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CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127–33

Background. The majority of adults will experience an episode of low back pain during their life. Patients with non-specific low back pain and lumbar disc degeneration (LDD) may experience spinal pain and morning stiffness because of a comparable inflammatory process as in patients with osteoarthritis of the knee and/or hip. Therefore, this study assessed the association between spinal morning stiffness, LDD and systemic inflammation in middle aged and elderly patients with low back pain. Methods. This cross-sectional study used the baseline data of the BACE study, including patients aged ≥55 years visiting a general practitioner with a new episode of back pain. The association between spinal morning stiffness, the radiographic features of lumbar disc degeneration and systemic inflammation measured with serum C-reactive protein was assessed with multivariable logistic regression models. Results. At baseline, a total of 661 back pain patients were included. Mean age was 66 years (SD 8), 416 (63%) reported spinal morning stiffness and 108 (16%) showed signs of systemic inflammation measured with CRP. Both LDD definitions were significantly associated with spinal morning stiffness (osteophytes OR=1.5 95% CI 1.1–2.1, narrowing OR=1.7 95% CI 1.2–2.4) and spinal morning stiffness >30 minutes (osteophytes OR=1.9 95% CI 1.2–3.0, narrowing OR=3.0 95% CI 1.7–5.2) For severity of disc space narrowing we found a clear dose response relationship with spinal morning stiffness. We found no associations between spinal morning stiffness and the features of LDD with systemic inflammation. Conclusions. This study demonstrated an association between the presence and duration of spinal morning stiffness and radiographic LDD features. No conflicts of interest. No funding obtained

Aims. To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod. Methods. This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining. Results. Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues. Conclusion. Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: Bone Joint J 2020;102-B(10):1375–1383

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To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment.

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Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date.

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This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

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A variety of surgical methods and strategies have been demonstrated for Andersson lesion (AL) therapy. In 2011, we proposed and identified the feasibility of stabilizing the spine without curettaging the vertebral or discovertebral lesion to cure non-kyphotic AL. Additionally, due to the excellent reunion ability of ankylosing spondylitis, we further came up with minimally invasive spinal surgery (MIS) to avoid the need for both bone graft and lesion curettage in AL surgery. However, there is a paucity of research into the comparison between open spinal fusion (OSF) and early MIS in the treatment of AL. The purpose of this study was to investigate and compare the clinical outcomes and radiological evaluation of our early MIS approach and OSF for AL.

Background and purpose. Modic changes (MC) are a risk factor for development of chronic low back pain (CLBP). There is no agreement about the cause of inflammation in MC, but autoimmunity has been suggested. The aim of the study was to investigate whether treatment with lactic acid bacteria for 100 days was associated with change of disability and pain, via a change in the gut microbiota inducing a change in the immune system, in patients with CLBP and type 1 MC during one year follow-up. Methods. Eighty-nine patients with CLBP and type 1 MC were randomized to receive either one capsule Lactobacillus Rhamnosis GG or placebo capsules twice daily for 100 days. Results. Missing values at one year were 4% and 3% in the disability and pain variables, respectively. The predefined outcomes disability and back and leg pain only changed little during follow-up with no statistically significant differences between groups. At one year, back pain had decreased by 1.1 more on a 0–10 scale (95% CI 0.20- 1.97) in the experimental group than in the control group. There were no differences regarding other predefined outcomes, i.e. global effect or percentage with minimal disability at one year. Nine percent of the patients reported gastrointestinal side-effects without difference between groups. Conclusions. No differences were found between groups regarding the predefined outcomes. Overall, the study confirmed that CLBP with MC1 is a grave back pain disorder, with little tendency to improvement. During follow-up, disability of the whole cohort was reduced by just 17%. Conflicts of interest: No conflicts of interest. Sources of funding: The study has been supported by The Danish Rheumatism Association and Peter and Helga Kornings Fond

Background. Degeneration of the intervertebral disc (IVD) is a leading cause of lower back pain, and a significant clinical problem. Inflammation mediated by IL-1β and TNF-α drives IVD degeneration through promoting a phenotypic switch in the resident nucleus pulposus (NP) cells towards a more catabolic state, resulting in extracellular matrix degradation. Bone marrow mesenchymal stem cells (MSCs) produce bioactive factors that modulate local tissue microenvironments and their anti-inflammatory potential has been shown in numerous disease models. Thus MSCs offer a potential therapy for IVD degeneration. In a clinical setting, adipose-derived stem cells (ASCs) might represent an alternative and perhaps more appealing cell source. However, their anti-inflammatory properties remain poorly understood. Methods. Here we assess the anti-inflammatory properties of donor-matched human ASCs and MSCs using qPCR and western blotting. Results. We demonstrate that stimulating ASCs or MSCs with IL-1β and/or TNF-α elicits a strong anti-inflammatory response with increased expression of IL-1 receptor antagonist (IL-1Ra), cyclooxygenase-2 (COX-2) and the tissue protective protein tumour-necrosis factor stimulated gene-6 (TSG-6). ASCs produced significantly higher levels of IL-1Ra and TSG-6 than their matched MSCs at both gene and protein levels, indicating that ASCs are potentially a more potent anti-inflammatory cell type. This anti-inflammatory response was also observed upon co-culture with degenerate NP cells without exogenous cytokine. Signalling analyses suggested this difference between cell types might be mediated through differences in the activation of inflammation-associated transcription factors. Conclusion. These data indicate that the anti-inflammatory properties of ASCs may be useful in developing future therapies for IVD degeneration. No conflicts of interest. Sources of funding: EPSRC-MRC Centre for Doctoral Training in Regenerative Medicine (EP/L014904/1)

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Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

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Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

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Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs).

Introduction. Internal transpedicular fixation for the treatment of scoliosis develops quite fast and is widely used in clinical practice. The purpose of the study was to assess the efficacy of internal transpedicular fixation in treatment of patients with scoliosis. Material and methods. The system of internal transpedicular fixation (Vertebra Stabilization System Ø 5.5-6.35, OIM, Turkey) was employed for treatment of 50 patients with scoliosis of various severity. There was 83% of female patients aged from 15 to 23 years. Clinical and radiological methods were used for assessment of treatment results. Results. An angle of scoliotic deformity measured 40-60° in 20 cases, 60-100° in 21 patients, and more than 100° in 9 cases. Two-staged procedure was produced for two patients, and one-staged intervention for 33 cases. The length of in-patient treatment was five days. The patients could sit on the bed on the next day after the surgery, walk after 3 days, and were discharged from the hospital after 5 days for the follow-up. The deformity was corrected by 95-100% in the group of patients with scoliosis of 40-60°. The deformity was corrected by 85-90% in the group of patients with scoliosis of 60-100°. One-staged procedure allowed for 70-75% correction in patients with scoliosis more than 100°. Discussion and conclusion. The results of treatment showed no loss of correction at one-year follow-up. Patient aged more than 20 showed changing the deformity angle by 2-5° due to degenerative changes of the spine. No complications associated with inflammation of soft tissues, broken metal constructs were observed in this cohort of patients. Long-term follow-ups were evaluated from one to two years. All the patients were satisfied with their cosmetic and functional result

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To study the associations of lumbar developmental spinal stenosis (DSS) with low back pain (LBP), radicular leg pain, and disability.

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To evaluate the histopathological examination of peri-implant tissue samples as a technique in the diagnosis of postoperative spinal implant infection (PSII).

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The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD).