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We investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients’ demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was

It is challenging to predict neurological outcomes of acute spinal cord injury (SCI) considering issues such as spinal shock and injury heterogeneity. Deep learning-based radiomics (DLR) were developed to quantify the radiographic characteristics automatically using a convolutional neural network (CNN), and to potentially allow the prognostic stratification of patients. We aimed to determine the functional prognosis of patients with cervical SCI using machine learning approach based on MRI and to assess the ability to predict the neurological outcomes. We retrospectively analyzed the medical records of SCI patients (n=215) who had undergone MRI and had an American Spinal cord Injury Association Impairment Scale (AIS) assessment at 1 month after injury, enrolled with a total of 294 MR images. Sagittal T2-weighted MR images were used for the CNN training and validation. The deep learning framework TensorFlow was used to construct the CNN architecture. After we calculated the probability of the AIS grade using the DLR, we built the identification model based upon the random forest using 3 features: the probability of each AIS grade obtained by the DLR method, age, and the initial AIS grade at admission. We performed a statistical evaluation between the actual and predicted AIS. The accuracy, precision, recall and f1 score of the ensemble model based on the DLR and RF were 0.714, 0.590, 0.565 and 0.567, respectively. The present study demonstrates that prediction of the short-term neurological outcomes for acute cervical spinal cord injury based on MRI using machine learning is feasible.

Sacral insufficiency fractures (SIFs) are common in the elderly. In patients with SIF, objective neurological abnormalities such as sphincter dysfunction or leg paresthesia are uncommon. We present a case of SIF accompanied by spinopelvic dissociation with late neurological compromise treated by spinopelvic fixation. A 61-year-old woman presented to our hospital with low back pain without obvious trauma history. She had a past history of eosinophilic granulomatosis with polyangiitis and treatment with steroids. Her low back pain became worse, and she started to have radiating left posterior thigh pain and motor weakness in the left ankle and both great toes with symptoms of stress urinary incontinence, constipation, and loss of anal sensation. Magnetic resonance imaging revealed an H-shaped sacrum fracture. We attributed the neurological symptoms to unstable SIF and performed lumbopelvic fixation. After the surgery, her leg pain and symptoms of stress urinary incontinence improved markedly, as did anal sensation. At a 6-month follow-up, the patient reported no low back pain and she was walking independently without pelvic complaints. CT showed bone union was achieved. Even minimally displaced SIF in patients with osteoporosis can be a cause of bowel and bladder disturbance. Lumbopelvic fixation is a treatment option for SIF with spinopelvic dissociation presenting neurological deficit.

A multicenter cross-sectional study. To clarify the relationship of trunk muscle mass with low back pain, spinal sagittal balance, and quality of life. Few reports have investigated the relationship of trunk muscle mass with lumbar spine function and spinal balance, and the clinical significance of trunk muscle mass remains unclear. Patients attending spinal outpatient clinics at 10 different medical institutions were enrolled in this study. Patient demographics, trunk muscle mass and appendicular skeletal muscle mass (ASM) measured by bioelectrical impedance analysis (BIA), body mass index (BMI), Charlson Comorbidity Index (CCI), the Oswestry Disability Index (ODI), visual analog scale (VAS) for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated. Multivariate nonlinear regression analysis was used to investigate the association of trunk muscle mass with the ODI, VAS score, SVA, and EQ5D score. Of 2551 eligible patients, 1738 (mean age 70.2 ± 11.0 years; 781 men and 957 women) were enrolled. Trunk muscle mass was significantly correlated with the ODI, VAS score, SVA, and EQ5D score (P

In recent years, fracture image diagnosis using a convolutional neural network (CNN) has been reported. The purpose of the present study was to evaluate the ability of CNN to diagnose distal radius fractures (DRFs) using frontal and lateral wrist radiographs. We included 503 cases of DRF diagnosed by plain radiographs and 289 cases without fracture. We implemented the CNN model using Keras and Tensorflow. Frontal and lateral views of wrist radiographs were manually cropped and trained separately. Fine-tuning was performed using EfficientNets. The diagnostic ability of CNN was evaluated using 150 images with and without fractures from anteroposterior and lateral radiographs. The CNN model diagnosed DRF based on three views: frontal view, lateral view, and both frontal and lateral view. We determined the sensitivity, specificity, and accuracy of the CNN model, plotted a receiver operating characteristic (ROC) curve, and calculated the area under the ROC curve (AUC). We further compared performances between the CNN and three hand orthopedic surgeons. EfficientNet-B2 in the frontal view and EfficientNet-B4 in the lateral view showed highest accuracy on the validation dataset, and these models were used for combined views. The accuracy, sensitivity, and specificity of the CNN based on both anteroposterior and lateral radiographs were 99.3, 98.7, and 100, respectively. The accuracy of the CNN was equal to or better than that of three orthopedic surgeons. The AUC of the CNN on the combined views was 0.993. The CNN model exhibited high accuracy in the diagnosis of distal radius fracture with a plain radiograph.

An occipital condyle fracture (OCF) is a relatively rare trauma that is now increasingly diagnosed because of the wide availability of computed tomography. For nondisplaced OCFs, conservative treatment is generally recommended, and there is no previous report of a nondisplaced OCF requiring surgery. We report a patient who had a nondisplaced OCF with craniocervical misalignment (a condyle-C1 interval > 2.0 mm) and C1-C2 translation treated with a halo vest and occipitocervical fusion surgery. An 87-year-old Asian woman fell from a 4-meter height and hit her head. She was transferred to our emergency room. Computed tomography revealed a nondisplaced impaction OCF with a 2.5 mm occipital condyle-C1 interval and a 5 mm C1-C2 translation. The fracture pattern was considered stable. However, since craniocervical misalignment and C1-C2 translation were present, the patient was placed in a halo device, and we reduced the occipitoatlantoaxial joint, adjusting the halo ring position preoperatively. Confirming reduction of the atlantooccipital facet joint and the atlantoaxial joint by computed tomography, we performed an occipitocervical fusion. This is the first report of a nondisplaced OCF with craniocervical misalignment and C1-C2 translation that required surgical treatment. Clinicians should be aware of craniocervical misalignment and atlantoaxial instability even in Tuli type 1 OCFs.

Study design A retrospective multicenter survey. Objective To investigate the perioperative complications of oblique lateral interbody fusion (OLIF) surgery. Summary of background data OLIF has been widely performed to achieve minimally invasive, rigid lumbar lateral interbody fusion. The associated perioperative complications are not yet well described. Methods The participants were patients who underwent OLIF surgery under the diagnosis of degenerative lumbar diseases between April 2013 and May 2015 at 11 affiliated medical institutions. The collected data were classified into intraoperative and early-stage postoperative (≤1 mo) complications. The intraoperative complications were then subcategorized into organ damage (neural, vertebral, vascular, and others) and other complications, mainly related to instrumental failure. The collected data were also divided and analyzed based on whether the surgeon was certified to perform the surgery and the incidence of complications in the early (April 2013-March 2014) and late stages (April 2014-May 2015) of OLIF introduction. Results In the 155 included patients, 75 complications were reported (incidence rate, 48.3%). The most common complication was endplate fracture/subsidence (18.7%), followed by transient psoas weakness and thigh numbness (13.5%) and segmental artery injury (2.6%). Almost all these complications were transient, except for three patients who had permanent damage: one had ureteral injury and two had neurological injury. Postoperative complications included surgical site infection (1.9%) and reoperation (1.9%). Whether the primary operator was experienced did not affect the incidence of complications. Regarding the introductory stage, the incidence of complications was 50% in the early stage and 38% in the late stage. Conclusion The overall incidence of perioperative complications of OLIF surgery reached 48.3%, of which only 1.9% resulted in permanent damage. Our analysis based on surgeon experience indicated that the OLIF procedure could be performed without increasing incidence of complications, under the guidance of experienced supervisors. Level of evidence 3.

We evaluated the feasibility and reliability of open source Digital Imaging and COmmunication in Medicine (DICOM) imaging software, OsiriX (Antoine Rosset, 2003-2009), in spine surgery. CT data were used and processed with OsiriX and with commercial software for comparison. Images were reconstructed and compared in volume rendering (VR) and multi-planar reconstruction (MPR) mode. When all images were compared, the three-dimensional (3D) reconstructed images from both software packages showed considerable consistency in VR mode. Measurements in MPR mode also showed similar values with no statistically significant difference. These results demonstrate that OsiriX has approximately equivalent values to commercial software and provides reliable preoperative 3D information for the surgical field. In addition, any clinician, can obtain information using OsiriX at any time. Thus, OsiriX is a helpful tool in preoperative planning for spine surgery.

Study design Case report. Objective To describe the usefulness of simulated surgery for evaluation of a patient with neurofibromatosis type-1 (NF-1) who had severe cervicothoracic kyphoscoliosis and an anomalous vertebral artery (VA). Summary of background data Several surgical procedures have been used in the treatment of cervicothoracic kyphoscoliosis associated with myelopathy in patients with NF-1. However, to our knowledge, there has been no report that describes a surgical procedure for NF-1 patients with anomalous VA at the cervical spine. Methods A 45-year-old man with NF-1 developed cervical myelopathy. Preoperative examinations revealed severe cervicothoracic kyphoscoliosis, dystrophic changes of the cervical vertebrae, and the anomalous course of a VA and VA aneurysms. To assist in the preoperative planning and intraoperative navigation, we created 3-dimensional (3D) full-scale models of the patient's spine. Using a model, we performed a simulation of the planned surgery for spinal cord decompression with spinal fusion through both anterior and posterior approaches. Results Through the simulation, we could evaluate the risk of VA injury at the process of corpectomy, and altered the surgical procedure for the spinal cord decompression with spinal fusion from a posterior approach and a bone graft alone from an anterior approach. We accomplished the surgery successfully without any neurovascular complications. After surgery, the patient experienced relief from myelopathy. Conclusion Preoperative surgical simulation using a 3D full-scale model was useful for improving the accuracy and safety of the surgery for cervicothoracic kyphoscoliosis with NF-1.

Posterior fusion is a standard procedure for C1/2 instability [1–5], and is indicated for a wide variety of conditions that cause atlantoaxial instability, such as inflammatory disease, trauma, degenerative disease, and anatomic anomalies. These pathological conditions often necessitate not only stabilization but also spinal cord decompression, but there are few reports that focus on the surgical technique for simultaneous decompression and fusion [6, 7]. Although conventional C1 laminectomy is the gold standard for decompression at the atlas, it provides little space for bone grafting to fuse, which is a serious deficiency when fusion is indicated. Innovations in surgical instruments have brought about remarkable progress in providing rigid initial fixation [2, 3, 5], but instrument failure, such as loosening and breakage leading to nonunion, is always a possibility [8, 9]. Bone grafting is indispensable in avoiding this complication, as permanent stability can be achieved once fusion has occurred. In this report, we introduce a new technique for achieving single-segment bone grafting, decompression, and fusion in patients with C1/2 canal stenosis. We also present two representative patients who underwent surgery with this technique, the first with an irreducible axis odontoid fracture secondary to trauma, and the second with a retro-odontoid pseudotumor.

Developing sensory neurons require neurotrophic support for survival, neurite outgrowth and myelination. The low-density lipoprotein receptor-related protein-1 (LRP1) transactivates Trk receptors and thereby functions as a putative neurotrophin. Herein, we show that LRP1 is abundantly expressed in developing dorsal root ganglia (DRG) and that LRP1-dependent cell signaling supports survival, neurite extension and receptivity to Schwann cells even in the absence of neurotrophins. Cultured embryonic DRG neurons (E15) were treated with previously characterized LRP1 ligands, LRP1-receptor binding domain of α2-macroglobulin (RBD), hemopexin domain of MMP-9 (PEX) or controls (GST) for two weeks. These structurally diverse LRP1 ligands significantly activated and sustained extracellular signal-regulated kinases (ERK1/2) 5-fold (p 2 weeks in vitro, to an extent equaling NGF, a finding associated with canonical signaling mechanisms and blockade of caspase-3 cleavage. LRP1 ligand-induced survival and sprouting were blocked by co-incubation with the LRP1 antagonist, receptor associated protein (RAP), whereas RAP had no effect on NGF-induced activity. Site directed mutagenesis of the LRP1 ligand, RBD, in which Lys(1370) and Lys(1374) are converted to alanine to preclude LRP1 binding, were ineffective in promoting cell signaling, survival or inducing neurite extension in primary sensory neurons, confirming LRP1 specificity. Furthermore, LRP1-induced neurite sprouting was mediated by Src-family kinase (SFK) activation, suggesting transactivation of Trk receptors. Co-cultures of primary embryonic neurons and Schwann cells showed that LRP1 agonists promoted axonal receptivity to myelination to Schwann cells. Collectively, these findings identify LRP1 as a novel and perhaps essential trophic molecule for sensory neuronal survival and development.

STUDY DESIGN An open-labeled multicenter prospective controlled clinical trial. OBJECTIVE To confirm the feasibility of granulocyte colony-stimulating factor (G-CSF) administration for patients with thoracic myelopathy. SUMMARY OF BACKGROUND DATA Although G-CSF is best known as an important cytokine commonly used to treat neutropenia, it also has nonhematopoietic functions. Previous experimental studies have shown that G-CSF can enhance tissue regeneration of several organs, such as the heart and the brain. We previously reported that G-CSF promotes functional recovery after spinal cord injury in rodents. On the basis of those findings, we started a clinical trial of neuroprotective therapy, using G-CSF for patients with worsening symptoms of thoracic myelopathy. METHODS Patients whose Japanese Orthopaedic Association (JOA) score for thoracic myelopathy had decreased 2 points or more during a recent 1-month period were eligible for entry. After giving informed consent, patients were assigned to G-CSF and control groups. The G-CSF group (n = 10) received G-CSF 10 μg/kg per day intravenously for 5 consecutive days. The control group (n = 14) received similar treatments as the G-CSF group except for G-CSF administration. The primary outcome was JOA recovery rate at 1 month after G-CSF administration or initial treatment. RESULTS There was greater improvement in neurological functioning between baseline and 1-month follow-up in the G-CSF group (JOA recovery rate: 29.1 ± 20.5%) than in the control group (JOA recovery rate: 1.1 ± 4.2%) (P < 0.01). No serious adverse events occurred during or after the G-CSF administration. CONCLUSION The results provide evidence that G-CSF administration caused neurological recovery in patients with worsening symptoms of thoracic compression myelopathy.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions and could potentially be used to treat neuronal injury. To confirm the safety and feasibility of G-CSF administration for acute spinal cord injury (SCI), we have initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF.The trial included a total of 16 SCI patients within 48 h of onset. In the first step, G-CSF (5 μg/kg/day) was intravenously administered for 5 consecutive days to 5 patients. In the second step, G-CSF (10 μg/kg/day) was similarly administered to 11 patients. We evaluated motor and sensory functions of patients using the American Spinal Cord Injury Association (ASIA) score and ASIA impairment scale (AIS) grade.In all 16 patients, neurological improvement was obtained after G-CSF administration. AIS grade increased by one step in 9 of 16 patients. A significant increase in ASIA motor scores was detected 1 day after injection (P0.01), and both light touch and pin prick scores improved 2 days after injection (P0.05) in the 10 μg group. No severe adverse effects were observed after G-CSF injection.These results indicate that intravenous administration of G-CSF (10 μg/kg/day) for 5 days is essentially safe, and suggest that some neurological recovery may occur in most patients. We suggest that G-CSF administration could be therapeutic for patients with acute SCI.

In peripheral nerve injury, Schwann cells (SCs) must survive to exert a continuing and essential role in successful nerve regeneration. Herein, we show that peripheral nerve injury is associated with activation of endoplasmic reticulum (ER) stress and the adaptive unfolded protein response (UPR). The UPR culminates in expression of C/EBP homology protein (CHOP), a proapoptotic transcription factor in SCs, unless counteracted by LDL receptor-related protein-1 (LRP1), which serves as a major activator of phosphatidylinositol 3-kinase (PI3K). Sciatic nerve crush injury in rats induced expression of the ER chaperone GRP78/BIP, reflecting an early, corrective phase of the UPR. However, when LRP1 signaling was inhibited with receptor-associated protein, PI3K activity was decreased and CHOP protein expression increased, particularly in myelinating SCs. In cultured SCs, the PKR-like ER kinase target eIF2α was phosphorylated and CHOP was induced by (1) inhibiting PI3K, (2) treating the cells with tumor necrosis factor-α (TNF-α), or (3) genetic silencing of LRP1. CHOP gene deletion in SCs decreased cell death in response to TNF-α. Furthermore, the effects of TNF-α on phosphorylated eIF2α, CHOP, and SC death were blocked by adding LRP1 ligands that augment LRP1-dependent cell signaling to PI3K. Collectively, our results support a model in which UPR-activated signaling pathways represent a major challenge to SC survival in nerve injury. LRP1 functions as a potent activator of PI3K in SCs and, by this mechanism, limits SC apoptosis resulting from increased CHOP expression in nerve injury.

Schwann cells play an important role in injury to the peripheral nervous system (PNS). These cells de-differentiate, migrate, and secrete cytokines and chemokines involved in recruitment of inflammatory cells (Jessen and Mirsky, 1999; Campana, 2007). Recruited macrophages are essential to clear irreversibly damaged debris so that Schwann cells may establish extracellular scaffolds and direct regenerating axons (Stoll and Muller, 1999). Although the molecular mediators that promote macrophage recruitment remain incompletely understood, monocyte chemattractant protein-1 (MCP-1/CCL-2) is known to play a central role (Martini et al., 2008). Shortly after PNS injury, the type-1 transmembrane protein LDL receptor-related protein-1 (LRP1) is substantially up-regulated in Schwann cells (Campana et al., 2006). LRP1 functions as a broad-spectrum endocytic receptor for diverse ligands and as a phagocytic receptor for apoptotic cells and degenerated myelin debris (Strickland et al., 2002; Kinchen and Ravichandran, 2007; Gaultier et al., 2009). In Schwann cells, LRP1 also functions as a robust cell-signaling receptor. Ligand binding to LRP1 activates ERK/MAP kinase and Akt, promoting Schwann cell survival and migration (Campana et al., 2006; Mantuano et al., 2008a,b). Tissue-type plasminogen activator (tPA) and matrix metalloprotease-9 (MMP-9) are examples of proteases implicated in the response to PNS injury (La Fleur et al., 1996; Akassoglou et al., 2000; Kobayashi et al., 2008), which bind directly to LRP1 and activate LRP1-dependent cell signaling (Hu et al., 2006; Mantuano et al., 2008b; Shi et al., 2009). Other proteases may bind to the protease inhibitor α2-macroglobulin (α2M) and trigger α2M conformational change so that the complex becomes a high-affinity ligand for LRP1 (Barrett and Starkey, 1973; Barrett et al., 1979; Imber and Pizzo, 1981; Sottrup-Jensen, 1989; Strickland et al., 2002). By this pathway, diverse proteases, including those that do not bind directly to LRP1, may trigger LRP1-dependent Schwann cell signaling. The goal of this study was to determine whether the cell-signaling pathways activated by ligand binding to LRP1, which are known to promote cell survival and migration, also regulate expression of chemokines and cytokines by Schwann cells. We performed these studies with primary cultures of rat Schwann cells. Our results demonstrate that binding of activated α2M to LRP1 substantially increases expression of MCP-1. This response is selective, because α2M does not induce expression of the potent proinflammatory cytokine tumor necrosis factor-α (TNF-α), which is expressed by Schwann cells in response to other mediators in vivo and in vitro (Campana, 2007). The increase in MCP-1 expression was dependent on ERK/MAP kinase activation downstream of LRP1 (Mantuano et al., 2008a). These results support a model in which LRP1-dependent cell signaling contributes to a wide spectrum of activities demonstrated by Schwann cells in PNS injury.