European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
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Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress. ⋯ AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.
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Bracing is the treatment of choice for idiopathic scoliosis (IS), unfortunately factors underlying brace response remain unknown. Clinicians are currently unable to identify patients who may benefit from bracing, and therefore, better molecular stratification is critically needed. The aim of this study is to evaluate IS patient outcomes at skeletal maturity in relation to biological endophenotypes, and determine specific endophenotypes associated to differential bracing outcomes. This is a retrospective cohort with secondary cross-sectional comparative studies. ⋯ Associations between biological endophenotypes and outcomes suggest differences in progression and/or bracing response among IS patients. Outcomes were most favorable in FG3 patients. The results pave the way for establishing personalized treatments, distinguishing who may benefit or not from treatment.
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Although risk factors for new low back pain (LBP) episodes and acute-to-chronic transition have been identified, risk factors for flares of LBP remain largely unknown. This case-crossover study aimed to identify: (1) risk factors LBP flares and (2) whether risk factors differed when flare is defined by pain increase (pain-defined flare: PDF) or identified by participants according to a broader flare definition that considered emotions and coping (self-reported flare: SRF). ⋯ LBP flare has been largely ignored but is more reflective of the LBP experience than conventional definitions of acute, sub-acute and chronic LBP. This study highlights risk factors for flare and that these differ depending on whether flare is defined by pain alone (PDF) or a broad multidimensional definition (SRF). Potential targets to reduce the intensity/frequency of LBP flares are identified, with strong indication for the potential role of sleep intervention to mitigate LBP flare risk.
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Although proximal junctional kyphosis (PJK) is common after long spinal fusion, the outcomes of revision surgery for symptomatic PJK are unclear. Our aim was to assess the outcomes of revision surgery for symptomatic PJK in patients with adult spinal deformity and elucidate the incidence and risk factors for recurrent PJK (rePJK). ⋯ III.
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This study aimed to examine which motion analysis parameters regarding the dynamic aspects and/or balance affect the development acute proximal junctional kyphosis (PJK) following adult spinal deformity (ASD) surgery. ⋯ Preoperative Ant-PT angle during walking was associated with a higher OR in acute PJK after surgery.