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Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 1 - 1
1 Oct 2022
Paskins Z Le Maitre C Farmer C Clark E Mason D Wilkinson C Andersson D Bishop F Brown C Clark A Jones R Loughlin J McCarron M Pandit H Richardson S Salt E Taylor E Troeberg L Wilcox R Barlow T Peat G Watt F
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Background. Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. The Musculoskeletal (MSK) Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across MSK disorders. Methods. The Child Health and Nutrition Research Initiative (CHRNI) method of setting research priorities with a range of stakeholders were utilised. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, the research priority exercise involved four stages and two surveys, to: 1) gather research uncertainties; 2) consolidate these; 3) score uncertainties using agreed criteria of importance and impact on a score of 1–10; and 4) analyse scoring, for prioritisation. Results. The first survey had 209 respondents, who described 1290 research uncertainties, which were refined into 68 research questions. 285 people responded to the second survey. The largest group of respondents represented patients and carers, followed by researchers and healthcare professionals. A ranked list was produced, with scores ranging between 12 and 18. Key priorities included developing and testing new treatments, better targeting of treatments, early diagnosis, prevention and better understanding and management of pain, with an emphasis on understanding underpinning mechanisms. Conclusions. For the first time, we have summarised priorities for research across MSKD, from discovery science to applied clinical and health research, including translation. We present a call to action to researchers and funders to target these priorities. Conflict of Interest: None. Sources of funding: We thank the funder, Versus Arthritis for their support of the research advisory groups and this activity


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

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


Bone & Joint Open
Vol. 5, Issue 5 | Pages 435 - 443
23 May 2024
Tadross D McGrory C Greig J Townsend R Chiverton N Highland A Breakwell L Cole AA

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


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 34 - 34
1 Oct 2019
Wood L Foster N Lewis M Bishop A
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Background and Aim of Study. Despite several hundred RCTs of exercise for persistent non-specific low back pain (NSLBP), the treatment targets of exercise are unclear. In a systematic review we observed 30 direct and indirect treatment targets of exercise described across 23 RCTs for persistent NSLBP. Since not all treatment targets and outcomes can be assessed in all RCTs, it is therefore important to prioritise these treatment targets through consensus from key stakeholders. These consensus workshops aimed to agree treatment targets for the use of exercise interventions in randomised controlled trials (RCTs) in persistent NSLBP using nominal group workshop (NGW) methodology. Methods and Results. The first UK workshop included people who had experience of exercise to manage their persistent NSLBP, clinicians who prescribe exercise for persistent NSLBP, and researchers who design exercise interventions tested in RCTs. The second workshop included participants attending an international back and neck pain research workshop. Twelve participants took part in the UK NGW and fifteen took part in the final ranking of the exercise treatment targets. In addition to the original list of 30 treatment targets, a further 26 ideas were generated. After grouping and voting, 18 treatment targets were prioritised. The top five ranked targets of exercise interventions for persistent NSLBP were: pain reduction, improvement in function, reduction of fear of movement, encouragement of normal movement and improvement of mobility. The results of the international NGW will also be presented. Conclusion. Future RCTs of exercise should consider more consistent assessment of these treatment targets. Sources of Funding: This PhD is funded by the Research Institute for Primary Care and Health Sciences, Keele University. Prof NE Foster is a UK National Institute for Health Research Senior Investigator, and was supported by a UK National Institute for Health Research Professorship (NIHR-RP-011-015). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Conflicts of Interest: No conflicts of interest


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 12 - 12
1 Sep 2019
Wood L Foster N Lewis M Bishop A
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Background. Exercise is a complex intervention, and often has more than one treatment target. Results from randomised controlled trials (RCTs) of exercise interventions for chronic low back pain (CLBP) typically show small to moderate effect sizes, but these may differ where outcomes better reflect the targets of interventions. This review aimed to describe what treatment targets, outcome domains and primary outcome measures are used in exercise RCTs, and examined how well the selected outcome domains match the treatment targets used in each RCT. Methods and Results. A computer-aided literature search was performed in eight databases, from inception to August 2018. Inclusion criteria: RCTs in CLBP, exercise compared to a non-exercise arm, sample size >60 per arm. Title and abstract review, subsequent full text review, data extraction and risk of bias assessment were independently undertaken by pairs of reviewers. Of 18251 initially identified titles and abstracts, 23 trials were included in the review. 30 treatment targets were extracted, and 6 primary outcome domains identified. A logic model of the treatment targets and outcomes demonstrated diverse relationships. Only 5 RCTs matched their primary outcome domain to the identified treatment targets, 12 used primary outcomes that did not match the reported treatment targets, and 6 were partially matched. Conclusion. The majority of included trials did not match the primary outcome domain to the treatment targets of the exercise intervention. Further research will explore if better matching between treatment targets and outcomes may change the conclusions of exercise trials in CLBP. No conflicts of interest. Sources of Funding: This PhD is funded by the Research Institute for Primary Care and Health Sciences, Keele University. Prof NE Foster is a UK National Institute for Health Research Senior Investigator, and was supported by a UK National Institute for Health Research Professorship (NIHR-RP-011-015). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 28 - 28
1 Oct 2022
Newton C Singh G O'Neill S Diver C Booth V Logan P O'Sullivan K O'Sullivan P
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Purposes of the study and background. Cognitive Functional Therapy (CFT) is a complex intervention that targets the biopsychosocial nature of low back pain (LBP). The barriers and facilitators to CFT have not previously been researched in the United Kingdom National Health Service (NHS). This study aimed to explore the barriers and facilitators of CFT in the NHS ahead of a future clinical trial. Methods and results. Participants who had completed a CFT intervention for persistent LBP and physiotherapists who had previously attended a CFT training workshop were recruited. Data were collected using one to one semi-structured interviews and were analysed thematically using framework method. Eight people with LBP and ten physiotherapists consented to participate. The key findings were that UK NHS physiotherapists can be trained to deliver CFT, they valued the training and felt confident to deliver CFT successfully to patients in NHS physiotherapy departments. Peer support and mentorship from a CFT practitioner was necessary for the physiotherapists to sustain changes to their clinical practice. Participants with LBP welcomed CFT as they felt it was beneficial and enabled them to self-manage their LBP and they could recognise the difference between CFT and usual care. The barriers, mainly related to the healthcare system, included short appointment times and poor availability of follow-up appointments. Conclusion. This is the first study to establish the barriers and facilitators to the implementation of CFT in the NHS. The findings of this study were used to inform the planning, design and delivery of a feasibility randomised controlled trial. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 27 - 27
7 Aug 2024
Zhou T Salman D McGregor A
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Purpose and Background. Clinical practice guidelines (CPGs) recommend self-management for low back pain (LBP). Our recent narrative review on self-management needs revealed a consensus with respect to the critical components of self-management interventions. With mobile health advancements, apps offer innovative support for LBP management. This study aims to identify current apps for the self-management of LBP, assessing them for their quality, intervention content, theoretical approaches, and risk management approaches. Methods and Results. We identified 69 apps for LBP self-management from a systematic search in the UK iTunes and Google Play stores. The most recommended interventions are muscle stretching (n=51, 73.9%), muscle strengthening (n=42, 60.9%), and core stability exercises (n=32, 46.4%). The average MARS (SD) overall score for the included apps was 2.4 (0.44) out of a possible 5 points, with the engagement and information dimension scoring the lowest at 2.1. In terms of theoretical and risk management approaches, no apps offered a theoretical care model and all failed to specify the age group targeted; only one (1.4%) provided a tailored care approach; 18 (26.1%) included intervention progression; and 11 (15.9%) reported management safety checks. Conclusion. This study shows that app developers generally select interventions endorsed by CPGs. However, the application of a biopsychosocial care model is not being considered. Most of them are of low quality, lacking theoretical approaches to care and consideration of associated risks. It is essential to involve clinicians and patients in developing LBP self-management apps to improve the quality and related approach. Conflicts of interest. None. Sources of funding. No funding obtained. This study has been published in JMIR mHealth and uHealth


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 41 - 41
7 Aug 2024
Pavlova A Cooper K Deane J Hart-Winks E Hemming R Johnson K
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Purpose and background. Nearly 70% of UK physiotherapists experience work-related musculoskeletal disorders (WRMSDs) during their career, with a significant proportion occurring in the back and being attributed to patient handling tasks. Evidence suggests that manual handling training alone is ineffective and interventions among nurses indicate that a tailored approach, including targeted exercise (TE), can reduce WRMSD rates. This study aimed to explore physiotherapists’ perspectives of WRMSDs, patient handling, and the role of TE in reducing WRMSDs among physiotherapists. Methods and Results. Key informant interviews were conducted with 4 physiotherapy operational leads and 1 manual handling trainer from NHS Grampian. Interviews were transcribed and Framework Analysis was utilised to identify key themes, including challenges, barriers, and facilitators. Following this, two online focus groups were conducted with 7 qualified NHS physiotherapists across the UK. Views of manual handling training varied across specialities, with some finding it comprehensive and adaptable, and others finding it less applicable to patients in their speciality or community setting. Physiotherapist views on fitness for work varied, with some highlighting the necessity of TE to ensure workforce health whilst others considered exercise to be a personal matter. Facilitators to implementation identified by participants were having support from management and a strong justification for the exercise content. Varied work schedules and facilities were identified as barriers to implementation of a work-based TE intervention. Conclusion. Varying perspectives on TE interventions and barriers to implementation were identified. This work will inform future research to develop TE interventions in consultation with key stakeholders. Conflicts of Interest. No conflicts of interest. Source of Funding. NHS Endowment Research Grant 22/001


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 20 - 20
1 Oct 2022
Newton C Singh G O'Neill S Diver C Booth V Logan P O'Sullivan K O'Sullivan P
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Purposes of the study and background. Cognitive Functional Therapy (CFT) is a psychologically informed, physiotherapist-led intervention that targets the biopsychosocial complexity of persistent low back pain (LBP). CFT has demonstrated positive outcomes in two randomised controlled trials (RCT) but has not previously been evaluated in the United Kingdom National Health Service (NHS). This study aimed to determine the feasibility of completing a definitive RCT, that will evaluate the clinical and cost-effectiveness of CFT in comparison to usual physiotherapy care (UPC) for people with persistent LBP in the NHS. Methods and results. A two-arm parallel feasibility RCT compared CFT with UPC in participants with persistent LBP. Data concerning study processes, resources, management and patient reported outcome measures (disability, pain intensity, quality of life and psychosocial function) were collected at baseline, three and six-month follow-up, analysed and evaluated in order to establish feasibility. Sixty participants (n=30 CFT and n=30 UPC) were recruited with 71.6% (n=43) retained at six-month follow-up. CFT was delivered to fidelity, relevant and clinically important outcome data were rigorously collected and CFT was tolerated by participants with no safety concerns. The Roland-Morris disability questionnaire was the most suitable primary outcome measure and sample size calculations were completed for a definitive RCT. Intention to treat analysis indicated a signal of effect in favour of CFT with moderate and large between group effect sizes observed across outcome measures at six-month follow-up. Conclusion. It is feasible to conduct a randomised study of CFT in comparison to UPC for NHS patients. A future fully powered clinical and cost effectiveness RCT could be completed. Conflicts of interest: No conflicts of interest. Sources of funding: Chartered Society of Physiotherapy, Physiotherapy Research Foundation


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 12 - 12
7 Aug 2024
Jenkins AL Harvie C O'Donnell J Jenkins S
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Introduction. Lumbosacral transitional vertebrae (LSTV) are increasingly recognized as a common anatomical variant and is the most common congenital anomaly of the lumbosacral spine. Patients can have symptomatic LSTV, known as Bertolotti's Syndrome, where transitional anatomy can cause back, L5 distribution leg, hip, and groin pain. We propose an outline for diagnosis and treatment of Bertolotti's Syndrome. Methods. We retrospectively reviewed over 500 patients presenting to the primary author with low back, buttock, hip, groin and/or leg pain from April 2009 through April 2024. Patients with radiographic findings of an LSTV and clinical presentation underwent diagnostic injections to confirm diagnosis of Bertolotti's syndrome. Treatment was determined based on patient's LSTV classification. 157 patients with confirmed Bertolotti's syndrome underwent surgical treatment. Results. Over 500 patients presented with an appropriate clinical presentation and radiographic findings of an LSTV. Diagnostic injections were targeted into the transitional anatomy confirming the LSTV as the primary pain generator to make the diagnosis of Bertolotti's syndrome. The decision in the type of surgical intervention, resection or fusion, was made based on patient's LSTV anatomy. 157 patients with confirmed Bertolotti's Syndrome underwent surgical treatment (121 fusions (77%), 36 resections (23%)). The classification system and surgical outcomes, in part, have been previously published in World Neurosurgery. Conclusion. We have outlined the best practice of diagnosis and treatment selection for Bertolotti's syndrome. We have shown significant improvement in outcomes based on this method. We hope to aid in both patient education and provide an outline on how clinicians can become knowledgeable on Bertolotti's syndrome. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 20 - 20
7 Aug 2024
Snuggs J Ciccione C Vernengo A Tryfonidou M Grad S Vadala G Maitre CL
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Background. Chronic low back pain is strongly linked to degeneration of the intervertebral disc (IVD), which currently lacks any targeted treatments. This study explores NPgel, a biomaterial combined with notochordal cells (NC), developmental precursor cells, as a potential solution. NCs, known for anti-catabolic effects on IVD cells, present a promising avenue for regenerating damaged IVD tissue. Methods. Bovine IVDs underwent enzymatic degeneration before NPgel (+/- NC) injection. Degenerated bovine IVDs were cultured under biomechanical loading for 21 days. Histology and immunohistochemistry assessed NC survival, phenotype, and matrix production. Within an in vivo sheep pilot study, NPgel (+/- NC) was injected into degenerated IVDs, blood was taken, and immune cell activation was monitored via flow cytometry over three months post-injection. Results. Within the ex vivo model, IVDs injected with NPgel (+/- NC) exhibited increased matrix expression and deposition. Viable NCs were detected post-culture, indicating survival and matrix production. In the in vivo model, NPgel injection into sheep IVDs did not significantly increase activation of immune cells compared to controls, suggesting no systemic inflammatory effects. Conclusion. NPgel, combined with NCs, shows promise for IVD regeneration. Ex vivo findings indicate NPgel supports NC survival and matrix production. Moreover, in vivo results demonstrate the absence of systemic immunogenic responses post-NPgel injection. This suggests NPgel's potential as a carrier for NCs in IVD regeneration therapy. These findings underscore NPgel's candidacy for further investigation in addressing chronic low back pain associated with IVD degeneration. Subsequent research, including long-term efficacy and safety evaluations, is imperative for clinical translation. Conflicts of interest. There are no conflicts of interest. Sources of funding. iPSpine, grant # 825925, Horizon 2020


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 12 - 12
1 Oct 2022
Mandani M Reagon C Hemming R Sparkes V
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Purpose and Background. Patients’ engagement with self-management strategies (SMS) is key when managing low back pain (LBP) and relies on appropriate information being delivered by the treating Clinician. However, patients have differing coping mechanisms which may affect success with SMS. This study aimed to determine Patient and Physiotherapist's perceptions of coping responses and SMS in patients with LBP. Methods. Patient completed a Pain Coping strategies questionnaire, before and after LBP treatment. Semi-structured interviews gathered data from of 10 patients (6 males; and 6 physiotherapists. Questionnaire data was described descriptively, and qualitative data was transcribed/analysed thematically. Results. 5 patients were categorized as ‘active copers’ and 5 as ‘passive copers’ before treatment. SMS success appeared to be impacted by patient coping strategies they adopted. Spiritual religious coping strategies linked to cultural beliefs was a common strategy for all patients. However, the active copers were more likely to engage with active strategies compared to passive copers. All patients felt they had not received full education/details about the home exercises. One patient became an ‘active coper’ following treatment demonstrating high self-confidence to self-manage pain and accepted exercises as a lifestyle. Physiotherapists did not use a valid method for screening purposes for coping, although they referred to ascertaining this verbally and they did tailor exercises differently for passive and active copers. Conclusion. Screening for individual coping strategies would enhance targeting treatments and all patients would benefit from full exercise programmes for self- management and pain self-efficacy approaches to change patients ‘behaviour and enhance patients’ self-confidence. Conflicts of interest: No conflicts of interest. Sources of funding: The study is sponsored by Kuwait Government


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_8 | Pages 8 - 8
1 Aug 2022
Sharma A Grannum S de Koning R Thakar C Nnadi C
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Surgical site infections following spinal surgery profoundly influence continued treatment, significantly impacting psychological and economic dimensions and clinical outcomes. Its reported incidence varies up to 20%, with the highest incidence amongst neuromuscular scoliosis and metastatic cord compression patients. We describe the first reported biphasic osteoconductive scaffold (Cerament G) with a logarithmic elution profile as a cumulative strategic treatment modality for adjacent spinal surgery infections. All patients who developed surgical site infections following instrumented fusion (May 2021-December 2021) had their demographics (age, sex), type and number of procedures, isolated organism, antibiotics given, comorbidities, and WHO performance status analysed. The infected wound was debrided to healthy planes, samples taken, and Cerament g applied. Thirteen patients were treated for deep SSI following spinal instrumentation and fusion procedures with intraoperative Cerament G application. There were four males and nine females with an average age of 40 ranging between 12 and 87. Nine patients underwent initial surgery for spinal deformity, and four were treated for fractures as index procedure. 77% of infections were attributable to MSSA and Cutibacteriousm acnes; others included Klebsiella, Pseudomonas and Streptococcus and targeted with multimodal cumulative therapy. A WHO performance score improved in 11 patients. In addition, there was no wound leak, and infection was eradicated successfully in 12/13 with a single procedure. This series shows the successful eradication of the infection and improved functional outcomes with Cerament G. However, the low numbers of patients in our series are an essential consideration for the broader applicability of this device


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 33 - 33
1 Oct 2019
Wood L Foster N Lewis M Bronfort G Groessl E Hewitt C Miyamoto G Reme S Bishop A
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Background. Complex interventions, such as exercise for LBP, often have many treatment targets. Matching a primary outcome to the target(s) of exercise interventions may provide greater standardized mean differences (SMDs) than using an unmatched primary outcome. We aimed to explore whether the conclusions of exercise trials for LBP might differ with i) improved matching of outcomes to treatment targets and ii) the use of composite outcome measures. Methods and Results. We investigated i) matching in five trials (n=1033) that used an unmatched primary outcome but included some of their matched outcomes as secondary outcomes; ii) composite outcomes in four trials (n=864). The composite consisted of standardised averaged matched outcomes. All analyses replicated the primary outcome analysis, applied to the matched or composite outcome in each dataset. When not possible, SMDs were calculated for the primary and matched outcomes. i) Of five trials, three had greater SMDs and increased statistical significance with matched outcomes (pooled effect SMD 0.35 (95% CI 0.16, 0.54), p=0.0003) compared to an unmatched primary outcome (pooled effect SMD 0.13 (95% CI 0.04, 0.23) p=0.007). ii) Of four composite outcomes: two matched trials had greater SMDs and improved statistical precision in the primary outcome than the composite outcome; two unmatched trials had greater SMDs and improved statistical precision in the composite compared to the primary outcome. Conclusion. Using an outcome that matches exercise targets in LBP trials appears to produce greater SMDs than an unmatched primary outcome. Future trials should consider primary outcome selection aligned with exercise treatment targets. Sources of Funding: L Wood's PhD is funded by the Research Institute for Primary Care and Health Sciences, Keele University. Prof NE Foster is a UK National Institute for Health Research Senior Investigator, and was supported by a UK National Institute for Health Research Professorship (NIHR-RP-011-015). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Conflicts of interest: No conflicts of interest


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 41 - 41
1 Oct 2019
Antoni-Pineda G Orchard D
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Background. Evidence supports that dysfunction of descending inhibition (endogenous analgesic (EA) modulation) contributes towards chronic pain conditions. Research suggests that manual therapy may influence EA modulation; however, this is poorly understood. Trials testing the effect of sustained digital pressure, a commonly used manual therapy technique, using pain pressure threshold (PPT) would give us a better understanding of the influence of manual therapy on EA modulation. A measurement of PPT has been shown to be most effective using fingertip pressure due to the palpatory feedback of symptomatic tissues. Design. A cross-sectional observational study, utilizing a repeated measure approach. Aim. The aim of this research study is to provide preliminary data on the variability of pressure in sustained fingertip pressure in comparison to algometer guided pressure. Methods. Utilizing a pressure algometer, 26 participants were used to test the variability of fingertip pressure in comparison to algometer guided pressure, over 120 seconds. In a randomized order and utilizing two sheets of skin, participants tried to attain, and sustain, a targeted pressure. In the fingertip pressure condition, participants were blinded to the exerted pressure. Conclusion. It was determined that, on average, participants were able to attain the target pressure, but this was highly variable from trial to trial. The test-retest measurement concluded that participants' accuracy was reproducible. Participants were not reproducible in variability when completing the test-retest measurement. There was a relatively higher variability with the lower pressures tested. The order in which the trial was performed, and type of skin did not affect the variability. It was concluded that, whilst some practitioners appear to have a high degree of accuracy with low variability of sustained finger-tip pressure, across a sample population this was not the case bringing into question the mechanism of effect of this common manual therapy technique. Conflict of interest: None. Funding: None


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_10 | Pages 5 - 5
1 May 2017
Marley J McDonough S Tully M Bunting B O'Hanlon J Porter-Armstrong A
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Background. Chronic musculoskeletal pain increases an individual's risk of developing many chronic diseases and the risk of all-cause early mortality. There is irrefutable evidence supporting the role of physical activity (PA) in reducing these risks. Sustaining changes to PA behaviours is challenging and efforts are needed to understand the barriers and facilitators of change. Understanding these factors is a vital step in developing behaviour change interventions. Objectives. Explore barriers and facilitators to engaging in PA in adults accessing pain services. Explore barriers and facilitators to promoting PA by healthcare professionals, exercise professionals and charity staff/expert patients. Methods. A qualitative study using the theoretical domains framework (TDF). Two focus groups were conducted with service users (n=18). Three focus groups were held with; healthcare professionals (n=8); exercise professionals (n=6) and charity staff/expert patients (n=8). Two independent reviewers thematically analysed transcripts. Barriers and facilitators were subsequently coded according to the domains of the TDF. Results. For all groups barriers were frequently mapped to the domain ‘environmental context and resources’. Although there was variation across the groups, barriers were also frequently mapped to the domains of ‘knowledge’, ‘beliefs about consequences’, and ‘belief about capabilities’. For service-users' facilitators were frequently mapped to ‘social influences’. Conclusion. The TDF was used to identify deficits that are likely to influence behaviours; targeted intervention strategies have been developed to specifically target these deficits. The interventions that have been developed consider not only the behaviour of those at whom the intervention is targeted, but also those involved in its delivery. No conflicts of interest. Sources of funding: This research was funded by the Public Health Agency, HSC R&D Division through a Doctoral Fellowship awarded to J Marle


Aims

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.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 133 - 137
10 Feb 2023
Liao H Tsai C

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.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 809 - 817
27 Sep 2024
Altorfer FCS Kelly MJ Avrumova F Burkhard MD Sneag DB Chazen JL Tan ET Lebl DR

Aims

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

Methods

Robotic planning software was used to map out bone removal for a laminar decompression after registration of CT scan images of one cadaveric specimen. A specialized acorn-shaped bone removal robotic drill was used to complete a robotic lumbar laminectomy. Post-procedure advanced imaging was obtained to compare actual bony decompression to the surgical plan. After confirming accuracy of the technique, a minimally invasive robotic-assisted laminectomy was performed on one 72-year-old female patient with lumbar spinal stenosis. Postoperative advanced imaging was obtained to confirm the decompression.