Aims. 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. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Conclusion. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state. Cite this article: Bone Joint Res 2023;12(3):189–198

Aims. 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. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

Aims. 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. Methods. A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes. Results. All patients had comorbidities and/or non-spinal procedures within the previous year. Most infections affected lumbar segments (20/32), with Escherichia coli the commonest organism (17/32). Causative organisms were identified by blood culture (23/32), biopsy/aspiration (7/32), or intraoperative samples (2/32). There were 56 different antibiotic regimes, with oral (PO) ciprofloxacin being the most prevalent (13/56; 17.6%). Multilevel, contiguous infections were common (8/32; 25%), usually resulting in bone destruction and collapse. Epidural collections were seen in 13/32 (40.6%). In total, five patients required surgery, three for neurological deterioration. Overall, 24 patients improved or recovered with a mean halving of CRP at 8.5 days (SD 6). At the time of review (two to six years post-diagnosis), 16 patients (50%) were deceased. Conclusion. This is the largest published cohort of gram-negative spinal infections. In older patients with comorbidities and/or previous interventions in the last year, a high level of suspicion must be given to gram-negative infection with blood cultures and biopsy essential. Early organism identification permits targeted treatment and good initial clinical outcomes; however, mortality is 50% in this cohort at a mean of 4.2 years (2 to 6) after diagnosis. Cite this article: Bone Jt Open 2024;5(5):435–443

Aims. 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. Methods. Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication. Results. A total of 32 cases of IPOS with a mean patient age of 68.7 years (37.6 to 84.1) were included. Diabetes, age > 60 years, and history of infection were identified as risk factors. Patient presentation upon admission included a mean body temperature of 36.7°C (36.1 to 38.0), back pain at rest (mean visual analogue scale (VAS) mean 5/10) and when mobile (mean VAS 6/10), as well as elevated levels of CRP (mean 76.8 mg/l (0.4 to 202.9)) and white blood cell count (mean 9.2 units/nl (2.6 to 32.8)). Pathogens were identified by CT-guided or conventional biopsy, intraoperative tissue sampling, or sonication, and Gram-positive cocci presented as the most common among them. Antibiotic therapy was established in all cases with pathogen-specific treatment in 23 (71.9%) subjects. Overall 27 (84.4%) patients received treatment by debridement, decompression, and fusion of the affected segment. Conclusion. Cases of IPOS are rare and share similarities with spontaneous spondylodiscitis. While procedures such as CT-guided biopsy and sonication are valuable tools in the diagnosis of IPOS, MRI and intraoperative tissue sampling remain the gold standard. Research on known principles of PJI such as implant retention versus implant exchange need to be expanded to the field of spine surgery. Cite this article: Bone Jt Open 2023;4(11):832–838

Endoscopic spine surgery is a promising and minimally invasive technique for the treatment of disc herniation and spinal stenosis. However, the literature on the outcome of interlaminar endoscopic decompression (IED) versus conventional microsurgical technique (CMT) in patients with lumbar spinal stenosis is scarce. We analyzed 88 patients (IED: 36/88, 40.9%; CMT: 52/88, 59.1%) presenting with lumbar central spinal stenosis between 2018–2020. Surgery-related (operation time, complications, time to hospital release (THR), ASA score, C-reactive protein (CRP), white blood cell count (WBC), side (unilateral/bilateral), patient-reported (ODI, NRS (leg-, back pain), eQ5D, COMI), and radiological (preoperative dural sack cross-sectional area (DSCA), Shizas score (SC), left (LRH) and right (RRH) lateral recess heights, left (LFA) and right (RFA) facet angle) parameters were extracted. Complication (most often re-stenosis due to hematoma and/or residual sensorimotor deficits) rates were higher in the endoscopic (38.9%) than microsurgical (13.5%) treatment group (p<0.01). Age, THR, SC, CRP, and DSCA revealed significant correlations with 3 weeks and 1 year postoperatively evaluated ODI, COMI, eQ5D, NRS leg, or NRS back values in our cohort. We did not observe significant differences in the endoscopic versus microsurgical group for the patient-reported outcomes. Age, THR, SC, CRP, and DSCA revealed significant correlations with patient-centered outcomes and should be considered in future studies. Endoscopic treatment of lumbar spinal stenosis was similarly successful as the conventional microsurgical approach, although it was associated with higher complication rates in our single-center study experience. This was probably because of the surgeons' lack of experience with this method and the resulting different learning curve compared with the conventional technique

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth. We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion. The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection

We report a series of 15 children, six male and nine female, of average age 20 months, seen at a paediatric orthopaedic clinic with torticollis. Orthopaedic examination revealed a normal range of neck movement in all cases but in seven there was palpable tightness in the absence of true shortening or contracture of the sternomastoid muscle.

The patients were prospectively referred for ocular examination. In five of the 15 an ocular cause for the torticollis was detected with underaction of the superior oblique muscle in three, paresis of the lateral rectus muscle in one and nystagmus in one. Another two patients were found to have an abnormal ocular examination which was thought to be unrelated to their torticollis. Three of the patients with ocular torticollis required extra-ocular muscle surgery to abolish the head tilt and one of these had a tight sternomastoid muscle. Two of the non-ocular group had surgical release of the sternomastoid muscle; in the rest, the condition either resolved with physiotherapy or required no active treatment.

We recommend that all patients with torticollis and no clear orthopaedic cause are referred for ocular assessment since it is not possible clinically to distinguish ocular from non-ocular causes.

Background. About 85% of the patients with low back pain seeking medical care have nonspecific low back pain (NsLBP), implying that no definitive cause can be identified. Many pain conditions are linked with elevated serum levels of (pro-)inflammatory biomarkers. Purpose. To unravel the etiology and get better insight in the prognosis of NsLBP, the aim of this study was to assess the association between (pro-)inflammatory biomarkers and the presence and severity of NsLBP. Methods. A systematic literature search was made in Embase, Medline, Cinahl, Web-of-science, and Google scholar up to January 19th 2017. Included were studies reporting on patients >18 years with NsLBP, in which one or more pro-inflammatory biomarkers were measured in blood plasma. The methodological quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS). A best-evidence synthesis was used to summarize the results from the individual studies. Results. Included were 10 studies which assessed 4 different (pro-)inflammatory biomarkers. For the association between the presence of NsLBP and C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α limited, conflicting and moderate evidence, respectively, was found. For the association between the severity of NsLBP and CRP and IL-6, moderate evidence was found. For the association between the severity of NsLBP and TNF-α and RANTES conflicting and limited evidence, respectively, was found. Conclusions. This study found moderate evidence for i) a positive association between the (pro-)inflammatory biomarkers CRP and IL-6 and the severity of NsLBP, and ii) a positive association between TNF-α and the presence of NsLBP. No conflicts of interest. No funding obtained

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

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The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).

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The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

Spinal disc infection is associated with a significant morbidity and mortality in the acute setting. On long term review it leads to significant moribidity due to the deformity and secondary osteoarthritic changes in the surrounding vertebral segments. Prospective collection of data of 21 patients suffering from discitis was collected over the span of last 10 years. The age group ranged between 21 -67 yrs. The male: female ratio was 1.2:1. The minimum delay in presentation since the onset of symptoms was 8 weeks. The detection of the micro-organism was either by needle/open biopsy or indirectly via blood cultures. Serial records were maintained of inflammatory markers. All patients received plain radiographs, gadolinium-enhanced magnetic resonance imaging scans, and bone/gallium radionuclide studies. Operative decompression was performed in 7 patients. Infection elsewhere was the most common predisposing factor. Leukocyte counts were elevated in 54% of spondylodiscitis cases. The erythrocyte sedimentation rate and CRP were elevated in all cases of epidural abscess. The most common organism was Staph Aureus. Antibiotics were administered for duration of at least 6 weeks. On long term, all patients developed deformity at the level of the infection, with half of them being symptomatic. Spinal infections are extremely morbid conditions demanding prompt diagnosis and urgent treatment to prevent complications. Ethics approval: Audit Committee Interest statement: No conflict of interest

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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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Spinal tuberculosis (TB) remains an important concern. Although spinal TB often has sequelae such as myelopathy after treatment, the predictive factors affecting such unfavourable outcomes are not yet established. We investigated the clinical manifestations and predictors of unfavourable treatment outcomes in patients with spinal TB.

We measured the serum concentration of C-reactive protein (CRP) by a high-sensitive method in patients with lumbar disc herniation. There were 48 patients in the study group and 53 normal controls. The level and type of herniation were evaluated. The clinical data including the neurological findings, the angle of straight leg raising and post-operative recovery as measured by the Japanese Orthopaedic Association (JOA) score, were recorded. The high-sensitive CRP (hs-CRP) was measured by an ultrasensitive latex-enhanced immunoassay. The mean hs-CRP concentration was 0.056 ± 0.076 mg/dl in the patient group and 0.017 ± 0.021 mg/dl in the control group. The difference was statistically significant (p = 0.006). There was no other correlation between the hs-CRP concentration and the level and type of herniation, or the pre-operative clinical data. A positive correlation was found between the concentration of hs-CRP before operation and the JOA score after. Those with a higher concentration of hs-CRP before operation showed a poorer recovery after. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to impingement of the nerve root caused by disc herniation and might be a predictor of recovery after operation

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

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During revision procedures for aseptic reasons, there remains a suspicion that failure may have been the result of an undetected subclinical infection. However, there is little evidence available in the literature about unexpected positive results in presumed aseptic revision spine surgery. The aims of our study were to estimate the prevalence of unexpected positive culture using sonication and to evaluate clinical characteristics of these patients.

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The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation.