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1.
Global Spine J ; : 21925682241270069, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39069374

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Patients with IBD are at an increased risk for postoperative complications following surgery. The goal of this study is to investigate if inflammatory bowel disease (IBD) is a risk factor for complications following lumbar discectomy. METHODS: We identified IBD patients who underwent lumbar discectomy for lumbar disc herniation (LDH) and matched to them with controls without IBD in a1:5 ratio. We excluded patients with a history of spinal injury, cancer, infection, trauma, or surgery to remove the digestive tract. We used multivariate logistic regression analyses to compare postoperative outcomes, including 90-day complications, 90-day emergency department visits, and 90-day readmissions. In addition, 2-year re-discectomy rates and a 3-year lumbar fusion rate were compared between the cohorts. RESULTS: After applying the study criteria, we identified 6134 IBD patients with LDH for further analysis. With the exception of dura tears, patients with IBD had significantly higher rates of medical complications, incision-related complications, ED visits, and readmission rates compared to patients without IBD, especially for the 2-year and 3-year rates of disc recurrence and revision surgery. CONCLUSIONS: Patients with IBD who underwent lumbar discectomy are at a significantly higher rate of complications. Therefore, spine surgeons and other health care providers should be aware of this higher risk associated with IBD patients and properly treat the patients' IBD before surgery to lower these risks.

2.
Int Immunopharmacol ; 139: 112717, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39067404

RESUMEN

Intervertebral disc degeneration (IVDD), a common degenerative disc disease, is a major etiological factor for back pain, affecting a significant number of middle-aged and elderly individuals worldwide. Thus, IVDD is a major socio-economic burden. The factors contributing to the complex IVDD etiology, which has not been elucidated, include inflammation, oxidative stress, and natural aging. In particular, inflammation and aging of nucleus pulposus cells are considered primary pathogenic factors. Isorhapontigenin (ISO) is a polyphenolic compound commonly found in traditional Chinese herbs and grapes. We have demonstrated that ISO exerts anti-inflammatory and anti-aging effects and mitigates extracellular matrix (ECM) degradation. In this study, in vitro experiments revealed that, ISO delays aging and ECM degradation by promoting PI3K/AKT/mTOR-mediated autophagy. Meanwhile, in vivo experiments affirmed that ISO delays the progression of IVDD.

3.
Vet Sci ; 11(7)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39058009

RESUMEN

In the context of veterinary medicine, minimally invasive techniques for feline spinal surgery remain underexplored, particularly for percutaneous laser disc ablation (PLDA) when using the Holmium:YAG (Ho:YAG) laser. This study aimed to refine the application of the Ho:YAG laser in PLDA by determining the optimal laser intensity and safe insertion angles for the thoracic and lumbar intervertebral discs (IVDs) in cats. Through utilizing computed tomography (CT) for precise guidance, this research involved a cadaveric study of 10 cats to evaluate the spatial configurations that allow for safe needle insertions and effective laser ablation. Various energy settings of the Ho:YAG laser (20 J, 40 J, and 60 J) were tested to ascertain the balance between adequate disc vaporization and minimal adjacent tissue damage. The results demonstrate that a 40 J setting is the most effective in achieving significant disc decompression without compromising surrounding tissue integrity. Additionally, the CT scans proved crucial in confirming the accuracy of the needle placement and the safety of the laser application angles. This study established that the 40 J setting on the Ho:YAG laser, combined with CT-guided insertion techniques, offers a reliable method for PLDA, thus enhancing the safety and efficacy of feline spinal surgeries.

4.
Pain Pract ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951955

RESUMEN

BACKGROUND: Herniated intervertebral disc (HIVD) with radiculopathy is a common degenerative spine disorder. Transforaminal epidural steroid injection (TFESI) is one of the pain relief treatments for lumbar radiculopathy recommended by evidence-based guidelines. Adequate contrast distribution is correlated with better pain control, but the best approach has not been confirmed yet. AIM: To confirm the distribution of contrast medium injected with a new approach of TFESI, that is, far lateral lateral recess approach (FLLR-TFESI). METHODS: Patients receiving TFESI due to HIVD with radiculopathy between 2010 January and 2020 August were retrospectively enrolled. While the FLLR-TFESI was taken as the experimental group, the conventional approach was viewed as the control group. The baseline characteristics, the pattern of contrast enhancement under fluoroscopic guidance, and the complications of these patients were collected and analyzed. RESULTS: A total of 380 patients were analyzed (143 in control group and 237 in experimental group). The two groups were balanced in most baseline characteristics, except disc extrusion (p = 0.01) and scoliosis (p = 0.04). The FLLR-TFESI have a better contrast distribution (p < 0.01), even after adjustment (p < 0.001). No intrathecal injection was noted, but higher rate of intra-disc injection was noted in FLLR-TFESI group (10% vs. 3%, p = 0.008). CONCLUSION: The FLLR-TFESI has a superior contrast enhancement and distribution in comparison to conventional approach. Prospective study to confirm the study result as well as the clinical benefits is suggested in the future.

5.
Int Immunopharmacol ; 138: 112616, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38959544

RESUMEN

Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which is one of the major factors leading to disability and severe economic burden. Necroptosis is an important form of programmed cell death (PCD), a highly regulated caspase-independent type of cell death that is regulated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL)-mediated, play a key role in the pathophysiology of various inflammatory, infectious and degenerative diseases. Recent studies have shown that necroptosis plays an important role in the occurrence and development of IDD. In this review, we provide an overview of the initiation and execution of necroptosis and explore in depth its potential mechanisms of action in IDD. The analysis focuses on the connection between NP cell necroptosis and mitochondrial dysfunction-oxidative stress pathway, inflammation, endoplasmic reticulum stress, apoptosis, and autophagy. Finally, we evaluated the possibility of treating IDD by inhibiting necroptosis, and believed that targeting necroptosis may be a new strategy to alleviate the symptoms of IDD.

6.
J Magn Reson Imaging ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963154

RESUMEN

BACKGROUND: Lower back pain affects 75%-85% of people at some point in their lives. The detection of biochemical changes with sodium (23Na) MRI has potential to enable an earlier and more accurate diagnosis. PURPOSE: To measure 23Na relaxation times and apparent tissue sodium concentration (aTSC) in ex-vivo intervertebral discs (IVDs), and to investigate the relationship between aTSC and histological Thompson grade. STUDY TYPE: Ex-vivo. SPECIMEN: Thirty IVDs from the lumbar spines of 11 human body donors (4 female, 7 male, mean age 86 ± 8 years). FIELD STRENGTH/SEQUENCE: 3 T; density-adapted 3D radial sequence (DA-3D-RAD). ASSESSMENT: IVD 23Na longitudinal (T1), short and long transverse (T2s* and T2l*) relaxation times and the proportion of the short transverse relaxation (ps) were calculated for one IVD per spine sample (11 IVDs). Furthermore, aTSCs were calculated for all IVDs. The degradation of the IVDs was assessed via histological Thompson grading. STATISTICAL TESTS: A Kendall Tau correlation (τ) test was performed between the aTSCs and the Thompson grades. The significance level was set to P < 0.05. RESULTS: Mean 23Na relaxation parameters of a subset of 11 IVDs were T1 = 9.8 ± 1.3 msec, T2s* = 0.7 ± 0.1 msec, T2l* = 7.3 ± 1.1 msec, and ps = 32.7 ± 4.0%. A total of 30 IVDs were examined, of which 3 had Thompson grade 1, 4 had grade 2, 5 had grade 3, 5 had grade 4, and 13 had grade 5. The aTSC decreased with increasing degradation, being 274.6 ± 18.9 mM for Thompson grade 1 and 190.5 ± 29.5 mM for Thompson grade 5. The correlation between whole IVD aTSC and Thompson grade was significant and strongly negative (τ = -0.56). DATA CONCLUSION: This study showed a significant correlation between aTSC and degenerative IVD changes. Consequently, aTSC has potential to be useful as an indicator of degenerative spinal changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

7.
Front Endocrinol (Lausanne) ; 15: 1391970, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962678

RESUMEN

Objective: To investigate the relationship between degeneration of cervical intervertebral disc and degeneration of paravertebral muscles[multifidus (MF), cervical semispinalis (SCer), semispinalis capitis (SCap) and splenius capitis (SPL)]. Methods: 82 patients with chronic neck pain were randomly selected, including 43 males and 39 females, with 50.73 0.7.51 years old. All patients were scanned by 3.0T MRI Philips Ingenia performed conventional MRI sequence scanning and fat measurement sequence mDIXON-Quant scanning of cervical. Fat infiltration (FI) and cross-sectional area (CSA) of cervical paravertebral muscle (MF, SCer, SCap and SPL) at central level of C5-6 disc were measured by Philips 3.0T MRI image post-processing workstation. According to Pfirrmann grading system, there was no grade I in the included cases. The number of grade IIr IV cases were n=16, 40, 19 and 7 respectively. CSA and FI of cervical paravertebral muscles were compared with t test or one-way ANOVA, Spearman correlation analysis was used to evaluate the correlation between age, disc degeneration, and CSA, FI of cervical paravertebral muscles, and multiple linear regression analysis was used to analyze the independent influencing factors of CSA and FI. Results: CSA of cervical paravertebral muscles in male patients was significantly higher than that in female patients (all P<0.001), but there was no significant difference in FI (all P>0.05). Age was weakly correlated with CSA of MF+SCer, moderately correlated with CSA of SCap and SPL (r=-0.256, -0.355 and -0.361, P<0.05), weakly correlated with FI of SCap and SPL (r= 0.182 and 0.264, P<0.001), moderately correlated with FI of MF+SCer (r=0.408, P<0.001). There were significant differences in FI with disc degeneration (P<0.001, P=0.028 and P=0.005). Further correlation analysis showed that disc degeneration was strongly correlated with FI of MF+SCer (r=0.629, P<0.001), and moderately correlated with FI of SCap and SPL (r=0.363, P=0.001; r=0.345, P=0.002). Multiple linear regression analysis showed that sex and age were the influencing factors of CSA of SCap and SPL, sex was the independent influencing factor of CSA of MF+SCer, and disc degeneration was the independent influencing factor of FI. Conclusions: Age is negatively correlated with CSA and positively correlated with FI. Disc degeneration was correlated with FI of paravertebral muscles, especially with FI of MF and SCer. Sex and age were the influencing factors of CSA, while disc degeneration was the independent influencing factor of FI.


Asunto(s)
Vértebras Cervicales , Degeneración del Disco Intervertebral , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/patología , Persona de Mediana Edad , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Imagen por Resonancia Magnética/métodos , Adulto , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/patología , Anciano
8.
J Orthop Surg Res ; 19(1): 421, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39034400

RESUMEN

BACKGROUND: Cellular senescence features irreversible growth arrest and secretion of multiple proinflammatory cytokines. Cyclic GMP-AMP synthase (cGAS) detects DNA damage and activates the DNA-sensing pathway, resulting in the upregulation of inflammatory genes and induction of cellular senescence. This study aimed to investigate the effect of cGAS in regulating senescence of nucleus pulposus (NP) cells under inflammatory microenvironment. METHODS: The expression of cGAS was evaluated by immunohistochemical staining in rat intervertebral disc (IVD) degeneration model induced by annulus stabbing. NP cells were harvested from rat lumbar IVD and cultured with 10ng/ml IL-1ß for 48 h to induce premature senescence. cGAS was silenced by cGAS specific siRNA in NP cells and cultured with IL-1ß. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-ß-gal) staining and flow cytometry. The expression of senescence-associated secretory phenotype including IL-6, IL-8, and TNF-a was evaluated by ELISA and western blotting. RESULTS: cGAS was detected in rat NP cells in cytoplasm and the expression was significantly increased in degenerated IVD. Culturing in 10ng/ml IL-1ß for 48 h induced cellular senescence in NP cells with attenuation of G1-S phase transition. In senescent NP cells the expression of cGAS, p53, p16, NF-kB, IL-6, IL-8, TNF-α was significantly increased while aggrecan and collagen type II was reduced than in normal NP cells. In NP cells with silenced cGAS, the expression of p53, p16, NF-kB, IL-6, IL-8, and TNF-α was reduced in inflammatory culturing with IL-1ß. CONCLUSION: cGAS was increased by NP cells in degenerated IVD promoting cellular senescence and senescent inflammatory phenotypes. Targeting cGAS may alleviate IVD degeneration by reducing NP cell senescence.


Asunto(s)
Senescencia Celular , Degeneración del Disco Intervertebral , Nucleotidiltransferasas , Núcleo Pulposo , Ratas Sprague-Dawley , Senescencia Celular/fisiología , Animales , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/metabolismo , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Células Cultivadas , Ratas , Masculino , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo
9.
Front Bioeng Biotechnol ; 12: 1400508, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045539

RESUMEN

Hemilaminectomy and laminectomy are decompressive procedures commonly used in case of lumbar spinal stenosis, which involve the removal of the posterior elements of the spine. These procedures may compromise the stability of the spine segment and create critical strains in the intervertebral discs. Thus, this study aimed to investigate if decompressive procedures could alter the biomechanics of the lumbar spine. The focus was on the changes in the range of motion and strain distribution of the discs after two-level hemilaminectomy and laminectomy. Twelve L2-S1 cadaver specimens were prepared and mechanically tested in flexion, extension and both left and right lateral bending, in the intact condition, after a two-level hemilaminectomy on L4 and L5 vertebrae, and a full laminectomy. The range of motion (ROM) of the entire segment was assessed in all the conditions and loading configurations. In addition, Digital Image Correlation was used to measure the strain distribution on the surface of each specimen during the mechanical tests, focusing on the disc between the two decompressed vertebrae and in the two adjacent discs. Hemilaminectomy did not significantly affect the ROM, nor the strain on the discs. Laminectomy significantly increased the ROM in flexion, compared to the intact state. Laminectomy significantly increased the tensile strains on both L3-L4 and L4-L5 disc (p = 0.028 and p = 0.014) in ipsilateral bending, and the compressive strains on L4-L5 intervertebral disc, in both ipsilateral and contralateral bending (p = 0.014 and p = 0.0066), with respect to the intact condition. In conclusion, this study found out that hemilaminectomy did not significantly impact the biomechanics of the lumbar spine. Conversely, after the full laminectomy, flexion significantly increased the range of motion and lateral bending was the most critical configuration for largest principal strain.

10.
World Neurosurg ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986949

RESUMEN

BACKGROUND: Among the causes of the progression of intervertebral disc (IVD) degeneration (IDD) is the loss of nutrient intake to the IVD through the microcirculation disruption of the sub-endplate. Also, the vertebral body fracture intervenes in degenerating the adjacent IVD. This research aimed to create an animal model of IDD using these two strategies. METHODS: 30 male Sprague-Dawley rats were split into 3 groups: a control group, a middle vertebral body injury (MI) associated with ethanol injection (MI+EtOH) group, and an MI associated with phosphate-buffered saline injection (MI+PBS) group. A vertebral body fracture with or without endplate injection of ethanol was generated by either drilling a hole in the center of a caudal rat vertebral body to form a fracture with an unabated endplate or drilling a hole in the center of a rat coccygeal vertebral body with endplate injection of ethanol to establish a vertebral body fracture with endplate damage. X-ray, macroscopic, histologic, and biochemical evaluations were utilized to assess IDD at weeks 3 and 6. RESULTS: According to X-ray findings, the MI+EtOH group demonstrated a significant decrease in intervertebral space height over time in comparison to the 2 other groups. The water content also was significantly decreased. Macroscopic and histological analysis demonstrated progressive degenerative changes in the IVD of the MI+EtOH group. CONCLUSION: The caudal vertebra fracture with ethanol injection is more likely to induce degeneration of adjacent IVD. This model effectively repreduced IDD, which may serve as a theoretical basis for future clinical intervention for IDD.

11.
JOR Spine ; 7(3): e1349, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38993524

RESUMEN

Background: Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD. Method: We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results. Result: We found interferon-gamma (IFN-γ, p = 2.14 × 10-6, OR = 0.870, 95% CI = 0.821-0.921), interleukin-1 beta (IL-1b, p = 0.012, OR = 0.951, 95% CI = 0.914-0.989), interleukin-4 (IL-4, p = 0.034, OR = 0.946, 95% CI = 0.899-0.996), interleukin-18 (IL-18, p = 0.028, OR = 0.964, 95% CI = 0.934-0.996), granulocyte colony-stimulating factor (GCSF, p = 0.010, OR = 0.919, 95% CI = 0.861-0.980), and Stromal cell-derived factor 1a (SDF1a, p = 0.014, OR = 1.072, 95% CI = 1.014-1.134) were causally associated with risk of IVDD. Conclusion: Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.

12.
Tzu Chi Med J ; 36(3): 298-303, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993826

RESUMEN

Objectives: Discectomy is the most common surgery for lumbar herniated intervertebral disc (HIVD) disease. However, 5%-24% of patients undergo a second surgery due to recurrent disc herniation. Materials and Methods: This study was aimed to identify the risk factors for reoperation after discectomy of lumbar HIVD and recommend treatment for patients with a high risk of reoperation. We recruited patients diagnosed as having single-level lumbar HIVD who underwent open discectomy from January 1, 2000, to December 31, 2012 in our hospital. We used a survival curve to inspect the survival time and reoperation rate after surgery. We discussed the correlation of reoperation rate with discectomy level, body mass index, heavy lifting after surgery, sex, and age. Furthermore, we investigated the correlation between the experience of a surgeon and the reoperation rate. Results: A total of 619 patients were enrolled in our study. Most patients were 40-60 years old (48.8%), and most of them had herniation at L4/5 level (48.9%). The 8-year survival rate was 92%. Weight lifting after surgery may increase the reoperation rate by 115 and 18 times for those >60 years and <40 years, respectively. In addition, less experience of the surgeon and female sex had a high reoperation rate. Conclusion: Postoperative working modification may be very important for preventing patients from recurrent HIVD. For elderly people with HIVD, a more conservative therapy could be selected. If patients with lumbar spine hypermobility or severe degeneration require wide laminectomy, primary fusion should be considered.

13.
BMC Musculoskelet Disord ; 25(1): 517, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970068

RESUMEN

BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.


Asunto(s)
Densidad Ósea , Estudio de Asociación del Genoma Completo , Degeneración del Disco Intervertebral , Análisis de la Aleatorización Mendeliana , Humanos , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/epidemiología , Factores de Riesgo , Masculino , Femenino , Análisis Multivariante
14.
Adv Sci (Weinh) ; : e2404275, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973294

RESUMEN

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

15.
Eur Spine J ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976000

RESUMEN

PURPOSE: To evaluate the influence of vertebral and disc wedging on the contribution of lumbar lordosis and the change of disc thickness before and after walking based on MRI. METHODS: Cross-sectional study. A total of 96 normally developing children, aged 5.7 ± 3.0 years old, 55 boys and 41 girls. They were divided into 3 groups: Pre-walking group, Walking group, and Post-walking group. PARAMETERS: lumbar lordosis Angle (LLA), the sum of the lumbar disc wedge Angle (∑D), the sum of the lumbar vertebral body wedge Angle (∑B), disc height (DH). RESULTS: (1) LLA, ∑D, ∑B, and DHL1-S1 were 33.2 ± 8.7°, 14.1 ± 8.6°, 11.9 ± 8.6°, and 6.9 ± 1.2 mm, 7.6 ± 1.4 mm, 8.2 ± 1.6 mm, 8.9 ± 1.7 mm, 8.5 ± 1.8 mm. (2) The difference in LLA values between the Pre-walking and the Post-walking group was statistically significant. DH were significantly different among the three groups. (3) In the Post-walking group, LLA value of girls was significantly higher than that of boys, and DHL3 - 4 and DHL4 - 5 values of girls were significantly lower than that of boys. (4) Age had a low positive correlation with LLA and ∑D and a moderate to strong positive correlation with DH; LLA showed a moderate positive correlation with ∑D, and a low positive correlation with ∑B and DH. CONCLUSION: Age and walking activity are the influencing factors of lumbar lordosis and disc thickening. Walking activity can significantly increase lumbar lordosis, and age is the main factor promoting lumbar disc thickening. DHL4-5 was the thickest lumbar intervertebral disc with the fastest intergroup thickening. Disc wedging contributes more to lumbar lordosis than vertebral wedging.

16.
Artículo en Inglés | MEDLINE | ID: mdl-38976178

RESUMEN

BACKGROUND AND OBJECTIVE: Accurate IVD segmentation is crucial for diagnosing and treating spinal conditions. Traditional deep learning methods depend on extensive, annotated datasets, which are hard to acquire. This research proposes an intensity-based self-supervised domain adaptation, using unlabeled multi-domain data to reduce reliance on large annotated datasets. METHODS: The study introduces an innovative method using intensity-based self-supervised learning for IVD segmentation in MRI scans. This approach is particularly suited for IVD segmentations due to its ability to effectively capture the subtle intensity variations that are characteristic of spinal structures. The model, a dual-task system, simultaneously segments IVDs and predicts intensity transformations. This intensity-focused method has the advantages of being easy to train and computationally light, making it highly practical in diverse clinical settings. Trained on unlabeled data from multiple domains, the model learns domain-invariant features, adeptly handling intensity variations across different MRI devices and protocols. RESULTS: Testing on three public datasets showed that this model outperforms baseline models trained on single-domain data. It handles domain shifts and achieves higher accuracy in IVD segmentation. CONCLUSIONS: This study demonstrates the potential of intensity-based self-supervised domain adaptation for IVD segmentation. It suggests new directions for research in enhancing generalizability across datasets with domain shifts, which can be applied to other medical imaging fields.

17.
Neurospine ; 21(2): 375-400, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38955515

RESUMEN

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

18.
Front Cell Dev Biol ; 12: 1409287, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015652

RESUMEN

Introduction: Intervertebral disc degeneration often occurs in the elderly population, but in recent years, there has been an increasing incidence of disc degeneration in younger individuals, primarily with mild degeneration. Methods: In order to explore the underlying mechanisms of disc degeneration in both young and aging individuals, we collected four types of nucleus pulposus (NP) single-cell sequencing samples for analysis based on Pfirrmann grading: normal-young (NY) (Grade I), normal-old (NO) (Grade I), mild degenerative-young (MY) (Grade II-III), and mild degenerative-old (MO) (Grade II-III). Results: We found that most NP cells in NO and MY samples exhibited oxidative stress, which may be important pathogenic factors in NO and MY groups. On the other hand, NP cells in MO group exhibited endoplasmic reticulum stress. In terms of inflammation, myeloid cells were mainly present in the degenerative group, with the MY group showing a stronger immune response compared to the MO group. Interestingly, dendritic cells in the myeloid lineage played a critical role in the process of mild degeneration. Discussion: Our study investigated the molecular mechanisms of intervertebral disc degeneration from an age perspective, providing insights for improving treatment strategies for patients with disc degeneration at different age groups.

19.
PeerJ ; 12: e17464, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006038

RESUMEN

Objective: The mechanisms of intervertebral disc degeneration (IVDD) in low back pain (LBP) patients are multiples. In this study, we attempt to investigate whether melatonergic system plays a potential role in IVDD patients with LBP by analyzing their clinical specimens. The fucus will be given to the correlation between the melatonin receptor expression and intervertebral disc tissue apoptosis. Methods: In this clinical study, 107 lumbar intervertebral disc nucleus pulposus (NP) specimens from patients with LBP were collected with patients' consents. The disc height (DH) discrepancy ratio, range of motion and sagittal parameters of the pathological plane were measured and Pfirrmann grade was used to classified the grades of IVDD level. Discs at grades 1-3 were served as normal control and grades 4-5 were considered as IVDD. The expression levels of melatonin receptor 1A (MT1) and 1B (MT2) were measured by immunohistochemistry. The apoptosis of NP was assessed using TUNEL staining. Their potential associations among MT1/2, DH, apoptosis, sagittal parameters with IVDD and LBP were evaluated with statistical analysis. Results: The incidence of IVDD was positively associated with age and negatively related to VAS scores for LBP (p < 0.001). Patients with higher degree of IVDD also have higher DH discrepancy ratio (p < 0.001), higher prevalence of lumbar instability (p = 0.003) and higher cell apoptosis compared to the control. Nevertheless, no statistically significant correlation was identified between Pfirrmann grade and lumbar sagittal parameters. MT1 and MT2 both were highly expressed in the NP tissues. Importantly, MT1 expression but not MT2 was significantly increased in the intervertebral disc tissue of patients with IVDD and its level correlated well with cell apoptosis level and the severity of IVDD as well as lower VAS scores for LBP. Conclusion: The highly elevated MT1 expression was found in NP tissues of patients with IVDD and LBP compared to the control. This phenomenon probably reflects the compensating response of the body to the pathological alteration of the IVDD and LBP. Therefore, these findings provide the novel information to use selective agonists of MT1 to target IVDD and LBP clinically.


Asunto(s)
Apoptosis , Degeneración del Disco Intervertebral , Dolor de la Región Lumbar , Humanos , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Vértebras Lumbares/patología , Receptor de Melatonina MT1/metabolismo , Receptor de Melatonina MT2/metabolismo , Anciano , Disco Intervertebral/patología , Disco Intervertebral/metabolismo
20.
Am J Transl Res ; 16(6): 2453-2463, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006261

RESUMEN

BACKGROUND: Percutaneous Endoscopic Lumbar Discectomy (PELD) has emerged as routine treatment for lumbar disc herniation (LDH) due to its minimal invasiveness and quick recovery. However, PELD demands high precision from the surgeon, as the risk of intraoperative complications is substantial, including potential damage to the nerve root and dura, and a higher likelihood of recurrence post-surgery. Thus, preoperative planning utilizing CT and MRI imaging is essential. METHODS: In this study, the clinical data of 140 patients treated with PELD for LDH from January 2021 to December 2023 were retrospectively analyzed. Patients were categorized into two groups based on whether CT and MRI registration (CMR) was employed for surgical planning: a CMR group (n=68) and a control group (n=72). Data collected included surgery time, hospital stay duration, and scores from the Visual Analog Scale (VAS) for low back and leg pain, as well as the Japanese Orthopaedic Association Lumbar Spine Score (JOA). Differences between the two groups were assessed using the Student's t-test. RESULTS: No significant difference was found in hospital stay length between the groups (P=0.277). Surgery time was significantly shorter in the CMR group (P<0.001). Prior to surgery, no significant differences in VAS scores for leg and low back pain were observed between the groups (P=0.341 and P=0.131, respectively); however, at 2 months postoperatively, both scores were significantly lower in the CMR group (P<0.001 and P=0.002, respectively). Similarly, no difference in preoperative JOA scores was noted (P=0.750), but at 2 months postoperative, the CMR group exhibited significantly higher scores (P<0.001). CONCLUSION: Compared with the traditional PELD, the preoperative use of CMR has shown to reduce surgery time, alleviate leg and low back pain, and increase the lumbar JOA score at 2 months after surgery, underscoring its efficacy in enhancing surgical outcomes.

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