Degenerative disorders of the intervertebral discs (IVDs) are generally characterized by enhanced matrix degradation, angiogenesis, innervation, and increased expression of catabolic cytokines. In this study, we investigated the effects of inflammatory cytokines, IL-1␤, and TNF-␣, on the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in human IVD degeneration. IL-1␤ and TNF-␣ stimulated the gene expression of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient tissues. Immunohistochemical results demonstrated a positive correlation between IL-1␤ and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression analysis of patient tissues also identified positive correlations between VEGF and platelet endothelial cell adhesion molecule-1 (PECAM-1) and between NGF/BDNF and protein gene product 9.5 (PGP9.5). Our findings suggest that IL-1␤ is generated during IVD degeneration, which stimulates the expression of VEGF, NGF, and BDNF, resulting in angiogenesis and innervation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop. Res. 29: 265-269, 2011 Keywords: interleukin-1␤; vascular endothelial growth factor (VEGF); angiogenesis; innervation; intervertebral disc (IVD) Degenerative changes in intervertebral discs (IVDs) include increased expression of catabolic cytokines, decreased synthesis of normal IVD matrix and enhanced matrix degradation, and disc cell senescence and apoptosis.1-5 IVD degeneration results in the loss of hydrophilic matrix molecules leading to spinal instability and is the main cause of disc-related diseases, such as disc herniation and spinal stenosis. Normal lumbar IVD is avascular and aneural except for the outer third of the annulus fibrosus (AF). However, previous studies have described the ingrowth of nerves into the AF and nucleus pulposus (NP) of degenerated IVD 6,7 and these nerves were usually accompanied by microvascular blood vessels.8 Though, the mechanisms underlying nerve ingrowth and neovascularization are largely unknown.Neurotrophins play a role in the survival, growth, differentiation, and function of neurons.9 The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been detected in human IVD degeneration and have been implicated in the promotion of nerve ingrowth and generation of discogenic pain. 8,10,11 A histologic study examining degenerative IVD tissues from rats demonstrated that the major population of disc-innervating dorsal root ganglion neurons was the NGF-dependent neurons.

Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.spinal cord injury | recovery neurobiology | mesenchymal stromal stem cell | PLGA | locomotion R epair of neurotrauma, stroke, and neurodegenerative diseases remains an unmet medical demand because of their pathophysiological complexity and the limited spontaneous healing capacity of adult mammalian CNS. Human mesenchymal stromal stem cells (hMSCs) offer autologous transplantation feasibility (1-4) and have been studied both experimentally and clinically for traumatic brain injury (TBI) and spinal cord injury (SCI) (5-8). Although MSCs possess homeostatic and proneurogenic activities (7, 9), studies relying on neural transdifferentiation (i.e., putative differentiations of MSCs into neural cells without reentering the pluripotency phase) did not show long-term functional improvement in SCI models. The poor outcomes were attributed mainly to suboptimal survival of MSCs, leaving key therapeutic mechanisms undetermined (10). We previously established a 3D cell delivery technology by seeding neural stem cells (NSCs) in biodegradable polymer scaffolds that significantly improved donor efficacy and enabled investigation of NSC repair mechanisms in t...

In most spinal diseases, including HLD and tumors, prepartum surgical treatment can be safely performed maintaining pregnancy. For patients with progressive neurologic deficit at 34 to 36 weeks gestation or later, spine surgery should be performed following the induction of delivery or a cesarean section, or at the same time.

Objective Bone mineral density (BMD) is an important consideration during fusion surgery. Although dual X-ray absorptiometry is considered as the gold standard for assessing BMD, quantitative computed tomography (QCT) provides more accurate data in spine osteoporosis. However, QCT has the disadvantage of additional radiation hazard and cost. The present study was to demonstrate the utility of artificial intelligence and machine learning algorithm for assessing osteoporosis using Hounsfield units (HU) of preoperative lumbar CT coupling with data of QCT. Methods We reviewed 70 patients undergoing both QCT and conventional lumbar CT for spine surgery. The T-scores of 198 lumbar vertebra was assessed in QCT and the HU of vertebral body at the same level were measured in conventional CT by the picture archiving and communication system (PACS) system. A multiple regression algorithm was applied to predict the T-score using three independent variables (age, sex, and HU of vertebral body on conventional CT) coupling with T-score of QCT. Next, a logistic regression algorithm was applied to predict osteoporotic or non-osteoporotic vertebra. The Tensor flow and Python were used as the machine learning tools. The Tensor flow user interface developed in our institute was used for easy code generation. Results The predictive model with multiple regression algorithm estimated similar T-scores with data of QCT. HU demonstrates the similar results as QCT without the discordance in only one non-osteoporotic vertebra that indicated osteoporosis. From the training set, the predictive model classified the lumbar vertebra into two groups (osteoporotic vs. non-osteoporotic spine) with 88.0% accuracy. In a test set of 40 vertebrae, classification accuracy was 92.5% when the learning rate was 0.0001 (precision, 0.939; recall, 0.969; F1 score, 0.954; area under the curve, 0.900). Conclusion This study is a simple machine learning model applicable in the spine research field. The machine learning model can predict the T-score and osteoporotic vertebrae solely by measuring the HU of conventional CT, and this would help spine surgeons not to under-estimate the osteoporotic spine preoperatively. If applied to a bigger data set, we believe the predictive accuracy of our model will further increase. We propose that machine learning is an important modality of the medical research field.

No abstract

BackgroundThe purpose of the current study was to investigate the incidence of preoperative deep vein thrombosis (DVT) after hip fractures in Korea.MethodsIn this prospective study, we enrolled 152 Korean geriatric patients who had suffered hip fractures due to a simple fall and were hospitalized between January 2013 and December 2013. There were 52 male and 100 female patients, and their mean age was 78.2 years. There were 96 trochanteric fractures and 56 femoral neck fractures. All patients were examined for DVT: 26 by ultrasonography and 126 by computed tomography venography. The patients having DVT underwent inferior vena cava filter insertion before the surgical intervention.ResultsPreoperatively, none of the patients had any signs or symptoms of DVT; however, 4 patients were identified as having asymptomatic DVT. The overall incidence of DVT was 2.6% (4/152). The mean time to arrival at emergency room after injury was 32.6 hours. Mean time elapsed to undergo surgery after hospitalization was 24.9 hours. The average time to hospitalization after injury was 237 hours for patients with DVT versus 27.5 hours for patients without DVT. DVT developed within 72 hours in two of the 137 patients (1.4%) and after 72 hours in two of the remaining 15 patients (13.3%) hospitalized.ConclusionsWhile the preoperative incidence of DVT after hip fractures was relatively low (2.6%) in the Korean geriatric population, we confirmed that getting no treatment within 72 hours after injury increased the incidence of DVT. Thus, we conclude from this study that a workup for DVT should be considered in cases where admission or surgery has been delayed for more than 72 hours after injury.

HFS can result from tumor, vascular malformation, and dolichoectatic artery. Therefore, appropriate preoperative radiological investigations are crucial to achieve a correct diagnosis. The authors emphasize that distal compression or only venous compression can be responsible for persistent or recurrent symptoms postoperatively. In cases of bilateral HFS, a definite differential diagnosis is necessary for appropriate therapy. MVD is recommended as the treatment of choice in patients younger than 30 years old or patients with painful tic convulsif.

No abstract