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[Extensive bony condensation of the vertebrae in intervertebral disc degeneration. (Study of 25 cases)].

The authors report 25 cases of extensive bony condensation of the vertebrae due to degeneration of the intervertebral discs, giving on lateral XRay a dome-shaped or helmet-shaped appearance. 19 cases occurred in women. Two-thirds of the patients were aged between 35 and 55 years, with an average of 45 years. The lesions were lumbar in 21 patients. They affected in 20 cases two adjacent vertebrae. All the clinical, radiological, pathological and discographic findings, together with the course, confirmed the degenerative origin of these bony condensations, the pathogenesis of which is still not perfectly understood.

Adult

Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.

Humans

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6&#x2009;months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p&#x2009;<&#x2009;0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3&#x2009;&#xb1;&#x2009;8.6) min, much shorter than the early phase (89.5&#x2009;&#xb1;&#x2009;10.3) min (p&#x2009;<&#x2009;0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p&#x2009;<&#x2009;0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p&#x2009;>&#x2009;0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans

The role of the brain-bone axis in skeletal degenerative diseases and psychiatric disorders, A genome-wide pleiotropic analysis.

INTRODUCTION: Skeletal degenerative diseases and psychiatric disorders often coexist clinically. However, the genetic correlations and underlying biological mechanisms between these two types of diseases remain unclear. OBJECTIVES: To investigate the genetic correlations between skeletal degenerative diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways. METHODS: This comprehensive genome-wide pleiotropic association study utilized summary statistics from publicly available genome-wide association data. Various statistical genetic correlation methods were employed, including LDSC, HDL, PLACO, Coloc, Hyprcoloc, and Mendelian randomization (MR) analysis, along with immune cell colocalization analysis. The study aimed to identify potential shared genetic factors among three skeletal degenerative diseases (osteoarthritis, intervertebral disc degeneration, and osteoporosis) and three psychiatric disorders (schizophrenia, anxiety disorder, and major depressive disorder). RESULTS: Analyses using LDSC, HDL, and Bonferroni corrections revealed significant genetic correlations between intervertebral disc degeneration (IVDD) and anxiety disorder (ANX); fractures, IVDD, and arthritis with major depressive disorder (MDD); and arthritis with schizophrenia (SCZ). Significant genetic correlations were also observed between VDD and ANX, fractures, IVDD, hip osteoarthritis (HipOA), knee osteoarthritis (KneeOA) and MDD, and KneeOA and SCZ. Pleiotropy analysis using PLACO, MAGMA, and multitrait colocalization Hyprcoloc identified 65 pleiotropic loci, 27 shared causal loci, and 9 shared risk loci involving immune cells related to both psychiatric and bone-related diseases. Additionally, tissue-specific enrichment analysis showed that genes mapped to these loci were enriched in brain, cardiovascular, pancreatic, and other tissues. The IVW method demonstrated that MDD increased the risk of IVDD and KneeOA, while IVDD increased the risk of ANX and MDD. Conversely, SCZ was associated with a reduced risk of KneeOA. Multiple sensitivity analyses further supported a positive causal effect of IVDD on MDD. CONCLUSION: These findings suggest significant genetic correlations between skeletal degenerative diseases and psychiatric disorders, highlighting multiple shared comorbid genes and key immune cell types. Importantly, the study supports the role of the brain-bone axis in the regulation of skeletal degenerative diseases and psychiatric disorders, which could provide valuable insights for potential therapeutic targets and interventions for these conditions.

Humans

Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression.

The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3'-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD.

3' Untranslated Regions

The spine in sport and veteran military parachutists.

Spinal injuries and symptoms were studied in 109 ex-military parachutists and 112 sport (free fall) parachutists by means of postal questionnaires. 46 ex-military parachutists aged 50 years or over had a radiological examination of the lumbar spine and 58 sport parachutists had a radiological examination of the cervical spine as part of the survey. A history of back pain was significantly (P<0.01) associated with body weight in sport parachutists but not with the number of descents or with the subject's age. In the older ex-military group neither age, weight, nor the number of descents was significantly associated with backache. Of those ex-military parachutists x-rayed, 10 (21.7%) were found to have vertebral body fractures (most frequently at D12), and 8 of these were unaware of these lesions. Vertebral fractures caused no disability and did not permanently curtail parachuting activities in either the sport or ex-military group. Of the ex-military parachutists x-rayed, 84.7% had lumbar disc degeneration of all grades of severity, 17.4% had moderate changes, and 10.8% had severe changes. The frequency of moderate and severe disc degeneration was significantly related to age but not to body weight or to the number of descents. Spondylolysis was found in 2 subjects (4.3%) and spondylolisthesis unassociated with spondylolysis in 4 (8.7%). Spondylolisthesis was always associated with a history of back pain.A low prevalence of radiological cervical intervertebral disc degeneration of all grades of severity of 8.7% was found among the free fall parachutists (mean age 33 years). 2 cases of cervical vertebral body fracture were seen, one related to a parachute landing injury and the other to a parachute opening injury. This study does not implicate parachuting as a cause of intervertebral disc degeneration, either cervical or lumbar, nor as a cause of spondylolysis or spondylolisthesis. Serious long-term disability from pain appears to be uncommon among parachutists despite the frequency of the spinal trauma they sustain.

Adult

The treatment of chronic back pain. A preliminary survey of the effect of radiofrequency denervation of the posterior vertebral joints.

Structures innervated by the dorsal primary ramus play a significant part in the genesis of chronic backache and associated leg pain. The features of this syndrome are described and compared with those in the more familiar clinical picture following intervertebral disc degeneration. However these clinical entities are seldom entirely separate and the diagnosis is often also complicated by psychosomatic factors and the consequences of previous back surgery. A technique of percutaneous facet denervation with a radiofrequency probe, although by no means successful in every case, is entirely safe and a very wothwhile procedure. It has helped many patients, who would otherwise have been disabled by pain and restricted in their activities.

Anesthesia, Local

Pathological changes in the lumbar spine of pigs: gross findings.

The lumbar vertebral columns from 60 sows and 30 slaughter weight pigs were examined grossly for pathological changes. Asymmetry of lumbar articular facets and minor periarticular osteophytes were seen in the slaughter weight group. Degeneration of intervertebral discs or vertebral osteophytes were not present. In contrast, 38% of 60 sows had vertebral osteophytes and 40% had degeneration of intervertebral discs. Extensive ankylosing spondylosis was present in two sows. Other vertebral lesions observed in sows include asymmetry and arthrosis of articular facets, fissures and areas of cavitation in the annulus fibrosus and vertebral end plate, and vertebral osteomyelitis and/or vertebral fracture. Extravertebral skeletal lesions, some of which could be related to a clinical history of lameness or posterior paralysis, include sacroiliac arthrosis, pelvic deformity, polyarthritis, femoral osteomyelitis, sacroiliac dislocation and epiphyseolysis involving the femoral head or tuber ischii.

Animals

CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.

Intervertebral disc (IVD) degeneration, a leading cause of chronic lower back pain, is associated with loss of vacuolated notochordal cells (NCs) and fibrotic remodeling of the nucleus pulposus. Emerging therapies increasingly focus on NCs, which are rare but therapeutically relevant cells for regenerating degenerated IVDs. In this study, we used CRISPR-based transactivation (CRISPRa) to direct the differentiation of human induced pluripotent stem cells (iPSCs) into the NC lineage. We tested CRISPRa-mediated activation of NOTO, TBXT, FOXA2, SOX5, SOX6, and SOX9, coupled with single-cell sequencing of Aggrecan-2A-mScarlet reporter iPSCs. This approach identified the SOX5/6/9 combination (SOX-trio) as critical for promoting NC lineage commitment. The SOX-trio yielded the largest cell population expressing a range of genes previously associated with NC identity, including SHH, FOXA1, FOXA2, FOXJ1, FN1, ALCAM, KRT8, and KRT18. Our study demonstrates the integration of CRISPRa with single-cell technologies as a powerful platform for investigating and enriching iPSC-derived NCs, supporting future regenerative strategies across various fields.

Humans

Analysis of gas in vacuum lumbar disc.

In three cases in which chemonucleolysis with chymopapain was used for the treatment of back and sciatic pain, gas from the vacuum phenomenon of a degenerated lumbar intervertebral disc was recovered. In one of these, the gas analyzed by gas chromatography contained 90%--92% nitrogen.

Chymopapain

Biomimetic Hydrogels with Nucleus Pulposus-like Viscoelasticity and ECM Peptides for Discogenic Differentiation of Stem Cells.

Intervertebral disc (IVD) degeneration is a leading cause of low back pain (LBP), primarily originating in the nucleus pulposus (NP). Regenerative strategies combining mesenchymal stem cells (MSCs) with biomaterials offer great potential for NP repair by replenishing cells and restoring extracellular matrix (ECM). However, key translational challenges remain, including limited stem cell differentiation, poor cell survival in the harsh degenerative niche, and insufficient biomaterial support. While matrix viscoelasticity has been shown to influence adipose-derived stem cell (ASC) discogenic differentiation, its interplay with cell-adhesive ligands for IVD regeneration remains unclear. Moreover, most current hydrogels fail to replicate the ultrafast stress relaxation properties of native non-degenerative human NP tissue. Here, we developed viscoelastic ECM peptide-functionalized hydrogels (VEPH), specifically designed to mimic healthy human NP biomechanics and promote ASC differentiation for NP regeneration. We biochemically conjugated NP ECM-derived adhesive peptides (IKVAV, hA5G26, CHAD) through maleimide-thiol click chemistry, achieving hydrogels with significantly faster stress relaxation (&#x223c;25 s) compared to conventional viscoelastic alginate hydrogels (>100 s). Our results demonstrated that VEPH supported >95% ASC viability and robust metabolic activity over 21 days in 3D culture. Notably, the IKVAV-functionalized hydrogel significantly enhanced ASC cell-matrix interactions, upregulated NP marker expression (KRT18, HIF-1&#x3b1;, ITGA3, and CD24), and promoted type-II collagen secretion, indicating an NP-committed cell fate. Our findings highlight the synergistic roles of matrix viscoelasticity and NP-specific biochemical cues in directing ASC discogenic differentiation and advancing novel biomaterial design for IVD regeneration.

cell-adhesive peptides

Postoperative Curvature Loss in Three-Level Anterior Cervical Discectomy and Fusion With Zero-Profile Device.

PURPOSE: Cervical curvature loss is a frequent complication following 3-level anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device. Consequently, the capacity of this device to maintain cervical sagittal alignment in 3-level ACDF remains highly controversial. This study aimed to identify potential predictors for postoperative curvature loss (PCL) and evaluate its impact on clinical outcomes. METHODS: A total of 113 patients who underwent ACDF for 3-level cervical degenerative disc disease (CDDD) between January 2021 and December 2023 were retrospectively reviewed. Demographic data, radiological parameters, and clinical outcomes were analyzed. Radiographic measures included cervical curvature, T1 slope, C2-7 sagittal vertical axis, and titanium plate and endplate (TPE) distance. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Statistical analyses were performed using paired and independent t-tests, as well as Pearson correlation coefficients. RESULTS: The average curvature loss was 6.82&#xb0; from 1&#x2009;week postoperatively to the final follow-up (p&#x2009;<&#x2009;0.001). However, the final curvature (11.65&#xb0;) was maintained, representing a 4.33&#xb0; improvement compared to preoperative values. Significant correlations were observed between PCL and preoperative curvature (r&#x2009;=&#x2009;-0.368, p&#x2009;=&#x2009;0.013), preoperative T1 slope (r&#x2009;=&#x2009;-0.546, p&#x2009;<&#x2009;0.001), &#x2206;T1 slope (r&#x2009;=&#x2009;0.443, p&#x2009;=&#x2009;0.002), and &#x2206;TPE distance (r&#x2009;=&#x2009;0.417, p&#x2009;=&#x2009;0.004). PCL did not correlate with Japanese Orthopaedic Association (JOA) scores or arm VAS scores at the final follow-up. Nevertheless, patients with a PCL&#x2009;&#x2265;&#x2009;6&#xb0; exhibited significantly higher neck VAS (p&#x2009;=&#x2009;0.028) and NDI scores (p&#x2009;=&#x2009;0.041). CONCLUSION: Although contiguous 3-level ACDF with a Zero-Profile device may result in PCL, it preserves an improved cervical lordosis compared to the preoperative baseline. Low preoperative curvature and a low preoperative T1 slope are potentially predictive factors for PCL. Postoperative changes in TPE distance and T1 slope are significantly associated with PCL, suggesting a potential biomechanical link that requires direct validation. Furthermore, PCL may lead to higher neck VAS and NDI scores. Consequently, the Zero-Profile device may require careful consideration in 3-level CDDD patients presenting with low preoperative curvature and a low T1 slope. Importantly, the 6&#xb0; PCL threshold identified is preliminary and requires prospective validation before clinical application.

Humans

Anatomo-radiological considerations about lumbar discography. An experimental study.

An experimental study was undertaken to determine the origin of lumbar pain associated with degeneration of lumbar intervertebral disc by examining their innervation, vascularization, and stages of evolution. The study included the comparison of discography on patients with an experimental reproduction of this examination on cadavers.

Adolescent

Cervical vertebral instability (wobbler syndrome) in the dog.

Observations on a series of 38 cases (35 Doberman Pinschers and three Great Danes) of the canine wobbler syndrome are described. Radiographic examinations suggested that the primary lesion is an intervertebral instability at C6/7, but with time, secondary changes of the disc degeneration and prolapse and vertebral body malformation causing stenosis of the vertebral canal occur. Cases detected at a young age and showing only the primary lesion were treated successfully, by disc fenestration alone or by disc fenestration and intervertebral screwing. The success rate in older cases with secondary lesions was poor and in this type of case, cord decompression by dorsal laminectomy appears necessary.

Animals

A radiologic survey of various configurations of the lumbar spine.

This paper reports an investigation to determine whether or not human spine configurations can be categorized into types by which one could predict the possibility of disablement at one specific level more than another. Configurations of the lumbar spine, the shape of the lower two lumbar discs, the anterior and posterior heights of discs, the sizes of the transverse processes of L4-5, the presence or absence of rudimentery ribs, and the presence of transitional vertebrae were studied in roentgenograms of 554 subjects. They concluded that the probable criteria for development of L4-5 degeneration were 1) high intercrestal line passing through the upper half of L4, 2) long transverse process on L5, 3) rudimentary rib, and 4) transitional vertebra. Criteria for development of L5-S1 degeneration were 1) intercrestal line passing through the body of L5, 2) short transverse process on L5, 3) no rudimentary rib, 4) no transitional vertebrae. A high intercrestal line and long transverse process probably act as antitorsional devices protecting the L5-S1 disc; hence the likelihood of degeneration at L4-5 is increased.

Adult

[Infarction of the spinal cord in the posterior spinal arterial supply area as a result of intervertebral disc embolism (author's transl)].

A female patient aged 49 developed an acute transverse lesion of the spinal cord from D11 downwards. Autopsy revealed spinal cord infarcts mainly in the dorsal parts corresponding to the posterior spinal arterial supply area, caused by multiple arterial and venous fibrocartilaginous emboli. This particular cause of spinal vascular syndrome has been reported previously only in 11 patients, all outside Austria. This case report serves to stress the poor clinical delineation of a distinct "posterior spinal syndrome". The source of the emboli is the intervertebral disc, mainly the nucleus pulposus. The spinal cord vessels are probably entered by the following route: extrusion of disc material into the venous bone marrow sinus (probably favoured by trauma or endocrine factors) yield basivertebral veins yield internal vertebral venous plexus; the spread is supported by blood stream changes caused by increased intraabdominal/intrathoracic pressure; there is also the possibility of direct penetration of disc material into the internal vertebral plexus, as demonstrated in dogs yield radicular veins yield meningeal and cord veins; sometimes entry occurs through arteriovenous shunts into cord arteries. The true incidence of this condition is unknown since cases are likely to be overlooked in the absence of extensive histopathological investigation.

Accidents, Home

[Radiographical and anatomical studies on the pathogenesis of degenerative spondylolisthesis (author's transl)].

In order to elucidate the causes of degenerative spondylolisthesis (D.S), the functional role of lumbar intervertebral joints and also laminae of the vertebral arch was studied by means of roentgenographic and also pathological exams. The inclination of the laminae of the vertebral arch and the intervertebral joints changed with age in accordance with statokinetic loading of the lumbar spine. In the group with increased lumbar lordosis at the upper level, movement of the 3rd and 4th lumbar vertebrae was great, accompanied by horizontal inclination of the laminae of the vertebral arch and the intervertebral joints and by osteoarthritic changes (O.A). This is similar to D.S. D.S is caused by abnormal spinal curvature and structural specificity of the lower limbs vertebrae, resulting in degeneration of the laminae of the vertebral arch and the intervertebral joints, changes in the inclination, decreased control of movement, and sliding of the vertebrae. Prodromal conditions resulting in the sliding of the vertebrae and in disc degeneration appear to be caused by D.S.

Adolescent

Anterior cervical fusion. A review of thirty-three patients with cervical disc degeneration.

Thirty-three patients who had undergone anterior cervical fusion for degenerative disc disease were reviewed to determine the efficacy of the procedure. Only patients who were available for examination and who had undergone operation at least one year previously were included in the review. Nearly all had had arm pain and three-quarters neck pain. Diminished neck movement and neurological abnormalities in the arms had been frequent findings. Diagnosis from the clinical features and plain radiographs is described. Myelography was not used routinely and discography was not used at all. Indications for operation and surgical technique are described. Results show that pain in the neck and arm was relieved in a high proportion of cases and that the neurological abnormalities often recovered. It is concluded that this operation is safe and has a definite place in the relief of pain from cervical disc degeneration resistant to conservative treatment.

Adult