Our ultimate goal of in vitro derivation of Schwann cells (SCs) from adult bone marrow stromal cells (BMSCs) is such that they may be used autologously to assist post-traumatic nerve regeneration. Existing protocols for derivation of SC-like cells from BMSCs fall short in the stability of the acquired phenotype and the functional capacity to myelinate axons. Our experiments indicated that neuro-ectodermal progenitor cells among the human hBMSCs could be selectively expanded and then induced to differentiate into SC-like cells. Co-culture of the SC-like cells with embryonic dorsal root ganglion neurons facilitated contact-mediated signaling that accomplished the switch to fate-committed SCs. Microarray analysis and in vitro myelination provided evidence that the human BMSC-derived SCs were functionally mature. This was reinforced by repair and myelination phenotypes observable in vivo with the derived SCs seeded into a nerve guide as an implant across a critical gap in a rat model of sciatic nerve injury.
Prediction of curve progression risk in adolescent idiopathic scoliosis (AIS) remains elusive. Prior studies have revealed the potential for three-dimensional (3D) morphological parameters to prognosticate progression, but these require specialized biplanar imaging equipment and labor-intensive software reconstruction. This study aimed to formulate a deep learning model with standing posteroanterior (PA) X-rays at first clinic visit to differentiate between progressive (P) and non-progressive (NP) curves. For this retrospective cohort study, we identified patients presenting with AIS between October 2015 to April 2020 at our tertiary referral centre. Patients with mild curvatures (11 – 30o) who were skeletally immature (Risser sign of ≤2) were recruited. Patients receiving biplanar X-ray radiographs (EOS™) were divided between a training-cross-validation cohort (328 patients) and independent testing cohort (110 patients). Another 52 patients receiving standard PA spinal X-rays were recruited for cross-platform validation. Following 3D reconstruction, we designated the major curve apex upon PA X-rays as the region of interest (ROI) for machine learning. A self-attentive capsule network was constructed to differentiate between curves manifesting P and NP trajectories. A two-stage transfer learning strategy was introduced to pre-train and fine-tune the model. Model performance (accuracy, sensitivity, specificity) was compared to that of traditional convolutional neural networks (CNNs) and a clinical parameter-based logistic regression model. 3D reconstruction identified that apical rotation of the major curve and torsion were significantly different between P and NP curve trajectories. Our predictive model utilizing an ROI centered on the major curve apex achieved an accuracy of 76.6%, a sensitivity of 75.2% and a specificity of 80.2% upon independent testing. Cross-platform performance upon standard standing PA X-rays yielded an accuracy of 77.1%, a sensitivity of 73.5% and a specificity of 81.0%. Errors in prediction occurred when the degree of apical rotation / torsion was discrepant from that of the subsequent curve trajectory but could be rectified by considering serial X-rays. Performance was superior to that of traditional CNNs as well as clinical parameter-based regression models. This is the first report of automated prediction of AIS curve progression based on radiomics and deep learning, towards directing treatment strategy at first visit. Patients predicted to be at-risk of progression may be counselled to receive early bracing with enforcement of treatment compliance. Over-treatment may be avoided in curves deemed to be non-progressive. Results need to be consolidated in larger sample populations of different ethnicities. The Society for the Relief of Disabled Children (SRDC).
Patella fractures managed by fixation with metal implants often cause local soft tissue irritation and necessitate implant removal. An alternative is to utilize suture-based fixation methods. We have adopted suture and hybrid fixation in the routine management of patella fractures. Here, we compare the results of 3 fixation techniques. Eighty-seven eligible patients underwent patella fracture fixation over a 3-year period. As determined by fracture configuration, patients received (1) suture fixation (transosseous sutures and figure-of-eight tension banding with FiberWire), (2) hybrid fixation (transosseous FiberWire sutures and metal tension banding), or (3) metal fixation. Primary outcome measures included reoperation rate and soft tissue irritation. Secondary outcomes included surgical complications, radiological, and functional parameters. Reoperation rate was highest for metal fixation (25/57, 43.9%) and lowest for suture fixation (2/13, 15.4%). Soft tissue irritation necessitating implant removal was the predominant reason for reoperation and was significantly less prevalent following suture fixation (1/13, 7.7%, P < .01). Hybrid fixation resulted in similar rates of soft tissue irritation (6/17, 35.3%) and implant removal (7/17, 41.2%) as compared to metal fixation. There was a significant increase in patella baja (13/17, 76.5%) and reduction in Insall-Salvati ratio (0.742; 95% confidence interval: 0.682-0.802) following hybrid fixation as compared to the other 2 fixation methods (P < .05). Suture fixation results in the least amount of soft tissue irritation and lowest reoperation rate, but these advantages are negated with the addition of a metal tension band wire. Hybrid fixation also unbalances the extensor mechanism. Patients should be counseled as to the expected sequelae of their fixation method. Suture fixation is the favored means to fix distal pole fractures of the patella. An additional metal tension band loop may confer additional stability but should be applied with caution.
1 February 2018 in Colloids and Surfaces B: Biointerfaces
Degenerative cervical myelopathy (DCM) is the most prevalent cause of spinal cord dysfunction in the aging population. Significant neurological deficits may result from a delayed diagnosis as well as inadequate neurological recovery following surgical decompression. Here, we review the pathophysiology of DCM with an emphasis on how blood-spinal cord barrier (BSCB) disruption is a critical yet neglected pathological feature affecting prognosis. In patients suffering from DCM, compromise of the BSCB is evidenced by elevated cerebrospinal fluid (CSF) to serum protein ratios and abnormal contrast-enhancement upon magnetic resonance imaging (MRI). In animal model correlates, there is histological evidence of increased extravasation of tissue dyes and serum contents, and pathological changes to the neurovascular unit. BSCB dysfunction is the likely culprit for ischemia–reperfusion injury following surgical decompression, which can result in devastating neurological sequelae. As there are currently no therapeutic approaches specifically targeting BSCB reconstitution, we conclude the review by discussing potential interventions harnessed for this purpose.