Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration.

OBJECTIVE: Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship. METHODS: IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1-4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I-V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses. RESULTS: COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD. CONCLUSIONS: Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.

Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

ATG9A as a potential diagnostic marker of intervertebral disc degeneration: Inferences from experiments and bioinformatics analysis incorporating sc-RNA-seq data.

BACKGROUND: Disfunctional autophagy plays a pivotal role in Intervertebral Disc Degeneration (IDD) progression. however, the connection between Autophagy-related gene 9A (ATG9A) and IDD has not been reported. METHODS: Firstly, transcriptome datasets from the GEO and Autophagy-related genes (ARGs) from GeneCards were carried out using R. Following this, IDD-specific signature genes were identified through methods such as least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine (SVM) analyses. Validation of these findings proceeded through in vitro experiments, evaluation of independent datasets, and analysis of receiver operating characteristic (ROC) curves. Subsequent steps incorporated co-expression analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA), and construction of competing endogenous RNA (ceRNA) network. The final section established the correlation between immune cell infiltration, ATG9A, and IDD utilizing the CIBERSORT algorithm and single-cell RNA (scRNA) sequencing data. RESULTS: Research identified 87 differentially expressed genes, with only ATG9A noted as an IDD signature gene. Analysis of in vitro experiments and independent datasets uncovered a decrease in ATG9A expression within the degeneration group. The area under the curve (AUC) of ATG9A exceeded 0.8 following ROC analysis. Furthermore, immune cell infiltration and scRNA sequencing data analysis elucidated the substantial role of immune cells in IDD progression. A ceRNA network was constructed, centered around ATG9A, included 4 miRNAs and 22 lncRNAs. CONCLUSION: ATG9A was identified as a diagnostic gene for IDD, indicating its viability as a effective target for therapy disease.

Identification of CXCL16 as a diagnostic biomarker for obesity and intervertebral disc degeneration based on machine learning.

Intervertebral disc degeneration (IDD) is the primary cause of neck and back pain. Obesity has been established as a significant risk factor for IDD. The objective of this study was to explore the molecular mechanisms affecting obesity and IDD by identifying the overlapping crosstalk genes associated with both conditions. The identification of specific diagnostic biomarkers for obesity and IDD would have crucial clinical implications. We obtained gene expression profiles of GSE70362 and GSE152991 from the Gene Expression Omnibus, followed by their analysis using two machine learning algorithms, least absolute shrinkage and selection operator and support vector machine-recursive feature elimination, which enabled the identification of C-X-C motif chemokine ligand 16 (CXCL16) as a shared diagnostic biomarker for obesity and IDD. Additionally, gene set variant analysis was used to explore the potential mechanism of CXCL16 in these diseases, and CXCL16 was found to affect IDD through its effect on fatty acid metabolism. Furthermore, correlation analysis between CXCL16 and immune cells demonstrated that CXCL16 negatively regulated T helper 17 cells to promote IDD. Finally, independent external datasets (GSE124272 and GSE59034) were used to verify the diagnostic efficacy of CXCL16. In conclusion, a common diagnostic biomarker for obesity and IDD, CXCL16, was identified using a machine learning algorithm. This study provides a new perspective for exploring the possible mechanisms by which obesity impacts the development of IDD.

Machine learning algorithm predicts fibrosis-related blood diagnosis markers of intervertebral disc degeneration.

BACKGROUND: Intervertebral disc cell fibrosis has been established as a contributing factor to intervertebral disc degeneration (IDD). This study aimed to identify fibrosis-related diagnostic genes for patients with IDD. METHODS: RNA-sequencing data was downloaded from Gene Expression Omnibus (GEO) database. The diagnostic genes was identified using Random forest based on the differentially expressed fibrosis-related genes (DE-FIGs) between IDD and control samples. The immune infiltration states in IDD and the regulatory network as well as potential drugs targeted diagnostic genes were investigated. Quantitative Real-Time PCR was conducted for gene expression valifation. RESULTS: CEP120 and SPDL1 merged as diagnostic genes. Substantial variations were observed in the proportions of natural killer cells, neutrophils, and myeloid-derived suppressor cells between IDD and control samples. Further experiments indicated that AC144548.1 could regulate the expressions of SPDL1 and CEP120 by combininghsa-miR-5195-3p and hsa-miR-455-3p, respectively. Additionally, transcription factors FOXM1, PPARG, and ATF3 were identified as regulators of SPDL1 and CEP120 transcription. Notably, 56 drugs were predicted to target these genes. The down-regulation of SPDL1 and CEP120 was also validated. CONCLUSION: This study identified two diagnostic genes associated with fibrosis in patients with IDD. Additionally, we elucidated their potential regulatory networks and identified target drugs, which offer a theoretical basis and reference for further study into fibrosis-related genes involved in IDD.

Identification of a potential novel biomarker in intervertebral disk degeneration by bioinformatics analysis and experimental validation.

Background: Intervertebral disk degeneration (IVDD) is a major cause of low back pain and one of the most common health problems all over the world. However, the early diagnosis of IVDD is still restricted. The purpose of this study is to identify and validate the key characteristic gene of IVDD and analyze its correlation with immune cell infiltration. Methods: 3 IVDD-related gene expression profiles were downloaded from the Gene Expression Omnibus database to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and gene set enrichment analysis (GSEA) were conducted to explore the biological functions. Two machine learning algorithms were used to identify characteristic genes, which were tested to further find the key characteristic gene. The receiver operating characteristic curve was performed to estimate the clinical diagnostic value of the key characteristic gene. The excised human intervertebral disks were obtained, and the normal nucleus pulposus (NP) and degenerative NP were carefully separated and cultured in vitro. The expression of the key characteristic gene was validated by real-time quantitative PCR (qRT-PCR). The related protein expression in NP cells was detected by Western blot. Finally, the correlation was investigated between the key characteristic gene and immune cell infiltration. Results: A total of 5 DEGs, including 3 upregulated genes and 2 downregulated genes, were screened between IVDD and control samples. GO enrichment analysis showed that DEGs were enriched to 4 items in BP, 6 items in CC, and 13 items in MF. They mainly included the regulation of ion transmembrane transport, transporter complex, and channel activity. GSEA suggested that the cell cycle, DNA replication, graft versus host disease, and nucleotide excision repair were enriched in control samples, while complement and coagulation cascades, Fc γ R-mediated phagocytosis, neuroactive ligand-receptor interaction, the NOD-like receptor signaling pathway, gap junctions, etc., were enriched in IVDD samples. Furthermore, ZNF542P was identified and tested as key characteristic gene in IVDD samples through machine learning algorithms and showed a good diagnostic value. The results of qRT-PCR showed that compared with normal NP cells, the expression of ZNF542P gene was decreased in degenerated NP cells. The results of Western blot suggested that compared with normal NP cells, the expression of NLRP3 and pro Caspase-1 was increased in degenerated NP cells. Finally, we found that the expression of ZNF542P was positively related to the proportions of T cells gamma delta (γδT cells). Conclusion: ZNF542P is a potential biomarker in the early diagnosis of IVDD and may be associated with the NOD-like receptor signaling pathway and the infiltration of γδT cells.

Objective outcome measures may demonstrate continued change in functional recovery in patients with ceiling effects of subjective patient-reported outcome measures after surgery for lumbar degenerative disorders.

BACKGROUND CONTEXT: The 6-minute walking test (6WT) has been previously shown to be a reliable and valid outcome measure. It is unclear if the 6WT may further help to detect differences in well performing patients that reach a ceiling effect in PROMs after surgery. PURPOSE: To evaluate changes and timing of change in objective functional impairment (OFI) as measured with the smartphone-based 6WT in relation to patient-reported outcome measures (PROMs) after surgery for degenerative lumbar disorders (DLD). STUDY DESIGN: Prospective observational cohort study. PATIENT SAMPLE: Fifty consecutive patients undergoing surgery for DLD. OUTCOME MEASURES: Patients self-determined their OFI using the 6WT application (6WT-app) and completed a set of paper-based PROMs before, 6 weeks and 3 months after surgery. METHODS: Fifty patients undergoing surgery for DLD were assessed preoperatively (baseline), 6 weeks (6W) and 3 months (3M) postoperatively. Paired sample t-tests were used to establish significant changes in raw 6-minute walking distance (6WD) and standardized Z-scores, as well as PROMs. Pearson correlation coefficient was used to define the relationship between 6WT and PROMs. Floor and ceiling effects were assessed for each PROM (visual analogue scale [VAS], core outcome measure index [COMI], Zurich claudication questionnaire [ZCQ]). RESULTS: Mean 6WT results improved from 377 m (standard deviation - SD 137; Z-score: 1.8, SD 1.8) to 490 m (SD 126; -0.7, SD 1.5) and 518 m (SD 112; -0.4, SD 1.41; all p<.05) at 6W and 3M follow-up. No significant improvement was observed between 6W and 3M for the ZCQ, VAS back and leg pain. While correlation between 6WT and all PROMs were weak at baseline, correlation coefficient increased to moderate at 3M. A considerable ceiling effect (best possible score) was observed, most notably for the ZCQ physical performance, VAS back and leg pain in 24%, 20%, and 16% of patient at 6W and in 30%, 24%, and 28% at 3M. CONCLUSIONS: Objective functional tests can describe the continued change in the physical recovery of a patient and may help to detect differences in well performing groups as well as in cases where patients' PROM results cannot further improve because of a ceiling effect.

Increase in serum nerve growth factor but not intervertebral disc degeneration following whole-body vibration in rats.

BACKGROUND: Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration. METHODS: Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration. FINDINGS: The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect. INTERPRETATION: This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.

Lumbar Facet Effusions and Other Degeneration Parameters and Its Association with Instability.

Background: Controversy exists in the literature about whether facet effusions and other degeneration parameters are associated with instability. Objective: To assess the association between facet effusions and other lumbar degeneration parameters and segmental instability. Material and Methods: In this study, 207 L4-L5 and L5-S1 levels in 104 patients were assessed. We divided the spinal levels into two groups: the small facet effusions (SFE) group in whom facet effusions were <1.5 mm or non-effusions were found, and the large facet effusions (LFE) group in whom they were ≥1.5 mm. The association between other degeneration parameters and instability was also assessed, such as disc degeneration, Modic changes (MC), spondylolisthesis, facet orientation and tropism, facet subchondral sclerosis, and facet cartilage degeneration. Furthermore, we subdivided the levels into subgroups to evaluate the association of LFE and instability within each one. Results: The main analysis comparing the presence of instability in SFE and LFE groups showed a non-statistically significant association between LFE and instability. The presence of MC type 1 and the existence of L4-L5 spondylolisthesis had a statistically significant association with instability. In the subset of 43 levels with L4-L5 degenerative spondylolisthesis, the presence of LFE and the existence of MC type 1 reached a significant association with instability. Conclusion: The presence of LFE and/or MC type 1 may act as red flags in patients with L4-L5 degenerative spondylolisthesis to suspect segmental instability.

Significance of Immune-Related Genes in the Diagnosis and Classification of Intervertebral Disc Degeneration.

Background: With the extensive development of intervertebral disc degeneration (IDD) research, IDD has been found to be a complex disease associated with immune-related gene (IRGs) changes. Nonetheless, the roles of IRGs in IDD are unclear. Methods: In our study, 11 IRGs were chosen using differential analysis between nondisc degeneration and degenerative patients from the GEO database. Then, we utilized a random forest (RF) model to screen six candidate IRGs to predict the risk of IDD. A nomogram was developed on the basis of six candidate IRGs, and DCA showed that patients could benefit from the nomogram. Based on the selected significant IRGs, a consensus clustering approach was used to differentiate disc degeneration patients into two immune patterns (immune cluster A and B). The PCA algorithm was constructed to compute immune scores for every sample, to quantify immune patterns. The immune scores of immune cluster B patients were higher than those of immune cluster A. Results: Through differential expression analysis between healthy and IDD samples, 11 significant IRGs (CTSS, S100Z, STAT3, KLRK1, FPR1, C5AR2, RLN1, IFGR2, IL2RB, IL17RA, and IL6R) were recognized through significant IRGs. The "Reverse Cumulative Distribution of Residual" and "Boxplots of Residual" indicate that the RF model has minimal residuals. The majority of samples in the model have relatively small residuals, demonstrating that the model is better. Besides, the nomogram model was constructed based on importance and the IRGs with importance scores greater than 2 (FPR1, RLN1, S100Z, IFNGR2, KLRK1, and CTSS). The nomogram model revealed that decision-making based on an established model might be beneficial for IDD patients, and the predictive power of the nomogram model was significant. In addition, we identified two different immune cluster patterns (immune cluster A and immune cluster B) based on the 11 IRGs. We found that immune cluster A had significantly higher levels of MDSC, neutrophil, plasmacytoid dendritic cell, and type 17 T helper cell expression than immune cluster B. And we calculated the score for each sample to quantify the gene patterns. The patients in immune cluster B or gene cluster B had higher immune scores than those in immune cluster A or gene cluster A. Conclusion: In conclusion, IRGs play an extremely significant role in the occurrence of IDD. Our study of immune patterns may guide the strategies of prevention and treatment for IDD in the future.

Correlation between serum angiotensin-converting enzyme (ACE) levels and intervertebral disc degeneration.

Studies have shown that the renin-angiotensin system (RAS) might play an essential role in intervertebral disc degeneration (IDD). The study aimed to investigate the relationship between serum angiotensin-converting enzyme (ACE) concentration and IDD and its predictive value for severe disc degeneration. 245 patients who came to our hospital for low back pain were recruited, and blood samples were collected for routine examination. Descriptive data and demographic parameters were collected. The cumulative grade 1 was calculated by summing up the Pfirrmann grade of all lumbar discs. ACE concentration grouping was determined via tertile split. Correlation analysis and multivariable linear regression analysis were performed to determine the relationship between ACE and IDD. The receiver's degree of disc degeneration (ROC) curve determined the ACE's predictive value. Results indicated that there was no significant difference in demographic parameters among groups. Correlation analysis and multivariate linear analysis showed that ACE was an independent risk factor for IDD. The cumulative grade 1 increased significantly with the increase in ACE concentration, which was consistent with the correlation analysis. Average Pfirrmann grade < 4 indicates mild to moderate degeneration, and grade ≥ 4 indicates severe degeneration in terms of an individual disc. From L1/2 to L5/S1, the mean plasma ACE concentration was significantly higher in the severe degeneration group than in the mild to moderate degeneration group. According to the ROC curve, the cut-off value of ACE levels was 22.5. patients with ACE > 22.5 had severe degeneration. The sensitivity and specificity were 0.762 and 0.521, respectively.

Is intervertebral disc degeneration associated with reduction in serum ferritin?

OBJECTIVE: Ferritin autophagy is characterized by intracellular ferroptosis and selective ferritin degradation. However, the role of ferritin in the development of intervertebral disc degeneration (IDD) has not been elucidated. The study aimed to investigate the role of serum iron metabolism markers, especially serum ferritin (SF), in IDD. METHODS: 217 patients who came to the spine surgery department of our hospital for low back pain were recruited, and blood samples were collected for routine examination after admission. The cumulative grade was also calculated by summing up the Pfirrmann grade of all lumbar discs. RESULTS: Correlation analysis showed that cumulative grade was correlated with SF (r = - 0.185, p = 0.006), not with serum iron (SI), transferrin saturation (TS), unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC) (all p > 0.05). In addition, SF levels in the low severity IDD were significantly higher than high severity IDD in cumulative grade (p = 0.003) and single disc grade. No statistically significant difference was found in the other four indicators. A statistically significant difference was observed between the high (cumulative grade > 17) and low score (cumulative grade ≤ 17) groups in terms of age. According to the ROC curve, the cut-off value of SF levels was 170.5. Patients with SF < 170.5 ng/mL had severe disc degeneration. The sensitivity and specificity were 0.635 and 0.602, respectively. CONCLUSION: This study preliminarily showed that SF was negatively correlated with the degree of IDD and can be used to predict IDD severity.

[A validated new classification for intervertebral disk degeneration]. / Novaya validizirovannaya klassifikatsiya klassov degeneratsii mezhpozvonkovykh diskov.

OBJECTIVE: To develop a new validated classification of intervertebral disc degeneration. MATERIAL AND METHODS: A retrospective observational single-center study included medical records of patients with and without degenerative disease of lumbar intervertebral discs. The interval values of apparent diffusion coefficient (ADC) of intervertebral discs were grouped into degeneration classes. RESULTS: The study included medical records of 100 patients. A quantitative analysis of data showed that mean ADC has a significant correlation with severity of lumbosacral disc degeneration according to classification by Pfirrmann et al. Lumbar intervertebral discs with degeneration grade 3-4 were less homogeneous compared to grade 2-3. Among discs with degeneration grade 4, mean ADC was significantly higher in case of hernia (p=0.01). Conversely, mean ADC was significantly higher in the absence of hernia for discs grade 3 (p=0.04). Combination of all data is presented as original classification of lumbosacral disc degeneration based on mean ADC. CONCLUSION: The developed classification can be recommended for radiologists, neurologists and neurosurgeons.

Preoperative and postoperative diagnostic efficiency of multi-inflammatory index on pain scoring of degenerated intervertebral disc.

BACKGROUND: The inflammatory index can be useful for neurosurgeons to understand and grade pain in degenerated intervertebral disc (DIVD). OBJECTIVES: The study focused on the value of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and the inflammatory multiple indices (MIs), and aimed to compare its efficiency with the preoperative and postoperative pain scale and scoring algorithms. MATERIAL AND METHODS: A total of 88 DIVD patients were included in this retrospective clinical cohort study. Visual Analogue Scale Back (VASB) and Visual Analogue Scale Leg (VASL), Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), and walking distance (WD) were used to assess pain. The multiple index (MI) was calculated as MI-1 = PLR × C-reactive protein (CRP) and MI-2 = NLR × CRP. RESULTS: Comparing the MI with ODI, no correlation was found in preoperative values, while a positive correlation (MI-1: r = 0.398, p < 0.001; MI-2: r = 0.285; p = 0.007) was found between the postoperative measurements. A significant correlation was found for VASB and both MI-1 (preoperative: r = 0.373, p = 0.001; postoperative: r = 0.232, p = 0.041) and MI-2 (preoperative: r = 0.388, p < 0.001; postoperative: r = 0.206, p = 0.044). The MI-1 index showed 71.4% sensitivity and 73.3% specificity, while the MI-2 index exhibited 78.6% sensitivity and 68.9% specificity. CONCLUSIONS: MI-1 and MI-2 showed a positive correlation with preand post-operative VASB score and had strong potential to predict postoperative pain in DIVD. They are easy-to-use, noninvasive and low-cost indices; therefore, our results are promising for routine application.

MiR-206 improves intervertebral disk degeneration by targeting GJA1.

BACKGROUND: A large amount of evidence suggested that miRNA was involved in the progression of intervertebral disk degeneration (IDD). The purpose of our study was to explore the function and potential mechanism of miR-206/GJA1 axis in IDD. METHODS: IDD nucleus pulposus (NP) cell model was established through treatment of LPS. IDD rat model was established by annulus fibrosus puncture. The expression of miR-206 and GJA1 was detected by RT-PCR, apoptosis was evaluated by flow cytometry or TUNEL, inflammatory factors were tested by ELISA, extracellular matrix related protein expression was detected by western blot, and HE and safranin-O staining were used to assess the pathological changes of IDD. RESULTS: GJA1 was found to be highly expressed in IDD tissues and LPS-induced NP cells. Down regulation of GJA1 reduced inflammatory factors, inhibited apoptosis and enhanced extracellular matrix in LPS-induced NP cells. MiR-206 was downregulated in IDD tissues and directly targeted GJA1, and the expression of miR-206 was negatively correlated with the expression of GJA1 in IDD tissues. Further, it was demonstrated that overexpression of miR-206 could attenuate LPS-induced NP cell injury by targeting GJA1. In vivo, the upregulation of miR-206 improved IDD and reduced NP cell apoptosis. CONCLUSION: Our study showed that miR-206 reduced the level of inflammatory factors, restrained NP cell apoptosis and increases extracellular matrix by targeting GJA1. These data suggested that miR-206/GJA1 might be potential therapeutic targets for IDD.

Oblique Lateral Interbody Fusion with Anterolateral Screw Fixation Is as Effective as with Posterior Percutaneous Pedicle Screw Fixation in Treating Single-Segment Mild Degenerative Lumbar Diseases.

BACKGROUND Oblique lateral interbody fusion (OLIF) is a new and minimally invasive surgery. This study aimed to compare the clinical efficacy and safety of oblique lateral interbody fusion with anterolateral screw fixation and with posterior percutaneous screw fixation in treating single-segment mild degenerative lumbar diseases. MATERIAL AND METHODS A retrospective analysis was performed on 51 patients with single-segment mild degenerative lumbar diseases who received OLIF from April 2017 to January 2020 in Hong Hui Hospital, Xi'an Jiao Tong University; 24 and 27 patients received OLIF with anterolateral screw fixation (OLIF+AF) and OLIF with posterior percutaneous screw fixation (OLIF+PF), respectively. Anesthesia time, operation time, intraoperative blood loss, intraoperative fluoroscopy number, hospital stay, postoperative complications, Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, anterior and posterior disc heights, foraminal height, and fusion rate of the 2 groups were compared to assess clinical and radiological outcomes. RESULTS Anesthesia time, operation time, intraoperative blood loss, number of intraoperative fluoroscopy, and VAS score in the OLIF+AF group were significantly better than those in the OLIF+PF group (P<0.05). There were no significant differences in ODI score, anterior and posterior disc heights, foraminal height, fusion rate, and incidence of complications between the 2 groups (P<0.05). CONCLUSIONS OLIF+AF in treating single-segment mild degenerative lumbar diseases produces a satisfactory clinical effect. Moreover, OLIF+AF does not invade the paraspinal muscle group, thereby reducing trauma, postoperative residual low back pain, operation time, bleeding, and frequency of fluoroscopy. Thus, OLIF+AF is a feasible treatment method for single-segment mild degenerative lumbar diseases.

Innovative Biological Treatment Methods for Degenerative Disc Disease.

Low back pain is the leading cause of work absences and years lived with disability, and it is often associated with degenerative disc disease. In recent years, biological treatment approaches such as the use of growth factors, cell injections, annulus fibrosus (AF) repair, nucleus pulposus replacement, and tissue-engineered discs have been explored as means for preventing or reversing degenerative disc disease. Both animal and clinical studies have shown promising results for cell-based therapy on the grounds of its regenerative potential. Clinical data also indicate that stem cell injection is safe when appropriately performed, albeit its long-term safety and efficacy are yet to be explored. Numerous challenges also remain to be overcome, such as isolating, differentiating, and preconditioning the disc cells, as well as managing the nutrient-deficient and oxygen-deficient micromilieu of the intervertebral disc (IVD). AF repair methods including devices used in clinical trials have shown success in decreasing reherniation rates and improving overall clinical outcomes. In addition, recent studies that combined AF repair and nucleus pulposus replacement have shown improved biomechanical stability in IVDs after the combined treatment. Tissue-engineered IVDs for total disc replacement are still being developed, and future studies are necessary to overcome the challenges in their delivery, efficacy, and safety.

Internal lumbar disc derangement with instability catch from monosegmental discopathy. The forgotten mechanical and kinetic surgical back pain syndrome.

STUDY DESIGN: This is a retrospective cohort experience reported with concurrent survey PROM outcomes. OBJECTIVE: To describe the results of open PLIF reconstruction for a select group of mechanical back pain patients who have mono- or bi-segmental discopathy on MRI imaging, a clinical history of repeated severe and disabling acute mechanical back pain symptoms, and the irregular lumbar motion pattern in returning erect from the flexed position known as the "instability catch". SUMMARY OF BACKGROUND DATA: The literature of fusion surgery for back pain relief in "mechanical" back pain reveals inconsistent results and in the majority presents only a vague description of these syndromes. Internal Lumbar Disc Degeneration with Instability catch "ILDDIC" may be one subset of these patients who are uniquely benefitted from spine stabilization. METHODS: The senior author (DAB) in midsummer 2015 began to offer smaller fusion procedures to selected patients on an overnight-stay basis using a standard perioperative care protocol. For practice audit, in December 2020 a mailed survey questionnaire requesting VAS pain scores and SF-36 physical function scores was sent out to all 111 patients who had been treated this way, which group included 30 cases of ILDDIC. We report here on the success of open PLIF reconstruction in achieving back pain relief for these patients. RESULTS: Some 24 of 30 patients returned the mailed survey questionnaire, and the remaining six could not be reached. All 24 responders reported significant relief of back pain and improved physical function, at a mean of 30 months from surgery. Review of the available clinical records (LFU < 1 year) from the six nonresponders also recorded positive early benefit. CONCLUSION: The diagnosis of ILDDIC requires both imaging and clinical correlates and may define a subgroup of the mechanical back pain population uniquely suited to achieve pain relief through lumbar fusion.

External Validation of the Minimum Clinically Important Difference in the Timed-up-and-go Test After Surgery for Lumbar Degenerative Disc Disease.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: The aim of this study was to provide external validation of the minimum clinically important difference (MCID) of the Timed-up-and-go (TUG) test. SUMMARY OF BACKGROUND DATA: The TUG test is one of the best explored and most frequently applied objective task-based functional outcome measure in patients with lumbar degenerative disc disease (DDD). The increased use of the TUG test is based on its solid psychometric properties; however, an external validation of the originally determined MCID is lacking. METHODS: Forty-nine patients with lumbar DDD, scheduled for elective spine surgery, were assessed pre- and 6-weeks (W6) postoperative. MCID values were calculate for raw TUG test times (seconds) and standardized TUG z scores using three different computation methods and the following established patient-reported outcome measures (PROMs) as anchors: Visual Analog Scales (VAS), Core Outcome Measures Index Back, Zurich Claudication Questionnaire (ZCQ). RESULTS: The three computation methods generated a range of MCID values, depending on the PROM used as anchor, from 0.9 s (z score of 0.3) based on the VAS leg pain to 3.0 seconds (z score of 2.7) based on the ZCQ physical function scale. The average MCID of the TUG test across all anchors and computation methods was 2.1 s (z score of 1.5). According to the average MCID of raw TUG test values or TUG z scores, 41% and 43% of patients classified as W6 responders to surgery, respectively. CONCLUSION: This study confirms the ordinally reported TUG MCID values in patients undergoing surgery for lumbar. A TUG test time change of 2.1 seconds (or TUG z score change of 1.5) indicates an objective and clinically meaningful change in functional status. This report facilitates the interpretation of TUG test results in clinical routine as well as in research.Level of Evidence: 3.

The CT assessment of uncovertebral joints degeneration in a healthy population.

BACKGROUND: A retrospective study investigated the degeneration trend of uncovertebral joints in a healthy population based on CT assessment. METHODS: A total of 200 males and 160 females, aged 21-79 years old (50.82 ± 17.06), who underwent CT examination in our hospital from September 2020 to March 2021 were enrolled. Sixty patients were included in each age group. According to the Kellgren and Lawrence classification and CT was used to evaluate the uncovertebral joints degeneration in different groups. RESULTS: With the increase of age, the degeneration of each segment was gradually aggravated. The uncovertebral joints started degenerating in the 20 s, and the C5-6 is the most degenerative segment, followed by the C4-5 and C6-7. Significant degeneration occurred in each segment between the 40 s and 60 s and became more severe after the 70 s. CONCLUSIONS: The modified Kellgren and Lawrence classification based on CT scan could provide a quantitative assessment of uncovertebral joints degeneration in a healthy population and could provide more details for artificial cervical arthroplasty.