Aims. 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). Methods. We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH. Cite this article: Bone Joint J 2023;105-B(6):679–687

Multiple thoracic disc herniations are rare and there are few reports in the literature. Between December 1998 and July 2002, we operated on 12 patients with multiple thoracic disc herniations. All underwent an anterior decompression and fusion through a transthoracic approach. The clinical outcomes were assessed using the Frankel neurological classification and the Japanese Orthopaedic Association (JOA) score. Under the Frankel classification, two patients improved by two grades (C to E), one patient improved by one grade (C to D), while nine patients who had been classified as grade D did not change. The JOA scores improved significantly after surgery with a mean recovery rate of 44.8% ± 24.5%. Overall, clinical outcomes were excellent in two patients, good in two, fair in six and unchanged in two. Our results indicate that anterior decompression and fusion for multiple thoracic disc herniations through a transthoracic approach can provide satisfactory results

Purpose of the study. We report septic shock as postoperative complication following an instrumented posterior spinal arthrodesis on a patient with multiple body piercings. The management of this potentially catastrophic complication and outcome of treatment is been discussed. Summary of Background Data. Body piercing has become increasingly more common due to change in culture or as a fashion statement. This has been associated with local or generalized ill effects including tissue injury, skin and systemic infections, and septic shock. There is no clear guideline pathway regarding removal and reinsertion of body piercings in patients who undergo major surgery. Complications following Orthopaedic or Spinal procedures associated with body piercing have not been reported. Methods. We reviewed the medical notes and radiographs of an adolescent patient with severe Scheuermann's kyphosis and multiple body piercings who underwent an uneventful posterior spinal arthrodesis with pedicle hook/screw/rod instrumentation and autologous iliac crest bone graft and developed septic shock. Results. Septic shock developed on postoperative day 2 after reinsertion of all piercings following patient's request. The patient became systemically very unwell and required intensive medical management, as well as a total course of antibiotics of 3 months. The piercings remained in situ. She did not develop a wound infection despite the presence of bacteraemia (coagulase-negative Staphylococci/Streptococci warneri) and spinal instrumentation. The patient had no new piercings subsequent to her deformity procedure. Two and a half years after spinal surgery she reported no medical problems, had a balanced spine with no loss of kyphosis correction and no evidence of nonunion or recurrence of deformity. Conclusion. The development of septic shock as a result of piercing reinsertion in the postoperative period has not been previously reported. This is an important consideration to prevent potentially life-threatening complications following major spinal surgery. Despite the wide array of complications associated to body art there are no clear guidelines for body piercing. There is growing public awareness and several countries are laying regulations which have not yet been internationally standardized. A clear practice guideline in the perioperative management of piercings is needed as the incidence of body piercing and associated complications is rising. There is need for surgeons to be aware of the hazards of body piercing and its implications. We propose that multiple piercings should not be reinserted after major surgery and appropriate counseling should be provided to the patients as part of the consent process

Introduction. Multiple studies have identified Cutibacterium acnes (C.acnes) and other microbes in intervertebral disc tissue using 16S DNA Sequencing and microbial cultures. However, it remains unclear whether these bacteria are native to the discs or result from perioperative contamination. Our study aimed to detect Gram-positive bacteria in non-herniated human disc samples and explore correlations with Toll-like receptors (TLR) 2, TLR4, NLRP3, and Gasdermin D. Methods. Immunohistochemical staining was conducted on 75 human IVD samples for Gram-positive bacteria, S. aureus, C.acnes, TLR2, TLR4, NLRP3, and Gasdermin D. Cell detection and classification were performed using QuPath. NP cells were treated with Lipopolysaccharide (LPS) and Peptidoglycan (PGN) in monolayer and alginate beads for up to 72 hours, followed by secretome analysis using Luminex. Statistical analysis included Kruskal-Wallis, Dunn's multiple comparison test, and Pearson correlation. Results. Immunohistochemical staining revealed Gram-positive bacteria exclusively within cells, with C. acnes positivity ranging from 5–99% and correlating with patient age (r=0.41, p= 0.007). TLR2 positivity ranged from 5–99% and TLR4 from 3–72%, showing a strong correlation (r= 0.62, p= 1.5e-006). Females with mid-degenerative grades exhibited significantly decreased TLR2 expression compared to those without degeneration signs. Treatment with LPS and PGN increased catabolic cyto- and chemokines associated with IVD degeneration. Conclusion. In conclusion, this study confirms Gram-positive bacteria presence in non-herniated human disc samples and highlights their role in triggering a catabolic response in disc cells. No conflicts of interest.  . Sources of funding. This project is part of the Disc4All Training network to advance integrated computational simulations in translational medicine, applies to intervertebral disc degeneration and funded by Horizon 2020 (H2020-MSCA-ITN-ETN-2020 GA: 955735)

Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods. The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results. A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion. The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535

Purpose and Background. Guidelines recommend biopsychosocial care for chronic, complex musculoskeletal conditions, including non-specific low back pain. The aims were: 1/ to assess how patients with low back pain respond to osteopathic treatment, both before and after an osteopath has completed a Biopsychosocial Pain Management (BPM) course; and 2/ to assess if it is feasible and acceptable for osteopath participants to receive weekly SCED data and use it to guide patient management. Methods and Results. A multiple baseline single case experimental design trial (. clinicaltrials.gov. , on 18/10/2021, ID number NCT05120921) with 11 UK osteopaths was conducted. Patients were randomised to early, middle or late treatment start dates. Statistical analysis assessed the change between baseline, intervention and follow-up periods. Primary outcomes were the Numeric Pain Rating (NPR) and Patient Specific Function Scales (PSFS), measured during the baseline, the 6-week intervention, and during a 12-week follow-up period. At baseline, the osteopaths reported stronger biopsychosocial attitudes to pain, compared to biomedical beliefs (PABS: 34 behavioural scale; 29 biomedical scale). Overall, patient participants showed daily increases in symptoms during the pre-treatment phase (+0.24/day, p<0.001), and daily decreases during treatment (−2.94 over the treatment phase, p<0.001), which continued post-treatment (−3.36 over 12 weeks, p=0.04). Similar improvements were observed for function. Conclusion. Osteopathic care was shown to help patients with persistent low back pain. Patient recruitment was challenging because of the randomisation. With further development, the method shows feasibility as a means of enhancing research activity among practising clinicians. Previous presentations or publications of the work. The protocol was published (. https://doi.org/10.1016/j.ijosm.2023.100660. ) and presented at SBPR in 2022. The results were presented to an osteopathic conference in October 2023. Ethics approval was received from the University College of Osteopathy Research Ethics Committee. Conflicts of interests. Jerry Draper-Rodi receives fees from the sales of the e-learning course on the biopsychosocial management on the UCO CPD platform. Sources of funding. The research was funded by the Osteopathic Foundation

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

Background. Osteopathy has been shown to be effective in the management of chronic low back pain. Guidelines recommend biopsychosocial care for chronic, complex musculoskeletal conditions, including non-specific low back pain but there is a lack of evidence comparing standard osteopathic care, which has traditionally been based on dated and disputed biomechanical theories of dysfunction, with more contemporary biopsychosocial approaches. Methods and results. A multiple baseline single case experimental design trial with 11 UK osteopaths and 60 patients is currently assessing effectiveness of osteopathic treatment for patients with non-specific low back pain of more than 12 weeks’ duration. Patients are randomised to early, middle, or late treatment start dates to increase the validity of inferences about the effects of treatment. Osteopaths have participated in one course on the study protocol and processes pre-participation and will take an e-learning course on the biopsychosocial management of patients with low back pain after the first patient recruitment stage. Statistical analysis will assess the degree and rate of change between baseline, intervention and follow-up periods, and whether differences in effect are observed after the osteopaths have completed the biopsychosocial patient management training course. Primary outcomes will be the Numeric Pain Rating and Patient Specific Function Scales, measured daily at baseline and for 6 weeks during the intervention stage, and weekly or fortnightly during a 12-week follow-up period. Conclusion. This experimental design will offer osteopaths in practice the opportunity to engage in research evaluating the effectiveness of osteopathic care and the influence of a training programme to augment biopsychosocial osteopathic care. Study registration: . https://clinicaltrials.gov/ct2/show/NCT05120921. Sources of funding: The Osteopathic Foundation. Conflict of interest: The authors declare no competing interests. Previous publication of work: This protocol is under review with a peer-reviewed journal

Purposes and background. Low back pain (LBP) is a common condition with substantial associated disability and costs, best understood using a biopsychosocial approach. Research demonstrates LBP beliefs are important, with biomedical beliefs influencing practitioner's management. LBP beliefs can be inconsistent amongst medical students. The aim of this study was to investigate graduate medical student's beliefs of LBP and what influences them. Method and results. A cross sectional study of phase one and phase three students at the University of Warwick was conducted. Participants were recruited via voluntary response sampling. A survey investigated LBP beliefs, utilising the Back Beliefs Questionnaire (BBQ) and Health Care Providers’ Pain and Impairment Relationship Scale (HC-PAIRS). Qualitative data was collected on what influences beliefs about the causes and management of LBP, which was analysed descriptively using thematic analysis. Fifty-seven students completed the questionnaire. Median BBQ and HC-PAIRS scores were consistent between both year groups. Three main themes emerged from the qualitative data: Sources of influence, influence of personal experience and influence of medical education. Participants discussed single or multiple sources influencing their beliefs. Another main theme was the influence of experiencing LBP personally or through discussions with others. The final main theme described the influence of medical education. Conclusions. Students in this sample tended to have positive beliefs about the outcome of LBP and functional expectations of chronic LBP patients. The mean BBQ and HC-PAIRS scores are comparable to studies of medical students. The findings from qualitative data suggest how medical students form beliefs about the causes and management of LBP is complex. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained. This work has not been previously published or presented at any national or international meeting

Introduction. Nucleus replacement surgery has the potential to be an early treatment option for chronic lower back pain. The surgery involves removal (nuclectomy) and replacement of the native degenerated nucleus with a material designed to restore the disc's physiological properties. Multiple techniques have been considered to perform a nuclectomy, however the advantages and disadvantages of each are not well understood. The aim of this study was to quantitatively compare three nuclectomy techniques: automated-shaver, rongeurs, and laser. Methods and results. Fifteen human vertebra-disc-vertebra lumbar specimens were split into three groups. Before and after nuclectomy axial mechanical tests were performed and T2-weighted 9.4T MRIs were acquired for each specimen. Using the automated-shaver and rongeur similar volumes of disc material were removed (2.51±1.10% and 2.76±1.39% of the total disc volume, respectively), whilst considerably less material was removed when using the laser (0.12±0.07%). Using the automated-shaver and rongeur significantly reduced the toe-region stiffness, while the linear region stiffness was significantly reduced only in the rongeur group. From the MRIs, more homogeneous cavities were seen in the center of the disc when using the automated shaver compared to rongeur, whilst laser ablation resulted in small, localized cavities. Conclusion. Results suggest that the current laser parameters are not suitable for removal of large volumes of material unless the technique is optimised for this application. Both rongeurs and automated-shavers can be used to remove large volumes of material but the reduced risk of collateral damage to surrounding tissues suggests that an automated-shaver may be more suitable. Conflicts of interest: No conflicts of interest. Sources of funding: Part of this work was funded by an Imperial College Research Fellowship for NN and an EPSRC DTP CASE Conversion Studentship for TR (EP/R513052/1)

A previously fit and well 58 year old male suffered from a bilateral psoas haematoma (PH) following 52 days of veno-venous extracorporeal membranous oxygenation (VV-ECMO) for severe Coronavirus disease (COVID-19), refractory to all non-invasive and medical therapies. He developed multiple complications, including inability to walk or weight-bear, due to lumbar plexopathy triggered by bilateral PH compression, compounded by COVID-19-related mononeuritis multiplex. The patient was referred to our institution with a known diagnosis of bilateral PH and after spinal multidisciplinary team (MDT) input, was deemed not for surgical or interventional radiology treatments. The patient received extensive neurorehabilitation, coordinated by multiple MDTs. Although PH has been correlated to COVID-19, to the best of our knowledge this is the first reported case of such a complex presentation resulting in a dramatic bilateral PH. Health records from 3 large UK teaching hospitals were collected regarding treatment and follow up appointments, following patient's written informed consent. Patient's comorbidities, duration in hospital units, MDT inputs, health assessments, mobilisation progress and neurologic assessments, were all recorded. Data was collected retrospectively then prospectively due to lengthy in-patient stay. The literature review was conducted via PubMed and open access sources, selecting all the relevant studies and the ECMO guidelines. Patient received treatment from 3 different units in 3 hospitals over 212 days including 103 days in neurorehabilitation. Involvement of physiotherapy, dietitians, speech and language teams, neurologist, neurophysiotherapists, occupational therapists was required. The patient progressed from a bed-bound coma and inability to walk, to standing with lower limb backslab at discharge. Additionally, he was referred for elective exploratory surgery of the psoas region for scar debridement and potential nerve graft repair of the lumbosacral plexus. The surgery outcome is cautiously optimistic, with some improvement in nerve conduction studies, however is currently unknown regarding recovery progress and return to premorbid functional baseline. The novelty of this presentation yields significant learning points regarding early recognition of PH, requirements for vast MDT input and specialist use of VV-ECMO in severe COVID-19 patients. It also highlights the broad pathophysiology of SARS-CoV-2 causing neuropathy and coagulopathy; understanding this will optimise robust anticoagulation guidelines, required in VV-ECMO

Introduction. Degenerative spondylosis (DS) represents a challenging condition to diagnose and treat. There are multiple modalities to investigate DS including X-ray, MRI and CT, but symptoms may not be equivocal to DS to support the clinical findings. The investigation of metastases commonly utilises SPECT/CT for identification of areas of increased osteoblastic activity to denote disease. The aim of the study was to analyse the prevalence of asymptomatic DS in a consecutive hospital cohort of oncology patients who had SPECT/CT for investigation of metastases. Methods. Oncology patients who underwent SPECT/CT at St. George's Hospital were analysed between 2015–2019. Exclusion criteria: back pain, inflammatory disorders, metastases, trauma, infection. Radiology reports were examined for DS and anatomical distribution of tracer uptake. Results. A total of 1182 patients had a Whole-Body SPECT CT used for the spinal analysis. After exclusions (age >80 [n=260], non-cancer [n=318], back pain [n=72]), 522 reports with cancer were utilised. Mean age was 65 (4–80). Age and distribution of DS are given in the table. Conclusion. The prevalence of radiological asymptomatic DS is prevalent in large proportions of patients without back pain, and its incidence increases with age. Approximately 60% of 60 year old and 70% of 70 years old patients have asymptomatic DS in the lumbosarcal region. We conclude that SPECT/CT will detect radiographic degenerative spondylosis in an asymptomatic hospital cohort and this prevalence increase with age. Therefore, this modality of imaging must be utilised with caution when investigating potential pain generators. For any figures or tables, please contact the authors directly

Aims. Magnetically controlled growing rods (MCGR) have been gaining popularity in the management of early-onset scoliosis (EOS) over the past decade. We present our experience with the first 44 MCGR consecutive cases treated at our institution. Methods. This is a retrospective review of consecutive cases of MCGR performed in our institution between 2012 and 2018. This cohort consisted of 44 children (25 females and 19 males), with a mean age of 7.9 years (3.7 to 13.6). There were 41 primary cases and three revisions from other rod systems. The majority (38 children) had dual rods. The group represents a mixed aetiology including idiopathic (20), neuromuscular (13), syndromic (9), and congenital (2). The mean follow-up was 4.1 years, with a minimum of two years. Nine children graduated to definitive fusion. We evaluated radiological parameters of deformity correction (Cobb angle), and spinal growth (T1-T12 and T1-S1 heights), as well as complications during the course of treatment. Results. The mean Cobb angles pre-operatively, postoperatively, and at last follow-up were 70° (53 to 103), 35° (15 to 71) and 39° (15 to 65) respectively (p < 0.001). Further, there was a mean of 14° (-6 to 27) of additional Cobb angle correction upon graduation from MCGR to definitive fusion. Both T1-T12 and T1-S1 showed significant increase in heights of 27 mm and 45 mm respectively at last follow-up (p < 0.001). Ten children (23%) developed 18 complications requiring 21 unplanned operations. Independent risk factors for developing a complication were single rod constructs and previous revision surgery. Conclusion. MCGR has the benefit of avoiding multiple surgeries, and is an effective tool in treatment of early-onset scoliosis. It also maintains the flexibility of the spine, allowing further correction at the time of definitive fusion. Cite this article: Bone Joint Open 2020;1-7:405–414

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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.

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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.

Aims. The timing of surgical fixation in spinal fractures is a contentious topic. Existing literature suggests that early stabilization leads to reduced morbidity, improved neurological outcomes, and shorter hospital stay. However, the quality of evidence is low and equivocal with regard to the safety of early fixation in the severely injured patient. This paper compares complication profiles between spinal fractures treated with early fixation and those treated with late fixation. Methods. All patients transferred to a national tertiary spinal referral centre for primary surgical fixation of unstable spinal injuries without preoperative neurological deficit between 1 July 2016 and 20 October 2017 were eligible for inclusion. Data were collected retrospectively. Patients were divided into early and late cohorts based on timing from initial trauma to first spinal operation. Early fixation was defined as within 72 hours, and late fixation beyond 72 hours. Results. In total, 86 patients underwent spinal surgery in this period. Age ranged from 16 to 88 years. Mean Injury Severity Score (ISS) was higher in the early stabilization cohort (p = 0.020). Age was the sole significant independent variable in predicting morbidity on multiple regression analysis (p < 0.003). There was no significant difference in complication rates based on timing of surgical stabilization (p = 0.398) or ISS (p = 0.482). Conclusion. Our results suggest that these patients are suitable for early appropriate care with spinal precautions and delayed definitive surgical stabilization. Earlier surgery conferred no morbidity benefit and had no impact on length of stay. Cite this article: Bone Joint J 2020;102-B(5):627–631

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The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI).

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The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

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We compared decompression alone to decompression with fusion surgery for lumbar spinal stenosis, with or without degenerative spondylolisthesis (DS). The aim was to evaluate if five-year outcomes differed between the groups. The two-year results from the same trial revealed no differences.

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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.