Association between serum interleukin-17 levels and ectopic bone formation in OPLL patients with DISH.

OBJECTIVE: To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group. METHODS: A total of 103 patients with OPLL (DISH (-), n = 50; DISH (+), n = 53) and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analyzed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types. RESULTS: No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (-) group, especially in female patients (p = 0.003). Additionally, IL-17 levels were positively correlated with the number of Flat vertebral units, meaning one of the characteristics of DISH ossification type (R2 = 0.199, p = 0.012). IL-17 levels in type 4 were significantly higher in the DISH (+) group than in the DISH (-) group. CONCLUSIONS: The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients.

Morphological characteristics of DISH in patients with OPLL and its association with high-sensitivity CRP: inflammatory DISH.

OBJECTIVES: To characterize and clarify evidence as to whether the ectopic bone formations of DISH in patients with ossification of the posterior longitudinal ligament (OPLL) are caused by inflammatory or degenerative processes. METHODS: Whole-spine CT and serum high-sensitivity CRP (hs-CRP) levels were obtained from 182 cervical OPLL patients (DISH+, n = 104; DISH-, n = 78). In the DISH+ group, ectopic bone formations were categorized into Flat and Jaggy types, then further divided into three subgroups: group 1 (Jaggy-dominant pattern), group 2 (Equivalence of pattern) and group 3 (Flat-dominant pattern). Data were compared between the DISH+ and DISH- groups, and among the three subgroups. RESULTS: The upper thoracic spine was most affected by the Flat type, whereas the Jaggy type was more frequent in the middle and lower thoracic regions. There was no difference in hs-CRP levels between the DISH+ and DISH- groups. Among the three subgroups, hs-CRP levels in group 3 [mean (s.d.) 0.16 (0.09) mg/dl] were significantly higher than in group 1 [0.04 (0.02) mg/dl] and group 2 [0.08 (0.06) mg/dl]. Higher levels of hs-CRP were associated with a greater number of vertebral units with Flat-type formations (ß = 0.691, P < 0.0001) and with a lesser number of vertebral units with Jaggy-type formations (ß = -0.147, P = 0.036). CONCLUSION: The Flat type in DISH might be caused by an inflammatory pathogenesis rather than a degenerative process presented in the Jaggy type.

Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes.

Objectives: The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes. Methods: In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1 flox/flox /EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study. Results: The results demonstrated a gradual deterioration of compression in the Enpp1 flox/flox /EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05). Conclusions: The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.

Sacroiliac Joint Variation in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: Ossification of the posterior longitudinal ligament (OPLL) reveals heterotopic ossification in the spinal ligament. OPLL also tends to ossify ligaments and entheses throughout the body. However, hallmarks of sacroiliac (SI) joint ossification and its variation in OPLL have not been clarified. Here, we investigated the morphological changes in SI joints in individuals with and without OPLL. METHODS: We included 240 age- and sex-matched patients (OPLL+, 120; OPLL-, 120) in the study. SI joint variations were classified into 4 types: Type 1, normal or small peripheral bone irregularity; Type 2, subchondral bone sclerosis and osteophyte formation; Type 3, vacuum phenomenon; and Type 4, bridging osteophyte and bony fusion. Type 4 was further divided into 3 subgroups as previously described. Interactions between the ossified spinal region in OPLL and morphological changes in the SI joint were evaluated. RESULTS: SI joint ankylosis occurs more frequently in patients with OPLL (51.7%) than in those without (non-OPLL) (33.3%). The SI joint vacuum phenomenon (49.2%) was the main finding in non-OPLL. SI joint ankylosis in OPLL was characterized by anterior bridging and intra-articular fusion. OPLL patients with multilevel ossification tend to develop degeneration and ankylosis of the SI joints. CONCLUSIONS: OPLL conferred a high risk of SI joint ossification compared with non-OPLL, and patients with extensive ossification had a higher rate of SI joint ankylosis. Understanding SI joint variation could help elucidate OPLL etiology and clarify the phenotypic differences in the SI joint between OPLL and other spinal disorders.

Assessment of Cervical Myelopathy Risk in Ossification of the Posterior Longitudinal Ligament Patients With Spinal Cord Compression Based on Segmental Dynamic Versus Static Factors.

OBJECTIVE: Using segmental dynamic and static factors, we aimed to elucidate the pathogenesis and relationship between ossification of the posterior longitudinal ligament (OPLL) and the severity of cervical myelopathy. METHODS: Retrospective analysis of 163 OPLL patients' 815 segments. Imaging was used to evaluate each segmental space available for the spinal cord (SAC), OPLL diameter, type, bone space, K-line, the C2-7 Cobb angle, each segmental range of motion (ROM), and total ROM. Magnetic resonance imaging was used to evaluate spinal cord signal intensity. Patients were divided into the myelopathy group (M group) and the without myelopathy group (WM group). RESULTS: Minimal SAC (p = 0.043), (C2-7) Cobb angle (p = 0.004), total ROM (p = 0.013), and local ROM (p = 0.022) were evaluated as an independent predictor of myelopathy in OPLL. Different from the previous report, the M group had a straighter whole cervical spine (p < 0.001) and poorer cervical mobility (p < 0.001) compared to the WM group. Total ROM was not always a risk factor for myelopathy, as its impact depended on SAC, when SAC > 5 mm, the incidence rate of myelopathy decreased with the increase of total ROM. Lower cervical spine (C5-6, C6-7) showing increased "Bridge-Formation," along with spinal canal stenosis and segmental instability (C2-3, C3-4) in the upper cervical spine, could cause myelopathy in M group (p < 0.05). CONCLUSION: Cervical myelopathy is linked to the OPLL's narrowest segment and its segmental motion. The hypermobility of the C2-3 and C3-4, contributes significantly to the development of myelopathy in OPLL.

Association of Inflammation, Ectopic Bone Formation, and Sacroiliac Joint Variation in Ossification of the Posterior Longitudinal Ligament.

Ossification of the posterior longitudinal ligament (OPLL) is considered a multifactorial condition characterized by ectopic new bone formation in the spinal ligament. Recently, its connections with inflammation as well as sacroiliac (SI) joint ankylosis have been discussed. Nevertheless, whether inflammation, spinal ligament ossification, and SI joint changes are linked in OPLL has never been investigated. In this study, whole-spinal computed tomography and serum high-sensitive C-reactive protein (hs-CRP) levels were obtained in 162 patients with cervical OPLL. Ossification lesions were categorized as plateau and hill shapes. Accordingly, patients were divided into plateau-shaped (51 males and 33 females; mean age: 67.7 years) and hill-shaped (50 males and 28 females; mean age: 67.2 years) groups. SI joint changes were classified into four types and three subtypes, as previously described. Interactions among ossification shapes, hs-CRP levels, and morphological changes in the SI joint were investigated. The plateau shape was more common in the vertebral segments (59.5%), compared to the hill shape, which was predominant in the intervertebral regions (65.4%). Serum hs-CRP levels in the plateau-shaped group (0.11 ± 0.10 mg/dL) were significantly higher than those in the hill-shaped group (0.07 ± 0.08 mg/dL). SI joint intra-articular fusion was the main finding in the plateau-shaped group and showed significantly higher hs-CRP levels compared to the anterior para-articular bridging, which more frequently occurred in the hill-shaped group. Our findings suggested a possible inflammation mechanism that might contribute to the new bone formation in OPLL, particularly the plateau shape.

Characterization of ligamentum flavum hypertrophy based on m6A RNA methylation modification and the immune microenvironment.

OBJECTIVE: N6-methyladenosine (m6A) has been implicated in the progression of several diseases, and the role of epigenetic regulation in immunity is emerging, particularly for RNA m6A modification. However, it is unclear how m6A-related genes affect the immune microenvironment of ligamentum flavum hyperplasia (LFH). Therefore, we aimed to investigate the effect of m6A modification on the LFH immune microenvironment. METHODS: The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. We systematically analyzed m6A regulators in eight patient samples and the corresponding clinical information of the samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and protein-protein interactions (PPIs) were used to explore the correlation of m6A clusters with the immune microenvironment in LFH. A least absolute shrinkage and selection operator (Lasso) regression was then used to further explore the m6A prognostic signature in LFH. The relative abundance of immune cell types was quantified using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. We explored the relationship between hub genes and small molecule drug sensitivity by clustering hub gene-based samples. In addition, Real-Time quantitative PCR (RT-qPCR) as well as western blotting (WB) were used to validate the gene expression of the differentially expressed genes. RESULTS: A total of 1259 differentially expressed genes were identified, of which 471 were upregulated and 788 were downregulated. A total of three genes showed significant differences (METTL16, PCIF1, and FTO). According to the enrichment analysis, immune factors may play a key role in LFH. ssGSEA was used to cluster the immune infiltration score, construct the hub gene diagnosis model, and screen a total of 6 LFH immune-related prediction model genes. The predictive diagnostic model of LFH was further constructed, revealing that METTL16, PCIF1, FTO and ALKBH5 had superior diagnostic efficiency. RT-qPCR results showed that 6 genes (METTL16, PCIF1, POSTN, TNNC1, MMP1 and ACTA1; P < 0.05) exhibited expression consistent with the results of the bioinformatics analysis of the mRNA microarray. Up-regulated METTL16, PCIF1, and ALKBH5 levels in LFH were validated by western blotting. CONCLUSION: Diversity and complexity of LFH's immune microenvironment are influenced by M6A modification, and our study provides strong evidence for predicting the diagnosis and prognosis of LFH.

Diagnostic imaging in a patient with an isolated blunt traumatic gallbladder injury.

Isolated gallbladder injuries are very uncommon in blunt abdominal trauma due to its small size. Further, they are well protected by the surrounding liver, omentum, and the rib cage. A case of traumatic gallbladder injury in a 47-year-old man with progressive right hypochondrial pain is presented. The gallbladder injury was caused due to a blunt abdominal trauma after a motor vehicle accident. The patient had a history of chronic alcoholism and narcotics abuse. The patient was also human immunodeficiency virus-positive and was on stable treatment for tuberculosis. A diagnosis of gallbladder contusion with intramural dissection was made after an ultrasound and computed tomography scan. However, the patient refused surgery and thus, an ultrasound-guided percutaneous transhepatic drainage of the gallbladder was performed as a temporary treatment. Subsequently, a successful cholecystectomy was performed. Isolated traumatic gallbladder injury has been reviewed due to the rarity of this condition and the diagnostic challenges it poses.