Publications by authors named "Akinobu Suzuki"

141 Publications

Gender-specific analysis for the association between trunk muscle mass and spinal pathologies.

Sci Rep 2021 Apr 9;11(1):7816. Epub 2021 Apr 9.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

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 < 26 kg in men and < 19 kg in women. Lower trunk muscle mass was associated with lumbar disability, spinal imbalance, and poor quality of life in both genders, with significant difference in muscle mass.
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http://dx.doi.org/10.1038/s41598-021-87334-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035169PMC
April 2021

Clinical Comparison of Combined Cortical Bone Trajectory and Transarticular Surface Screw Versus Standard Pedicle Screw Insertion by Wiltse Approach for L5 Isthmic Spondylolisthesis.

Clin Spine Surg 2021 Mar 24. Epub 2021 Mar 24.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka Department of Orthopedic Surgery, Shimada Hospital, Habikino, Osaka Prefecture, Japan.

Study Design: This was a retrospective cohort study.

Objective: The objective of this study was to assess the effectiveness and invasiveness of a combined screw insertion technique [using cortical bone trajectory (CBT) screw and transarticular surface screw (TASS)] for patients with L5 isthmic spondylolisthesis.

Summary Of Background Data: Lumbosacral posterior fixation using TASS is safe, with high biomechanical strength. However, data regarding its clinical outcomes, effectiveness, and invasiveness, are lacking.

Materials And Methods: This study included 111 patients who underwent single-level L5-S1 posterior lumbar interbody fusion (PLIF) for L5 isthmic spondylolisthesis. The cohort was stratified into 2 groups: the Wiltse group included patients who underwent PLIF between 2008 and 2013 with standard pedicle screw fixation via Wiltse approach and the CBT/TASS group included those who underwent PLIF from 2014 onward with CBT/TASS fixation. After propensity score matching of the CBT/TASS and Wiltse groups, the surgical times, estimated blood loss (EBL), length of in-hospital stays, clinical scores, serum creatine kinase concentration, radiographic parameters, and bone union rate were compared using the χ2 test or Mann-Whitney U test. In addition, multivariate linear regression analyses, with surgical time and EBL as objective variables applied after Box-Cox transformation, were performed.

Results: The matched CBT/TASS group showed significantly shorter surgical times (P<0.001), lower EBL (P=0.032), shorter in-hospital stays (P=0.005), and lower 3-day postoperative serum creatine kinase concentrations (P=0.014) than the matched Wiltse group. However, neither the postoperative grade of spondylolisthesis, the L5-S1 lordotic angle, nor the clinical scores were significantly different between matched groups. The bone union rates were 94.7% and 96.2% in the matched CBT/TASS and Wiltse groups, respectively (P=1.000). Regression analysis showed that CBT/TASS was an independent factor significantly related to shorter surgical times and lower EBL (P<0.001 and P=0.001, respectively).

Conclusion: Compared with Wiltse approach, CBT/TASS is a less invasive technique, with a shorter surgical time and sufficient clinical outcomes for patients with L5 isthmic spondylolisthesis.

Level Of Evidence: Level III-treatment benefits.
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http://dx.doi.org/10.1097/BSD.0000000000001170DOI Listing
March 2021

Using artificial intelligence to diagnose fresh osteoporotic vertebral fractures on magnetic resonance images.

Spine J 2021 Mar 13. Epub 2021 Mar 13.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

Background Context: Accurate diagnosis of osteoporotic vertebral fracture (OVF) is important for improving treatment outcomes; however, the gold standard has not been established yet. A deep-learning approach based on convolutional neural network (CNN) has attracted attention in the medical imaging field.

Purpose: To construct a CNN to detect fresh OVF on magnetic resonance (MR) images.

Study Design/setting: Retrospective analysis of MR images PATIENT SAMPLE: This retrospective study included 814 patients with fresh OVF. For CNN training and validation, 1624 slices of T1-weighted MR image were obtained and used.

Outcome Measure: We plotted the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC) in order to evaluate the performance of the CNN. Consequently, the sensitivity, specificity, and accuracy of the diagnosis by CNN and that of the two spine surgeons were compared.

Methods: We constructed an optimal model using ensemble method by combining nine types of CNNs to detect fresh OVFs. Furthermore, two spine surgeons independently evaluated 100 vertebrae, which were randomly extracted from test data.

Results: The ensemble method using VGG16, VGG19, DenseNet201, and ResNet50 was the combination with the highest AUC of ROC curves. The AUC was 0.949. The evaluation metrics of the diagnosis (CNN/surgeon 1/surgeon 2) for 100 vertebrae were as follows: sensitivity: 88.1%/88.1%/100%; specificity: 87.9%/86.2%/65.5%; accuracy: 88.0%/87.0%/80.0%.

Conclusions: In detecting fresh OVF using MR images, the performance of the CNN was comparable to that of two spine surgeons.
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http://dx.doi.org/10.1016/j.spinee.2021.03.006DOI Listing
March 2021

Biglycan expression and its function in human ligamentum flavum.

Sci Rep 2021 Mar 1;11(1):4867. Epub 2021 Mar 1.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi Machi, Abeno-Ku, Osaka, 545-8585, Japan.

Hypertrophy of the ligamentum flavum (LF) is a major cause of lumbar spinal stenosis (LSS), and the pathology involves disruption of elastic fibers, fibrosis with increased cellularity and collagens, and/or calcification. Previous studies have implicated the increased expression of the proteoglycan family in hypertrophied LF. Furthermore, the gene expression profile in a rabbit experimental model of LF hypertrophy revealed that biglycan (BGN) is upregulated in hypertrophied LF by mechanical stress. However, the expression and function of BGN in human LF has not been well elucidated. To investigate the involvement of BGN in the pathomechanism of human ligamentum hypertrophy, first we confirmed increased expression of BGN by immunohistochemistry in the extracellular matrix of hypertrophied LF of LSS patients compared to LF without hypertrophy. Experiments using primary cell cultures revealed that BGN promoted cell proliferation. Furthermore, BGN induces changes in cell morphology and promotes myofibroblastic differentiation and cell migration. These effects are observed for both cells from hypertrophied and non-hypertrophied LF. The present study revealed hyper-expression of BGN in hypertrophied LF and function of increased proteoglycan in LF cells. BGN may play a crucial role in the pathophysiology of LF hypertrophy through cell proliferation, myofibroblastic differentiation, and cell migration.
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http://dx.doi.org/10.1038/s41598-021-84363-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921587PMC
March 2021

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

J Orthop Sci 2021 Feb 23. Epub 2021 Feb 23.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures.

Methods: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-β1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-β1-induced myofibroblast differentiation and fibrosis.

Results: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-β1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-β1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells.

Conclusion: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-β1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.
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http://dx.doi.org/10.1016/j.jos.2021.01.004DOI Listing
February 2021

Risk factors of the poor long-term prognosis of osteoporotic vertebral fractures: A multicenter cohort study.

J Orthop Surg (Hong Kong) 2021 Jan-Apr;29(1):2309499021994969

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.

Introduction: The presence of existing osteoporotic vertebral fracture (OVF) increases the mortality risk. However, the influence of the characteristics of OVF is unclear. This study aimed to investigate the influence of new OVF on patients' long-term prognosis using our past cohort study.

Method: This is an extension study of our cohort study carried out between 2005 and 2007. In the present extension study, of 420 patients, 197 whose contact information was available at the 6-month follow-up were included in the telephone survey in 2018. Five patients refused to participate in the survey, and 82 could not be contacted. Eventually, 110 patients were enrolled. Of the Demographic data, radiological findings, medical history, and clinical outcome were investigated at injury onset and at the 6-month follow-up. A proportional hazard model was used to investigate the risk factors for mortality.

Results: Among 110 patients, 33 died. Male sex and low body mass index (BMI <18.5 kg/m) were significant risk factors for mortality [hazard ratio (HR) = 6.40, 1.01-40.50; 5.24, 1.44-19.04, respectively]. The history of stroke and liver disease increased the risk of mortality (HR = 13.37, 1.93-92.7; 6.62, 1.15-38.14, respectively). As regards radiological findings, local kyphosis progression per 1° or ≥7° were significant risk factors of mortality (HR = 1.20, 1.06-1.36; 5.38, 1.81-16.03, respectively).

Conclusions: A telephone survey at 12 years after the occurrence of OVF analyzed risk factors for mortality and showed that a progression of local kyphosis in fractures between injury onset and 6 months after injury was a risk factor of poor prognosis.
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http://dx.doi.org/10.1177/2309499021994969DOI Listing
February 2021

Expression and function of FGF9 in the hypertrophied ligamentum flavum of lumbar spinal stenosis patients.

Spine J 2021 Feb 10. Epub 2021 Feb 10.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background Context: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF.

Purpose: To evaluate FGF9 expression and function in human LF with and without hypertrophy.

Study Design: This study employed a basic research study design utilizing human LF tissue for histological analyses.

Patient Samples: Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery.

Methods: LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF.

Results: Histological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients' age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells.

Conclusion: The present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration.

Clinical Significance: The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.
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http://dx.doi.org/10.1016/j.spinee.2021.02.004DOI Listing
February 2021

Classification and prognostic factors of residual symptoms after minimally invasive lumbar decompression surgery using a cluster analysis: a 5-year follow-up cohort study.

Eur Spine J 2021 Apr 8;30(4):918-927. Epub 2021 Feb 8.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, Japan.

Purpose: Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years after minimally invasive lumbar decompression surgery using a cluster analysis.

Methods: The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster.

Results: The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis.

Conclusions: This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.
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http://dx.doi.org/10.1007/s00586-021-06754-yDOI Listing
April 2021

Relationship between number of radiological risk factors for delayed union after osteoporotic vertebral fracture and clinical outcomes.

Arch Osteoporos 2021 02 1;16(1):20. Epub 2021 Feb 1.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

This study demonstrated that number of three specific radiological risk factors (MR T2WI confined high-intensity pattern and diffuse low-intensity pattern, thoracolumbar vertebrae involvement, middle column injury) added prognostic information for delayed union, kyphotic deformity, and prolonged pain.

Purpose: Delayed union after osteoporotic vertebral fracture (OVF) causes prolonged pain, QOL impairment, progression of collapse, kyphotic deformity, and neurologic impairment. Some specific radiological findings can be useful for predicting delayed union. We aimed to explore the prevalence and concomitance of various types of radiological risk factors for delayed union after osteoporotic vertebral fracture (OVF) and to assess the impact of risk factor number on clinical outcomes.

Methods: A total of 508 patients with fresh OVF from 25 institutes were evaluated. All patients were treated conservatively without surgical interventions. At the 6-month follow-up, the patients were classified into bone union and delayed union groups based on plain X-ray findings. We examined the presence and absence of three specific radiological risk factors (MR T2WI confined high-intensity pattern and diffuse low-intensity pattern, thoracolumbar vertebrae involvement, middle column injury) and analyzed clinical outcomes according to numbers of radiological risk factors.

Results: Delayed union was observed in 101 patients (19.9%) at the 6-month follow-up. The most common radiological risk factor was thoracolumbar vertebrae involvement (73.8%), followed by middle column injury (33.9%) and specific MRI findings (T2WI confined high-intensity pattern and diffuse low-intensity pattern) (29.7%). Overall, 85 (16.7%) patients had zero radiological risk factors, 212 (42.7%) had one, 137 (27.0%) had two, and 69 (13.6%) had three. When assessing the number of radiographic risk factors which included the MRI findings (the 3-risk factor method), the odds ratio for delayed union after acute OVF was 5.8 in the 2/3-risk factor group and 13.1 in the 3/3-risk factor group. Even when assessing the number of radiographic risk factors without MRI findings (2-risk factor method), the odds ratio was 3.2 in the 1/2-risk factor group and 10.2 in the 2/2-risk factor group.

Conclusion: Number of radiological risk factors added prognostic information for delayed union, kyphotic deformity, and prolonged pain.
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http://dx.doi.org/10.1007/s11657-021-00884-yDOI Listing
February 2021

Topical co-administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment.

BMC Musculoskelet Disord 2021 Jan 20;22(1):94. Epub 2021 Jan 20.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka, Japan.

Background: Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite.

Methods: β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson's trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7).

Results: Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05).

Conclusions: The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.
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http://dx.doi.org/10.1186/s12891-021-03971-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819170PMC
January 2021

Presence of sarcopenia does not affect the clinical results of balloon kyphoplasty for acute osteoporotic vertebral fracture.

Sci Rep 2021 Jan 8;11(1):122. Epub 2021 Jan 8.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Sarcopenia has been associated with poor clinical outcomes in several diseases. Herein, the clinical results of balloon kyphoplasty (BKP) for acute osteoporotic vertebral fracture (OVF) treatment were assessed and compared between sarcopenia and non-sarcopenia patients. Sixty patients who underwent BKP for treatment of acute OVF with poor prognostic factors between April 2016 and September 2017 and were assessed for sarcopenia were enrolled. Clinical results (back pain on visual analogue scale [VAS]; short-form [SF] 36; vertebral deformity; activities of daily living levels; and incidence of adjacent vertebral fractures) were compared between the two groups at 6 months post-BKP. Data analysis revealed that back pain on VAS, SF-36 scores, and vertebral deformity improved from baseline to 6 months after BKP. Thirty-nine patients (65.0%) were diagnosed with sarcopenia and demonstrated a lower body mass index (21.2 vs. 23.3 kg/m, p = 0.02), skeletal muscle mass index (5.32 vs. 6.55 kg/m, p < 0.01), hand-grip strength (14.7 vs. 19.2 kg, p = 0.01), and bone mineral density of the femoral neck (0.57 vs. 0.76 g/cm, p < 0.01) than those of patients without sarcopenia. However, no significant differences were observed in the clinical results between these groups. Therefore, BKP's clinical results for the treatment of acute OVF are not associated with sarcopenia.
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http://dx.doi.org/10.1038/s41598-020-80129-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794449PMC
January 2021

Patterns of Lumbar Disc Degeneration: Magnetic Resonance Imaging Analysis in Symptomatic Subjects.

Asian Spine J 2020 Dec 28. Epub 2020 Dec 28.

USC Spine Center, Department of Orthopedic Surgery, Faculty of Medicine, University of Southern California, Los Angeles, CA, USA.

Study Design: Cross-sectional study.

Purpose: To evaluate lumbar disc degeneration (LDD) on magnetic resonance imaging (MRI) in symptomatic subjects to accumulate baseline data on the pattern of degeneration.

Overview Of Literature: LDD plays an important role in the diagnosis and treatment of low-back pain in patients. Few studies have focused on the pattern of LDD to understand how the lumbar spine ages.

Methods: This study included 1,095 patients (mean age, 44.29 years; range, 16-85 years) who underwent upright lumbar MRI. LDD was graded into five categories (I-V). Positive LDD was defined as grade III or greater. The prevalence and pattern of LDD were analyzed, and the correlations between age and total grade of LDD were evaluated.

Results: The average number of LDD levels and the total grade of LDD increased with age. LDD moved cephalad with age. The rate of LDD increased rapidly during the decade before the prevalence of LDD and became >50%. In the single-level LDD group, the levels L5-S1 were the most common levels (60.3%). In the two-level group, L4-L5 and L5-S1 were the most common levels (53.5%). In the three-level group, L3-L4, L4-L5, and L5-S1 were the most common levels (55.7%). In the multilevel LDD group, contiguous multilevel disc degeneration (CMDD) was more common than the skipped level disc degeneration (SLDD). The levels L4-L5 were the most common levels in the CMDD group, and L5-S1 were the most common levels among SLDD.

Conclusions: LDD was found to correlate with age, and the specific patterns and rates of LDD depended on lumbar disc level and age. These LDD pattern data can be used before spinal procedures to predict the probability of natural LDD progression with age.
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http://dx.doi.org/10.31616/asj.2020.0325DOI Listing
December 2020

Long-term, Time-course Evaluation of Ligamentum Flavum Hypertrophy Induced by Mechanical Stress: An Experimental Animal Study.

Spine (Phila Pa 1976) 2021 May;46(9):E520-E527

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Experimental animal study.

Objective: The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model.

Summary Of Background Data: LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated.

Methods: Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts.

Results: In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group.

Conclusion: We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.
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http://dx.doi.org/10.1097/BRS.0000000000003832DOI Listing
May 2021

Time Course of Physical and Mental Well-being Improvements After Cervical Surgery.

Spine (Phila Pa 1976) 2021 Mar;46(5):E303-E309

Department of Orthopedics, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Retrospective cohort study.

Objective: To elucidate the postoperative time course of improvements in physical and mental well-being in patients with cervical spondylotic myelopathy (CSM).

Summary Of Background Data: Spinal surgeons should understand the postoperative course in detail. However, data are still needed regarding the time course of improvements in well-being, a fundamental aspect of human life, after cervical surgery for CSM.

Methods: One hundred consecutive patients who underwent laminoplasty for CSM, with complete clinical data preoperatively and 3 months and 2 years postoperatively, were enrolled. The Short Form-36 physical component summary (PCS) and mental component summary (MCS) scores were used as parameters of physical and mental well-being, respectively, and 4.0 was defined as the minimal clinically important difference (MCID) for both parameters.

Results: On average, PCS and MCS scores were significantly improved after surgery (P < 0.001, P=0.004, respectively). Moreover, 64 and 48 patients achieved meaningful improvement (>MCID) in PCS and MCS scores at 3 months postoperatively, with maintained improvement (to 2 yr) in 46/64 (71.9%) and 34/48 patients (70.8%), respectively (PCS vs. MCS: P = 0.912). Additionally, 15 of 36 patients (41.7%) and 8 of 52 patients (15.4%) achieved late improvement (meaningful improvement at 2 yr but not at 3 months) in PCS and MCS scores, respectively (PCS vs. MCS: P = 0.007). In multivariate regression analysis, improvement in cJOA score was significantly associated with PCS improvement, but not MCS improvement, at both 3 months and 2 years (P = 0.001, P > 0.001, respectively).

Conclusion: The overall outcome of physical well-being improvement is decided within 3 months postoperatively, in proportion to the recovery in myelopathy, with a relatively high chance of meaningful improvement over the next 21 months. The outcome of improvement in mental well-being is decided within 3 months postoperatively, independently from the recovery in myelopathy, with a low chance of meaningful improvement over the next 21 months.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003787DOI Listing
March 2021

Risk Factor for Poor Patient Satisfaction After Lumbar Spine Surgery in Elderly Patients Aged Over 80 years.

Clin Spine Surg 2020 Oct 13. Epub 2020 Oct 13.

Department of Orthopaedic Surgery, Chiba University, Chiba, Japan.

Study Design: Retrospective cohort study.

Objective: To clarify the poor patient satisfaction after lumbar spinal surgery in elderly patients.

Summary Of Background Data: As the global population continues to age, it is important to consider the surgical outcome and patient satisfaction in the elderly. No studies have assessed patient satisfaction in elderly patients undergoing surgical treatment and risk factors for poor satisfaction in elderly patients after lumbar spinal surgery.

Materials And Methods: A retrospective multicenter survey was performed in 169 patients aged above 80 years who underwent lumbar spinal surgery. Patients were followed up for at least 1 year after surgery. We assessed patient satisfaction from the results of surgery by using a newly developed patient questionnaire. Patients were assessed by demographic data, surgical procedures, complications, reoperation rate, pain improvement, and risk factors for poor patient satisfaction with surgery for lumbar spinal disease.

Results: In total, 131 patients (77.5%, G-group) were satisfied and 38 patients (22.5%, P-group) were dissatisfied with surgery. The 2 groups did not differ significantly in baseline characteristics and surgical data. Postoperative visual analog scale score for low back pain and leg pain were significantly higher in the P-group than in the G-group (low back pain: G-group, 1.7±1.9 vs. P-group, 5.2±2.5, P<0.001; leg pain: G-group, 1.4±2.0 vs. P-group, 5.5±2.6, P<0.001). Multivariate regression analysis revealed that postoperative vertebral fracture (P=0.049; odds ratio, 3.096; 95% confidence interval, 1.004-9.547) and reoperation (P=0.025; odds ratio, 5.692; 95% confidence interval, 1.250-25.913) were significantly associated with the patient satisfaction after lumbar spinal surgery.

Conclusions: Postoperative vertebral fracture and reoperation were found to be risk factors for poor patient satisfaction after lumbar spinal surgery in elderly patients, which suggests a need for careful treatment of osteoporosis in addition to careful determination of surgical indication and procedure in elderly patients.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001101DOI Listing
October 2020

Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?

Asian Spine J 2020 Oct 19. Epub 2020 Oct 19.

Department of Orthopaedic Surgery, Osaka City University, Osaka, Japan.

Study Design: Retrospective radiological comparative design.

Purpose: To investigate whether conventional magnetic resonance imaging (MRI) could substitute three-dimensional (3D)-MRI for the calculation of the foraminal stenotic ratio (FSR) and clarification of which patients can be assessed more accurately using 3D-MRI.

Overview Of Literature: Previous studies have indicated that 3D-MRI is useful for diagnosing lumbar foraminal stenosis. The FSR obtained using 3D-MRI, described as the ratio of stenosis length, characterized by perineural fat obliteration, to the length of the entire foramen, could indicate the stenosis severity; however, this method is time-consuming and expensive. The FSR also can be calculated using conventional MRI.

Methods: We investigated 154 foramina at L5-S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed.

Results: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI.

Conclusions: FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.
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http://dx.doi.org/10.31616/asj.2020.0133DOI Listing
October 2020

Advanced glycation end products in musculoskeletal system and disorders.

Methods 2020 Sep 26. Epub 2020 Sep 26.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Japan.

The human population is ageing globally, and the number of old people is increasing yearly. Diabetes is common in the elderly, and the number of diabetic patients is also increasing. Elderly and diabetic patients often have musculoskeletal disorder, which are associated with advanced glycation end products (AGEs). AGEs are heterogeneous molecules derived from non-enzymatic products of the reaction of glucose or other sugar derivatives with proteins or lipids, and many different types of AGEs have been identified. AGEs are a biomarker for ageing and for evaluating disease conditions. Fluorescence, spectroscopy, mass spectrometry, chromatography, and immunological methods are commonly used to measure AGEs, but there is no standardized evaluation method because of the heterogeneity of AGEs. The formation of AGEs is irreversible, and they accumulate in tissue, eventually causing damage. AGE accumulation has been confirmed in neuromusculoskeletal tissues, including bones, cartilage, muscles, tendons, ligaments, and nerves, where they adversely affect biomechanical properties by causing charge changes and forming cross-linkages. AGEs also bind to receptors, such as the receptor for AGEs (RAGE), and induce inflammation by intracellular signal transduction. These mechanisms cause many varied aging and diabetes-related pathological conditions, such as osteoporosis, osteoarthritis, sarcopenia, tendinopathy, and neuropathy. Understanding of AGEs related pathomechanism may lead to develop novel methods for the prevention and therapy of such disorders which affect patients' quality of life. Herein, we critically review the current methodology used for detecting AGEs, and present potential mechanisms by which AGEs cause or exacerbate musculoskeletal disorders.
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http://dx.doi.org/10.1016/j.ymeth.2020.09.012DOI Listing
September 2020

Residual numbness of the upper extremity after cervical surgery in patients with cervical spondylotic myelopathy.

J Neurosurg Spine 2020 Jul 31:1-8. Epub 2020 Jul 31.

Objective: Although numbness is one of the chief complaints of patients with cervical spondylotic myelopathy (CSM), preoperative factors relating to residual numbness of the upper extremity (UE) and impact of the outcomes on cervical surgery are not well established. The authors hypothesized that severe preoperative UE numbness could be a risk factor for residual UE numbness after surgery and that the residual UE numbness could have a negative impact on postoperative outcomes. Therefore, this study aimed to identify the preoperative factors that are predictive of residual UE numbness after cervical surgery and demonstrate the effects of residual UE numbness on clinical scores and radiographic parameters.

Methods: The study design was a retrospective cohort study. The authors analyzed data of 103 patients who underwent cervical laminoplasty from January 2012 to December 2014 and were followed up for more than 2 years postoperatively. The patients were divided into two groups: the severe residual-numbness group (postoperative visual analog scale [VAS] score for UE numbness > 40 mm) and the no/mild residual-numbness group (VAS score ≤ 40 mm). The outcome measures were VAS score, Japanese Orthopaedic Association scores for cervical myelopathy, physical and mental component summaries of the 36-Item Short-Form Health Survey (SF-36), radiographic film parameters (C2-7 sagittal vertical axis, range of motion, C2-7 lordotic angle, and C7 slope), and MRI findings (severity of cervical canal stenosis, snake-eye appearance, severity of foraminal stenosis). Following univariate analysis, which compared the preoperative factors between groups, the variables with p values < 0.1 were included in the multivariate linear regression analysis. Additionally, the changes in clinical scores and radiographic parameters after 2 years of surgery were compared using a mixed-effects model.

Results: Among 103 patients, 42 (40.8%) had residual UE numbness. In the multivariate analysis, sex and preoperative UE pain were found to be independent variables correlating with residual UE numbness (p = 0.017 and 0.046, respectively). The severity of preoperative UE numbness did not relate to the residual UE numbness (p = 0.153). The improvement in neck pain VAS score and physical component summary of the SF-36 was significantly low in the severe residual-numbness group (p < 0.001 and 0.040, respectively).

Conclusions: Forty-one percent of the CSM patients experienced residual UE numbness for at least 2 years after cervical posterior decompression surgery. Female sex and preoperative severe UE pain were the predictive factors for residual UE numbness. The patients with residual UE numbness showed less improvement of neck pain and lower physical status compared to the patients without numbness.
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http://dx.doi.org/10.3171/2020.4.SPINE191566DOI Listing
July 2020

Do rheumatoid arthritis patients have low back pain or radiological lumbar lesions more frequently than the healthy population? - Cross-sectional analysis in a cohort study with age and sex-matched healthy volunteers.

Spine J 2020 12 2;20(12):1995-2002. Epub 2020 Jul 2.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background Context: Rheumatoid arthritis (RA) can affect the spine; however, the epidemiology of lumbar lesions and/or low back pain (LBP) in RA patients has not been well-studied.

Purpose: The purpose of this study was to compare the prevalence of lumbar lesions and LBP in RA patients with that in healthy volunteers, and to elucidate the influence of RA on lumbar disease.

Study Design: Cross-sectional analysis in a cohort study with age- and sex-matched healthy volunteers.

Patient Sample: This study included 185 patients with RA and 188 gender/age-matched healthy volunteers without RA.

Outcome Measures: Lumbar spondylolisthesis and prevalent vertebral fractures were evaluated using plain lateral X-ray images. Thoraco-lumbar scoliosis was evaluated using dual-energy X-ray absorptiometric images. LBP was assessed using the visual analogue scale (VAS) and Rolland-Morris disability questionnaire (RDQ).

Methods: The prevalence of radiological lumbar lesion and LBP was compared between the RA and control groups. In the RA group, factors associated with lumbar lesion and LBP were analyzed using a multiple logistic regression model.

Results: The prevalence rates of spondylolisthesis and prevalent vertebral fracture were significantly higher in the RA group than in the control group; the prevalence of thoraco-lumbar scoliosis tended to be higher in the RA group. There was no significant difference in the average LBP-VAS between the groups. However, the percentage of analgesic drug use was significantly higher, and RDQ scores tended to be worse in the RA group than the control group. Multivariate analysis revealed that age and disease activity score were both related to LBP in the RA group.

Conclusions: RA patients are more likely to have radiological lumbar lesions. LBP in RA patients is well controlled, similar to the level in the healthy population; however, disease activity was related to LBP in RA patients. These results suggest that disease control is important for lumbar care in RA patients.
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http://dx.doi.org/10.1016/j.spinee.2020.06.020DOI Listing
December 2020

The Severity of Cervical Disc Degeneration Does Not Impact 2-year Postoperative Outcomes in Patients With Cervical Spondylotic Myelopathy Who Underwent Laminoplasty.

Spine (Phila Pa 1976) 2020 Sep;45(18):E1142-E1149

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to evaluate the impact of cervical disc degeneration (CDD) severity on 2-year postoperative outcomes following laminoplasty.

Summary Of Background Data: The impact of CDD on postoperative outcomes of cervical laminoplasty has not been well established.

Methods: A total of 144 patients who underwent open-door laminoplasty for cervical spondylotic myelopathy (CSM) were enrolled. Six cervical discs were independently analyzed for degeneration severity using a previously reported grading system (grade 0: none, grade 3: severest). The relationship between the segmental range of motion (ROM) and the severity of CDD was evaluated. Subsequently, after dividing overall patients into mild and severe CDD groups by the average of CDD scores, the mixed-effect model was applied to assess 2-year postoperative outcomes, including physician-assessed myelopathy scores, patient-reported outcomes, and preoperative radiographic parameters. Finally, as additional analysis, the severe CDD group was further divided into two groups: group 1 included patients with a grade 3 CDD change in their most stenotic level and group 2 included the others. The 2-year postoperative myelopathy score was compared between groups 1 and 2.

Results: The cervical segments with grade 3 CDD showed significantly smaller ROM compared with those with grade 0, 1, or 2 CDD (P < 0.01). There were no significant differences in postoperative improvements in myelopathy, pain, patient-reported physical and mental status, and radiographic parameters, except for quality of life (QOL) scores between CDD groups. A significant (P = 0.02) postoperative improvement in QOL scores was noted in the severe CDD group. In an additional analysis, myelopathy score at 2 years postoperatively was significantly higher in group 1 than group 2 (P = 0.041).

Conclusion: The severity of CDD did not negatively impact 2-year postoperative laminoplasty outcomes. The postulated reason is that the decreased segmental instability in the level with severe CDD may affect surgical outcomes positively.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003528DOI Listing
September 2020

Patient-reported outcomes for cervical disease in end-stage renal disease patients: Propensity matching analysis using volunteer data.

J Clin Neurosci 2020 Feb 6;72:130-133. Epub 2020 Jan 6.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Japan.

As the number of patients with end-stage renal disease (ESRD) has been increasing, the number of cervical spine surgeries for the patients with ESRD has also been increasing. The purpose is to identify the differences in cervical disease-specific patient-reported outcomes (PROs) between a healthy population and patients with ESRD, adjusting for subjects' age and physical activity.

Methods: The ESRD group included patients with ESRD who were treated with hemodialysis in our outpatient clinic and healthy volunteers were individuals who attended public health lectures. Volunteers with a history of cervical disease were excluded. All participants answered the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and questionnaires that evaluate the disability in performing physical activities.

Results: A total of 111 participants were enrolled and divided into the ESRD group (n = 40) and the control group (n = 71). After adjusting for age and sex using propensity score, cervical function (p = 0.008), lower-extremity function (p = 0.007), and QOL (p < 0.001) in patients in the adjusted ESRD group were significantly lower than those in the control group. In multivariate linear regression, the use of hemodialysis was a significant variable that was negatively related to lower-extremity function (p = 0.004) and QOL (p = 0.011) independent of age and disability in performing physical activity.

Conclusion: The ESRD was a significant negative factor of lower-extremity function and QOL, independent of age, sex, and disability in performing physical activity. These results can help understand the cervical status of patients with ESRD and adjust the goal for such patients after cervical surgery.
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http://dx.doi.org/10.1016/j.jocn.2019.12.045DOI Listing
February 2020

Characteristic radiological findings for revision surgery after balloon kyphoplasty.

Sci Rep 2019 12 6;9(1):18513. Epub 2019 Dec 6.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Balloon kyphoplasty (BKP) sometimes fails to improve patients' outcomes, with revision surgery, using anterior or posterior reconstruction, being required. The purpose of this study was to investigate the radiological risk factors of failure after BKP in the treatment of osteoporotic vertebral fractures (OVFs). This case-control study included 105 patients treated with single BKP and 14 patients  who required revision BKP. We evaluated radiological findings differentiating both groups, using plain radiography and computed tomography, before BKP. Angular flexion-extension motion was significantly greater in the revision than BKP group. While the frequency of pedicle fracture and posterior wall injury was not different between the groups, a split type fracture was more frequent in the revision group. Split type fracture had the highest adjusted odds ratio (OR) for revision (16.5, p = 0.018). Angular motion ≥14° increased the risk for revision surgery by 6-fold (p = 0.013), with endplate deficit having an OR of revision of 5.0 (p = 0.032). The revision rate after BKP was 3.8%, with split type fracture, greater angular motion and large endplate deficit being risk factors for revision. Treatment strategies for patients with these risk factors should be carefully evaluated, considering the inherent difficulties in performing revision surgery after BKP.
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http://dx.doi.org/10.1038/s41598-019-55054-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898586PMC
December 2019

Improvement in Patient Mental Well-being After Surgery for Cervical Spondylotic Myelopathy.

Spine (Phila Pa 1976) 2020 May;45(10):E568-E575

Department of Orthopedics, Osaka City University Graduate School of Medicine, Asahimachi, Abenoku, Osaka, Japan.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to investigate changes in mental well-being after surgery for cervical spondylotic myelopathy (CSM) and identify factors associated with improvement.

Summary Of Background Data: Posterior cervical surgery with laminoplasty significantly improves myelopathy and physical function in patients with CSM. However, its impact on mental well-being is unclear.

Methods: Patients who underwent laminoplasty for CSM and had >2 years of follow-up were reviewed (n = 111). The mental component summary (MCS) score was used as a measure of mental well-being. The trend in MCS score change was evaluated using the Jonckheere-Terpstra trend test. Preoperative clinical scores were compared between patients with improvements greater and less than the minimal clinically important difference (MCID). Significant variables were included in a multinomial logistic regression analysis and further validated in a receiver-operating characteristic (ROC) curve analysis. Additionally, the results were confirmed in a long-term observation cohort of patients followed up for >5 years (n = 46).

Results: The improvement in the average MCS score (5.6) was greater than the MCID (4.0). The trend of improvement was sustained for 2 years (P = 0.002), but not for 5 years (P = 0.130). In terms of individual cases, 56 patients (50.5%) achieved MCS score improvement greater than the MCID. These patients showed significantly lower preoperative MCS scores than those without meaningful improvement (P < 0.001). The preoperative "social functioning (SF)" score was independently associated with MCS score improvement (P = 0.001). ROC curve analysis validated the ability of preoperative SF to predict MCS score improvement at 2 and 5 years postoperatively (area under the curve: 0.744, 0.893, respectively).

Conclusion: Half of the patients achieved meaningful improvement in mental well-being. A lower preoperative SF score was independently associated with improvement. These results may help identify patients who could experience an improvement in mental well-being after surgery and develop novel approaches to achieve further improvement.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003337DOI Listing
May 2020

Impact of Sarcopenia on Clinical Outcomes of Minimally Invasive Lumbar Decompression Surgery.

Sci Rep 2019 11 12;9(1):16619. Epub 2019 Nov 12.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

The purpose of this study was to clarify the clinical impact of sarcopenia on the outcome of minimally invasive lumbar decompression surgery. The records of 130 patients who were >65 years and underwent minimally invasive lumbar decompression surgery were retrospectively reviewed. We collected the Japanese Orthopaedic Association (JOA) score before surgery and at the final follow-up and measured appendicular muscle mass using bioimpedance analysis, hand-grip strength and gait speed. We diagnosed the patients with sarcopenia, dynapenia and normal stages using the European Working Group on Sarcopenia in Older People definition and used cutoff thresholds according to the algorithm set by the Asian Working Group for Sarcopenia. The average age of patients undergoing surgery was 76.9 years old. The JOA score improved from 12.6 points preoperatively to 24.3 points at final follow up. The prevalence of the sarcopenia, dynapenia and normal stages was 20.0, 31.6 and 43.8%. Clinical outcomes, such as JOA score, JOA score improvement ratio, visual analog scale for low back pain, leg pain and numbness, were not significantly different among each group. Multiple regression analysis showed that preoperative JOA score and low physical performance (low gait speed) were independently associated with poor clinical outcomes. The JOA score improved after minimally invasive lumbar decompression surgery even when the patients were diagnosed as being at different stages of sarcopenia. Low physical performance had the greater clinical impact on the clinical outcome of lumbar surgery than low skeletal muscle index.
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http://dx.doi.org/10.1038/s41598-019-53053-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851360PMC
November 2019

Design, Synthesis, and Photochemical Properties of Clickable Caged Compounds.

J Vis Exp 2019 10 15(152). Epub 2019 Oct 15.

Department of Biomolecular Science, Faculty of Science, Toho University;

Caged compounds enable the photo-mediated manipulation of the cell physiology with high spatiotemporal resolution. However, the limited structural diversity of currently available caging groups and the difficulties in synthetic modification without sacrificing their photolysis efficiencies are obstacles to expanding the repertoire of caged compounds for live cell applications. As the chemical modification of coumarin-type photo-caging groups is a promising approach for the preparation of caged compounds with diverse physical and chemical properties, we report a method for the synthesis of clickable caged compounds that can be modified easily with various functional units via the copper(I)-catalyzed Huisgen cyclization. The modular platform molecule contains a (6-bromo-7-hydroxycoumarin-4-yl)methyl (Bhc) group as a photo-caging group, which exhibits a high photolysis efficiency compared to those of the conventional 2-nitrobenzyls. General procedures for the preparation of clickable caged compounds containing amines, alcohols, and carboxylates are presented. Additional properties such as the water solubility and cell targeting ability can be readily incorporated into clickable caged compounds. Furthermore, the physical and photochemical properties, including the photolysis quantum yield, were measured and were found to be superior to those of the corresponding Bhc caged compounds. The described protocol could therefore be considered a potential solution for the lack of structural diversity in the available caged compounds.
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http://dx.doi.org/10.3791/60021DOI Listing
October 2019

Risk Factors for Proximal Junctional Fracture Following Fusion Surgery for Osteoporotic Vertebral Collapse with Delayed Neurological Deficits: A Retrospective Cohort Study of 403 Patients.

Spine Surg Relat Res 2019 Apr 19;3(2):171-177. Epub 2018 Oct 19.

Department of Orthopaedic Surgery, Keio University, Tokyo, Japan.

Introduction: Approximately 3% of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC.

Methods: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for ≥2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis.

Results: Sixty-three patients (15.6%) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm (sensitivity, 76.5%; specificity, 58.3%), but that of the hip was not (p=0.228).

Conclusions: PJFr was found in 16% cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.
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http://dx.doi.org/10.22603/ssrr.2018-0068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690093PMC
April 2019

Impact of Hemodialysis on Surgical Outcomes and Mortality Rate after Lumbar Spine Surgery: A Matched Cohort Study.

Spine Surg Relat Res 2019 Apr 25;3(2):151-156. Epub 2018 Aug 25.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Introduction: Despite ongoing improvements in both dialysis and surgical techniques, spinal surgery in patients undergoing hemodialysis (HD) is a challenge to surgeons because of the high mortality rate. However, no previous studies have examined clinical outcomes after lumbar surgery in HD patients. The purpose of this study is to compare clinical outcomes and complication rates after lumbar spinal surgery in patients with or without hemodialysis.

Methods: This retrospective, matched cohort study was conducted to compare surgical outcomes between HD vs non-HD patients who underwent lumbar surgery at our hospital. Controls were individually matched to cases at a ratio of 1:2. Clinical outcomes, complications, and mortality rates were compared between the two groups.

Results: Twenty-nine patients in the HD group and 57 in the non-HD group were included in the current study. Five patients in the HD group died during the follow-up period, whereas no patients died in the non-HD group (mortality rate, 17.2% vs. 0%, = 0.003). Japanese Orthopaedic Association (JOA) scores were significantly less improved in the HD group than in the non-HD group (11.9 vs. 14.2 preoperatively, = 0.001; 19.9 vs. 25.1 at final follow-up, < 0.001). Five patients underwent repeat surgery in the HD group, which was significantly higher than the non-HD group (17.2% vs. 3.5%, = 0.041).

Conclusions: The current study indicates that patients undergoing HD had poor outcomes after lumbar spinal surgery. Moreover, 5 of 29 patients died within a mean 2.4-years follow-up. The indications for lumbar spine surgery in HD patients must be carefully considered because of poor surgical outcomes and high mortality rate.
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http://dx.doi.org/10.22603/ssrr.2018-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690081PMC
April 2019

Sarcopenia is related to spinal sagittal imbalance in patients with spinopelvic mismatch.

Eur Spine J 2019 Sep 17;28(9):1929-1936. Epub 2019 Jul 17.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abenoku, Osaka, 545-8585, Japan.

Purpose: To clarify the relationship between sarcopenia and spinopelvic parameters.

Methods: Among outpatients of spine surgery department, 126 patients (mean age 77.2 years. M/F = 71/55) were included. We diagnosed patients with sarcopenia using the diagnostic algorithm of the Asian Working Group for Sarcopenia. Spinopelvic parameters and the prevalence of spinopelvic mismatch (pelvic incidence minus lumbar lordosis ≥ 10°) were investigated and compared between patients with and without sarcopenia. Furthermore, we compared the spinopelvic parameters between the Sarcopenia and No Sarcopenia groups under each condition of spinopelvic match and mismatch.

Results: The prevalence of sarcopenia in this study was 21.4%. Overall, the spinopelvic parameters except thoracic kyphosis (TK) (Sarcopenia: 34.7°, No Sarcopenia: 24.3°, p < 0.01) were not significantly different between the Sarcopenia and No Sarcopenia groups. Prevalence of patients with spinopelvic mismatch was also not significantly different between the Sarcopenia and No Sarcopenia groups (37.0% vs. 42.4%, p = 0.66). Among patients without spinopelvic mismatch, there was no spinopelvic parameter with a significant difference between the 2 groups. However, among patients with spinopelvic mismatch, sagittal vertebral axis (SVA) (115.7 mm vs. 58.7 mm, p < 0.01) and TK (36.6° vs. 21.3°, p < 0.01) of the Sarcopenia group were significantly larger than those of the No Sarcopenia group. Moreover, sarcopenia was independently related to a significant increase in SVA (β = 50.7, p < 0.01) and TK (β = 14.0, p < 0.01) in patients with spinopelvic mismatch, after adjustment for age.

Conclusions: Sarcopenia is related to spinal sagittal imbalance because of insufficient compensation by flattening thoracic kyphosis in patients with spinopelvic mismatch. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-06066-2DOI Listing
September 2019

Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons.

Commun Biol 2019 2;2:247. Epub 2019 Jul 2.

1Center for Neural Science, New York University, New York, NY 10003 USA.

Glycogenolysis and lactate transport from astrocytes to neurons is required for long-term memory formation, but the role of this lactate is poorly understood. Here we show that the Krebs cycle substrates pyruvate and ketone body B3HB can functionally replace lactate in rescuing memory impairment caused by inhibition of glycogenolysis or expression knockdown of glia monocarboxylate transporters (MCTs) 1 and 4 in the dorsal hippocampus of rats. In contrast, either metabolite is unable to rescue memory impairment produced by expression knockdown of MCT2, which is selectively expressed by neurons, indicating that a critical role of astrocytic lactate is to provide energy for neuronal responses required for long-term memory. These responses include learning-induced mRNA translation in both excitatory and inhibitory neurons, as well as expression of Arc/Arg3.1. Thus, astrocytic lactate acts as an energy substrate to fuel learning-induced de novo neuronal translation critical for long-term memory.
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http://dx.doi.org/10.1038/s42003-019-0495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606643PMC
May 2020

Increased advanced glycation end products in hypertrophied ligamentum flavum of diabetes mellitus patients.

Spine J 2019 10 10;19(10):1739-1745. Epub 2019 Jun 10.

Department of Orthopaedic Surgery, Osaka City University, 1-4-3 Asahi Machi, Abeno-Ku, Osaka 545-8585, Japan.

Background Context: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). Although LSS prevalence is known to be higher in patients with diabetes mellitus (DM), the underlying pathomechanisms are not well understood. Abnormal advanced glycation end products (AGEs) formation occurs in DM and promotes tissue damage in various organs through degeneration and inflammation.

Purpose: To analyze and compare LF histology focused on AGE status between control patients, LSS patients with DM, and LSS patients without DM.

Study Design/setting: Basic research study design utilizing human LF tissue for histologic analyses.

Patient Sample: LF tissue samples were collected from patients who underwent lumber decompression surgery for LSS in the author's institution.

Outcome Measures: Quantitative visualization of Masson's Trichrome (MT) stains, and AGE immunohistochemistry (IHC) for the three groups.

Methods: Ten LF specimens from LSS patients with DM (DM group, mean age 71.4 years), 10 from LSS patients without DM (non-DM group, mean age 71.2 years), and 9 from patients with lumbar disc herniation or cauda equina tumor (control group, mean age 49.0 years) were harvested during surgery and histologically analyzed. Percentage of elastic fiber areas (%EF) was measured with MT staining, and the percentage of AGE immuno-positive areas (%AGEs) was measured with IHC.

Results: The average %EFs were 12.8 in the DM group, 17.1 in the non-DM group, and 24.9 in the control group. The decrease in the elastic fibers was significantly more in the DM group than in the non-DM (p<.01) and control groups (p<.001). Accumulation of AGEs was found mainly in the extracellular matrix in areas of elastic fiber disruption. The %AGEs were 18.3 in the DM group, 12.1 in the non-DM group, and 4.6 in the control group. These were significantly larger in the DM group than in the non-DM (p<.01) and control (p<.01) groups. The %AGEs also positively correlated with patient age (p<.01, R=0.47).

Conclusions: Accumulation of AGEs is significantly greater in the LF of DM patients and correlates with patient age. AGEs may accelerate degeneration and hypertrophy of LF with age and may lead to higher prevalence of LSS in patients with DM.

Clinical Significance: The present results partly reveal the molecular mechanism of LF hypertrophy, suggesting that AGEs may be involved in the process of LF degeneration in the elderly and patients with DM.
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http://dx.doi.org/10.1016/j.spinee.2019.06.001DOI Listing
October 2019