confidence interval (95% CI), following an allelic model of inheritance.

Results

The study included a total of nine studies and indicated that the presence of rs17576 in the MMP9 gene was significantly associated with an increased risk of IDD diseases (GG: 1.30, 95% CI [1.09–1.55], p = 0.004). The presence of other polymorphisms in extracellular matrix-degrading enzymes did not exhibit a significant association with the susceptibility to IDD.

Conclusion

The current study demonstrated a noteworthy correlation between the GG genotype of MMP-9 rs17576 and susceptibility to IDD. The available evidence is insufficient to substantiate the correlation between other extracellular matrix-degrading enzymes and susceptibility to IDD. The constraints of this analysis necessitate further research involving larger sample sizes across diverse ethnicities to provide a comprehensive understanding of the true impact of these polymorphisms on susceptibility to IDD.

目的 本研究旨在探讨细胞外基质降解酶多态性与椎间盘退变(IDD)疾病风险之间的相关性。 方法 系统查询从开始到 2023 年 3 月的 PubMed、Embase 和 Cochrane 数据库,以确定符合资格标准的研究。使用标准化的数据收集表从各项研究中提取数据。按照等位基因遗传模型,使用几率比(OR)及其相应的 95% 置信区间(95% CI)对数据进行量化。 研究结果表明,MMP9 基因中的 rs17576 与 IDD 疾病风险的增加显著相关(GG:1.30,95% CI [1.09-1.55],p = 0.004)。细胞外基质降解酶的其他多态性与 IDD 易感性无明显关联。 结论 目前的研究表明,MMP-9 rs17576 的 GG 基因型与 IDD 易感性之间存在显著相关性。现有证据不足以证实其他细胞外基质降解酶与 IDD 易感性之间的相关性。由于本分析的局限性,有必要对不同种族的更大样本量进行进一步研究,以全面了解这些多态性对 IDD 易感性的真正影响。
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引用次数: 0
Effect of cigarette smoke exposure and cessation on regional diffusion properties in rat intervertebral discs 吸烟和戒烟对大鼠椎间盘区域扩散特性的影响
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-14 DOI: 10.1002/jsp2.70015
Joshua Kelley, Nathan Buchweitz, Avery Madden, Hongming Fan, Glenn Hepfer, Michael Kern, Danyelle M. Townsend, Tong Ye, Hai Yao, Yongren Wu

Background

Cigarette smoking is a recognized risk factor for orthopedic disorders, particularly intervertebral disc (IVD) degenerative disease. However, the IVD pathophysiology, especially the spatial–temporal remodeling progression in the context of cigarette smoking, remains unclear. This study aimed to address this knowledge gap through a quantitative assessment of IVD structural composition and diffusion properties using a Sprague–Dawley rat model.

Methods

Twenty-four rats were divided into control and smoke exposure cohorts, each with two sub-groups of six rats. One smoke exposure sub-group was sacrificed after 2 months of daily cigarette smoke exposure in a custom smoking apparatus, while the other was sacrificed after an additional 5 months of smoke cessation. The control groups were age-matched to the smoke exposure groups. A fluorescent recovery after photobleaching (FRAP) technique was used to determine solute diffusivities and multi-photon excitation (MPE) imaging was performed to characterize structural changes in the annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP).

Results

A decrease in diffusivity was observed in the CEP and the AF (radial direction only) after 2 months of smoke exposure. MPE imaging showed aberrant CEP calcification and reduced AF radial collagen fiber bundle diameter, suggesting that the IVD exhibits regionally dependent structural remodeling due to smoke exposure. Furthermore, the smoke cessation group showed deteriorating alterations of structure and diffusivities in all three-disc regions, including the NP, indicating that five-month smoke cessation alone didn't reverse the progression of IVD degenerative remodeling during aging.

Conclusion

This study advances the understanding of IVD pathophysiology in the context of cigarette smoke exposure and cessation, laying the groundwork for potential earlier diagnosis and optimized interventions.

背景:吸烟是骨科疾病,尤其是椎间盘(IVD)退行性疾病的公认危险因素。然而,IVD的病理生理学,尤其是吸烟导致的时空重塑进展仍不清楚。本研究旨在通过使用 Sprague-Dawley 大鼠模型对 IVD 结构组成和扩散特性进行定量评估来填补这一知识空白:将 24 只大鼠分为对照组和烟雾暴露组,每组 6 只。其中一个烟雾暴露亚组在定制吸烟装置中每天暴露于香烟烟雾 2 个月后被处死,而另一个亚组在戒烟 5 个月后被处死。对照组与烟雾暴露组的年龄相匹配。采用光漂白后荧光恢复(FRAP)技术测定溶质扩散率,并进行多光子激发(MPE)成像以描述纤维环(AF)、髓核(NP)和软骨终板(CEP)的结构变化:结果:烟雾暴露 2 个月后,CEP 和 AF(仅径向)的扩散率下降。MPE 成像显示 CEP 出现异常钙化,而 AF 的径向胶原纤维束直径减小,这表明 IVD 因暴露于烟雾而出现区域性结构重塑。此外,戒烟组包括NP在内的所有三个椎间盘区域的结构和弥散度都出现了恶化,表明仅戒烟5个月并不能逆转衰老过程中IVD退行性重塑的进展:这项研究加深了人们对卷烟暴露和戒烟背景下 IVD 病理生理学的理解,为潜在的早期诊断和优化干预奠定了基础。
{"title":"Effect of cigarette smoke exposure and cessation on regional diffusion properties in rat intervertebral discs","authors":"Joshua Kelley,&nbsp;Nathan Buchweitz,&nbsp;Avery Madden,&nbsp;Hongming Fan,&nbsp;Glenn Hepfer,&nbsp;Michael Kern,&nbsp;Danyelle M. Townsend,&nbsp;Tong Ye,&nbsp;Hai Yao,&nbsp;Yongren Wu","doi":"10.1002/jsp2.70015","DOIUrl":"10.1002/jsp2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cigarette smoking is a recognized risk factor for orthopedic disorders, particularly intervertebral disc (IVD) degenerative disease. However, the IVD pathophysiology, especially the spatial–temporal remodeling progression in the context of cigarette smoking, remains unclear. This study aimed to address this knowledge gap through a quantitative assessment of IVD structural composition and diffusion properties using a Sprague–Dawley rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four rats were divided into control and smoke exposure cohorts, each with two sub-groups of six rats. One smoke exposure sub-group was sacrificed after 2 months of daily cigarette smoke exposure in a custom smoking apparatus, while the other was sacrificed after an additional 5 months of smoke cessation. The control groups were age-matched to the smoke exposure groups. A fluorescent recovery after photobleaching (FRAP) technique was used to determine solute diffusivities and multi-photon excitation (MPE) imaging was performed to characterize structural changes in the annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A decrease in diffusivity was observed in the CEP and the AF (radial direction only) after 2 months of smoke exposure. MPE imaging showed aberrant CEP calcification and reduced AF radial collagen fiber bundle diameter, suggesting that the IVD exhibits regionally dependent structural remodeling due to smoke exposure. Furthermore, the smoke cessation group showed deteriorating alterations of structure and diffusivities in all three-disc regions, including the NP, indicating that five-month smoke cessation alone didn't reverse the progression of IVD degenerative remodeling during aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study advances the understanding of IVD pathophysiology in the context of cigarette smoke exposure and cessation, laying the groundwork for potential earlier diagnosis and optimized interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620588","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
Pharmacokinetics of PP353, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first-in-human, Phase 1b, open-label, single-dose study 用于椎间盘给药的利奈唑胺制剂 PP353 在慢性腰背痛和 1 型莫迪病患者中的药代动力学:首次人体 1b 期开放标签单剂量研究。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-14 DOI: 10.1002/jsp2.70009
Shiva S. Tripathi, Robert Sneath, Aprajay Golash, Parag Desai, Duncan McHale, Sarah Guest, Charlie Brindley, Paul Cummings, Shane Smith, Conrad Stroud, Graham Scott, Steve Ruston, Lloyd Czaplewski

Background

Bacterial infection of the intervertebral disc is difficult to treat because the tissue is usually not vascularized and systemic antibiotic therapy may not reach optimal antibacterial exposure. Here we characterize the safety, tolerability, and pharmacokinetics of PP353, a suspension of micronized linezolid, formulated for direct intervertebral disc administration.

Methods

The safety, tolerability, and pharmacokinetics of an intradiscal administration of PP353, was assessed in Part A of a Phase 1b study and consisted of a single injection of study drug (3 mL of PP353 and 150 mg linezolid). Clinical assessment included initial safety and tolerability of PP353 with continued follow-up for 12 months. Assessment of linezolid concentration in plasma samples enabled characterization of the pharmacokinetics. Deconvolution of systemic linezolid was used to estimate intervertebral disc linezolid concentration.

Results

Intradiscal administration of 3 mL of PP353 (linezolid 50 mg/mL) to the nucleus pulposus was well tolerated with no reported study treatment-related severe or serious adverse events and resulted in an average geometric mean linezolid plasma Cmax of 1300 ng/mL at 7.27 h post-administration. The linezolid plasma Cmax observed with intradiscal PP353 is approximately 10% that observed with a standard oral or iv administration of 600 mg linezolid. Pharmacokinetic deconvolution estimated that a single dose of PP353 (150 mg linezolid) provided intradiscal bactericidal concentration of linezolid for 96 h and bacteriostatic exposure for up to 120 h after dosing.

Conclusion

Intradiscal administration of 3 mL of PP353 is well-tolerated and based on the pharmacokinetics following a single injection, a two-dose regimen of PP353 (150 mg linezolid) on Day 1 and Day 5 ± 1 was selected to explore safety, tolerability, pharmacokinetics, and efficacy in Part B of the Persica 002 study.

背景:椎间盘的细菌感染很难治疗,因为该组织通常没有血管,全身抗生素治疗可能无法达到最佳抗菌效果。在此,我们对用于椎间盘直接给药的微粉化利奈唑胺混悬液 PP353 的安全性、耐受性和药代动力学进行了研究:1b期研究的A部分评估了PP353椎间盘内给药的安全性、耐受性和药代动力学,包括单次注射研究药物(3毫升PP353和150毫克利奈唑胺)。临床评估包括 PP353 最初的安全性和耐受性,并持续随访 12 个月。通过评估血浆样本中利奈唑胺的浓度,可以确定药物动力学的特征。通过对全身利奈唑胺进行解卷积来估算椎间盘利奈唑胺的浓度:髓核椎间盘内注射3毫升PP353(利奈唑烷50毫克/毫升)的耐受性良好,未出现与研究治疗相关的严重不良反应,在给药后7.27小时,利奈唑烷血浆C最大几何平均浓度为1300纳克/毫升。通过椎间盘内PP353观察到的利奈唑胺血浆C最大值约为标准口服或静脉注射600毫克利奈唑胺的10%。据药代动力学分解估计,单剂量PP353(150毫克利奈唑胺)可在用药后96小时内提供利奈唑胺的椎管内杀菌浓度,并在用药后120小时内提供抑菌暴露:3毫升PP353的椎间盘内给药耐受性良好,根据单次注射后的药代动力学,PP353(150毫克利奈唑胺)在第1天和第5±1天分两次给药,以探索Persica 002研究B部分的安全性、耐受性、药代动力学和疗效。
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引用次数: 0
Preclinical development and characterisation of PP353, a formulation of linezolid for intradiscal administration 用于椎管内给药的利奈唑胺制剂 PP353 的临床前开发和特性分析。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-14 DOI: 10.1002/jsp2.70010
Graham Hagger, Sarah Guest, Stephen Birchall, Alys Bradley, Charlie Brindley, David Corbett, Paul J. Cummings, Cristina Freire, James Harris, Andrew Wise, Melanie Wood, Lloyd G. Czaplewski

Introduction

Bacterial infection of the intervertebral disc can lead to vertebral endplate edema known as Modic changes, with associated chronic low back pain. Oral antimicrobial therapy has shown efficacy but relies on prolonged dosing and may not be optimal in terms of patient outcome, side effects, or antibiotic stewardship. There is no antibiotic formulation approved for intradiscal administration. Here, we describe the development and preclinical characterization of a formulation of linezolid, a suspension of 50 mg/mL micronized powder, for intradiscal administration.

Methods

Micronization, particle size analysis, Franz cell diffusion assays, ex vivo bioassay, and estimates of gelling temperature were used to optimize the composition and properties of the formulation. Performance of the formulation was assessed using sheep to characterize the pharmacokinetics and a model of intradiscal infection was developed to demonstrate efficacy. Suitability for human administration was demonstrated in a Good Laboratory Practice (GLP) local tolerance study.

Results

Micronized linezolid, formulated as a powder suspension using a vehicle containing poloxamer 407 and iohexol, provided a temperature-dependent radio-opaque gel that was suitable for image-guided percutaneous intradiscal administration. Efficacy in a sheep model of intradiscal Staphylococcus aureus infection was demonstrated. The formulation provides a high level of sheep disc tissue exposure, with Cmax of 6500 μg/g and limited systemic exposure, with a plasma Cmax of 0.04 μg/mL per 0.1 mL dose (5 mg of linezolid). Deconvolution of plasma linezolid pharmacokinetics correlated with linezolid remaining in the disc over time. Observations from a GLP local tolerance study with the linezolid formulation were of a minor nature and related to the intradiscal administration procedure.

Conclusions

Linezolid can be formulated for image-guided percutaneous intradiscal administration. The formulation is now in a Phase 1b clinical trial to evaluate safety, pharmacokinetics, and efficacy in patients with CLBP and suspected bacterial infection.

导言:椎间盘的细菌感染可导致椎体终板水肿,即莫迪克病变,并伴有慢性腰背痛。口服抗菌药有一定疗效,但需要长期用药,在患者疗效、副作用或抗生素管理方面可能并不理想。目前还没有抗生素制剂获准用于椎间盘内给药。在此,我们介绍了用于椎管内给药的利奈唑胺制剂(50 毫克/毫升微粉化粉末悬浮液)的开发和临床前特性分析:方法:采用微粉化、粒度分析、弗朗茨细胞扩散试验、体内外生物测定和胶凝温度估算来优化制剂的成分和特性。用绵羊评估了制剂的药代动力学特性,并建立了椎间盘内感染模型来证明其疗效。在一项良好实验室规范(GLP)局部耐受性研究中证明了该制剂对人体的适用性:结果:微粉化利奈唑胺被配制成粉末悬浮液,并使用含有聚氧乙烯-407和碘海醇的载体,形成了一种温度依赖性放射性不透明凝胶,适合在图像引导下经皮椎间盘内给药。在绵羊椎间盘内金黄色葡萄球菌感染模型中的疗效得到了证实。该制剂的绵羊椎间盘组织暴露水平高,Cmax 为 6500 μg/g,全身暴露水平有限,每 0.1 mL 剂量(5 mg 利奈唑胺)的血浆 Cmax 为 0.04 μg/mL。血浆利奈唑胺药代动力学解旋与利奈唑胺在椎间盘中的残留时间相关。对利奈唑胺制剂进行的GLP局部耐受性研究发现,利奈唑胺的性质较轻,与椎间盘内给药程序有关:结论:利奈唑胺可配制成图像引导下的经皮椎间盘内给药。结论:利奈唑胺制剂可用于图像引导下的经皮椎间盘内给药,该制剂目前正处于1b期临床试验阶段,以评估其对CLBP和疑似细菌感染患者的安全性、药代动力学和疗效。
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引用次数: 0
Melatonin attenuates degenerative disc degression by downregulating DLX5 via the TGF/Smad2/3 pathway in nucleus pulposus cells 褪黑激素通过髓核细胞中的TGF/Smad2/3途径下调DLX5,从而减轻椎间盘退行性变。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-13 DOI: 10.1002/jsp2.70014
Kuibo Zhang, Hua Wang, Ling Mo, Xiaohui Huang, Chao Yuan, Caijun Liu

Background

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal-less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported.

Aim

This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD.

Materials & Methods

Western blotting, RT–qPCR, immunohistochemistry, si-DLX5, Ex-DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice.

Results

The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF-α-induced degenerative NP cells. Degenerative NP cells transfected with si-DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice.

Discussion

The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5-induced apoptosis and extracellular matrix imbalance by inhibiting the TGF-β/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation-induced apoptosis IVDD-associated inflammation-induced apoptosis.

Conclusion

DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD-associated inflammation and apoptosis.

背景:椎间盘变性(IVDD)是腰痛的主要原因,而细胞凋亡在其发病机制中起着关键作用。据报道,无远端同源框 5(Dlx5)可诱导细胞凋亡。目的:本研究旨在探讨 DLX5 在 IVDD 发病机制中的作用,以及褪黑激素靶向 DLX5 在 IVDD 中的潜在治疗作用:采用Western印迹、RT-qPCR、免疫组化、si-DLX5、Ex-DLX5、流式细胞术和免疫荧光等方法研究DLX5对细胞凋亡的调控作用。通过向 IVDD 小鼠腹腔注射褪黑素评估疗效:结果:DLX5在IVDD中的表达水平明显升高,其表达水平与IVDD的分级呈正相关。DLX5在TNF-α诱导的变性NP细胞中明显上调。转染si-DLX5的退行性NP细胞的凋亡率明显低于对照组细胞。褪黑素能明显缓解手术诱导的IVDD模型小鼠的IVDD:讨论:研究结果表明,DLX5的表达与IVDD的严重程度呈正相关,褪黑激素通过抑制TGF-β/Smad信号通路改善了DLX5诱导的细胞凋亡和细胞外基质失衡。这项研究可为缓解炎症诱导的细胞凋亡提供治疗策略:结论:DLX5通过促进细胞凋亡在IVDD进展中发挥重要作用,而褪黑素是缓解IVDD相关炎症和细胞凋亡的一种有前途的治疗策略。
{"title":"Melatonin attenuates degenerative disc degression by downregulating DLX5 via the TGF/Smad2/3 pathway in nucleus pulposus cells","authors":"Kuibo Zhang,&nbsp;Hua Wang,&nbsp;Ling Mo,&nbsp;Xiaohui Huang,&nbsp;Chao Yuan,&nbsp;Caijun Liu","doi":"10.1002/jsp2.70014","DOIUrl":"10.1002/jsp2.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal-less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>Western blotting, RT–qPCR, immunohistochemistry, si-DLX5, Ex-DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF-α-induced degenerative NP cells. Degenerative NP cells transfected with si-DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5-induced apoptosis and extracellular matrix imbalance by inhibiting the TGF-β/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation-induced apoptosis IVDD-associated inflammation-induced apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD-associated inflammation and apoptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620604","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
The proteomic landscape of extracellular vesicles derived from human intervertebral disc cells 从人类椎间盘细胞中提取的细胞外囊泡的蛋白质组图谱。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-05 DOI: 10.1002/jsp2.70007
Li Li, Hadil Al-Jallad, Aiwei Sun, Miltiadis Georgiopoulos, Rakan Bokhari, Jean Ouellet, Peter Jarzem, Hosni Cherif, Lisbet Haglund

Background

Extracellular vesicles (EVs) function as biomarkers and are crucial in cell communication and regulation, with therapeutic potential for intervertebral disc (IVD)-related low back pain (LBP). EV cargo is often affected by tissue health, which may affect the therapeutic potential. There is currently limited knowledge of how the cargo of IVD cell-derived EVs varies with tissue health and how differences in proteomic profile affect the predicted biological functions.

Methods

Our study purified EVs from human IVD cell conditioned media by size-exclusion chromatography. Nanoparticle tracking analysis was conducted to measure EV size and concentration. Transmission electron microscopy and Western blot were performed to examine EV structure and markers. Tandem mass tag-mass spectrometry was conducted to determine protein cargo.

Results

Most EVs were exosomes and intermediate microvesicles with an increasing amount linked to disease progression. Of the proteins detected, 88.6% were shared across the non-degenerate, mildly-degenerate, and degenerate samples. GO and KEGG analyses revealed that cargo from the mildly-degenerate samples was the most distinct, with the proteins in high abundance strongly associated with extracellular matrix (ECM) organization and structure. Shared proteins, highly expressed in the non-degenerate and degenerate samples, showed strong associations with cell adhesion, ECM–receptor interaction, and vesicle-mediated transport, respectively.

Conclusions

Our findings indicate that EVs from IVD cells from tissue with different degrees of degeneration share a majority of the cargo proteins. However, the level of expression differs with degeneration grade. Cargo from the mildly-degenerate samples exhibits the most differences. A better understanding of changes in EV cargo in the degenerative process may provide novel information related to molecular mechanisms underlying IVD degeneration and suggest new potential treatment modalities for IVD-related LBP.

背景:细胞外囊泡(EVs)具有生物标志物的功能,在细胞通讯和调节中起着关键作用,对与椎间盘(IVD)相关的腰背痛(LBP)具有治疗潜力。EV 货物通常会受到组织健康状况的影响,这可能会影响治疗潜力。目前,人们对 IVD 细胞衍生 EVs 的载体如何随组织健康状况而变化,以及蛋白质组谱的差异如何影响预测的生物功能了解有限:我们的研究通过大小排阻色谱法从人类 IVD 细胞条件培养基中纯化了 EVs。我们采用纳米粒子追踪分析来测量EV的大小和浓度。透射电子显微镜和 Western 印迹检查了 EV 的结构和标记。采用串联质量标签质谱法确定蛋白质货物:结果:大多数EV是外泌体和中间微囊泡,其数量的增加与疾病进展有关。在检测到的蛋白质中,88.6%是非变性、轻度变性和变性样本共有的。GO和KEGG分析显示,轻度变性样本中的货物最为独特,高丰度蛋白质与细胞外基质(ECM)的组织和结构密切相关。在非变性和变性样本中高表达的共有蛋白质分别与细胞粘附、ECM-受体相互作用和囊泡介导的运输密切相关:我们的研究结果表明,来自不同变性程度组织的 IVD 细胞的 EVs 共享大多数载货蛋白。结论:我们的研究结果表明,来自不同退化程度组织的 IVD 细胞的 EVs 分享了大部分载体蛋白。来自轻度变性样本的货物差异最大。更好地了解变性过程中EV载体的变化可能会提供与IVD变性的分子机制有关的新信息,并为IVD相关的腰椎间盘突出症提供新的潜在治疗方法。
{"title":"The proteomic landscape of extracellular vesicles derived from human intervertebral disc cells","authors":"Li Li,&nbsp;Hadil Al-Jallad,&nbsp;Aiwei Sun,&nbsp;Miltiadis Georgiopoulos,&nbsp;Rakan Bokhari,&nbsp;Jean Ouellet,&nbsp;Peter Jarzem,&nbsp;Hosni Cherif,&nbsp;Lisbet Haglund","doi":"10.1002/jsp2.70007","DOIUrl":"10.1002/jsp2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extracellular vesicles (EVs) function as biomarkers and are crucial in cell communication and regulation, with therapeutic potential for intervertebral disc (IVD)-related low back pain (LBP). EV cargo is often affected by tissue health, which may affect the therapeutic potential. There is currently limited knowledge of how the cargo of IVD cell-derived EVs varies with tissue health and how differences in proteomic profile affect the predicted biological functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our study purified EVs from human IVD cell conditioned media by size-exclusion chromatography. Nanoparticle tracking analysis was conducted to measure EV size and concentration. Transmission electron microscopy and Western blot were performed to examine EV structure and markers. Tandem mass tag-mass spectrometry was conducted to determine protein cargo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most EVs were exosomes and intermediate microvesicles with an increasing amount linked to disease progression. Of the proteins detected, 88.6% were shared across the non-degenerate, mildly-degenerate, and degenerate samples. GO and KEGG analyses revealed that cargo from the mildly-degenerate samples was the most distinct, with the proteins in high abundance strongly associated with extracellular matrix (ECM) organization and structure. Shared proteins, highly expressed in the non-degenerate and degenerate samples, showed strong associations with cell adhesion, ECM–receptor interaction, and vesicle-mediated transport, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that EVs from IVD cells from tissue with different degrees of degeneration share a majority of the cargo proteins. However, the level of expression differs with degeneration grade. Cargo from the mildly-degenerate samples exhibits the most differences. A better understanding of changes in EV cargo in the degenerative process may provide novel information related to molecular mechanisms underlying IVD degeneration and suggest new potential treatment modalities for IVD-related LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590605","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
Finite element analysis of two-level discontinuous cervical hybrid revision surgery strategy to reduce biomechanical responses of adjacent segments 两级不连续颈椎混合翻修手术策略的有限元分析,以减少相邻节段的生物力学反应。
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2024-10-31 DOI: 10.1002/jsp2.70008
Weishi Liang, Duan Sun, Bo Han, Yihan Yang, Peng Yin, Yong Hai

Background

Hybrid surgery (HS) combined cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) is emerging, but its biomechanical effects as a revision surgery (RS) on adjacent segments were unclear.

Objectives

This finite element (FE) study aimed to investigate the biomechanical characteristics of HS to treat two-level discontinuous ASD in ACDF RS.

Methods

A C2-T1 intact FE model was established and modified to a primary C5/6 ACDF model and five RS models. These RS models' segments C4/5 and C6/7 were revised using cage plus plate (C), zero-profile devices (P), and Bryan disc (D), respectively, generating C-C-C, P-C-P, D-C-P, P-C-D, and D-C-D models. In the intact and C5/6 ACDF models, a 1.0 Nm moment was used to produce the range of motion (ROM). A displacement load was applied to all RS models, to achieve a total ROM match that of the primary C5/6 ACDF model.

Results

In the P-C-P model, biomechanical responses including ROM, Intradiscal pressure (IDP), Facet joint force (FJF), and Maximum von Mises stresses of discs at segments C3/4 and C7/T1 were slightly lower than the C-C-C model. The biomechanical response parameters at segments C3/4 and C7/T1 of P-C-D, D-C-P, and D-C-D were smaller than those in C-C-C and P-C-P models. D-C-D had the most significant effect on reducing all biomechanical responses among all RS models in segments C3/4 and C7/T1. Moreover, the disc stress cloud maps showed that the maximum von Mises stress of the C3/4 disc was higher than that of C7/T1.

Conclusions

D-C-D, P-C-D, and D-C-P are good RS choices for reducing the biomechanical responses, and D-C-D was the best choice. P-C-P can be the best recommendation when it does not meet the CDA indications. This study provided a biomechanical reference for hybrid surgical decision-making in the ACDF RS for preventing ASD recurrence.

背景:混合手术(HS)联合颈椎间盘关节成形术(CDA)与颈椎前路椎间盘切除融合术(ACDF)正在兴起,但其作为翻修手术(RS)对邻近节段的生物力学影响尚不清楚:本有限元(FE)研究旨在探讨 HS 治疗 ACDF RS 两级不连续 ASD 的生物力学特征:建立了一个 C2-T1 完整 FE 模型,并将其修改为一个初级 C5/6 ACDF 模型和五个 RS 模型。这些RS模型的C4/5和C6/7节段分别使用笼加板(C)、零轮廓装置(P)和布莱恩椎间盘(D)进行了修正,生成了C-C-C、P-C-P、D-C-P、P-C-D和D-C-D模型。在完整模型和 C5/6 ACDF 模型中,使用 1.0 牛米的力矩来产生运动范围 (ROM)。对所有 RS 模型都施加了位移负荷,以实现与主要 C5/6 ACDF 模型相匹配的总 ROM:结果:在 P-C-P 模型中,C3/4 和 C7/T1 节段椎间盘的生物力学响应(包括 ROM、椎间盘内压力(IDP)、面关节力(FJF)和最大 von Mises 应力)略低于 C-C-C 模型。P-C-D、D-C-P 和 D-C-D 模型 C3/4 和 C7/T1 节段的生物力学响应参数小于 C-C-C 和 P-C-P 模型。在 C3/4 和 C7/T1 节段的所有 RS 模型中,D-C-D 对降低所有生物力学响应的效果最为显著。此外,椎间盘应力云图显示,C3/4 椎间盘的最大 von Mises 应力高于 C7/T1:结论:D-C-D、P-C-D 和 D-C-P 是减少生物力学反应的良好 RS 选择,其中 D-C-D 是最佳选择。在不符合 CDA 适应症的情况下,P-C-P 可以作为最佳推荐。该研究为 ACDF RS 预防 ASD 复发的混合手术决策提供了生物力学参考。
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引用次数: 0
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