Background. FORECAST is a prospective longitudinal cohort study exploring mechanism-based prognostic factors for pain persistence in sciatica. Here, we share an update on this largest deeply-phenotyped primary care sciatica cohort. Methods/results. Our cohort includes 180 people with sciatica (score >4 on Stynes’ Sum Score), aged 18–85, within 3 months of symptom onset. Psychosocial factors, self-reported sensory profiling, clinical examination, quantitative sensory testing (QST), biological samples (blood and skin samples), and Magnetic Resonance Neurography of lumbar nerve roots were collected at baseline. Pain persistence was determined at three and twelve months with the Sciatica Bothersomeness Index (SBI) and a numeric pain rating scale (NRS) as primary outcomes. Recruitment nears completion, with 160 participants enrolled to date. 127 and 96 participants have completed 3 and 12 months follow-up respectively. Overall, 56% of our cohort are female, with a mean age (SD) of 54.14yrs (16.57). Ethnicity data approximates local populations. SBI at baseline was (median [IQR]) 13[10-17], and interim longitudinal data shows stepwise improvement at 3 and 12 months. Baseline ‘average’ pain intensity was 5.56 (2.15) for leg pain, and 4.14(2.82) for low back pain (LBP). Overall, pain scores decreased at 3 and 12 months, with greater reductions in leg pain than LBP at 12 months. However, around 55–80% and 40–65% of people reported persistent pain at 3 and 12 months respectively. Conclusion. Leg pain severity was moderate and higher than LBP at baseline. All primary outcome measures demonstrate improvement over time, however 40–65% of patients report persistent pain at 12 months. Conflicts of interest. LR: Paid facilitation of post-graduate courses internationally. SK, MT, FP, KM, WS, CP, CR, SC: No conflicts of interest. GC: Editor in Chief of Health Psychology Review. Director of board of directors, MentalCHealth Care setting NoordWestVlaanderen. JF: Copyright holder of ODI (Oswestry Disability Index). Served on a data monitoring committee for a clinical trial of 2 different surgical approaches to cervical disc herniation (FORVAD). Member of HTA Prioritisation Committee B: Inside hospital Care from 2015-February 2019. Member of HTA Interventional Procedures Panel from 2010–2015. Trustee and board member of 3 spine related charities – Back to Back; British Scoliosis Research Foundation and BackCare. Expert instructed by both claimant and defendant solicitors in negligence and person injury cases. GB: Paid consultancy (RNA-seq) with Ivy Farm and Coding.bio. ABS: Paid post-graduate lecturing internationally. Co-chair NeupSig sciatica working group (unpaid). Sources of funding. This project is funded by UKRI and Versus Arthritis as part of the UKRI Strategic Priorities Fund (SPF) Advanced Pain Discovery Platform (APDP), a co-funded initiative by UKRI (MRC, BBSRC, ESRC), Versus Arthritis, the Medical Research Foundation and Eli Lilly and Company Ltd (Grant MR/W027003/1). Additional funding has been received from the back to back charity to expand longitudinal components of the study. LR has received support with PhD fees from the CSP charitable trust. ABS is supported by a Wellcome Trust Clinical Career Development Fellowship. (222101/Z/20/Z). WS is partly funded through the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. FP is funded by a Dorothy Hodgkin Career Development Fellowship in Chemistry in association with Somerville College. GB is supported by the Wellcome Trust (223149/Z/21/Z) and Diabetes UK (19/0005984). GC and KRM are partly funded by UKRI and Versus Arthritis as part of the Advanced Pain Discovery Platform (APDP) PAINSTORM (MR/W002388/1). The UKRI and Versus Arhthritis (APDP) are the major funders of FORECAST. All other funders provided either some people support, or funded projects with legacy data that we reuse

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

Purpose. Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. Methods. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10. –7. ) & genome-wide significant (p<5×10. –8. ) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases. Results. Genome-wide significant association was found for intron variant rs12310519 in SOX5 (OR=1.08, p=7.2×10. −10. ). This was replicated in the independent sample n = 283,752, comprising 50,915 cases (OR 1.06, p=5.3×10. −11. ); in joint meta-analysis OR=1.07, p=4.5×10. −19. exceeding genome-wide significance. We found three other suggestive associations in discovery, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant rs7833174 located between CCDC26 and GSDMC (OR 1.05, p=4.4×10. −13. ), and an intron variant, rs4384683, in DCC (OR 0.97, p=2.4×10. −10. ). Conclusion. We have identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC) which will shed light on the pathogenic mechanisms underlying CBP. Conflicts of interest: YA and LK are owners of Maatschap PolyOmica. This study was supported by the European Community's Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) and conducted using the UK Biobank Resource (project # 18219). CHARGE and other cohort-specific funding sources to be submitted- see below

Aims

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

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.

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.

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Introduction. From the many human studies that attempt to identify genes for adolescent idiopathic scoliosis (AIS), the view emerging is that AIS is a complex genetic disorder with many predisposing genes exhibiting complex phenotypes through environmental interactions. Although advancements in genomic technology are transforming how we undertake genetic and genomic studies, only some success has been reached in deciphering complex diseases such as AIS. Moreover, the present challenge in AIS research is to understand the causative and correlative effects of discovered genetic perturbations. An important limitation to such investigations has been the absence of a method that can easily stratify patients with AIS. To overcome these challenges, we have developed a functional test that allows us to stratify patients with AIS into three functional subgroups, representing specific endophenotypes. Interestingly, in families with multiple cases of AIS, a specific endophenotype is shared among the affected family members, indicating that such a transmission is inherited. Moreover, increased vulnerability to AIS could be attributable to sustained exposure to osteopontin (OPN), a multifunctional cytokine that appears to be at the origin of the Gi-coupled receptor signalling dysfunction discovered in AIS. We examined the molecular expression profiles of patients with AIS and their response to OPN. Methods. Osteoblasts isolated from patients with AIS were selected for each functional subgroup and compared with osteoblasts obtained from healthy matched controls. We used the latest gene chip human genome array Affymetrix (HuU133 Plus 2.0 array) that allows for the analysis of the expression level of 38 000 well characterised human genes. Raw data were normalised with robust multiarray analysis method. Statistical analysis was done by the EB method with FlexArray software. Selection criteria for in-depth analysis include the magnitude of change in expression (at least □} 3-fold) and 5% false discovery rate as stringency selection. Validation of selected candidate genes was done by qPCR and at the protein level by Western blot and ELISA methods. Plasma OPN concentrations were measured by ELISA on a group of 683 consecutive patients with AIS and were compared with 262 healthy controls and 178 asymptomatic offspring, born from at least one scoliotic parent, and thus considered at risk of developing the disorder. The regulation of OPN signalling pathway in normal and AIS cells were validated in vitro by cellular dielectric spectroscopy (CDS). Results. Of 38 000 human genes tested, we have found eight genes specifically associated with the functional subgroup 1, 16 genes with the functional subgroup 2, and 11 genes with the functional subgroup 3. Interestingly, only 19 genes were shared and affected to the same extent in all AIS functional subgroups exhibiting a similar curve pattern (double major), suggesting their role in the formation of this curve pattern. Indeed, most of these genes encode for regulatory proteins such as transcription factors regulating axial skeleton, somite development, and extracellular matrix proteins. Mean plasma OPN concentrations were significantly increased in patients with AIS and correlated with disease severity. Increased plasma OPN concentrations were also detected in the asymptomatic at-risk group, suggesting that these changes precede scoliosis onset. CDS experiments clearly showed that OPN exposure triggers a Gi-coupled receptor signalling dysfunction, which is exacerbated by oestrogens. Conclusions. Our data further support our functional method of stratification of patients with AIS and allow the identification of genes triggering scoliosis onset versus those predisposing to the development of a specific curve pattern. Furthermore, our clinical and experimental data show that OPN is essential for scoliosis onset and curve progression, thus offering a first molecular concept to explain the pathomechanism leading to the asymmetrical growth of the spine in AIS. Acknowledgments. This research project was supported by grants from La Fondation Yves Cotrel de l'Institut de France, Canadian Institutes of Health Research, and Paradigm Spine LLC

Aims

This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM).