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. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion. This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396

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. 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. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90

Aims. 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. Methods. A total of 39 patients diagnosed with AL who underwent surgery from January 2004 to December 2022 were retrospectively screened for eligibility. Patients with AL were divided into an MIS group and an OSF group. The primary outcomes were union of the lesion on radiograph and CT, as well as the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores immediately after surgery, and at the follow-up (mean 29 months (standard error (SE) 9)). The secondary outcomes were total blood loss during surgery, operating time, and improvement in the radiological parameters: global and local kyphosis, sagittal vertical axis, sagittal alignment, and chin-brow vertical angle immediately after surgery and at the follow-up. Results. Data for 30 patients with AL were evaluated: 14 in the MIS group and 16 in the OSF group. All patients were followed up after surgery; no nonunion complications or instrumentation failures were observed in either group. No significant differences in the VAS and ODI scores were identified between the two groups. Mean ODI improved from 51 (SE 5) to 17 (SE 5) in the MIS group and from 52 (SE 6) to 19 (SE 5) in the OSF group at the follow-up. There were significant improvements in total blood loss (p = 0.025) and operating time (p < 0.001) between the groups. There was also no significant difference in local kyphosis six months postoperatively (p = 0.119). Conclusion. Early MIS is an effective treatment for AL. MIS provides comparable clinical outcomes to those treated with OSF, with less total blood loss and shorter operating time. Our results support and identify the feasibility of solid immobilization achieved by posterior instrumentation without bone graft via MIS for the treatment of AL. Cite this article: Bone Jt Open 2024;5(10):886–893

Aims. Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre. Methods. Included in this retrospective cohort study were 48 patients (12 females; mean age 55.79 years (SD 8.94)) who were diagnosed with cervical OPLL, received treatment in our centre, and were followed up for 10.22 to 15.25 years. Of them, 24 patients (six females; mean age 52.88 years (SD 8.79)) received ADF, and the other 24 patients (five females; mean age 56.25 years (SD 9.44)) received PLF. Clinical data including age, sex, and the OPLL canal-occupying ratio were analyzed and compared. The primary outcome was Japanese Orthopaedic Association (JOA) score, and the secondary outcome was visual analogue scale neck pain. Results. Compared with the baseline, neurological function improved significantly after surgery in all patients of both groups (p < 0.001). The JOA recovery rate in the ADF group was significantly higher than that in the PLF group (p < 0.001). There was no significant difference in postoperative cervical pain between the two groups (p = 0.387). The operating time was longer and intraoperative blood loss was greater in the PLF group than the ADF group. More complications were observed in the ADF group than in the PLF group, although the difference was not statistically significant. Conclusion. Long-term neurological function improved significantly after surgery in both groups, with the improvement more pronounced in the ADF group. There was no significant difference in postoperative neck pain between the two groups. The operating time was shorter and intraoperative blood loss was lower in the ADF group; however, the incidence of perioperative complications was higher. Cite this article: Bone Jt Open 2024;5(9):768–775

Aims. Frailty has been gathering attention as a factor to predict surgical outcomes. However, the association of frailty with postoperative complications remains controversial in spinal metastases surgery. We therefore designed a prospective study to elucidate risk factors for postoperative complications with a focus on frailty. Methods. We prospectively analyzed 241 patients with spinal metastasis who underwent palliative surgery from June 2015 to December 2021. Postoperative complications were assessed by the Clavien-Dindo classification; scores of ≥ Grade II were defined as complications. Data were collected regarding demographics (age, sex, BMI, and primary cancer) and preoperative clinical factors (new Katagiri score, Frankel grade, performance status, radiotherapy, chemotherapy, spinal instability neoplastic score, modified Frailty Index-11 (mFI), diabetes, and serum albumin levels). Univariate and multivariate analyses were developed to identify risk factors for postoperative complications (p < 0.05). Results. Overall, 57 postoperative complications occurred in 47 of 241 (19.5%) patients. The most common complications were wound infection/dehiscence, urinary tract infection, and pneumonia. Univariate analysis identified preoperative radiotherapy (p = 0.028), mFI (p < 0.001), blood loss ≥ 500 ml (p = 0.016), and preoperative molecular targeted drugs (p = 0.030) as potential risk factors. From the receiver operating characteristic curve, the clinically optimal cut-off value of mFI was 0.27 (sensitivity, 46.8%; specificity, 79.9%). Multivariate analysis identified mFI ≥ 0.27 (odds ratio (OR) 2.94 (95% CI 1.44 to 5.98); p = 0.003) and preoperative radiotherapy (OR 2.11 (95% CI 1.00 to 4.46); p = 0.049) as significant risk factors. In particular, urinary tract infection (p = 0.012) and pneumonia (p = 0.037) were associated with mFI ≥ 0.27. Furthermore, the severity of postoperative complications was positively correlated with mFI (p < 0.001). Conclusion. The mFI is a useful tool to predict the incidence and the severity of postoperative complications in spinal metastases surgery. Cite this article: Bone Joint J 2024;106-B(12):1469–1476

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

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To report the development of the technique for minimally invasive lumbar decompression using robotic-assisted navigation.

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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.

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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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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

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The aims of this study were first, to determine if adding fusion to a decompression of the lumbar spine for spinal stenosis decreases the rate of radiological restenosis and/or proximal adjacent level stenosis two years after surgery, and second, to evaluate the change in vertebral slip two years after surgery with and without fusion.

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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Psychoeducative prehabilitation to optimize surgical outcomes is relatively novel in spinal fusion surgery and, like most rehabilitation treatments, they are rarely well specified. Spinal fusion patients experience anxieties perioperatively about pain and immobility, which might prolong hospital length of stay (LOS). The aim of this prospective cohort study was to determine if a Preoperative Spinal Education (POSE) programme, specified using the Rehabilitation Treatment Specification System (RTSS) and designed to normalize expectations and reduce anxieties, was safe and reduced LOS.

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With resumption of elective spine surgery services in the UK following the first wave of the COVID-19 pandemic, we conducted a multicentre British Association of Spine Surgeons (BASS) collaborative study to examine the complications and deaths due to COVID-19 at the recovery phase of the pandemic. The aim was to analyze the safety of elective spinal surgery during the pandemic.

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With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values.

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Spinal fusion remains the gold standard in the treatment of idiopathic scoliosis. However, anterior vertebral body tethering (AVBT) is gaining widespread interest, despite the limited data on its efficacy. The aim of our study was to determine the clinical efficacy of AVBT in skeletally immature patients with idiopathic scoliosis.

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The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease.

Objectives

Pedicle-lengthening osteotomy is a novel surgery for lumbar spinal stenosis (LSS), which achieves substantial enlargement of the spinal canal by expansion of the bilateral pedicle osteotomy sites. Few studies have evaluated the impact of this new surgery on spinal canal volume (SCV) and neural foramen dimension (NFD) in three different types of LSS patients.