Substance Repurposing pertaining to Rare Conditions A Role for Academia

STUDY DESIGN Experimental analysis of the thoracic ligamentum flavum cell osteogenic differentiation process. OBJECTIVE This study aimed to explore the role of miR-29a-5p and special AT-rich sequence-binding protein 2 (SATB2) in a pathological osteogenic process. SUMMARY OF BACKGROUND DATA Thoracic ossification of the ligamentum flavum (TOLF) is an uncommon disease wherein ligaments within the spine undergo progressive ossification, resulting in stenosis of the spinal canal and myelopathy. MiR-29a-5p was found to be downregulated in ligament cells from ossified ligament tissue in a previous study. However, whether miR-29a-5p is involved in the process of TOLF has not been investigated. METHODS The expression of miR-29a-5p in ligament tissues or in the context of TOLF osteogenic cell differentiation were measured via qRT-PCR. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were used to analyze cellular osteogenesis. The protein-level expression of SATB2, SIRT1 and Smad3 were measured via im the SIRT1/Smad3 deacetylation pathway. LEVEL OF EVIDENCE N/A.STUDY DESIGN Case-control study. OBJECTIVE The objective of this study was to identify the best laboratory and imaging factors to predict bone biopsy culture positivity in the setting of vertebral discitis/osteomyelitis (VDO). SUMMARY OF BACKGROUND DATA Good predictors of bone biopsy culture positivity in the setting of VDO are unknown. METHODS Retrospective review was performed for 46 patients who underwent CT-guided bone biopsy for evaluation of clinically confirmed VDO. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), mean CT attenuation of the biopsied bone, and the change in the CT attenuation of the bone compared to unaffected vertebral bone (delta CT attenuation) were measured. Receiver-operator characteristic (ROC) curve analyses were performed to identify the optimal threshold value for each variable. A multivariable logistic regression model was used to predict the probability of a positive bone culture using delta CT attenuation and CRPx100% fold above normal. RESULTS For one of the 46 VDO patients, bone cultures were not obtained. Approximately 35.6% (16/45) of bone cultures were positive. The most significant predictors of bone culture positivity were CRP x100% fold above normal (p = 0.011) and delta CT attenuation (p = 25.9 HU lower relative to unaffected bone (93.8% sensitivity, 75.0% specificity). CONCLUSIONS Delta CT attenuation, as well as CRP level over 4 times the upper limits of normal, were the strongest predictors for bone culture positivity in patients with VDO. LEVEL OF EVIDENCE 3.STUDY DESIGN Case Report (level IV evidence). OBJECTIVE To describe a potential novel application of Hyperbaric Oxygen Therapy (HBOT) in the successful treatment of a post-operative spinal cord injury. SUMMARY OF BACKGROUND DATA A 68 year old man presented with an acute spinal cord injury (ASIA impairment scale D), on the background of degenerative lower thoracic and lumbar canal stenosis. He underwent emergent decompression and instrumented fusion (T9 to L5), with an uncomplicated intra-operative course and no electrophysiological changes. Immediate post-operative assessment demonstrated profound bilateral limb weakness (1/5 on the Medical Research Council [MRC] grading scale, ASIA impairment scale B), without radiological abnormality. METHODS Conventional medical management (hypertension, level 2 care) was instigated with the addition of Riluzole, with no effect after 30 hours. At 36 hours 100% oxygen at 2.8 atmospheres was applied for 90 minutes, and repeated after 8 hours, with a further 3 treatments over 48 hours. RESULTS The patient demonstrated near-immediate improvement in lower limb function to anti-gravity (MRC grading 3/5) after 1 treatment. Motor improvement continued over the following treatments, and after 2 weeks the patient was ambulatory. At 4 months, the patient demonstrated normal motor function with no sphincteric disturbance. CONCLUSION The application of HBOT contributed to the immediate and sustained improvement (ASIA B to ASIA E) in motor recovery after post-operative spinal cord injury. read more HBOT may represent a new avenue of therapy for spinal cord injury, and requires further prospective investigation. LEVEL OF EVIDENCE 4.STUDY DESIGN Analysis of a prospective, multicenter cohort study. OBJECTIVE The aim of our study was to compare thresholds of published minimal clinically important differences (MCID) for the 3-level EuroQol-5D health survey (EQ-5D-3L) summary index (range -0.53 to 1.00) with our anchor-based estimate and evaluate how useful these thresholds are in determining treatment success in patients undergoing surgery for degenerative lumbar spinal stenosis (DLSS). SUMMARY OF BACKGROUND DATA MCID values for EQ-5D-3L are specific to the underlying disease and only three studies have been published for DLSS patients reporting different values. METHODS Patients of the multi-center Lumbar Stenosis Outcome Study (LSOS) with confirmed DLSS undergoing first-time decompression or fusion surgery with 12-month follow-up were enrolled in this study. To calculate MCID we used the Spinal Stenosis Measure (SSM) satisfaction subscale as anchor. RESULTS For this study, 364 patients met the inclusion criteria; of these, 196 were very satisfied, 72 moderately satisfied, 43 somewhat satisfied and 53 unsatisfied 12-month after surgery. The MCID calculation estimated for EQ-5D-3L a value of 0.19. Compared to published MCID values (ranging from 0.30 to 0.52), our estimation is less restrictive. CONCLUSIONS In patients with LSS undergoing surgery, we estimated an MCID value for EQ-5D-3L summary index of 0.19 with help of the average change anchor-based method, which we find to be the most suitable method for assessing patient change scores. LEVEL OF EVIDENCE 3.STUDY DESIGN Cross-sectional design. OBJECTIVE To investigate the prevalence of sarcopenia and identify factors associated with sarcopenia in patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA Patients with LSS have a higher prevalence of sarcopenia compared with healthy older adults. However, the clinical features of sarcopenia in patients with LSS are poorly understood and the factors affecting sarcopenia in patients with LSS remain unclear. METHODS Patients diagnosed with LSS based on clinical examination and magnetic resonance imaging findings, and referred to physical therapy, were enrolled. Muscle mass was measured using bioelectrical impedance using InBody S10. We collected a numerical rating scale (NRS) for back pain, the 36-Item Short-Form Survey (SF-36), the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), bone mineral density (BMD), and radiographic measurements of spinal alignment. Sarcopenia was defined according to the Asian Working Group for Sarcopenia guidelines and patients were classified into sarcopenia or nonsarcopenia groups.