Faculty Profiles - NAKASHIMA Hiroaki

Papers - NAKASHIMA Hiroaki

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Circulating miRNA-122 is associated with knee osteoarthritis progression: A 6-year longitudinal cohort study in the Yakumo study Reviewed

Funahashi, H; Takegami, Y; Osawa, Y; Nakashima, H; Ishizuka, S; Fujii, R; Yamada, H; Suzuki, K; Hasegawa, Y; Imagama, S

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 29 ( 6 ) page： 1411 - 1416 2024.11

Language：English Publisher：Journal of Orthopaedic Science

Objective: The association between knee osteoarthritis (OA) and miRNAs has been widely reported. However, the utility of miRNAs as predictors of knee osteoarthritis (KOA) progression in longitudinal studies has not been reported. We aimed to identify circulating miRNAs (c-miRNAs) associated with KOA progression in the general population and to examine their potential use as predictors of KOA progression. Methods: In 2012 and 2018, 66 participants (128 knees) took part in a resident health check-up in the Yakumo study. If the KL classification progressed two or more levels, the patient was classified as having progressive OA. Quantitative real-time polymerase chain reaction was used to screen 21 c-miRNAs. The expression levels of those c-miRNAs were compared between the progressive OA group and non-progressive OA group using student-t-test. Logistic analysis was performed in c-miRNAs less than p < 0.10 in univariate analysis. Results: The progressive OA group consisted of 78 knees. The results of the comparison between the progressive OA group and the non-progressive OA group showed that six c-miRNAs as follows; let7d (p = 0.030), c-miRNA-122 (p < 0.001), 150 (p = 0.070), 199 (p = 0.078), 21 (p = 0.016) and 320 (p = 0.093) were extracted as factors related to the progression of knee OA. In addition, logistic regression analysis identified c-miRNA-122 as an independent factor involved in the progression of knee osteoarthritis (odds ratio: 1.510, 95% confidence interval: 1.060–2.140, p = 0.023). The ROC curve showed by c-miRNA-122 for the progression of OA risk had an area under the curve of 0.702 (95% CI: 0.609–0.795). The threshold of c-miRNA-122 was −4.609. Conclusion: The expression level of c-miRNA-122 was associated with the risk of KOA progression in community dwelling Japanese people.

DOI： 10.1016/j.jos.2023.10.004

Prevalence and treatment rates of osteoporosis among individuals with rotator cuff tears Reviewed

Kawashima, I; Ishizuka, S; Oba, H; Sakaguchi, T; Nakashima, H; Takegami, Y; Imagama, S

JOURNAL OF SHOULDER AND ELBOW SURGERY Vol. 33 ( 11 ) page： e606 - e609 2024.11

Language：English Publisher：Journal of Shoulder and Elbow Surgery

Background: The relationship between osteoporosis and rotator cuff tears has been reported previously. However, the treatment rate of osteoporosis in individuals with rotator cuff tear is still unknown. The aim of this study was to investigate the prevalence and treatment rate of osteoporosis in individuals with rotator cuff tears. Methods: In this cross-sectional study, we enrolled 207 participants. Participants underwent comprehensive assessments, including shoulder ultrasonographic examinations and quantitative ultrasound measurements for bone status evaluation. Osteoporosis diagnosis was predicated on a calcaneus ultrasound bone densitometry, and the cutoff value was set as a T score of −1.455, with reference to a previous report. Results: One hundred fifty-six participants were classified as individuals without rotator cuff tears (group A), and 51 participants were classified as those with (group B). The mean age in group A was significantly lower than that in group B (63 ± 10 vs. 68 ± 9, respectively; P = .003). In terms of the T score examined by quantitative ultrasound, the mean T score in group A was significantly higher than that in group B (−1.4 ± 1.3 vs. −1.9 ± 1.6, respectively; P = .0412). The percentage of subjects with a T score of −1.455 or less in group B was 60.8% (31/51). The proportion of subjects with a T score of −1.455 or less undergoing osteoporosis treatment was 14.5% (12/83) in group A and 12.9% (4/27) in group B, showing no significant difference. Conclusions: Participants with a rotator cuff tear had relatively high prevalence of osteoporosis. Among those with both a rotator cuff tear and osteoporosis, the proportion receiving osteoporosis treatment was l2.9%, a very low rate.

DOI： 10.1016/j.jse.2024.02.026

The prevalence and characteristics of diffuse idiopathic skeletal hyperostosis in the community-living middle-aged and elderly population: The Yakumo study Reviewed

Ohshima, K; Nakashima, H; Segi, N; Ito, S; Ouchida, J; Takegami, Y; Ishizuka, S; Hasegawa, Y; Imagama, S

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 29 ( 6 ) page： 1346 - 1352 2024.11

Language：English Publisher：Journal of Orthopaedic Science

Background: The incidence of diffuse idiopathic skeletal hyperostosis (DISH) is increasing with the aging of the population. Asymptomatic DISH can decrease the spinal range of motion (ROM) and cause fractures. However, the prevalence or physical function of patients with DISH before experiencing fractures and other serious conditions is unclear. This study aimed to investigate the prevalence of DISH in the community residents on the basis of age and sex and characterize their physical function, ROM, and bone fragility. Methods: The subjects were community volunteers who attended a health checkup in 2018 and 2019. Overall, 455 subjects (mean age, 64.2 ± 9.7 years; 177 men) were included for analysis. We performed whole-spine lateral radiography for detecting DISH according to the criteria reported by Resnick. We compared the age, sex, body mass index (BMI), results of muscle strength and walking tests, ROM measured by SpinalMouse®, and quantitative ultrasound (QUS) of calcaneus with and without DISH. Results: DISH was detected in 83 (18.2%) cases. The DISH group was older (69.8 y.o. vs. 63.0 y.o.; p < 0.05) and comprised more men (prevalence: men, 27.7%; women, 12.2%; p < 0.001). BMI was high in the DISH group (24.8 vs. 23.3 kg/m<sup>2</sup>, p < 0.05). SpinalMouse measurements showed the DISH group had a significantly decreased ROM in the lumbar spine (43.2°, 57.2°, p < 0.05). The DISH group had a significantly lower T-score on the QUS measurement in the calcaneus (−2.0, −1.5, p < 0.05). There were, however, no significant differences between groups in both muscle strength test and walking test. Conclusion: Subjects with DISH had decreased ROM in the lumbar spine and bone mineral density in calcaneal QUS. However, physical functions such as muscle strength and walking ability were similar among subjects with and without DISH without subjective symptoms.

DOI： 10.1016/j.jos.2023.10.005

A class of chemical compounds enhances clustering of muscle nicotinic acetylcholine receptor in cultured myogenic cells Reviewed Open Access

Miyairi, Y; Ohkawara, B; Sato, A; Sawada, R; Ishii, H; Tomita, H; Inoue, T; Nakashima, H; Ito, M; Masuda, A; Hosono, Y; Imagama, S; Ohno, K

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Vol. 731 page： 150400 2024.10

Language：English Publisher：Biochemical and Biophysical Research Communications

Neuromuscular signal transmission is affected in various diseases including myasthenia gravis, congenital myasthenic syndromes, and sarcopenia. We used an ATF2-luciferase system to monitor the phosphorylation of MuSK in HEK293 cells introduced with MUSK and LRP4 cDNAs to find novel chemical compounds that enhanced agrin-mediated acetylcholine receptor (AChR) clustering. Four compounds with similar chemical structures carrying benzene rings and heterocyclic rings increased the luciferase activities 8- to 30-folds, and two of them showed continuously graded dose dependence. The effects were higher than that of disulfiram, a clinically available aldehyde dehydrogenase inhibitor, which we identified to be the most competent preapproved drug to enhance ATF2-luciferase activity in the same assay system. In C2C12 myotubes, all the compounds increased the area, intensity, length, and number of AChR clusters. Three of the four compounds increased the phosphorylation of MuSK, but not of Dok7, JNK. ERK, or p38. Monitoring cell toxicity using the neurite elongation of NSC34 neuronal cells as a surrogate marker showed that all the compounds had no effects on the neurite elongation up to 1 μM. Extensive docking simulation and binding structure prediction of the four compounds with all available human proteins using AutoDock Vina and DiffDock showed that the four compounds were unlikely to directly bind to MuSK or Dok7, and the exact target remained unknown. The identified compounds are expected to serve as a seed to develop a novel therapeutic agent to treat defective NMJ signal transmission.

DOI： 10.1016/j.bbrc.2024.150400

Does global spinal alignment affect the use of walking aids after multi-segment spinal fixation for patients with ASD? A multicenter retrospective study Reviewed Open Access

Ouchida, J; Nakashima, H; Ito, S; Segi, N; Yamauchi, I; Oishi, R; Miyairi, Y; Morita, Y; Ode, Y; Nagatani, Y; Okada, Y; Tsushima, M; Machino, M; Ota, K; Tachi, H; Kagami, Y; Shinjo, R; Ohara, T; Tsuji, T; Kanemura, T; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 33 ( 10 ) page： 3833 - 3841 2024.10

Language：English Publisher：European Spine Journal

Purpose: This study aimed to clarify the relation between global spinal alignment and the necessity of walking aid use in patients with adult spinal deformity (ASD) and to investigate the impact of spinal fixation on mobility status after surgery. Methods: In total, 456 older patients with ASD who had multi-segment spinal fixation surgery and were registered in a multi-center database were investigated. Patients under 60 years of age and those unable to walk preoperatively were excluded. Patients were classified by their mobility status into the independent, cane, and walker groups. Comparison analysis was conducted using radiographic spinopelvic parameters and the previously reported global spine balance (GSB) classification. In addition, preoperative and 2 years postoperative mobility statuses were investigated. Results: Of 261 patients analyzed, 66 used walking aids (canes, 46; walkers, 20). Analysis of preoperative radiographical parameters showed increased pelvic incidence and pelvic incidence-lumbar lordosis mismatch in the walker group and increased sagittal vertebral axis in the cane and walker groups versus the independent group. Analysis of GSB classification showed a higher percentage of walker use in those with severe imbalance (grade 3) in the sagittal classification but not in the coronal classification. While postoperative radiographical improvements were noted, there was no significant difference in the use of walking aids before and 2 years after surgery (P = 0.085). Conclusion: A significant correlation was found between “sagittal” spinal imbalance and increased reliance on walking aids, particularly walkers. However, the limitation of improvement in postoperative mobility status suggested that multiple factors influence the mobility ability of elderly patients with ASD.

DOI： 10.1007/s00586-024-08380-w

Longitudinal impact of multi-segment spinal fixation surgery on mobility status and clinical outcomes in adult spinal deformity: a multicenter retrospective study Reviewed Open Access

Ouchida, J; Nakashima, H; Ito, S; Segi, N; Yamauchi, I; Oishi, R; Miyairi, Y; Morita, Y; Ode, Y; Nagatani, Y; Okada, Y; Tsushima, M; Kanemura, T; Machino, M; Ohara, T; Ota, K; Tachi, H; Tsuji, T; Kagami, Y; Shinjo, R; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 33 ( 10 ) page： 3894 - 3903 2024.10

Language：English Publisher：European Spine Journal

Purpose: To investigate changes in postoperative mobility status in patients with ASD, and the determining factors that influence these changes and their impact on clinical outcomes, including the rate of home discharge and long-term mobility. Methods: A total of 299 patients with ASD who underwent multi-segment posterior spinal fusion were registered in a multi-center database were investigated. Patient mobility status was assessed using walking aids and classified into five levels (1: independent, 2: cane, 3: walker, 4: assisted, and 5: wheelchair) preoperatively, at discharge, and after 2 years. We determined improvements or declines in the patient's mobility based on changes in the classification levels. The analysis focused on the factors contributing to the deterioration of postoperative mobility. Results: Two years postoperatively, 87% of patients maintained or improved mobility. However, 27% showed decreased mobility status at discharge, associated with a lower rate of home discharge (49% vs. 80% in the maintained mobility group) and limited improvement in mobility status (35% vs. 5%) after 2 years. Notably, postoperative increases in thoracic kyphosis (7.0 ± 12.1 vs. 2.0 ± 12.4°, p = 0.002) and lower lumbar lordosis (4.2 ± 13.1 vs. 1.8 ± 12.6°, p = 0.050) were substantial factors in mobility decline. Conclusion: Postoperative mobility often temporarily decreases but generally improves after 2 years. However, an overcorrection in sagittal alignment, evidenced by increased TK, could detrimentally affect patients’ mobility status. Transient mobility decline associated with overcorrection may require further rehabilitation or hospitalization. Further studies are required to determine the biomechanical effects of surgical correction on mobility.

DOI： 10.1007/s00586-024-08397-1

Peri-implant fractures after Intramedullary fixation for femoral trochanteric fracture: a multicenter (TRON Group) study Reviewed

Kaneda, T; Takegami, Y; Tokutake, K; Nakashima, H; Mishima, K; Mabuchi, M; Imagama, S

EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY Vol. 50 ( 5 ) page： 2587 - 2594 2024.10

Language：English Publisher：European Journal of Trauma and Emergency Surgery

Background: With the rise in elderly populations, the incidence of femoral trochanteric fractures has also increased. Although intramedullary nail therapy is commonly used, the incidence of peri-implant fractures (PIFs) as a complication and its associated factors are not fully understood. The purpose of this study was to determine the incidence of PIFs and treatment strategies and outcomes. Methods: A retrospective study across 11 hospitals from 2016 to 2020 examined 1855 patients with femoral trochanter fracture. After excluding 69 patients treated without intramedullary nailing, 1786 patients were analyzed. Parameters studied included age, sex, body mass index, medical history, and treatment methods. PIFs were categorized using the Chan classification. Treatment outcomes and patient mobility were assessed using the Parker Mobility Score, and postoperative complications and one-year survival data were compiled. Results: The incidence of PIFs was 8 in 1786 cases. Chan classification showed 1 case of N1A, 6 of N2A, and 1 of N2B. Only the type N1 case was a transverse fracture, whereas all cases of type N2 were oblique fractures. Among these cases, five patients had fractures extending to the upper part of the femoral condyle. The patient with N1A and one bedridden patient with N2A fracture underwent conservative treatment, one patient with N2A in which the fracture did not extend to the condyle was treated with nail replacement, and 5 patients (N2A: 4, N2B: 1) with fractures extending to the condyle were treated with additional plate fixation. All patients had survived at one year after treatment for PIF, and no reoperations were required. Conclusions: The incidence of PIF was very low (0.45%). Of the 6 PIF cases, excluding the bedridden patients, the treatment of choice for PIF was an additional plate if the fracture line extended to the femoral condyle; otherwise, the nail was replaced. All patients achieved bony fusion. Level of evidence: Therapeutic Level IV.

DOI： 10.1007/s00068-024-02567-y

Ten-Year Follow-up of Posterior Decompression and Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament Reviewed Open Access

Ito, S; Nakashima, H; Segi, N; Ouchida, J; Oishi, R; Yamauchi, I; Miyairi, Y; Morita, Y; Ode, Y; Imagama, S

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Vol. 106 ( 17 ) page： 1600 - 1609 2024.9

Language：English Publisher：Journal of Bone and Joint Surgery

Background: We evaluated the clinical, functional, and quality of life (QoL) outcomes of surgical treatment of thoracic ossification of the posterior longitudinal ligament (T-OPLL). Methods: We retrospectively evaluated 51 patients followed for ‡10 years after posterior decompression and corrective fusion surgery for T-OPLL. The data collected included demographics, comorbidities, and pre- and postoperative symptoms. The Japanese Orthopaedic Association (JOA) score, numerical rating scale (NRS) for back and leg pain, and EuroQol-5 Dimension-5 Level (EQ-5D-5L) were used to assess neurological function, pain, and QoL. Imaging evaluations were conducted to assess changes in kyphotic angles and ossification progression. Results: A significant improvement was observed in the JOA score from preoperatively (3.7) to 2 years postoperatively (7.9) (p < 0.05); the score remained stable thereafter. The mean EQ-5D-5L score improved from 0.53 preoperatively to 0.68 at 10 years postoperatively (p < 0.001). NRS scores for back and leg pain decreased from 5.4 to 3.5 and 4.0 to 3.0, respectively, from preoperatively to 10 years (p < 0.001 for both). Radiographic outcomes showed changes in kyphotic angles and ossification areas, with no significant progression after 2 years. Fourteen (27.5%) of the patients experienced postoperative complications. Of these, 8 (15.7%) required reoperation, 6 (11.8%) in the perioperative period and 2 (3.9%) later. Four (7.8%) of the patients underwent additional surgeries for conditions including lumbar spinal canal stenosis and cervical OPLL. Nonetheless, physical function in all cases with postoperative complications or additional surgery remained stable over the decade. Conclusions: Surgical treatment of T-OPLL is effective in improving neurological function, QoL, and pain management over an extended period. The long-term outcomes of T-OPLL surgery revealed that, although cervical and lumbar spinal lesions led to reoperations, they did not affect QoL, and relative improvement was maintained even after 10 years. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

DOI： 10.2106/JBJS.23.01475

Trabecular Bone Remodeling After Posterior Lumbar Interbody Fusion: Comparison of Three-Dimensional Porous Tantalum and Titanium-Coated Polyetheretherketone Interbody Cages Reviewed Open Access

Segi, N; Nakashima, H; Shinjo, R; Kagami, Y; Machino, M; Ito, S; Ouchida, J; Morishita, K; Oishi, R; Yamauchi, I; Imagama, S

GLOBAL SPINE JOURNAL Vol. 14 ( 7 ) page： 2106 - 2115 2024.9

Language：English Publisher：Global Spine Journal

Study Design: Retrospective cohort study Objectives: The criteria for determining completion of intervertebral stability after posterior lumbar interbody fusion (PLIF) remain controversial. Several new radiological indicators of bone growth and osteointegration have been established. We compared computed tomography (CT) findings related to osteointegration after PLIF with interbody cages of two different materials and designs. Methods: We retrospectively analyzed data from 103 patients who underwent PLIF with three-dimensional porous tantalum (Tn) cages or titanium-coated polyetheretherketone (TiP) cages. CT images obtained 3 months and 1 year after surgery were examined for trabecular bone remodeling (TBR), cancellous condensation (CC), and vertebral endplate cyst (VEC) formation. The incidences of each finding were compared by cage type, and rates of instrument failure and pseudarthrosis were determined. Results: Three months postoperatively, 87% of the levels with Tn cages exhibited TBR, whereas 96% of those with TiP cages did not (P <.001). Most levels with Tn cages levels exhibited TBR and no CC 3 months (81%) and 1 year (94%) after surgery. Although 78% of levels with TiP cages exhibited CC and no TBR 3 months after surgery, 59% exhibited both CC and TBR 1 year after surgery. Significantly fewer VECs formed around the Tn cages than around the TiP cages both 3 months (P =.002) and 1 year (P <.001) after surgery. Implant-related problems occurred at levels that exhibited neither TBR nor CC. Conclusions: The porous tantalum cage may enable intervertebral stability that is comparable to bony fusion soon after surgery.

DOI： 10.1177/21925682231170613

Safety and feasibility of intravenous administration of a single dose of allogenic-Muse cells to treat human cervical traumatic spinal cord injury: a clinical trial Reviewed Open Access

Koda, M; Imagama, S; Nakashima, H; Ito, S; Segi, N; Ouchida, J; Suda, K; Matsumoto, SH; Komatsu, M; Endo, T; Suzuki, S; Inami, S; Ueda, H; Miyagi, M; Inoue, G; Takaso, M; Nagata, K; Yamada, H; Kamei, N; Nakamae, T; Suzuki, H; Nishida, N; Funaba, M; Kumagai, G; Furuya, T; Yamato, Y; Funayama, T; Takahashi, H; Yamazaki, M

STEM CELL RESEARCH & THERAPY Vol. 15 ( 1 ) page： 259 2024.8

Language：English Publisher：Stem Cell Research and Therapy

Introduction: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. Methods: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 10<sup>6</sup> cells, 2.1–2.7 × 10<sup>5</sup> cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. Results: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. Conclusion: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. Trial registration: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764.

DOI： 10.1186/s13287-024-03842-w

Neuromodulation with transcranial direct current stimulation contributes to motor function recovery via microglia in spinal cord injury Reviewed Open Access

Oishi, R; Takeda, I; Ode, Y; Okada, Y; Kato, D; Nakashima, H; Imagama, S; Wake, H

SCIENTIFIC REPORTS Vol. 14 ( 1 ) page： 18031 2024.8

Language：English Publisher：Scientific Reports

Spinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.

DOI： 10.1038/s41598-024-69127-7

連載 What's new by subspecialty What's New in Spine Surgery

中島宏彰, 今釜史郎

整形外科 Vol. 75 ( 9 ) page： 937 - 945 2024.8

A novel technique for C1-C2 posterior screw insertion using patient-specific guides created by CT-based 3D printing Reviewed Open Access

Kagami, Y; Nakashima, H; Segi, N; Ito, S; Ouchida, J; Shinjo, R; Imagama, S

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 86 ( 3 ) page： 487 - 496 2024.8

Language：English Publisher：Nagoya Journal of Medical Science

C1-C2 fixation has been developed for the rigid fusion of atlantoaxial instability. C1 lateral mass screw (C1 LMS)-C2 pedicle screw fixation is used more frequently due to its rigid fixation and high bone fusion rate. However, C1 screw placement is relatively unsafe even with recently developed image-based navigation systems. Patient-specific screw guide templates (PSGT) were developed to improve the accuracy and safety of C1 screw placement. Herein, we investigated the outcomes of the C1-C2 posterior fixation technique using PSGT. This was a retrospective study of six patients who underwent posterior cervical spinal fusion using the PSGT between January 2022 and April 2023. Operative time, estimated blood loss, intraoperative radiation dose, surgical cost, and screw placement accuracy were evaluated and compared with those achieved with preoperative CT-based navigation (navigation group, n = 15). Screw accuracy was assessed using Neo’s classification. PSGT showed good results, although the differences were not statistically significant (operation time: 104.3 ± 9.7 min vs 116.4 ± 20.8 min; estimated blood loss: 56.7 ± 72.4 mL vs 123.2 ± 162.3 mL; and radiation dose: 1.8 ± 1.2 mSv vs 2.6 ± 0.8 mSv, respectively). PSGT was particularly better in terms of the accuracy of C1 LMS (PSGT: 100%, navigation: 83.3%). The deviation at the entry point was minimal, and the difference between the sagittal and transversal angles from the preoperative plan was small. We investigated the clinical efficacy of using the PSGT for C1-C2 posterior fixation. PSGT improved the accuracy of C1 LMS insertion.

DOI： 10.18999/nagjms.86.3.487

Analysis of spinopelvic parameters in adult patients with lumbosacral transitional vertebrae Reviewed Open Access

Ouchida, J; Nakashima, H; Kanemura, T; Tsushima, M; Ito, S; Segi, N; Tomita, H; Morishita, K; Oyama, H; Oshima, K; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 33 ( 8 ) page： 2952 - 2959 2024.8

Language：English Publisher：European Spine Journal

Purpose: Spinopelvic sagittal alignment is crucial for assessing balance and determining treatment efficacy in patients with adult spinal deformity (ASD). Only a limited number of reports have addressed spinopelvic parameters and lumbosacral transitional vertebrae (LSTV). Our primary objective was to study spinopelvic sagittal parameter changes in patients with LSTV. A secondary objective was to investigate clinical symptoms and quality of life (QOL) in patients with LSTV. Methods: In this study, we investigated 371 participants who had undergone medical check-ups for the spine. LSTV was evaluated using Castellvi’s classification, and patients were divided into LSTV+ (type II-IV, L5 vertebra articulated or fused with the sacrum) and LSTV- groups. After propensity score matching for demographic data, we analyzed spinopelvic parameters, sacroiliac joint degeneration, clinical symptoms, and QOL for these two participant groups. Oswestry Disability Index (ODI) scores and EQ-5D (EuroQol 5 dimensions) indices were compared between the two groups. Results: Forty-four patients each were analyzed in the LSTV + and LSTV- groups. The LSTV + group had significantly greater pelvic incidence (52.1 ± 11.2 vs. 47.8 ± 10.0 degrees, P = 0.031) and shorter pelvic thickness (10.2 ± 0.9 vs. 10.7 ± 0.8 cm, P = 0.018) compared to the LSTV- group. The “Sitting” domain of ODI (1.1 ± 0.9 vs. 0.6 ± 0.7, P = 0.011) and “Pain/Discomfort” domain of EQ-5D (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.005) were larger in the LSTV + group. Conclusion: There was a robust association between LSTV and pelvic sagittal parameters. Clinical symptoms also differed between the two groups in some domains. Surgeons should be aware of the relationship between LSTV assessment, radiographic parameters and clinical symptoms. Level of evidence: 3.

DOI： 10.1007/s00586-024-08378-4

Adenosine triphosphate release inhibitors targeting pannexin1 improve recovery after spinal cord injury Reviewed Open Access

Morishita, K; Nakashima, H; Machino, M; Ito, S; Segi, N; Miyairi, Y; Morita, Y; Imagama, S

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 86 ( 3 ) page： 392 - 406 2024.8

Language：English Publisher：Nagoya Journal of Medical Science

Traumatic spinal cord injury is characterized by immediate and irreversible tissue loss at the lesion site and secondary tissue damage. Secondary injuries should, in principle, be preventable, although no effective treatment options currently exist for patients with acute spinal cord injury. Traumatized tissues release excessive amounts of adenosine triphosphate and activate the P2X purinoceptor 7/pannexin1 complex, which is associated with secondary injury. We investigated the neuroprotective effects of the blue dye Brilliant Blue FCF, a selective inhibitor of P2X purinoceptor 7/pannexin1 that is approved for use as a food coloring, by comparing it with Brilliant Blue G, a P2X7 purinoceptor antagonist, and carbenoxolone, which attenuates P2X purinoceptor 7/pannexin1 function, in a rat spinal cord injury model. Brilliant Blue FCF administered early after spinal cord injury reduced spinal cord anatomical damage and improved motor recovery without apparent toxicity. Brilliant Blue G had the highest effect on this neurological recovery, with Brilliant Blue FCF and carbenoxolone having comparable improvement. Furthermore, Brilliant Blue FCF administration reduced local astrocytic and microglial activation and neutrophil infiltration, and no differences in these histological effects were observed between compounds. Thus, Brilliant Blue FCF protects spinal cord neurons after spinal cord injury and suppresses local inflammatory responses as well as Brilliant Blue G and carbenoxolone.

DOI： 10.18999/nagjms.86.3.392

特集胸椎後縦靭帯骨化症-手術治療の進歩胸椎後縦靭帯骨化症における術後遺残疼痛

中島宏彰, 伊藤定之, 世木直喜, 大内田隼, 今釜史郎

脊椎脊髄ジャーナル Vol. 37 ( 6 ) page： 455 - 459 2024.7

特集胸椎後縦靭帯骨化症-手術治療の進歩胸椎後縦靭帯骨化症に対する当科の2期的後方手術strategy-特に後方除圧矯正固定術について

今釜史郎, 中島宏彰, 伊藤定之, 世木直喜, 大内田隼

脊椎脊髄ジャーナル Vol. 37 ( 6 ) page： 393 - 398 2024.7

Descriptive analysis of incidence and risk factors for short intramedullary nail breakage in femoral intertrochanteric fractures: a multicenter (TRON group) retrospective study Reviewed

Noritake, H; Takegami, Y; Tokutake, K; Nakashima, H; Mishima, K; Ito, T; Imagama, S

EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY Vol. 34 ( 5 ) page： 2605 - 2611 2024.7

Language：English Publisher：European Journal of Orthopaedic Surgery and Traumatology

Background: The incidence of hip fractures is increasing. Femoral intertrochanteric fractures make up 50% of hip fractures and are treated by intramedullary nails. Implant breakage is a recognized complication that can have rare and serious implications. This study aimed to investigate implant breakage rates after surgical treatment for femoral intertrochanteric fractures. Methods: This was a retrospective multicenter analysis. All 1854 patients who underwent surgical treatment for femoral intertrochanteric fractures were selected from 12 hospitals (TRON group) between 2016 and 2020. Exclusion criteria included implants other than those specified and follow-up periods less than three months. Demographic data, surgical details, and radiographic assessments were collected from medical records and X-ray evaluations. Results: Among the 983 study patients, consisting of 245 males (24.9%) and 738 females (75.1%), the implant breakage rate was 0.31%, with three confirmed cases. The average age was 83.9 years. The mean follow-up period was 640.9 days. Two cases were linked to ASULOCK implants, and one to an OLSII implant. Statistical analysis showed a significantly higher incidence of ASULOCK implant breakage (p < 0.001). In the two cases of ASULOCK implant breakage and one case of OLSII implant breakage, breakage in all three implants occurred at the anti-rotation screws. Conclusions: There were no implant breakages of the main body of the implants; all breakages occurred in the additional anti-rotation screw. The necessity of the anti-rotation screw will require further discussion. These results can potentially inform clinical decisions and guide further research in preventing implant breakage.

DOI： 10.1007/s00590-024-03957-z

Neurologic recovery following laminectomy and tumor resection of a pediatric cervical synovial osteochondromatosis causing paralysis Reviewed

Yamauchi, I; Nakashima, H; Inoue, T; Nojima, T; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 33 ( 7 ) page： 2904 - 2908 2024.7

Language：English Publisher：European Spine Journal

Purpose: To report the surgical outcome of synovial osteochondromatosis, a rare tumor of the cervical spine, in a 6-year-old boy. Methods: A 6-year-old boy presented with muscle weakness in the right deltoid (2) and biceps (4) during a manual muscle test. Magnetic resonance imaging showed a 3 × 2 × 1.5 cm mass within the spinal canal at the C4–6 level, compressing the cervical spinal cord from the right side. Computed tomography revealed hyperintense areas within the tumor and ballooning of the right C4–5 and C5–6 facet joints. Results: After a biopsy confirmed the absence of malignancy, a gross total resection was performed. The pathological diagnosis of synovial osteochondromatosis was established. Postoperatively, muscle weakness improved fully in the manual muscle test, and there were no neurological findings after 3 months. However, the patient is under careful follow-up owing to the detection of a regrowth site within the right C4–5 and C5–6 intervertebral foramen 2 years postoperatively. Conclusions: Synovial osteochondromatosis of the cervical spine in children is rare, and this is the first report of its regrowth after surgery. Synovial osteochondromatosis should be included in the differential diagnosis of pediatric cervical spine tumors.

DOI： 10.1007/s00586-024-08304-8

Preoperative low Hounsfield units in the lumbar spine are associated with postoperative mechanical complications in adult spinal deformity Reviewed

Yamauchi, I; Nakashima, H; Ito, S; Segi, N; Ouchida, J; Oishi, R; Miyairi, Y; Morita, Y; Ode, Y; Nagatani, Y; Okada, Y; Morishita, K; Takeichi, Y; Kagami, Y; Tachi, H; Ohshima, K; Ogura, K; Shinjo, R; Ohara, T; Tsuji, T; Kanemura, T; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 33 ( 7 ) page： 2824 - 2831 2024.7

Language：English Publisher：European Spine Journal

Purpose: To determine the most valid bone health parameter to predict mechanical complications (MCs) following surgery for adult spinal deformity (ASD). Methods: This multicenter study retrospectively examined the records of patients who had undergone fusion of three or more motion segments, including the pelvis, with a minimum two-year follow-up period. Patients with moderate and severe global alignment and proportion scores were included in the study and divided into two groups: those who developed MCs and those who did not. Bone mineral density (BMD) of the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry, and Hounsfield units (HUs) were measured in the lumbar spine on computed tomography. Radiographic parameters were evaluated preoperatively, immediately after surgery, and at final follow-up. Results: Of 108 patients, 30 (27.8%) developed MCs, including 26 cases of proximal junctional kyphosis/failure, 2 of distal junctional failure, 6 of rod fracture, and 11 reoperations. HUs were significantly lower in patients who experienced MCs (113.7 ± 41.1) than in those who did not (137.0 ± 46.8; P = 0.02). BMD did not differ significantly between the two groups. The preoperative and two-year postoperative global tilt, as well as the immediately postoperative sagittal vertical axis, were significantly greater in patients who developed MCs than in those who did not (P = 0.02, P < 0.01, and P = 0.01, respectively). Conclusion: Patients who experienced MCs following surgery for ASD had lower HUs than those who did not. HUs may therefore be more useful than BMD for predicting MCs following surgery for ASD.

DOI： 10.1007/s00586-024-08261-2

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