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
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
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
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
Background and Aim of Study. Despite several hundred RCTs of exercise for persistent non-specific low back pain (NSLBP), the treatment
Background. Exercise is a complex intervention, and often has more than one treatment
Purposes of the study and background. Cognitive Functional Therapy (CFT) is a complex intervention that
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
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
Purposes of the study and background. Cognitive Functional Therapy (CFT) is a psychologically informed, physiotherapist-led intervention that
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
Background. Chronic low back pain is strongly linked to degeneration of the intervertebral disc (IVD), which currently lacks any
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
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
Background. Complex interventions, such as exercise for LBP, often have many treatment
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
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;
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. 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.Aims
Methods
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. 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.Aims
Methods
To report the development of the technique for minimally invasive lumbar decompression using robotic-assisted navigation. 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.Aims
Methods