Publications by authors named "Shiro Imagama"

442 Publications

Activation of transient receptor potential vanilloid 4 protects articular cartilage against inflammatory responses via CaMKK/AMPK/NF-κB signaling pathway.

Sci Rep 2021 Jul 30;11(1):15508. Epub 2021 Jul 30.

Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 446-8560, Japan.

Transient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV4 activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.
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http://dx.doi.org/10.1038/s41598-021-94938-3DOI Listing
July 2021

Metabolic reprogramming in chondrocytes to promote mitochondrial respiration reduces downstream features of osteoarthritis.

Sci Rep 2021 Jul 23;11(1):15131. Epub 2021 Jul 23.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Metabolic dysfunction in chondrocytes drives the pro-catabolic phenotype associated with osteoarthritic cartilage. In this study, substitution of galactose for glucose in culture media was used to promote a renewed dependence on mitochondrial respiration and oxidative phosphorylation. Galactose replacement alone blocked enhanced usage of the glycolysis pathway by IL1β-activated chondrocytes as detected by real-time changes in the rates of proton acidification of the medium and changes in oxygen consumption. The change in mitochondrial activity due to galactose was visualized as a rescue of mitochondrial membrane potential but not an alteration in the number of mitochondria. Galactose-replacement reversed other markers of dysfunctional mitochondrial metabolism, including blocking the production of reactive oxygen species, nitric oxide, and the synthesis of inducible nitric oxide synthase. Of more clinical relevance, galactose-substitution blocked downstream functional features associated with osteoarthritis, including enhanced levels of MMP13 mRNA, MMP13 protein, and the degradative loss of proteoglycan from intact cartilage explants. Blocking baseline and IL1β-enhanced MMP13 by galactose-replacement in human osteoarthritic chondrocyte cultures inversely paralleled increases in markers associated with mitochondrial recovery, phospho-AMPK, and PGC1α. Comparisons were made between galactose replacement and the glycolysis inhibitor 2-deoxyglucose. Targeting intermediary metabolism may provide a novel approach to osteoarthritis care.
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http://dx.doi.org/10.1038/s41598-021-94611-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302637PMC
July 2021

The Level of Conus Medullaris in 629 Healthy Japanese Individuals.

J Clin Med 2021 Jul 19;10(14). Epub 2021 Jul 19.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

The conus medullaris typically terminates at the L1 level; however, variations in its level and the factors associated with the conus medullaris level are unclear. We investigated the level of conus medullaris on magnetic resonance imaging in healthy volunteers. In total, 629 healthy adult volunteers (≥50 individuals of each sex and in each decade of age from 20 to 70) were enrolled. The level of the conus medullaris was assessed based on the T2-weighted sagittal magnetic resonance images, and factors affecting its level were investigated employing multivariate regression analysis including the participants' background and radiographical parameters. L1 was the most common conus medullaris level. Participant height was significantly shorter in the caudally placed conus medullaris ( = 0.013). With respect to the radiographical parameters, pelvic incidence ( = 0.003), and pelvic tilt ( = 0.03) were significantly smaller in participants with a caudally placed conus medullaris. Multiple regression analysis showed that the pelvic incidence ( < 0.0001) and height ( < 0.0001) were significant factors affecting the conus medullaris level. These results indicated that the length of the spinal cord varies little among individuals and that skeletal differences affect the level of the conus medullaris.
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http://dx.doi.org/10.3390/jcm10143182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305241PMC
July 2021

Age-related degenerative changes and sex-specific differences in osseous anatomy and intervertebral disc height of the thoracolumbar spine.

J Clin Neurosci 2021 Aug 21;90:317-324. Epub 2021 Jun 21.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

The aim of this study was to determine age-related changes and sex-specific differences in sagittal alignment, range of motion (ROM), and intervertebral disc height of the thoracolumbar spine in healthy subjects. Lateral neutral and flexion-extension radiographs of the thoracolumbar spine of 627 asymptomatic subjects (307 males and 320 females; average age, 49.6 ± 16.5 years) were evaluated. We included at least 50 males and 50 females in each decade of life between the 20s and the 70s. Intervertebral disc height from T10/T11 to L5/S1, local lordotic alignment, and ROM from T10-T11 to L5-S1 were measured. T10-L2 kyphosis and T12-S1 lordosis as well as flexion, extension, and total ROM were measured. T10-L2 kyphosis did not markedly change with age in subjects of either sex but a sudden increase was noted in the 70s females. T12-S1 lordosis increased with age in both sexes, except the 70s. Flexion, extension, and total ROM at T10-L2 and T12-S1 decreased with age in most subjects. The levels from L3-L4 to L5-S1 were conspicuous as mobile segments. Intervertebral disc height gradually increased from T10/T11 to L4/L5; the shortest was at T10/T11 and the longest at L3/L4 or L4/L5 in all subjects. Age-related decreases in intervertebral disc height were most prominent at L4/L5 in middle-aged and elderly individuals of both sexes. Normative values of sagittal alignment, ROM, and intervertebral disc height at each segmental level were established in both sexes and all age groups in healthy subjects.
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http://dx.doi.org/10.1016/j.jocn.2021.06.020DOI Listing
August 2021

Dermatan sulfate is an activating ligand of anaplastic lymphoma kinase.

J Biochem 2021 Jul 16. Epub 2021 Jul 16.

Departments of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that harbors a tyrosine kinase domain in its intracellular region and is expressed in both central and peripheral nervous systems. RTKs are activated upon ligand binding and receptor clustering; however, ALK remains an orphan receptor despite its pathological significance, especially in malignancy. Recent biochemical work showed that heparan sulfate (HS), an unbranched sulfated glycan, acts as a ligand for and activates ALK. Here we show that dermatan sulfate (DS, chondroitin sulfate B) directly interacts with the extracellular N-terminal region of ALK as well as HS. The tetrasaccharide of DS was required and was sufficient for inducing autophosphorylation of ALK at tyrosine 1604, a marker for activated ALK. Interestingly, longer oligosaccharides caused enhanced activation of ALK, as was the case for HS. Our results provide a novel example of glycans as signaling molecules and shed light on the pathophysiological roles of ALK.
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http://dx.doi.org/10.1093/jb/mvab085DOI Listing
July 2021

The impact of ossification spread on cervical spine function in patients with ossification of the posterior longitudinal ligament.

Sci Rep 2021 Jul 12;11(1):14337. Epub 2021 Jul 12.

Department of Orthopaedic Surgery, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo , Japan.

Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. The bridging of ossified lesions to the vertebral body gradually increases, thereby decreasing the mobility of the cervical spine; thus, cervical spine function may decrease over time. However, cervical spine function in patients with cervical OPLL has not been evaluated in large prospective studies. Therefore, we conducted a prospective multicenter study to clarify whether ossification spread can influence cervical spine function and quality of life (QOL) in patients with cervical OPLL. In total, 238 patients (162 men, 76 women; mean age, 63.9 years) were enrolled from 16 institutions. Each patient underwent whole spine computed tomography and was evaluated for cervical spine function and QOL using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). In the multivariate regression analysis, a higher neck VAS score and a larger number of bridge formations of OPLL in the whole spine were significant predictors of adverse outcomes related to cervical spine function. This is the first prospective multicenter study to reveal the impact of ossification spread on cervical spine function. These findings are important to understand the natural course of OPLL and can serve as controls when evaluating postoperative cervical spine function.
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http://dx.doi.org/10.1038/s41598-021-93602-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275804PMC
July 2021

Ossification of the posterior longitudinal ligament located on the concave side of the apex vertebra in adult spinal deformity.

Nagoya J Med Sci 2021 May;83(2):387-392

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

A 48-year-old female patient presented with discomfort in the front of the chest. Whole spinal X-ray revealed a thoracic curve of 52°, and thoracic computed tomography (CT) myelography and magnetic resonance imaging (MRI) showed that ossification of the posterior longitudinal ligament (OPLL) on the concave side of the apex vertebra (T9) had highly compressed the spinal cord. Cervical MRI also showed that the C4-C5 intervertebral disc herniation mildly compressed the spinal nerve. In concomitant surgery, the patient underwent cervical laminoplasty, in which OPLL was removed by decompressive laminectomy and posterior correction surgery.In patients with adult spinal deformity (ASD), asymmetric mechanical stress at the apex vertebra can cause various abnormal conditions. Long-term local mechanical stress on the concave side of the apex vertebra might have affected OPLL formation in the present case. This is the first report of a surgical case for an ossification located on the concave side of the apex vertebra in a patient with ASD. Mechanical stress at the concave side of the apex vertebra was suspected to be a cause of formation of OPLL.
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http://dx.doi.org/10.18999/nagjms.83.2.387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236683PMC
May 2021

Overexpression of KIAA1199, a novel strong hyaluronidase, is a poor prognostic factor in patients with osteosarcoma.

J Orthop Surg Res 2021 Jul 7;16(1):439. Epub 2021 Jul 7.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.

Background: Hyaluronan (HA) has been shown to play important roles in the growth, invasion, and metastasis of malignant tumors. KIAA1199, which has potent HA-degrading activity, has been reported to be expressed in various malignancies and associated with patient prognosis. However, there are no reports on the expression of KIAA1199 in osteosarcoma. The aim of this study was to investigate the impact of KIAA1199 and HA expression in osteosarcoma tissues on the prognosis and other clinical characteristics of osteosarcoma patients.

Methods: From 2003 to 2013, we included 49 patients with osteosarcoma at our institution, whose FFPE (formalin fixed paraffin embedded) tissue was available at the time of biopsy. The expressions of KIAA1199 and HA in each sample were assessed by immunohistochemistry using the primary antibody for KIAA1199 and HA-binding protein (HABP), respectively. For evaluation of the positivity of KIAA1199 staining, we divided the samples into two groups: High group with more than 75% positive staining and Low group with less than 75% positive staining. In the HABP staining, those with more than and less than 60% were assigned to a High group, and Low group respectively. Various clinical features were correlated with staining positivity. Prognostic factors including positivity of the staining were analyzed. Levels of mRNA expression for enzymes related to HA metabolism were assessed in two osteosarcoma cell lines using real-time RT-PCR.

Results: In KIAA1199 staining, high positivity was significantly correlated with occurrence of distant metastases (P = 0.002). The necrosis rate after preoperative chemotherapy was significantly lower in the High positivity group (59%), compared to that in the Low group (84.8%) (P = 0.003). HABP positivity was not correlated with any demographic variables, although the Low positivity group had a significantly better overall survival than the High group with KIAA1199 and HABP staining (P = 0.026 and P = 0.029, respectively). In multivariable analysis, KIAA1199 (P = 0.036) and HABP staining (P = 0.002), location (P = 0.001), and distant metastasis at initial diagnosis (P < 0.001) were identified as significant prognostic factors. KIAA1199 and hyaluronan synthase mRNA were expressed at different levels in the two osteosarcoma cell lines.

Conclusions: Our results showed that high expression of KIAA1199 and HA are both poor prognostic factors in osteosarcoma. KIAA1199 may be a useful marker for distant metastasis and chemoresistance.
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http://dx.doi.org/10.1186/s13018-021-02590-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262042PMC
July 2021

Efficacy of Intraoperative Neuromonitoring Using Transcranial Motor-Evoked Potentials for Degenerative Cervical Myelopathy: A Prospective Multicenter Study by the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

Spine (Phila Pa 1976) 2021 Jul 1. Epub 2021 Jul 1.

Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan Department of Orthopedic Surgery, Yamaguchi Rosai Hospital, Yamaguchi, Japan Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan Department of Orthopedic Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan Department of Orthopedic Surgery, Kansai Medical University, Osaka, Japan Department of Orthopedic Surgery, Kurume University, Kurume, Japan Department of Orthopedic Surgery, Wakayama Medical University, Wakayama, Japan Department of Orthopedic Surgery, Kochi University, Kochi, Japan Department of Orthopedic Surgery, Kyorin University, Tokyo, Japan Department of Orthopedic Surgery, Hirosaki University, Hirosaki, Japan Department of Orthopedic Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan Department of Orthopedic Surgery, Nara Medical University, Nara, Japan Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan Division of Central Clinical Laboratory, Nara Medical University, Nara, Japan Department of Orthopedic Surgery, Kubokawa Hospital, Kochi, Japan The Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

Study Design: A prospective multicenter observational study.

Objective: To elucidate the efficacy of transcranial motor-evoked potentials (Tc(E)-MEPs) in degenerative cervical myelopathy (DCM) surgery by comparing cervical spondylotic myelopathy (CSM) to cervical ossification of the posterior longitudinal ligament (OPLL) and investigate the timing of Tc(E)-MEPs alerts and types of interventions affecting surgical outcomes.

Summary Of Background Data: Although CSM and OPLL are the most commonly encountered diseases of DCM, the benefits of Tc(E)-MEPs for DCM remain unclear and comparisons of these two diseases have not yet been conducted.

Methods: We examined the results of Tc(E)-MEPs from 1176 DCM cases (840 CSM /336 OPLL) and compared patients background by disease, preoperative motor deficits, and the type of surgical procedure. We also assessed the efficacy of interventions based on Tc(E)-MEPs alerts. Tc(E)-MEPs alerts were defined as an amplitude reduction of more than 70% below the control waveform. Rescue cases were defined as those in which waveform recovery was achieved after interventions in response to alerts and no postoperative paralysis.

Results: Overall sensitivity was 57.1%, and sensitivity was higher with OPLL (71.4%) than with CSM (42.9%). The sensitivity of acute onset segmental palsy including C5 palsy was 40% (OPLL/CSM: 66.7%/0%) whereas that of lower limb palsy was 100%. The most common timing of Tc(E)-MEPs alerts was during decompression (63.16%), followed by screw insertion (15.79%). The overall rescue rate was 57.9% (OPLL/CSM: 58.3%/57.1%).

Conclusion: Since Tc(E)-MEPs are excellent for detecting long tract injuries, surgeons need to consider appropriate interventions in response to alerts. The detection of acute onset segmental palsy by Tc(E)-MEPs was partially possible with OPLL, but may still be difficult with CSM. The rescue rate was higher than 50% and appropriate interventions may have prevented postoperative neurological complications.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004156DOI Listing
July 2021

Impact of Neck and Shoulder Pain on Health-Related Quality of Life in a Middle-Aged Community-Living Population.

Biomed Res Int 2021 8;2021:6674264. Epub 2021 Jun 8.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Japan.

Purpose: Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup.

Methods: This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool.

Results: Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76).

Conclusions: The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.
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http://dx.doi.org/10.1155/2021/6674264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208860PMC
June 2021

Human Nonmercaptalbumin Is a New Biomarker of Motor Function.

J Clin Med 2021 Jun 2;10(11). Epub 2021 Jun 2.

Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan.

The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group; f[HMA] ≥ 70%) and low (L group; f[HMA] < 70%) groups. There were 124 non-elderly (<65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.
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http://dx.doi.org/10.3390/jcm10112464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199584PMC
June 2021

A Longitudinal Study of Lumbar Sagittal Change in Middle-Aged Healthy Volunteers.

Spine Surg Relat Res 2021 23;5(3):160-164. Epub 2020 Sep 23.

Department of Orthopedic Surgery, Nagoya University Hospital, Graduate School of Medicine, Aichi, Japan.

Introduction: Recent research has shown that spinal sagittal alignment plays a critical role in health-related quality of life. However, most of these studies were cross-sectional in nature, and longitudinal studies of lumbar lordosis (LL) in healthy subjects were few. This study aims to evaluate the change in lumbar sagittal parameters during a 10-year period.

Methods: The study population included 45 individuals (mean age, 65.7 years; male, n=20; female, n=25) who underwent sagittal lumbar radiography and a basic health checkup during a 10-year period. The radiologic parameters were LL, disc angle, sacral slope angle (SS), and pelvic incidence (PI). The change of LL during the 10-year period was defined as ΔLL. The subjects were divided into the LL maintenance group (n=33) and the LL non-maintenance group (n=12) based on their LL values.

Results: The radiologic baseline/final parameters were as follows: LL, 45/34 degrees (P<0.001); L1/L2 disc angle, 4.5/2.5 degrees; L2/L3 disc angle, 5.5/2.7 degrees; L3/L4 disc angle, 6.2/4.2 degrees; L4/L5 disc angle, 8.1/5.1 degrees; L5/S disc angle, 14.2/12.2 degrees; and SS, 32.0/32.1 degrees. The mean PI (50.5 degrees) was tended to be associated with the final LL (R=0.31, P=0.044) and was correlated with the ΔLL (R=0.43, P<0.01). The data of the LL maintenance/non-maintenance groups were as follows: age, 65.0/67.0; primary LL, 43.2/50.2 degrees (P<0.05); final LL, 36.2/27.8 degrees (P<0.05); and PI, 52.8/43.8 degrees (P<0.01).

Conclusions: During the 10-year study period, the LL in middle-aged and elderly volunteers decreased by 11 degrees. The factor of maintenance of LL was PI.
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http://dx.doi.org/10.22603/ssrr.2020-0123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208952PMC
September 2020

Does pulmonary function improve after surgical correction of adult idiopathic scoliosis?

Spine Deform 2021 Jun 27. Epub 2021 Jun 27.

Pediatric Pulmonary Division, Room OC.7.721, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA, 98145, USA.

Purpose: The aim was to investigate pulmonary function after surgical correction of adult idiopathic scoliosis.

Methods: This study included 146 adult scoliosis patients aged 20-50 years (main curve in thoracic spine). Respiratory function was assessed as predicted forced vital capacity (%FVC) and the ratio of forced expiratory volume in 1 s / FVC (%FEV) preoperatively and 2 years postoperatively and classified as a normal function (≥ 80%), mild impairment (≥ 65% and < 80%), and moderate impairment (< 65%).

Results: Preoperative %FVC and %FEV were 85.3% and 85.4%, which were 81.5% and 87.5% at 2 years post-surgery. The preoperative %FVC was mild and moderate in 39 (26.7%) and 12 patients (11.6%), respectively. The %FVC significantly improved (+ 6.2% ± 11.4%, P < 0.001) postoperatively for moderate severity but significantly decreased postoperatively (- 6.4% ± 9.4%, P < 0.001) for normal function. The preoperative %FEV was mild and moderate in 27 (18.5%) and 0 patients, respectively. The %FEV1 significantly improved postoperatively (6.3% ± 5.3%, P < 0.001) for mild severity but did not significantly change for normal severity. Twenty-three (15.8%) and 41 (28.1%) patients showed improved ⊿%FVC and ⊿% FEV > 5%. Logistic regression analysis showed that preoperative %FVC and %FEV severities were independent factors affecting postoperative recovery of %FVC (OR 0.95) and %FEV (OR 0.85).

Conclusion: Pulmonary function improved in patients with preoperative pulmonary impairment of < 65% in %FVC and < 80% in %FEV, and the real improvement was limited to patients with severe preoperative impairment.
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http://dx.doi.org/10.1007/s43390-021-00379-3DOI Listing
June 2021

Does surgical treatment for unstable fragility fracture of the pelvis promote early mobilization and improve survival rate and postoperative clinical function?

Eur J Trauma Emerg Surg 2021 Jun 22. Epub 2021 Jun 22.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Purpose: This retrospective multicenter study aimed to compare rates of early mobilization and survival and functional outcome of surgical treatment (S) with that of conservative treatment (C) according to each unstable fragility fracture of the pelvis (FFP) classification type with displacement of the posterior component ≥ 5 mm.

Methods: We analyzed 64 patients with unstable type III and IV FFP who could move and transfer themselves before injury and had ≥ 5 mm displacement of the posterior component. We compared survival rate, early mobilization, walking ability at final follow-up, and complications at admission for each type of surgical and conservative treatment.

Results: Most of the unstable FFP were type IIIa and IVb in the study population. Type III comprised 40 cases (group S:13/group C:27) and type IV comprised 24 cases (group S:7/group C:17). There were no significant differences in 3 month and 1 year survival rates, although group C (III) had the tendency of higher mortality rate (p = 0.08). Mobilization (transferring to a wheelchair) was enabled significantly earlier in group S (III) than in group C (III) (p = 0.02), but in type IV, most patients enabled early mobilization even without surgical intervention. There were no significant differences in hospital complications and walking ability at final follow-up.

Conclusion: In this study, the superiority of surgical treatment for unstable FFP was not proven. However, the results suggest that type IVb may be a relatively stable type compared to type III and that type IVb should be considered separately from bilaterally complete unstable sacral fractures due to high-energy trauma.
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http://dx.doi.org/10.1007/s00068-021-01729-6DOI Listing
June 2021

Association Between Knee Alignment and Meniscal Tear in Pediatric Patients with Anterior Cruciate Ligament Injury.

J Bone Joint Surg Am 2021 Jun 18. Epub 2021 Jun 18.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: The present study aimed to evaluate the association between elapsed time from anterior cruciate ligament (ACL) injury to surgical treatment and the incidence of meniscal tears in a cohort of patients ≤16 years old with varus-aligned and non-varus-aligned knees.

Methods: The study cohort included 123 patients ≤16 years old who underwent primary ACL reconstruction between January 2016 and March 2020. Knee alignment was expressed as the hip-knee-ankle angle (HKAA), as measured preoperatively on an anteroposterior view of 3-dimensional computed tomography of the full length of the lower limb. Varus alignment was defined as an HKAA ≥181.0°, and non-varus alignment was defined as an HKAA <181.0°. Patients were divided into groups according to knee alignment and the elapsed time from injury to surgical treatment: early-treatment group (<60 days) and delayed-treatment group (≥60 days).

Results: A total of 64 varus-aligned and 59 non-varus-aligned knees were identified. Among patients with varus-aligned knees, those in the delayed-treatment group showed a significantly lower rate of lateral meniscal tears (6 of 30, 20%) compared with those in the early-treatment group (17 of 34, 50%; p = 0.015). Among patients with non-varus-aligned knees, there was no significant difference in meniscal tears of any type between the early and delayed-treatment groups. Among patients without medial meniscal injury identified on initial magnetic resonance imaging, those with varus-aligned knees in the delayed-treatment group showed a significantly higher rate of medial meniscal tears at the time of the surgical procedure (8 of 20, 40%) compared with those with non-varus-aligned knees (1 of 18, 6%; p = 0.015).

Conclusions: Delayed ACL reconstruction in patients ≤16 years old with varus-aligned knees might be associated with an increased incidence of secondary medial meniscal tears. Accordingly, earlier ACL reconstruction in patients with varus-aligned knees should be considered.

Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.01219DOI Listing
June 2021

Comparison of the effects of baricitinib and tocilizumab on disease activity in patients with rheumatoid arthritis: a propensity score matching analysis.

Clin Rheumatol 2021 Aug 16;40(8):3143-3151. Epub 2021 Jun 16.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Objective: This study aimed to compare the effects of baricitinib, a Janus kinase inhibitor, and tocilizumab, a monoclonal anti-interleukin-6 receptor antibody, on disease activity in patients with rheumatoid arthritis (RA), and to investigate the influence of inflammation on improvement in patient global assessment (PGA) of disease activity.

Methods: This study was performed based on data from a multicenter registry, and included 284 and 113 patients treated with tocilizumab and baricitinib, respectively, who were observed for longer than 24 weeks. Propensity score matching was performed to address potential treatment-selection bias. To assess the influence of inflammation on PGA, patients were divided into two groups based on whether or not they achieved improvement in C-reactive protein (CRP, an objective marker of inflammation) at 24 weeks.

Results: A total of 48 matched pairs of patients were identified. Compared to treatment with tocilizumab, baricitinib showed a similar improvement in tender and swollen joint count and serum CRP levels, and a significantly greater improvement in PGA at 24 weeks. As a result, the baricitinib group had a significantly higher proportion of patients who achieved Boolean remission at 24 weeks. In subgroups of patients who did not achieve 50% or 70% CRP improvement, significant decreases from baseline to 24 weeks were observed in PGA in patients treated with baricitinib, but not in those treated with tocilizumab.

Conclusion: Compared to tocilizumab, baricitinib significantly improved PGA despite similar effects on inflammation in patients with RA. Moreover, the influence of inflammation on PGA improvement differed between baricitinib and tocilizumab. Key-points • Baricitinib and tocilizumab had similar effects on inflammation in RA patients. • Baricitinib improved patient global assessment (PGA) more than tocilizumab. • Baricitinib had a higher Boolean remission rate than tocilizumab at 24 weeks. • Influence of inflammation on PGA improvement differed between the two drugs.
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http://dx.doi.org/10.1007/s10067-021-05815-3DOI Listing
August 2021

Characteristics of cases with and without calcification in spinal meningiomas.

J Clin Neurosci 2021 Jul 29;89:20-25. Epub 2021 Apr 29.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.

Purpose: To quantify calcification in spinal meningiomas using Hounsfield unit (HU) values on CT, and to analyze the characteristics of cases with and without calcification and with different histologic subtypes.

Methods: The subjects were 53 patients who underwent surgical resection of spinal meningioma between January 1999 and December 2019. Clinical and surgical data were collected, and all patients were examined neurologically preoperatively and at final follow-up using the modified McCormick scale and the American Spinal Injury Association scale. Calcification was quantified on CT of the spine prior to surgery. A HU value >60 was considered to indicate calcification.

Results: The 53 patients (11 males, 42 females) were aged 62.4 ± 14.3 (range 19 to 91) years at surgery, and had a symptom duration of 10.8 ± 9.0 (1-36) months. The histological type was meningothelial in 35 cases, psammomatous in 13, and others in 5. The mean tumor volume was 1166 ± 350 (593-2176) mm, and the mean HU value was 212.2 ± 192.8 (43-648). Forty cases (75%) had calcification (HU value > 60). HU values were significantly related to duration of symptoms (R = 0.590, p < 0.05) and significantly higher in psammomatous cases (p < 0.05). Cases with calcification had longer operative times and greater blood loss, and a significantly lower rate of neurological improvement.

Conclusion: CT was effective for detecting calcification based on HU values. Detection of a HU value > 60 in spinal meningioma may be useful to narrow the differential diagnosis, evaluate the difficulty of resection, and improve intraoperative management, all of which may improve outcomes.
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http://dx.doi.org/10.1016/j.jocn.2021.04.019DOI Listing
July 2021

Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphorylation in the anti-inflammatory effect of 2-deoxyglucose.

Arch Biochem Biophys 2021 Sep 8;708:108962. Epub 2021 Jun 8.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. But, changes in the metabolism of normal synovial membranes or synovial cells during the early stages of inflammation remains unknown. Moreover, there are still many aspects of inflammatory signaling pathways altered by glycolysis inhibitors, that remain unclear. In this study we found that, in normal, non-pathological bovine synovial cells, most of ATP synthesis was generated by mitochondrial respiration. However, during the early of stages inflammation, initiated by lipopolysaccharide (LPS) exposure, synovial cells shifted to glycolysis for ATP production. The glycolysis inhibitor 2-deoxyglucose (2DG) reversed LPS induced increases in glycolysis for ATP production and suppressed the expression of inflammatory cytokines and proteolytic enzymes. 2DG suppressed the phosphorylation of the transcription factor cAMP response element binding protein (CREB) enhanced by LPS. Treatment with a CREB inhibitor reversed the expression of LPS-stimulated inflammatory cytokines and proteolytic enzymes. This study showed that changes in metabolism occur during the early stages of inflammation of synovial cells and can be reversed by 2DG and signaling pathways associated with CREB phosphorylation.
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http://dx.doi.org/10.1016/j.abb.2021.108962DOI Listing
September 2021

Lumbar Thecal Sac Dimensions and Axial Spinal Cord Areas on Magnetic Resosnace Imaging in 626 Healthy Subjects.

Spine (Phila Pa 1976) 2021 Jun 10. Epub 2021 Jun 10.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan Department of Orthopedics Surgery, Chubu Rosai Hospital, Minato-ku, Nagoya, Japan.

Study Design: A cross-sectional study.

Objective: The aim of this study was to investigate the lumbar thecal sac dimensions and spinal cord area on magnetic resonance (MR) imaging in healthy volunteers.

Summary Of Background Data: There are few reports regarding lumbar spine MRI in healthy subjects, and the difference in spinal canal dimensions by age remains unclear.

Methods: A total of 629 healthy volunteers were enrolled, including ≥50 males, females, and subjects in each of the 20s to 70s age decades. The anteroposterior and transverse diameters of the thecal sac and axial areas of the thecal sac and spinal cord were measured at the disc levels on T2-weighted axial MR images. The anteroposterior-to-transverse ratio of the thecal sac (APTR) was calculated.

Results: The thecal sac area from T12/L1 to L4/5 was reduced in older age group, but there was no significant difference in L5/S1. The thecal sac area was significantly reduced in older age group: 89.9%, 86.0%, 84.6%, 80.3% at T12/L1, L1/2, L2/3, and L3/4, respectively, and 79.9% at L4/5 in subjects in their 70 s relative to that in subjects in their 20 s. The APTR was significantly reduced in older age group from T11/12 to L2/L3 in males and at T10/11, L3/4 and from T11/12 to L2/3 in females. Narrow thecal sac areas <80 mm2 were found in 10 subjects. The spinal cord area was significantly reduced in older age group at T10/11 in males and at T9/10, T10/11, and T11/12 in females. The area was 92.0% at T10/11 in subjects in their 70s relative to the area of subjects in their 20s.

Conclusion: The thecal sac area was reduced in older age group from T12/L1 to L4/5, and the thecal sac area was reduced in the anteroposterior and all directions in the upper and lower lumbar area in age group, respectively. Approximately, 3.0% of healthy population in their 50s or older will have severe asymptomatic stenosis.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000004143DOI Listing
June 2021

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital.

Sci Rep 2021 Jun 7;11(1):11933. Epub 2021 Jun 7.

Department of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.
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http://dx.doi.org/10.1038/s41598-021-91345-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184989PMC
June 2021

Neurological improvement is associated with neck pain attenuation after surgery for cervical ossification of the posterior longitudinal ligament.

Sci Rep 2021 Jun 7;11(1):11910. Epub 2021 Jun 7.

Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan.

Although favourable surgical outcomes for myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) have been reported, factors significantly associated with post-operative neck pain attenuation still remain unclear. The primary aim of the present study was to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL. Significant postoperative neck pain reduction (50% reduction of neck pain) was achieved in 31.3% of patients. There was no significant difference in neck pain attenuation between surgical procedures. Statistical analyses with univariate analyses followed by stepwise logistic regression revealed neurological recovery as a factor having a significant positive association with post-operative neck pain attenuation (p = 0.04, odds ratio 5.68 (95% confidence interval: 1.27-22.2)). In conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.
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http://dx.doi.org/10.1038/s41598-021-91268-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184776PMC
June 2021

Normative Magnetic Resonance Imaging Data of Age-Related Degenerative Changes in Cervical Disc Morphology.

World Neurosurg 2021 Jun 16. Epub 2021 Jun 16.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi, Nagoya, Aichi, Japan.

Objective: Few studies have examined a possible correlation between cervical disc degeneration and disc height. The aim of this study was to establish age-related changes and sex-specific differences of cervical disc height using magnetic resonance imaging (MRI) and to evaluate the relationship between degree of cervical disc degeneration and disc height in asymptomatic subjects.

Methods: We measured the intervertebral disc anteroposterior diameter and disc height in each disc level using MRI in 1211 relatively healthy volunteers (606 men and 605 women, mean age 49.5 years). We included at least 100 males and 100 females in each decade of life between the 20s and the 70s. Cervical disc degeneration was defined according to the modified Pfirrmann classification system, and disc index and intervertebral disc height narrowing ratio were evaluated on sagittal plane MRI.

Results: Intervertebral disc height decreased gradually with increasing age in both sexes. The grade of disc degeneration significantly increased with age in both sexes at every level. Mild disc degeneration was observed even in subjects their 20s. Disc degeneration occurred around the C5-C6 level. The average disc height decreased with aging after the 40s. Disc index and intervertebral disc height narrowing ratio decreased with a progression in the disc degeneration grade in both sexes.

Conclusions: This large-scale cross-sectional analysis of cervical spine MRI data in healthy subjects demonstrated that cervical disc height narrowing progresses with age. Cervical disc height narrowing is highly correlated with the progression of disc degeneration.
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http://dx.doi.org/10.1016/j.wneu.2021.05.123DOI Listing
June 2021

Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine receptor clustering at the in vitro neuromuscular junction.

Neuropharmacology 2021 Jun 5;195:108637. Epub 2021 Jun 5.

Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan. Electronic address:

Decreased acetylcholine receptor (AChR) clustering compromises signal transmission at the neuromuscular junction (NMJ) in myasthenia gravis, congenital myasthenic syndromes, and motor neuron diseases. Although the enhancement of AChR clustering at the NMJ is a promising therapeutic strategy for these maladies, no drug is currently available for this enhancement. We previously reported that zonisamide (ZNS), an anti-epileptic and anti-Parkinson's disease drug, enhances neurite elongation of the primary spinal motor neurons (SMNs). As nerve sprouting occurs to compensate for the loss of AChR clusters in human diseases, we examined the effects of ZNS on AChR clustering at the NMJ. To this end, we established a simple and quick co-culture system to reproducibly make in vitro NMJs using C2C12 myotubes and NSC34 motor neurons. ZNS at 1-20 μM enhanced the formation of AChR clusters dose-dependently in co-cultured C2C12 myotubes but not in agrin-treated single cultured C2C12 myotubes. We observed that molecules that conferred responsiveness to ZNS were not secreted into the co-culture medium. We found that 10 μM ZNS upregulated the expression of neuregulin-1 (Nrg1) in co-cultured cells but not in single cultured C2C12 myotubes or single cultured NSC34 motor neurons. In accordance with this observation, inhibition of the Nrg1/ErbB signaling pathways nullified the effect of 10 μM ZNS on the enhancement of AChR clustering in in vitro NMJs. Although agrin was not induced by 10 μM ZNS in co-cultured cells, anti-agrin antibody attenuated ZNS-mediated enhancement of AChR clustering. We conclude that ZNS enhances agrin-dependent AChR-clustering by upregulating the Nrg1/ErbB signaling pathways in the presence of NMJs.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108637DOI Listing
June 2021

The characteristics of the young patients with cervical ossification of the posterior longitudinal ligament of the spine: A multicenter cross-sectional study.

J Orthop Sci 2021 Jun 3. Epub 2021 Jun 3.

Department of Orthopedic Surgery, Keio University, School of Medicine, Tokyo, Japan; Japanese Organization of the Study for Ossification of Spinal Ligament (JOSL), Tokyo, Japan.

Background: Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by heterotopic bone formation in the posterior longitudinal ligament of the spine. Although the patients with OPLL are more common in the 60s and 70s, we know that there are markedly young patients (e.g., early 40s). However, to the best of our knowledge, there is few reports characterize young patients with cervical OPLL in terms of the imaging features, subjective symptoms, and ADL problems.

Methods: This is the multicenter cross-sectional study. Two hundred and thirty-seven Japanese symptomatic patients with cervical OPLL confirmed by standard X-rays collected from 16 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament formed by the Japanese Ministry of Health, Labor and Welfare were recruited. Whole spine CT data as well as demographic data such as age, gender, patients-based evaluations, and the 36-item Short Form Health Survey (SF-36) were evaluated.

Results: Young group (≦ 45 years old) consisted of 23 patients (8 females and 15 males), accounting for 9.7% of the total. Their characteristics were high body mass index (BMI), significant involvement of trauma in the onset and deterioration of symptoms, and the predominance of thoracic OPLL. The patient-based evaluations did not show a significant difference between the young and non-young groups, or between the genders in the young group except for bodily pain (BP) of SF-36. Female patients in young group had significantly lower BP score of SF-36 than that of male in young group.

Conclusions: Characteristics of young patients with cervical OPLL were high BMI, significant involvement of trauma in the onset and deterioration of symptoms, lower BP score of SF-36 in female, and the predominance of thoracic OPLL.
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http://dx.doi.org/10.1016/j.jos.2021.04.010DOI Listing
June 2021

Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears.

J Orthop Sci 2021 May 31. Epub 2021 May 31.

Tokyo Sports & Orthopaedic Clinic, 4-29-9 Kami-ikebukuro, Toshima, Tokyo, 170-0012, Japan.

Background: Recently, to treat the long head of the biceps tendon lesions in addition to rotator cuff repair has been recommended. However, the differences in clinical outcomes between biceps tenotomy and tenodesis for middle-aged and elderly females remains unclear. The purpose of this study was to compare the outcomes of biceps tenotomy and soft-tissue tenodesis that were performed concurrently with arthroscopic rotator cuff repair in ≥60-year-old females.

Methods: Female shoulders that underwent arthroscopic rotator cuff repair in our institute in 2016 were retrospectively reviewed. This study included 66 shoulders with concurrent biceps tenotomy or soft-tissue tenodesis: tenotomy group, 41 shoulders; soft-tissue tenodesis group, 25 shoulders. Clinical scores, biceps pain (visual analogue scale, VAS), Popeye deformity, and biceps strength (%contralateral side) were compared between the two groups.

Results: The mean age was significantly higher in the tenotomy group than the soft-tissue tenodesis group (72 ± 4 and 68 ± 6 years, respectively; P = 0.002). There were no significant differences in post-operative JOA and UCLA scores between the groups. VAS for biceps pain was significantly higher at postoperative 6 months in the tenotomy group than the soft-tissue tenodesis group (2.9 ± 2.5 and 1.7 ± 1.6, respectively, P = 0.03), though there were no significant differences at postoperative 3, 12, and ≥24 months. Subjective evaluation of Popeye deformity was not significantly different between the groups. Postoperative biceps strength was significantly lower in the tenotomy group than the soft-tissue tenodesis group (89.9% and 102.8%, respectively, P = 0.02).

Conclusions: Both biceps tenotomy and soft-tissue tenodesis concurrent with rotator cuff repair in ≥60-year-old female patients resulted in good outcomes. Shoulders with soft-tissue tenodesis demonstrated earlier improvement in postoperative biceps pain and better postoperative biceps strength than those with tenotomy. There were no differences in objective and subjective Popeye deformity between tenotomy and soft-tissue tenodesis. The LHB procedures, tenotomy or tenodesis, can be selected depending on surgeons' preference.
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http://dx.doi.org/10.1016/j.jos.2021.04.012DOI Listing
May 2021

Clinical features and prognostic factors in spinal meningioma surgery from a multicenter study.

Sci Rep 2021 Jun 2;11(1):11630. Epub 2021 Jun 2.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19-91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1-93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan-Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.
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http://dx.doi.org/10.1038/s41598-021-91225-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172892PMC
June 2021

Factors Negatively Influencing Postoperative Improvement After Laminoplasty in Degenerative Cervical Myelopathy.

Clin Spine Surg 2021 May 26. Epub 2021 May 26.

Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo Department of Orthopaedics, Jichi Medical University, Tochigi Department of Orthopaedic Surgery, Tokyo Medical University, Tokyo Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chiba Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, Toyama Department of Orthopedic Surgery, Imakiire General Hospital, Kagoshima, Japan.

Study Design: This was a retrospective study of prospectively collected data.

Objective: In this study, we aimed to characterize a population of patients with degenerative cervical myelopathy (DCM) and a history of poor postoperative neurological recovery and to identify risk factors associated with poor neurological recovery after laminoplasty.

Summary Of Background Data: Kyphotic cervical alignment has been considered a relative contraindication to laminoplasty in recent years; hence, laminoplasty has been decreasingly performed for the treatment of DCM in patients with cervical kyphosis. However, the effect of global spinal alignment on postoperative outcomes has not been extensively investigated.

Materials And Methods: We prospectively enrolled patients who were scheduled for laminoplasty for DCM. Outcome (at enrollment and 1 y after surgery) and risk factor analyses were performed by comparing the good recovery and poor recovery groups. The Spearman correlation coefficient was used to evaluate the relationships between the recovery rate and the preoperative radiographic factors.

Results: In total, 101 patients completed the 1-year follow-up. Regarding clinical outcomes, the Japanese Orthopedic Association score for the assessment of cervical myelopathy, European Quality of Life-5 Dimensions, and Neck Disability Index scores improved postoperatively. The recovery rate was significantly correlated with the preoperative sagittal vertical axis (SVA). The patients in the poor recovery group were older than those in the good recovery group. Univariate analyses showed that the SVA and T1 pelvic angle were significantly higher in the poor recovery group. Lastly, stepwise logistic regression analysis showed that a higher SVA was an independent predictor of poor recovery after laminoplasty.

Conclusions: The SVA and T1 pelvic angle were significantly higher in the poor recovery group. A high preoperative SVA is an independent predictor for poor recovery after laminoplasty. Therefore, indications for laminoplasty in elderly DCM patients with a high preoperative SVA should be carefully considered.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001207DOI Listing
May 2021

Effects of Preoperative Motor Status on Intraoperative Motor-evoked Potential Monitoring for High-risk Spinal Surgery: A Prospective Multicenter Study.

Spine (Phila Pa 1976) 2021 Jun;46(12):E694-E700

The Monitoring Committee of the Japanese Society for Spine Surgery and Related Research, Japan.

Study Design: Prospective multicenter observational study.

Objective: To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease.

Summary Of Background Data: Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation.

Methods: IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score.

Results: The 949 patients (mean age 52.5 ± 23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit.

Conclusion: In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003994DOI Listing
June 2021

Machine Learning Approach in Predicting Clinically Significant Improvements After Surgery in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.

Spine (Phila Pa 1976) 2021 May 21. Epub 2021 May 21.

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan Department of Orthopedic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo Ward, Tokyo 113-8519, Japan Department of Orthopedic Surgery, Saiseikai Kawaguchi General Hospital, 5-11-5 Nishikawaguchi, Kawaguchishi, Saitama, 332-8558, Japan Department of Orthopedic Surgery, Kudanzaka Hospital, 1-6-12 Kudanminami, Chiyadaku, 102-0074, Japan Department of Orthopaedic Surgery, Wakayama Medical University Kihoku Hospital 210 Myoji, Katsuragi-cho, Itogun, Wakayama 649-7113, Japan Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan Department of Orthopedic Surgery, Niigata University Medical and Dental General Hospital, 1-754 Asahimachidori, Chuo Ward, Niigata, Niigata 951-8520, Japan Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 2- 1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan Department of Orthopedics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan Department of Orthopedic Surgery, School of Medicine, Keio University, Shinanomachi, Shinjuku Ward, Tokyo 160-8582, Japan Department of Orthopedic Surgery, Yamaguchi University School of Medicine 1144 Kogushi, Ube, Yamaguchi 755-8505, Japan Department of Orthopedic Surgery, Osaka Rosai Hospital, 1179-3 Nagasonecho, Sakaishi, Osaka, 591-8025, Japan Department of Orthopaedic Surgery, The University of Tokyo Hospital 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112-8688, Japan Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showa Ward, Nagoya, Aichi 466-0065, Japan Orthopedic Surgery, Reconstructive Surgery and Rehabilitation Medicine, Division of Advanced Medical Science, Hokkaido University, Graduate School of Medicine Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa- cho, Seta, Otsu, Shiga 520-2192, Japan Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan Department of Orthopedic Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan Department of Orthopedic Surgery, Imakiire General Hospital, 4-16 Shimotatsuocho, Kagoshima-shi, 892-8502, Japan Department of Orthopedic Surgery, Graduate School of Medicine, Osaka University 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan Department of Orthopaedic Surgery, Kurume University School of Medicine 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1- 20-1 Handayama, Hamamatsu, Shizuoka 431-3125, Japan Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan Department of Orthopedic Surgery, University of Yamanashi, 1110 Shimokato, Chuo Ward, Yamanashi 409-3898, Japan Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba Ward, Sendai, Miyagi 980-8574, Japan Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan Japanese Multicenter Research Organization for Ossification of the Spinal Ligament.

Study Design: A retrospective analysis of prospectively collected data.

Objective: This study aimed to create a prognostic model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using machine learning (ML).

Summary Of Background Data: Determining surgical outcomes helps surgeons provide prognostic information to patients and manage their expectations. ML is a mathematical model that finds patterns from a large sample of data and makes predictions outperforming traditional statistical methods.

Methods: Out of 478 patients, 397 and 370 patients had complete follow-up information at 1 and 2 year respectively and were included in the analysis. A minimal clinically important difference (MCID) was defined as an acquired Japanese Orthopaedic Association (JOA) score of 2.5 points or more, after which a ML model that predicts whether MCID can be achieved 1 and 2 years after surgery was created. Patient background, clinical symptoms, and imaging findings were used as variables for analysis. The ML model was created using LightGBM, XGBoost, random forest, and logistic regression, after which the accuracy and area under the receiver operating characteristic curve (AUC) were calculated.

Results: The mean JOA score was 10.3 preoperatively, 13.4 at 1 year after surgery, and 13.5 at 2 years after surgery. XGBoost showed the highest AUC (0.72) and high accuracy (67.8) for predicting MCID at 1 year, while random forest had the highest AUC (0.75) and accuracy (69.6) for predicting MCID at 2 years. Among the included features, total preoperative JOA score, duration of symptoms, body weight, sensory function of the lower extremity sub-score of the JOA, and age were identified as having the most significance in most of ML models.

Conclusion: Constructing a prognostic ML model for surgical outcomes in patients with OPLL is feasible, suggesting the potential application of ML for predictive models of spinal surgery.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000004125DOI Listing
May 2021

The impact of vitamin D supplementation on body fat mass in elite male collegiate athletes.

Nutr Metab (Lond) 2021 May 21;18(1):51. Epub 2021 May 21.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Background: Whether vitamin D supplementation has any effect on body fat percentage, especially among elite athletes, remains unclear. The aim of this study was to evaluate the effect of vitamin D supplementation on serum vitamin D level in elite male collegiate athletes and to analyze its effect on body fat percentage.

Methods: We enrolled a total of 42 elite male collegiate athletes in this prospective cohort study. In March 2020, body composition monitoring and blood test were performed. All athletes were provided with vitamin D3 supplement tablets of 25 μg/day. The use of the supplement was dependent on athletes' preference. During the study period, their club activities were stopped for 2 months due to the coronavirus disease 2019 outbreak. A second examination, similar to the first one, was performed after approximately 3 months. Supplement usage by each athlete was also confirmed. The participants were divided into a non-supplement group (without supplementation, n = 15) and a supplement group (with supplementation, n = 27).

Results: Regarding baseline data at initial examination, the non-supplement and supplement groups showed significant differences in the mean body fat percentage (9.0% and 12.1%, respectively; P = 0.03) and serum 25(OH)D level (22.7 and 18.5 ng/mL, respectively, P = 0.02). At the time of the second examination, there were no significant differences in the results of both the groups. In terms of mean change value from the first to the second examination, there were significant differences in body fat percentage (1.9 and 0.2%, respectively, P = 0.02) and serum 25(OH)D level (1.7 and 7.2 ng/mL, respectively, P < 0.001) between the two groups. A significant negative correlation was observed between the change ratio of body fat percentage and change value of serum 25(OH)D level (r =  - 0.37, P = 0.02).

Conclusions: Vitamin D supplementation of 25 μg/day significantly increased the serum 25(OH)D level in elite male collegiate athletes. Vitamin D supplementation may play a role in maintaining athletes' body fat percentage under circumstances where sports activity has decreased.
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http://dx.doi.org/10.1186/s12986-021-00578-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138511PMC
May 2021
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