Disc Degeneration Research Articles

The Onset of Systemic Lupus Erythematosus Triggers Nucleus Pulposus Cell Pyroptosis to Exacerbate Intervertebral Disc Degeneration.

Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations. The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65. MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65. Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.

Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.

Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (≤ 3-level) TLIFs between January 2018 and October 2022. Patients were either exposed to semaglutide or not. A comprehensive 1:3 (exposure vs no exposure) matching was performed based on age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking status, osteoporosis, levels of surgery, and basal-bolus insulin dependence. Kaplan-Meier survival curves and log-rank testing were performed to study the probability of additional lumbar fusion surgery within 1 year. After the 1:3 matching, 1781 patients were identified, with 447 in the semaglutide-exposed cohort and 1334 in the nonexposed cohort. Most patients in both groups were 55-69 years old, and 59.3% were female. Analysis showed that the likelihood of undergoing additional lumbar fusion surgery within 1 year post-TLIF was significantly higher in the semaglutide-exposed group than in the nonexposed group (OR 11.79, 95% CI 8.17-17.33). Kaplan-Meier plots and log-rank testing further confirmed a statistically significant divergent probability in the need for additional surgery within 1 year between the cohorts (log-rank, p < 0.001). Semaglutide exposure appears to be associated with a higher likelihood of additional lumbar fusion surgeries within 1 year post-TLIF, especially in patients receiving the medication for longer durations. Although the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.

Correlation Between Osteoporosis and Endplate Damage in Degenerative Disc Disease Patients: A Study Based on Phantom-Less Quantitative Computed Tomography and Total Endplate Scores

BackgroundOsteoporosis and degenerative disc disease (DDD) are prevalent in the elderly population. Damage to the vertebral endplate, which impairs nutrient supply to the disc, serves as both a significant initiator and a hallmark of DDD. This study was aimed to explore the association between osteoporosis and endplate damage. MethodsThis retrospective study included 205 patients with DDD who were treated at tianjin hospital from January 2019 to May 2023. We collected data on age, sex, body mass index (BMI), phantom-less quantitative computed tomography (PL-QCT) values, and total endplate scores (TEPS). The average PL-QCT value of L1-L4 and TEPS were used to represent volumetric bone mineral density (v-BMD) and the degree of endplate damage, respectively. Based on the average PL-QCT value of L1 and L2, patients were divided into three groups: normal group (BMD > 120 mg/cm3), osteopenic group (80 mg/cm3 ≤ BMD ≤ 120 mg/cm3), and osteoporosis group (BMD < 80 mg/cm3). Multiple linear regression models were used to identify independent factors associated with endplate damage. ResultsThe overall TEPS (4.3±1.3 vs 5.0±1.0 vs 5.9±1.5, p<0.01) and segment (L1/2-L4/5) TEPS (p<0.05) in each group showed significant difference (R=-0.5), increasing in order from normal group to osteoporosis group. A significant negative correlation was found between TEPS and PL-QCT values in overall and each segments (p<0.001). The PL-QCT values and age (p<0.05) were independent factors influencing endplate damage. There were significant differences in the average number of TEPS ≥7 segments per patient among the three groups, with 1.16, 0.41, and 0.2 segments/person from osteoporosis group to normal group. ConclusionsOur study showed a significant positive correlation between osteoporosis and endplate damage. Attention is warranted for patients with osteopenia to prevent progression to osteoporosis, potentially leading to exacerbated DDD. The management of patients with both DDD and osteoporosis necessitates comprehensive treatment strategies that address both the BMD and endplate aspects of these conditions.

Risk factors of bone loss after Prestige-LP cervical disc arthroplasty.

Cervical disc arthroplasty (CDA) is widely employed for patients diagnosed with cervical degenerative disc disease (CDDD). Postoperative bone loss (BL) represents a radiological alteration that is a relatively novel consideration in the realm of CDA. This study endeavors to examine the risk factors associated with BL following CDA, aiming to elucidate the underlying mechanisms and the impact of BL on surgical outcomes. A retrospective study was undertaken, encompassing consecutive patients subjected to one-level CDA, two-level CDA, or two-level hybrid surgery (HS) for the treatment of CDDD at our institution. Patient demographic and perioperative data were systematically recorded. Radiological images obtained preoperatively, at 1-week post-operation, and during the last follow-up were collected and evaluated, following with statistical analyses. A total of 295 patients and 351 arthroplasty segments were involved in this study. Univariate logistic regressions indicated that age ≥ 45years and two-level HS was associated with lower risk of BL; and a greater ΔDA (change of disc angle before and after surgery) was correlated with an increased risk of BL. Multivariate logistic regression determined that two-level HS and greater ΔDA were independent preventative and risk factors for BL, respectively. Further analysis revealed that severe BL significantly elevated the risk of implant subsidence compared to non-BL and mild BL. This study posited bone remodeling and micromotion as potential underlying mechanisms of BL. Subsequent research endeavors should delve into the divergent mechanisms and progression observed between lower- and higher-grade BL, aiming to prevent potential adverse outcomes associated with severe BL.

Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.

Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes. Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared. A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties. Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.

LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway.

Intervertebral disc degeneration (IDD)-induced cervical and lumbar herniations are debilitating diseases. The function of intervertebral disc (IVD) mainly depends on the cartilage endplate (CEP), which provides support and waste removal. Therefore, IDD stems from the degeneration of CEP. Our study shows that the expression of lactotransferrin (LTF), an iron-binding protein, is significantly decreased in degenerated human and rat CEP tissues. In addition, we found that LTF knockdown promoted calcification, senescence, and extracellular matrix (ECM) degradation in human endplate chondrocytes. Furthermore, the invivo experiment results confirmed that the JAK2/STAT3 pathway inhibitor AG490 significantly reversed these effects. In addition to investigating the role and mechanism of LTF in CEP degeneration, this study provides a theoretical basis and experimental evidence to improve IDD treatment.

Revolutionizing Intervertebral Disc Regeneration: Advances and Future Directions in Three-Dimensional Bioprinting of Hydrogel Scaffolds.

Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.

Effects of hydrostatic pressure, osmotic pressure, and confinement on extracellular matrix associated responses in the nucleus pulposus cells ex vivo

Spinal movement in both upright and recumbent positions generates changes in physicochemical stresses including hydrostatic pressure (HP), deviatoric stress, and confinement within the intradiscal compartment. The nucleus pulposus (NP) of the intervertebral disc is composed of highly negatively charged extracellular matrix (ECM), which increases osmotic pressure (OP) and generates tissue swelling. In pursuing regenerative therapies for intervertebral disc degeneration, the effects of HP on the cellular responses of NP cells and the ECM environment remain incompletely understood. We hypothesized that anabolic turnover of ECM in NP tissue is maintained under HP and confinement. We first clarified the effects of the relationships among HP, OP, and confinement on swelling NP explants isolated from bovine caudal intervertebral discs over 12 hours. We found that the application of confinement and constant HP significantly inhibits the free swelling of NP (p < 0.01) and helps retain the sulfated glycosaminoglycan. Since confinement and HP inhibited swelling, we incubated confined NPs under HP in high-osmolality medium mimicking ECM-associated OP for 7 days and demonstrated the effects of HP on metabolic turnover of ECM molecules in NP cells. The aggrecan core protein gene was significantly upregulated under confinement and constant HP compared to confinement and no HP (p < 0.01). We also found that confinement and constant HP helped to significantly retain smaller cell area (p < 0.01) and significantly prevent the severing of actin filaments compared to no confinement and HP (p < 0.01). Thus, we suggest that NP's metabolic turnover and cellular responses are regulated by the configuration of intracellular actin and fibrillar ECMs under HP.

Changes in the Centers of Rotation in Different Prosthetic Segments Following Continuous Two-Level Cervical Disc Replacement: A Retrospective Study

To observe the short-term to medium-term therapeutic effects and radiological outcomes of adjacent 2-level cervical spondylosis treated with artificial cervical disc replacement (ACDR) using Mobi-C and Bryan discs. To observe changes and discrepancies in the flexion-extension centers of rotation (FE-COR) of different ACDR segments. Twenty-four patients undergoing 2-level (C4/5 and C5/6) ACDR were analyzed retrospectively (11 patients in the Mobi-C group and 13 patients in the Bryan group). Clinical outcomes were assessed using modified Japanese Orthopedic Association score, Neck Disability Index, and visual analog scale. Preoperative and 2years' follow-up radiographs were collected to compare total cervical spine curvature (C2-C7) range of motion (ROM), upper and lower ACDR segmental ROM, and the operated adjacent segmental ROM. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The degree of disc degeneration in the adjacent segment was observed. At the 2years' follow-up, in both group, the modified Japanese Orthopedic Association score increased significantly, and the Neck Disability Index and neck and upper extremity visual analog scale scores decreased significantly compared with preoperative (P<0.05). There were no significant statistical differences in postoperative scores between the 2 groups (P > 0.05). The overall cervical ROM, the upper and lower segmental ROM at the 2years' follow-up showed no significant statistical differences compared with the preoperative period (P > 0.05). There was no statistically significant difference in the adjacent segmental ROMs compared with the preoperative period (P > 0.05). Furthermore, the statistical analysis revealed no significant differences in the measurements of the ROM at each time points between the Mobi-C Group and the Bryan Group (P > 0.05). There was no significant difference in the preoperative FE-COR-X (indicating the horizontal position of the point in the coordinate system) and FE-COR-Y (indicating the vertical position of the point in the coordinate system) of upper or lower ACDR segments between the 2 groups (P > 0.05). At the 2years' follow-up, there were significant differences both in FE-COR-X and FE-COR-Y between the 2 groups (P < 0.05). For the Mobi-C group, in both the upper and lower segment, the FE-COR-X significantly increased compared with preoperative (P < 0.05), while the FE-COR-Y decreased compared with preoperative (P < 0.05). For the Bryan group, no significant changes were observed in the upper or lower segment in both FE-COR-X and FE-COR-Y compared with preoperative (P > 0.05). Fourty-eight adjacent segments (24 superior and 24 inferior segments) were included in the studies of adjacent segment disease. Four segments showed imaging adjacent segment disease (4/48, 8.33%) in 4 patients, of which 2 were mild and 2 were moderate according to the grading criteria. Among them, 2 were from the Mobi-C group and 2 were from the Bryan group. No severe imaging degeneration was observed. In continuous 2-level cervical ACDR surgery, both Mobi-C and Bryan artificial cervical discs achieved satisfactory clinical outcomes in the short to medium term postoperatively. The FE-COR exhibited different trends of change. In the Mobi-C group, the FE-COR for both upper and lower segments shifted anteriorly and inferiorly, whereas in the Bryan group, whether upper or lower, the FE-COR remained closer to the preoperative state. The changes in FE-COR did not significantly affect the short-term to medium-term clinical outcomes postoperatively.

A data-driven microstructure-based model for predicting circumferential behavior and failure in degenerated human annulus fibrosus

The degeneration of the intervertebral disc annulus fibrosus poses significant challenges in understanding and predicting its mechanical behavior. In this article, we present a novel approach, enriched with detailed insights into microstructure and degeneration progression, to accurately predict the mechanics of the degenerated human annulus. Central to this framework is a fully three-dimensional continuum-based model that integrates hydration state and multiscale structural features, including proteoglycan macromolecules and interpenetrating collagen fibrillar networks across various hierarchical levels within the multi-layered lamellar/inter-lamellar soft tissue, capable of sustaining deformation-induced damage. To ensure accurate and comprehensive predictions of the degenerated annulus mechanical behavior, we establish a data-driven correlation between disc degeneration grade and individual age, which influences the composition and mechanical integrity of annulus constituents while accounting for regional variations. The methodology includes a thorough identification of age- and grade-related evolutions of model inputs, followed by a detailed quantitative evaluation of the model predictive capabilities, with a focus on circumferential behavior and failure. The model successfully replicates experimental data, accurately capturing stiffness, transverse response (Poisson's ratio), and ultimate properties across different annulus regions, while also accommodating the modulation of the age/grade relationship. The reduction rates between normal and severe degeneration align reasonably well with experimental data, with the inner region exhibiting the largest decrease in stiffness (34.63%) and no significant change observed in the outer region. Failure stress drops considerably in both regions (49.86% in the inner and 45.33% in the outer), while failure strain decreases by 36.39% in the outer and 24.74% in the inner. Our findings demonstrate that the proposed framework significantly enhances the predictive accuracy of annulus mechanics across a spectrum of degeneration levels, from normal to severely degenerated states. This approach promises improved predictive accuracy, deeper insights into disc health and injury risk, and a robust foundation for further research on the impact of degeneration on disc integrity. Statement of SignificanceUnderstanding and predicting the mechanical behavior of degenerated human annulus fibrosus remains a significant challenge due to the complex interplay of structural, biochemical, and age-related factors. This study presents a microstructure-based approach to address this challenge by integrating hydration state, detailed structural features across hierarchical scales, and deformation-induced damage and failure, alongside age-related changes and degeneration grade factors. This approach enables accurate simulations of annulus mechanics across regions, with model results thoroughly compared to available data, reinforcing its applicability in capturing degeneration effects. By capturing the intricate interactions between microstructure and mechanical behavior in degenerated discs, the model lays a strong foundation for improving clinical assessments and guiding future treatment strategies for disc-related conditions.

Polyphenol-Mediated Adhesive and Anti-Inflammatory Double-Network Hydrogels for Repairing Postoperative Intervertebral Disc Defects.

Hydrogels have garnered tremendous attention for their applications in the repair of intervertebral disk (IVD) degeneration and postoperative IVD defects. However, it is still challenging to develop a hydrogel fulfilling the requirements for high mechanical properties, adhesive capability, biocompatibility, antibacterial properties, and anti-inflammatory performance. Herein, we report a multifunctional double-network (DN) hydrogel composed of physically cross-linked carboxymethyl chitosan (CMCS) and tannic acid (TA) networks as well as chemically cross-linked acrylamide (AM) networks, which integrates the properties of high strength, adhesion, biocompatibility, antimicrobial activity, and anti-inflammation for the repair of postoperative IVD defects. The treatment with CMCS/TA/PAM DN hydrogels can significantly decrease the levels of inflammatory cytokines and degeneration-related factors and upregulated collagen type II alpha 1. In addition, the hydrogels can effectively seal the annulus fibrosus defect, prevent nucleus pulposus degeneration, retain IVD height, and restore the biomechanical properties of the disc to some extent. This polyphenol-mediated DN hydrogel is promising for sealing IVD defects and preventing herniation after lumbar discectomy.

Midterm Follow-Up Of Tlif In Single-Level Lumbar Disc Degeneration

OBJECTIVES This study aims to evaluate the midterm clinical and radiological outcomes of TLIF in patients with single-level lumbar disc degeneration. The focus is on assessing the procedure's effectiveness in terms of pain relief, functional improvement, and any potential complications. METHODOLOGY A retrospective cohort study was conducted at Hayatabad Medical Complex, Peshawar involving 120 patients who underwent single-level TLIF for lumbar disc degeneration between 2018-2023. The patients with a diagnosis of single-level lumbar disc degeneration confirmed by MRI, failure of conservative treatment for at least 6 months, and who underwent TLIF during the study period were included in the study. Data were collected on preoperative and postoperative pain scores, Oswestry Disability Index (ODI), and radiological parameters. SPSS version 24 was used. RESULTSThe mean follow-up period was 36 months (range 24-48 months). There was a statistically significant improvement in both pain scores (p &lt; 0.001) and ODI scores (p &lt; 0.001). Fusion rates were high, with 92% of patients achieving solid fusion by the final follow-up. Complications were observed in 15% of the cases, with adjacent segment disease being the most common. CONCLUSION TLIF provides significant pain relief and functional improvement in patients with single-level lumbar disc degeneration at midterm follow-up. The procedure demonstrates a high fusion rate with an acceptable complication profile, making it a reliable option for this patient population

Integration of bioinformatics and multi-layered experimental validation reveals novel functions of acetylation-related genes in intervertebral disc degeneration

BackgroundThe molecular mechanisms underlying intervertebral disc degeneration (IDD) remain poorly understood. The purpose of this work is to elucidate key molecules and investigate the roles of acetylation-related RNAs and their associated pathways in IDD. MethodDatasets GSE70362 and GSE124272 were obtained from the Gene Expression Omnibus (GEO) and combined to investigate differentially expressed genes (DEGs) associated with acetylation in IDD patients compared to healthy controls. Critical genes were pinpointed by integrating GO, KEGG and PPI networks. Furthermore, CIBERSORTx analysis was used to investigate the differences in immune cell infiltration between different groups and the biological processes (BP), cellular components (CC) and molecular functions (MF) were calculated by GSEA and GSVA. In addition, The single-cell database GSE165722 was incorporated to validate the specific expression patterns of hub genes in cells and identify distinct cell subtypes. This provides a theoretical basis for a more in-depth understanding of the roles played by critical cell subtypes in the process of IDD. Subsequently, tissues from IVD with varying degrees of degeneration were collected to corroborate the key DEGs using western blot, RT-qPCR, and immunofluorescence staining. ResultsBy integrating various datasets and references, we identified a total of 1620 acetylation-related genes. These genes were subjected to a combined analysis with the DEGs from the databases included in this study, resulting in the discovery of 358 acetylation-related differentially expressed genes (ARDEGs). A comparative analysis with differentially expressed genes obtained from three databases yielded 19 ARDEGs. The PPI network highlighted the top 10 genes (IL1B, LAMP1, PPIA, SOD2, LAMP2, FBL, MBP, SELL, IRF1 and KHDRBS1) based on their protein interaction relationships. CIBERSORTx immune infiltration analysis revealed a moderate positive correlation between the gene IL1β and Mast.cells.activated, as well as a similar correlation between the gene IRF1 and Mast.cells.activated. Single-cell dataset was used to identify cell types and illustrate the distribution of hub genes in different cell types. The two cell types with the highest AUCell scores (Neutrophils and Monocytes) were further explored, leading to the subdivision of Neutrophils into two new cell subtypes: S100A9-type Neutrophils and MARCKS-type Neutrophils. Monocytes were labeled as HLA-DRA9-type Monocytes and IGHG3-type Monocytes. Finally, molecular biology techniques were employed to validate the expression of the top 10 hub genes. Among them, four genes (IL1β, SOD2, LAMP2, and IRF1) were confirmed at the gene level, while two (IL1β and SOD2) were validated at the protein level. ConclusionIn this study, we carried out a thorough analysis across three databases to identify and compare ARDEGs between IDD patients and healthy individuals. Furthermore, we validated a subset of these genes using molecular biology techniques on clinical samples. The identification of these differently expressed genes has the potential to offer new insights for diagnosing and treating IDD.

Efficacy of Chemonucleolysis with Condoliase in Patients Aged under 20 Years.

Chemonucleolysis with condoliase is a minimally invasive treatment option for lumbar disk herniation (LDH). However, studies reporting the efficacy of condoliase in patients aged <20 years are scarce. Therefore, the present study aimed to evaluate the efficacy of condoliase therapy for LDH in the aforementioned population. Condoliase administration was determined based on adequate informed consent. The study enrolled 138 patients (mean age, 41.3±15.4 years) with LDH who received condoliase injections with a follow-up period of 1 year. The patients were divided into Group Y (age, <20 years) and Group A (age, 20-70 years). The clinical outcomes were visual analog scale (VAS) scores for leg and back pain and Oswestry Disability Index (ODI) values. Changes in disk height and degeneration were evaluated. These data were obtained at baseline and at the 3-month and 1-year follow-ups. Condoliase therapy was considered to be effective if it improved the VAS score for leg pain by ≥50% at 1 year from baseline and prevented surgery. Groups Y and A consisted of 15 and 123 patients, respectively. Condoliase therapy was effective in 9 patients (60.0%) in Group Y and 96 patients (78.0%) in Group A. The rates of Pfirrmann grade deterioration and recovery were substantially higher in Group Y than in Group A (83.3% vs. 45.8% and 50.0% vs. 16.3%, respectively). While the disk height reduction in Group Y was greater at 3 months, it recovered to the same level as that in Group A at 1 year. In Group Y, patients who did not respond to the treatment exhibited a considerably higher preoperative ODI (P<0.05). Chemonucleolysis with condoliase is considered to have limited efficacy in patients aged <20 years. Caution should be taken when managing cases showing lumbar instability or existing disability. While chemonucleolysis with condoliase is a less invasive treatment option for LDH, the administration should be decided upon with sufficient consent considering the potential limited efficacy and disk degeneration.

Risk factor analysis of persistent low back pain after microdiscectomy: A retrospective study

ObjectiveMicrodiscectomy is an effective and safe treatment for patients with symptomatic lumbar disc herniation (LDH) that is refractory to conservative interventions. However, some patients experience persistent low back pain (PLBP) after microdiscectomy that is secondary to progressive disc degeneration and segmental instability. This study aimed to clarify the definition of PLBP and analyze its prevalence and associated risk factors. MethodsThis retrospective study included patients who underwent microdiscectomy for LDH at our hospital between 2015 and 2019. We divided this cohort into patients who did (PLBP group) or did not (non-PLBP group) experience PLBP after microdiscectomy and compared their clinical, radiological, and anatomical parameters. We analyzed the relationship between PLBP post-microdiscectomy and the following variables: age, sex, disk herniation level, recurrent disk herniation, body mass index (BMI), modic changes on MRI, facet subluxation, preoperative lumbar pain, and lumbosacral transitional vertebrae (LSTV). ResultsPLBP after microdiscectomy was diagnosed in 99 (29.8 %) of the 332 patients enrolled in this study. Based on our multivariate logistic regression analysis, L5-S1 disc herniation level, recurrent disc herniation after microdiscectomy, obesity, modic changes on preoperative MRI, and facet subluxation were independent risk factors for PLBP post-microdiscectomy. Women and patients aged <50 years showed a trend of increased risk for developing PLBP after microdiscectomy; however, this trend did not reach statistical significance. ConclusionsPLBP after microdiscectomy is a frequent and understudied condition. We found that an L5-S1 disc herniation level, recurrent disc herniation, obesity, modic MRI changes, and facet subluxation were risk factors for PLBP after microdiscectomy. These results can help surgeons in developing a better understanding of lumbar microdiscectomy outcomes.

Use of two-point and six-point Dixon MRI for fat fraction analysis in the lumbar vertebral bodies and paraspinal muscles in healthy dogs: comparison with magnetic resonance spectroscopy.

Fatty degeneration of the vertebral bodies and paravertebral muscles is associated with the presence, severity, and prognosis of spinal disease such as intervertebral disc degeneration. Therefore, the fat fraction (FF) of the vertebral bodies and paraspinal muscles has been considered a potential biomarker for assessing the pathophysiology, progression, and treatment response of spinal disease. Magnetic resonance spectroscopy (MRS) is considered the reference standard for fat quantification; however, it has limitations of a long acquisition time and is technically demanding. Chemical shift-encoding water-fat imaging, called the Dixon method, has recently been applied for rapid fat quantification with high spatial resolution. However, the Dixon method has not been validated in veterinary medicine, and we hypothesized that the Dixon method would provide a comparable assessment of the FF to MRS but would be faster and easier to implement in dogs. In this prospective study, we assessed the FF of the lumbar vertebral bodies and paravertebral muscles from the first to sixth lumbar vertebrae using MRS, the two-point Dixon method (LAVA-FLEX), and the six-point Dixon method (IDEAL-IQ) and compared these techniques. The FFs of vertebral bodies and paravertebral muscles derived from LAVA-FLEX and IDEAL-IQ showed significant correlations and agreement with those obtained with MRS. In particular, the FFs obtained with IDEAL-IQ showed higher correlations and better agreement with those obtained with MRS than those derived by LAVA-FLEX. Both Dixon methods showed excellent intra- and interobserver reproducibility for FF analysis of the vertebral bodies and paraspinal muscles. However, the test-retest repeatability of vertebral body and paraspinal muscle FF analysis was low for all three sequences, especially for the paraspinal muscles. The results of this study showed that LAVA-FLEX and IDEAL-IQ have high reproducibility and that their findings were highly correlated with the FFs of the lumber vertebral bodies and paraspinal muscles determined by MRS in dogs. The FF analysis could be performed much more easily and quickly using LAVA-FLEX and IDEAL-IQ than using MRS. In conclusion, LAVA-FLEX and IDEAL-IQ can be used as routine procedures in spinal magnetic resonance imaging in dogs for FF analysis of the vertebral bodies and paraspinal muscles.

Association Between Cumulative G-force Exposure and Cervical Spine Degenerative Changes.

Fighter pilots work in a unique environment and are subject to high G-force loads under simultaneous head movements. Neck pain is reported to be a common health problem among fighter pilots leading to time lost flying and flight duty limitations. The present study aimed to find out if differences in early military flight career G-force exposure levels could increase the risk for degenerative changes in the cervical spine. The study population consisted of 56 20-year-old Finnish Air Force male fighter pilot cadets, who underwent MRI of the cervical spine at baseline and after 5 years. During follow-up, the G-force exposure was measured using the individual Fatigue Index (FI) recordings. The FI data were collected from each flight with BAE Hawks and is determined by the number of times certain levels of G-forces are exceeded during the flights. The incidence or progression of each degenerative change was compared to individual FI values using Pearson correlation coefficients. The pilots flew on average 220 (±21) hours with high performance aircraft during follow-up, resulting in an average FI of 1.98 (±0.47). A statistically significant progression was found in intervertebral disc (IVD) degeneration sum score with no correlation to corresponding FI values. A statistically significant increase was also found in the prevalence of IVD herniations with a negative correlation with FI values. Other degenerative cervical spine changes did not progress or did not correlate with corresponding FI values. The prevalence of IVD degeneration and IVD herniations increases in the early phases of fighter pilots' career. Only the incidence of IVD herniations correlated with FI values and the correlation was negative. The negative correlation may be attributed to avoidance behavior due to neck pain, which was not measured in our study, or other unmeasured confounding factors. This was the first study to compare individual G-force exposure levels to high-quality MRI data over a follow-up of several years. Finnish fighter pilots are known to report increasing cervical symptoms during the Hawk training phase, but longer follow-up periods are likely needed to determine the association between G-force exposure levels and cervical degenerative changes.

Bone graft substitutes used in anterior lumbar interbody fusion: a contemporary systematic review of fusion rates and complications.

Anterior lumbar interbody fusion (ALIF) uses a broad-footprint interbody cage designed to maximize fusion rates for treating degenerative disc disease. Bone graft substitutes are being increasingly utilized during ALIF to replace or supplement autologous iliac crest bone grafts. This approach aims to optimize fusion efficacy while minimizing associated postoperative complications. The objective of this systematic review was to examine recent studies on fusion rates and postoperative complications associated with bone graft substitutes used in ALIF. We conducted a systematic review of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, MEDLINE, and PubMed databases, to critically examine a decade of research (January 1, 2012, to July 6, 2023) on the effectiveness and safety of various bone graft substitutes in ALIF. This timeframe was chosen to build on a previous systematic review published in 2013. The PRISMA guidelines were used. In total, 27 articles met our stringent inclusion and exclusion criteria. A substantial portion of these studies (67%) focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and highlighted its efficacy for achieving high fusion rates. However, the literature presents a dichotomy regarding the association of rhBMP-2 with increased postoperative complications. Notably, the methodologies for evaluating spinal fusion varied across studies. Only one-third of studies employed computed tomography to assess interbody fusion at 12 months postoperatively, highlighting the urgent need to establish uniform fusion criteria to facilitate more accurate comparative analyses. Moreover, there was considerable variability in the criteria used for diagnosing and detecting postoperative complications, significantly influencing the reported incidence rates. This review underscores the need for continued research into bone graft substitutes, particularly focusing on assessment of long-term complications. Future research endeavors should concentrate on developing comprehensive clinical guidelines to aid in the selection of the most suitable bone graft substitutes for use in ALIF, thereby enhancing patient outcomes and surgical efficacy.

Protective effects of alpinetin against interleukin-1β-exposed nucleus pulposus cells: Involvement of the TLR4/MyD88 pathway in a cellular model of intervertebral disc degeneration

Intervertebral disc degeneration (IDD) causes a variety of symptoms such as low back pain, disc herniation, and spinal stenosis, which can lead to high social and economic costs. Alpinetin has an anti-inflammatory potential, but its effect on IDD is unclear. Herein, we investigated the effect of alpinetin on IDD. To mimic an in vitro model of IDD, nucleus pulposus cells (NPCs) were exposed to interleukin 1β (IL-1β). The viability of NPCs was assessed by CCK-8 assay. The expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), aggrecan, collagen-2, and matrix metalloproteinase-3 (MMP-3) was examined by qRT-PCR and western blotting. The protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated protein X (Bax), and cleaved caspase-3 were scrutinized by western blotting. The flow cytometry assay was performed to assess apoptosis of NPCs. The contents of inflammatory factors were examined by ELISA kits. Results showed that alpinetin repressed IL-1β-tempted activation of the TLR4/MyD88 pathway and apoptosis in NPCs. Alpinetin alleviated IL-1β-tempted inflammatory responses and oxidative stress in NPCs. Moreover, alpinetin lessened IL-1β-tempted extracellular matrix (ECM) degeneration in NPCs by enhancing the expression of aggrecan and collagen-2 and reducing the expression of MMP-3. The effects of alpinetin on IL-1β-exposed NPCs were neutralized by TLR4 upregulation. In conclusion, alpinetin repressed IL-1β-tempted apoptosis, inflammatory responses, oxidative stress, and ECM degradation in NPCs through the inactivation of the TLR4/MyD88 pathway.

Hydrogel and Microgel Collaboration for Spatiotemporal Delivery of Biofactors to Awaken Nucleus Pulposus‐Derived Stem Cells for Endogenous Repair of Disc

AbstractDepletion of nucleus pulposus‐derived stem cells (NPSCs) is a major contributing factor to the attenuation of endogenous regenerative capacity in intervertebral disc degeneration (IVDD). Introducing a hydrogel drug delivery system is a potential strategy for counteracting endogenous cell depletion. The present study proposes a delivery platform for the spatiotemporal release of multiple drugs by combining sodium alginate hydrogels with gelatin microgels (SCGP hydrogels). The SCGP hydrogels facilitated the initial release of chondroitin sulfate (ChS) and the gradual release of an independently developed parathyroid hormone‐related peptide (P2). The combined action of these two small molecule drugs “awakened” the reserve NPSCs, mitigated cell damage induced by H2O2, significantly enhanced their biological activity, and promoted their differentiation toward nucleus pulposus cells. The mechanical and viscoelastic properties of the hydrogel are enhanced by physical and chemical dual cross‐linking to adapt to the loading environment of the degenerated disc. A rat IVDD model is used to validate that the SCGP hydrogel can significantly inhibit the progression of IVDD and stimulate the endogenous repair of IVDD. Therefore, the spatiotemporal differential drug delivery system of the SCGP hydrogel holds promise as a convenient and efficacious therapeutic strategy for minimally invasive IVDD treatment.