論文 - 渡邉　航太

Risk predictors of perioperative complications for the palliative surgical treatment of spinal metastasis

Isogai N., Yagi M., Nishimura S., Nishida M., Mima Y., Hosogane N., Suzuki S., Fujita N., Okada E., Nagoshi N., Tsuji O., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science）  26 （ 6 ） 1107 - 1112 2021年11月

ISSN  09492658

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Background: The complication rate for palliative surgery in spinal metastasis is relatively high, and major complications can impair the patient's activities of daily living. However, surgical indications are determined based primarily on the prognosis of the cancer, with the risk of complications not truly considered. We aimed to identify the risk predictors for perioperative complications in palliative surgery for spinal metastasis. Methods: A multicentered, retrospective review of 195 consecutive patients with spinal metastasis who underwent palliative surgeries with posterior procedures from 2001 to 2016 was performed. We evaluated the type and incidence of perioperative complications within 14 days after surgery. Patients were categorized into either the complication group (C) or no-complication group (NC). Univariate and multivariate analyses were used to identify potential predictors for perioperative complications. Results: Thirty patients (15%) experienced one or more complications within 14 days of surgery. The most frequent complications were surgical site infection (4%) and motor weakness (3%). A history of diabetes mellitus (C; 37%, NC; 9%: p < 0.01) and surgical time over 300 min (C; 27%, NC; 12%: p < 0.05) were significantly associated with complications according to univariate analysis. Increased blood loss and non-ambulatory status were determined to be potential risk factors. Of these factors, multivariate logistic regression revealed that a history of diabetes mellitus (OR: 6.6, p < 0.001) and blood loss over 1 L (OR: 2.7, p < 0.05) were the independent risk factors for perioperative complications. There was no difference in glycated hemoglobin A1c between the diabetes patients with and without perioperative complications. Conclusions: Diabetes mellitus should be used for the risk stratification of surgical candidates regardless of the treatment status, and strict prevention of bleeding is needed in palliative surgeries with posterior procedures to mitigate the risk of perioperative complications.

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Risk factors for delayed diagnosis of spinal fracture associated with diffuse idiopathic skeletal hyperostosis: A nationwide multiinstitution survey

Kobayashi K., Okada E., Yoshii T., Tsushima M., Yamada T., Watanabe K., Katsumi K., Hiyama A., Katoh H., Watanabe M., Nakagawa Y., Okada M., Endo T., Shiraishi Y., Takeuchi K., Matsunaga S., Maruo K., Sakai K., Kobayashi S., Ohba T., Wada K., Ohya J., Mori K., Nishimura H., Tsuji T., Watanabe K., Okawa A., Matsumoto M., Imagama S.

Journal of Orthopaedic Science （Journal of Orthopaedic Science）  26 （ 6 ） 968 - 973 2021年11月

ISSN  09492658

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Background: Patients with DISH are susceptible to spinal fractures and subsequent neurological impairment, including after minor trauma. However, DISH is often asymptomatic and fractures may have minimal symptoms, which may lead to delayed diagnosis. The purpose of this study was to identify risk factors for delayed diagnosis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH). Methods: The subjects were 285 patients with DISH surgically treated at 18 medical centers from 2005 to 2015. Cause of injury, imaging findings, neurological status at the times of injury and first hospital examination, and the time from injury to diagnosis were recorded. A delayed diagnosis was defined as that made >24 h after injury. Results: Main causes of injury were minor trauma due to a fall from a standing or sitting position (51%) and high-energy trauma due to a fall from a high place (29%) or a traffic accident (12%). Delayed diagnosis occurred in 115 patients (40%; 35 females, 80 males; mean age 76.0 ± 10.4 years), while 170 (60%; 29 females, 141 males; mean age 74.6 ± 12.8 years) had early diagnosis. Delayed group had a significantly higher rate of minor trauma (n = 73, 63% vs. n = 73, 43%), significantly more Frankel grade E (intact neurological status) cases at the time of injury (n = 79, 69% vs. n = 73, 43%), and greater deterioration of Frankel grade from injury to diagnosis (34% vs. 8%, p < 0.01). In multivariate analysis, a minor trauma fall (OR 2.08; P < 0.05) and Frankel grade E at the time of injury (OR 2.29; P < 0.01) were significantly associated with delayed diagnosis. Conclusion: In patients with DISH, it is important to keep in mind the possibility of spinal fracture, even in a situation in which patient sustained only minor trauma and shows no neurological deficit. This is because delayed diagnosis of spinal fracture can cause subsequent neurological deterioration.

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Association between severity of diffuse idiopathic skeletal hyperostosis and ossification of other spinal ligaments in patients with ossification of the posterior longitudinal ligament

Nishimura S., Hirai T., Nagoshi N., Yoshii T., Hashimoto J., Mori K., Maki S., Katsumi K., Takeuchi K., Ushio S., Furuya T., Watanabe K., Nishida N., Kaito T., Kato S., Nagashima K., Koda M., Nakashima H., Imagama S., Murata K., Matsuoka Y., Wada K., Kimura A., Ohba T., Katoh H., Watanabe M., Matsuyama Y., Ozawa H., Haro H., Takeshita K., Matsukura Y., Inose H., Yamazaki M., Watanabe K., Matsumoto M., Nakamura M., Okawa A., Kawaguchi Y.

Journal of Clinical Medicine （Journal of Clinical Medicine）  10 （ 20 ）  2021年10月

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Background: Although diffuse idiopathic skeletal hyperostosis (DISH) is known to coexist with the ossification of spinal ligaments (OSLs), details of the radiographic relationship remain unclear. Methods: We prospectively collected data of 239 patients with symptomatic cervical ossification of the posterior longitudinal ligament (OPLL) and analyzed the DISH severity on whole-spine computed tomography images, using the following grades: grade 0, no DISH; grade 1, DISH at T3–T10; grade 2, DISH at both T3–T10 and C6–T2 and/or T11–L2; and grade 3, DISH beyond C5 and/or L3. Ossification indices were calculated as the sum of vertebral and intervertebral levels with OSL for each patient. Results: DISH was found in 107 patients (44.8%), 65 (60.7%) of whom had grade 2 DISH. We found significant associations of DISH grade with the indices for cervical OPLL (r = 0.45, p < 0.0001), thoracic ossification of the ligamentum flavum (OLF; r = 0.41, p < 0.0001) and thoracic ossification of the supra/interspinous ligaments (OSIL; r = 0.53, p < 0.0001). DISH grade was also correlated with the index for each OSL in the whole spine (OPLL: r = 0.29, p < 0.0001; OLF: r = 0.40, p < 0.0001; OSIL: r = 0.50, p < 0.0001). Conclusion: The DISH grade correlated with the indices of OSL at each high-prevalence level as well as the whole spine.

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Efficacy of hyaluronic acid on intervertebral disc inflammation: An in vitro study using notochordal cell lines and human disc cells

Yamamoto T., Suzuki S., Fujii T., Mima Y., Watanabe K., Matsumoto M., Nakamura M., Fujita N.

Journal of Orthopaedic Research （Journal of Orthopaedic Research）  39 （ 10 ） 2197 - 2208 2021年10月

ISSN  07360266

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Hyaluronic acid (HA) is widely recognized as a therapeutic target and currently used in medicine. However, HA metabolism during intervertebral disc degeneration (IVDD) has not been completely elucidated. This study aimed to evaluate the efficacy of HA on intervertebral disc (IVD) inflammation and identify the main molecules modulating HA degradation in IVDs. To assess HA function in IVD cells in vitro, we treated human disc cells and U-CH1-N cells, a notochordal nucleus pulposus cell line, with HA or hyaluronidase. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis showed that tumor necrosis factor alpha (TNF-α)-mediated induction of the expression of TNF-α and cyclooxygenase-2 (COX2) was clearly neutralized by HA treatment, and the expression of TNF-α and COX2 was significantly induced by hyaluronidase treatment in both cell types. Additionally, Western blot analysis showed that hyaluronidase-induced phosphorylation of p38 and Erk1/2, and that TNF-α-mediated phosphorylation of p38 and Erk1/2 was clearly reduced by HA addition. In degenerating human IVD samples, immunohistochemistry for hyaluronidase showed that the expression of hyaluronidases including HYAL1, HYAL2, and cell migration-inducing protein (CEMIP) tended to increase in accordance with IVDD. In particular, HYAL1 showed statistically significant differences. In vitro study also confirmed a similar phenomenon that TNF-α treatment increased both messenger RNA and protein expression in both cell types. Our results demonstrated that HA could potentially suppress IVDD by regulating p38 and Erk1/2 pathways, and that the expression of HYAL1 was correlated with IVDD progression. These findings indicated that HYAL1 would be a potential molecular target for suppressing IVDD by controlling HA metabolism.

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Does Selective Posterior Correction and Fusion Surgery Influence Cervical Sagittal Alignment in Patient with Lenke Type 5 Adolescent Idiopathic Scoliosis?-A 5-year Follow-up Retrospective Cohort Study

Okubo T., Yagi M., Suzuki S., Nori S., Tsuji O., Nagoshi N., Okada E., Fujita N., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine）  46 （ 18 ） E976 - E984 2021年09月

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STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The aim of this study was to examine the changes in cervical sagittal alignment (CSA) following surgical correction in a patient with Lenke type 5 adolescent idiopathic scoliosis (AIS) and evaluate any possible factors influencing postoperative CSA. SUMMARY OF BACKGROUND DATA: Few studies have assessed the association between CSA and thoracic or lumbar sagittal alignment in AIS patients with major thoracolumbar/lumbar curve who underwent posterior correction and fusion surgery. METHODS: Sixty-six patients with Lenke type 5 AIS (two males and 64 females, the mean age at surgery of 16.2 years) were included in this study. They were followed up for minimum 5 years after surgery. Multiple linear regression analysis was used to evaluate possible factors influencing the postoperative CSA. To determine the influence of upper end vertebra (UEV) level on postoperative CSA, the subjects were divided into two groups according to UEV level of ≥T9 or ≤T10. The outcome variables were compared between the two groups and analyzed for changes in various spinal sagittal profiles using radiographic outcomes. RESULTS: Multiple linear regression analysis revealed that preoperative T10-L2 kyphosis and LL were significantly correlated with postoperative C2-7 lordosis. However, CSA did not significantly change at 5 years after surgery. Sub-analysis of the cohort revealed that in the UEV ≥T9 group, the mean thoracic kyphosis significantly increased from 20.3° ± 10.6° to 24.0° ± 8.9° and the mean C2-7 lordosis also significantly increased from -12.5° ± 8.3° to -4.3° ± 10.3° at 5-year postoperatively. SRS-22 outcomes were comparable between the groups. CONCLUSION: We indicated that the CSA was not influenced by surgical correction in most Lenke type 5 AIS patients. However, in a patient whose UEV was located at T9 or higher levels, CSA was influenced through the changes in thoracic kyphosis following posterior correction surgery.Level of Evidence: 4.

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Cobalt-Chromium Alloy Has Superior Antibacterial Effect Than Titanium Alloy: In Vitro and In Vivo Studies

Watanabe K., Fukuzaki S., Sugino A., Benson N., Metcalf N., Nakamura M., Matsumoto M.

Spine （Spine）  46 （ 17 ） E911 - E915 2021年09月

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STUDY DESIGN: In vitro and in vivo laboratory studies. OBJECTIVE: This study aimed to compare bacterial survival on titanium alloy (Ti) and cobalt-chromium alloy (CC) using in vitro and in vivo experiments. SUMMARY OF BACKGROUND DATA: Spinal implants are frequently manufactured from Ti and CC. These foreign materials are thought to be susceptible to biofilm formation that contributes to the development of surgical site infections. Certain metals (i.e., silver, cobalt) are known to have antibacterial properties. METHODS: In the in vitro study, discs made of Ti or CC were incubated with one of two common bacteria: Staphylococcus aureus (S. aureus) and Propionibacterium acnes (P. acnes). After incubation, discs were assessed to determine the number of viable bacterial cells. In the in vivo study, the discs that were made of CC or Ti were implanted into the subcutaneous layer of BALB/c mice. After skin closure, a suspension including either S. aureus or P. acnes was directly inoculated on the implanted discs. The discs were retrieved and analyzed to determine the number of viable bacteria at 0.5, 1, and 3 days after inoculation. RESULTS: The number of viable S. aureus cultured from the CC discs was 0.9 ± 0.2 × 103 CFU/disc, which was significantly lower than the cultured Ti discs (114.8 ± 18.3 × 103 CFU/disc). Moreover, a significantly lower mean number of P. acnes were cultured with CC (1.9 ± 1.2 × 103 CFU/disc) compared with the Ti (180.0 ± 72.1 × 103 CFU/disc). The in vivo infection model testing against S. aureus or P. acnes showed a significantly lower number of viable S. aureus or P. acnes on CC discs than Ti discs. The result was seen at all measured time points. CONCLUSION: CC suppressed S. aureus and P. acnes proliferation compared with Ti in vitro and in an in vivo infection model.Level of Evidence: N/A.

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Associations between clinical findings and severity of diffuse idiopathic skeletal hyperostosis in patients with ossification of the posterior longitudinal ligament

Hirai T., Nishimura S., Yoshii T., Nagoshi N., Hashimoto J., Mori K., Maki S., Katsumi K., Takeuchi K., Ushio S., Furuya T., Watanabe K., Nishida N., Watanabe K., Kaito T., Kato S., Nagashima K., Koda M., Nakashima H., Imagama S., Murata K., Matsuoka Y., Wada K., Kimura A., Ohba T., Katoh H., Watanabe M., Matsuyama Y., Ozawa H., Haro H., Takeshita K., Matsumoto M., Nakamura M., Yamazaki M., Matsukura Y., Inose H., Okawa A., Kawaguchi Y.

Journal of Clinical Medicine （Journal of Clinical Medicine）  10 （ 18 ）  2021年09月

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Background: This study investigated how diffuse idiopathic skeletal hyperostosis (DISH) influences clinical characteristics in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although DISH is considered unlikely to promote neurologic dysfunction, this relationship remains unclear. Methods: Patient data were prospectively collected from 16 Japanese institutions. In total, 239 patients with cervical OPLL were enrolled who had whole-spine computed tomography images available. The primary outcomes were visual analog scale pain scores and the results of other self-reported clinical questionnaires. Correlations were sought between clinical symptoms and DISH using the following grading system: 1, DISH at T3-T10; 2, DISH at both T3–10 and C6–T2 and/or T11–L2; and 3, DISH beyond the C5 and/or L3 levels. Results: DISH was absent in 132 cases, grade 1 in 23, grade 2 in 65, and grade 3 in 19. There were no significant correlations between DISH grade and clinical scores. However, there was a significant difference in the prevalence of neck pain (but not in back pain or low back pain) among the three grades. Interestingly, DISH localized in the thoracic spine (grade 1) may create overload at the cervical spine and lead to neck pain in patients with cervical OPLL. Conclusion: This study is the first prospective multicenter cross-sectional comparison of subjective outcomes in patients with cervical OPLL according to the presence or absence of DISH. The severity of DISH was partially associated with the prevalence of neck pain.

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Surgical Site Infection Following Primary Definitive Fusion for Pediatric Spinal Deformity: A Multicenter Study of Rates, Risk Factors, and Pathogens

Watanabe K., Yamaguchi T., Suzuki S., Suzuki T., Nakayama K., Demura S., Taniguchi Y., Yamamoto T., Sugawara R., Sato T., Fujiwara K., Murakami H., Akazawa T., Kakutani K., Hirano T., Yanagida H., Watanabe K., Matsumoto M., Uno K., Kotani T., Takeshita K., Ohara T., Kawakami N.

Spine （Spine）  46 （ 16 ） 1097 - 1104 2021年08月

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STUDY DESIGN: A retrospective multicenter study. OBJECTIVE: To determine the surgical site infection (SSI) rate, associated risk factors, and causative pathogens in pediatric patients with spinal deformity. SUMMARY OF BACKGROUND DATA: There have been no extensive investigations of the risk factors for SSI in Japan. METHODS: Demographic data, radiographic findings, and the incidence of SSI were retrospectively analyzed in 1449 pediatric patients who underwent primary definitive fusion surgery for spinal deformity at any of 15 institutions from 2015 to 2017. SSI was defined according to the US Centers for Disease Control and Prevention guideline. RESULTS: The incidence of all SSIs was 1.4% and that of deep SSIs was 0.76%. The most common pathogenic microbes were methicillin-resistant staphylococci (n = 5) followed by gram-negative rods (n = 4), methicillin-sensitive staphylococci (n = 1), and others (n = 10). In univariate analysis, younger age, male sex, a diagnosis of kyphosis, type of scoliosis, American Society of Anesthesiologists (ASA) class ≥3, mental retardation urinary incontinence, combined anterior-posterior fusion, greater magnitude of kyphosis, three-column osteotomy, use of blood transfusion, and number of antibiotic administration were associated with the likelihood of SSI (all P < 0.05). Multivariate logistic regression analysis identified the following independent risk factors for SSI: syndromic scoliosis etiology (vs. idiopathic scoliosis; adjusted odds ratio [OR] 16.106; 95% confidence interval [CI] 2.225-116.602), neuromuscular scoliosis etiology (vs. idiopathic scoliosis; adjusted OR 11.814; 95% CI 1.109-125.805), ASA class 3 (vs. class 2; adjusted OR 15.231; 95% CI 1.201-193.178), and administration of antibiotic therapy twice daily (vs. three times daily; adjusted OR 6.121; 95% CI 1.261-29.718). CONCLUSION: The overall infection rate was low. The most common causative bacteria were methicillin-resistant followed by gram-negative rods. Independent risk factors for SSI in pediatric patients undergoing spinal deformity surgery were scoliosis etiology, ASA class 3, and administration of antibiotic therapy twice daily.Level of Evidence: 3.

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How Preoperative Motor Weakness Affects the Extent of Recovery After Elective Spine Surgery in Patients with Degenerative Lumbar Spinal Stenosis

Yagi M., Suzuki S., Nori S., Okada E., Tsuji O., Nagoshi N., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine）  46 （ 16 ） 1118 - 1127 2021年08月

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STUDY DESIGN: Retrospective review. OBJECTIVE: This study sought to determine how baseline motor weakness (MW) affects elective spine surgery in patients with degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: Favorable clinical outcomes have been described for elective spine surgery in patients with LSS. However, the way preoperative MW affects the patient's health-related quality of life (HRQoL) after surgery is not well understood. METHODS: A retrospective review of prospectively collected data from 305 surgically treated patients with LSS who had 2-year follow-up was performed (age 71 ± 9 yrs, male 62%). Demographic, radiographic, and clinical outcomes were analyzed at baseline and at 1-year, 2-year, and 3-year postoperation. The Japanese Orthopedic Association Back Pain Evaluation Questionnaire was used to assess the HRQoLs. The HRQoLs were compared between those with or without preop MW. Adjusted multivariate logistic regression analyses were performed to determine whether MW affected HRQoLs. RESULTS: One hundred sixteen patients (38%) were categorized as MW+. The patient background including age, sex, presence of degenerative spondylolisthesis, type of surgery, and presence of neurological claudication were similar between the two groups. However, the 1-, 2-, and 3-year postoperative visual analogue scale of back pain, leg pain, leg numbness, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire lumbar function, social life, mental health, and walking ability were all inferior in the MW+ group, whereas a similar percentage of patients achieved a minimum clinically important difference in all subdomains at 3 years. The adjusted multivariate logistic regression analyses showed that having ≥2 muscles with MW, and severity of MW (manual motor test grade) were independent risk factors for both difficulty climbing stairs and walking >15 minutes. (muscles with MW≥2; stair climbing: OR 6.4[2.3-17.4], walking: OR 3.2[1.4-7.3], severity of MW; stair climbing: OR 2.5[1.4-4.4], walking: OR 2.2[1.3-3.7]). CONCLUSION: The patients with baseline MW had inferior HRQoL for up to 3 years compared with that of those without MW; however, the amount of improvement in HRQoL was comparable. Timely follow-up is important to find out the deterioration of motor function.Level of Evidence: 4.

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Impact of diabetes mellitus on cervical spine surgery for ossification of the posterior longitudinal ligament

Kimura A., Takeshita K., Yoshii T., Egawa S., Hirai T., Sakai K., Kusano K., Nakagawa Y., Wada K., Katsumi K., Fujii K., Furuya T., Nagoshi N., Kanchiku T., Nagamoto Y., Oshima Y., Nakashima H., Ando K., Takahata M., Mori K., Nakajima H., Murata K., Matsunaga S., Kaito T., Yamada K., Kobayashi S., Kato S., Ohba T., Inami S., Fujibayashi S., Katoh H., Kanno H., Watanabe K., Imagama S., Koda M., Kawaguchi Y., Nakamura M., Matsumoto M., Yamazaki M., Okawa A.

Journal of Clinical Medicine （Journal of Clinical Medicine）  10 （ 15 ）  2021年08月

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Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (_30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up.

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Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use

Otomo N., Lu H.F., Koido M., Kou I., Takeda K., Momozawa Y., Kubo M., Kamatani Y., Ogura Y., Takahashi Y., Nakajima M., Minami S., Uno K., Kawakami N., Ito M., Sato T., Watanabe K., Kaito T., Yanagida H., Taneichi H., Harimaya K., Taniguchi Y., Shigematsu H., Iida T., Demura S., Sugawara R., Fujita N., Yagi M., Okada E., Hosogane N., Kono K., Nakamura M., Chiba K., Kotani T., Sakuma T., Akazawa T., Suzuki T., Nishida K., Kakutani K., Tsuji T., Sudo H., Iwata A., Kaneko K., Inami S., Kochi Y., Chang W.C., Matsumoto M., Watanabe K., Ikegawa S., Terao C.

Journal of Bone and Mineral Research （Journal of Bone and Mineral Research）  36 （ 8 ） 1481 - 1491 2021年08月

ISSN  08840431

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Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10−40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10−10) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10−8), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10−4). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).

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The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation

Okada E., Suzuki S., Nori S., Tsuji O., Nagoshi N., Yagi M., Fujita N., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science）  26 （ 4 ） 548 - 554 2021年07月

ISSN  09492658

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Background: Chemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase. Methods: Inclusion criteria for this procedure were 1) 18–70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective. Results: Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006–26.204) was significantly associated with clinical effectiveness. Conclusions: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc.

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Characterization of Patients with Poor Risk for Clinical Outcomes in Adult Symptomatic Lumbar Deformity Surgery

Yagi M., Michikawa T., Suzuki S., Okada E., Nori S., Tsuji O., Nagoshi N., Asazuma T., Hosogane N., Fujita N., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine）  46 （ 12 ） 813 - 821 2021年06月

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STUDY DESIGN: Retrospective review of 159 surgically treated consecutive adult symptomatic lumbar deformity (ASLD) (65 ± 9 years, female: 94%) from a multicenter database. OBJECTIVE: The aim of this study was to provide a comprehensive analysis of the risk of a poor clinical outcome in ASLD surgery. SUMMARY OF BACKGROUND DATA: Poor-risk patients with ASLD remain poorly characterized. METHODS: ASLD was defined as age >40 years with a lumbar curve ≥30° or C7SVA ≥5 cm and Scoliosis Research Society 22 (SRS22) pain or function <4. Poor outcome was defined as 2y SRS22 total <4 or pain, function or satisfaction ≤3. The outcomes of interest included age, sex, body mass index, bone mineral density, Schwab-SRS type, frailty, history of arthroplasty, upper-instrumented vertebral, lower-instrumented vertebral, levels involved, pedicle subtraction osteotomy, lumbar interbody fusion, sagittal alignment, global alignment and proportion (GAP) score, baseline SRS22r score, estimated blood loss, time of surgery, and severe adverse event (SAE). Poisson regression analyses were performed to identify the independent risks for poor clinical outcome. A patient was considered at poor risk if the number of risks was >4. RESULTS: All SRS22 domains were significantly improved after surgery. In total, 21% (n = 34) reported satisfaction ≤3 and 29% (n = 46) reported pain or function ≤3. Poisson regression analysis revealed that frailty (odds ratio [OR]: 0.2 [0.1-0.8], P = .03), baseline mental-health (OR: 0.6 [0.4-0.9], P = .01) and function (OR: 1.9 [1.0-3.6], P < .01), GAP score (OR: 4.6 [1.1-18.7], P = .03), and SAE (OR: 3.0 [1.7-5.2], P < .01) were identified as independent risk for poor clinical outcome. Only 17% (n = 6) of the poor-risk patients reached SRS22 total score >4.0 at 2 years. CONCLUSION: The overall clinical outcome was favorable for ASLD surgery. Poor-risk patients continue to have inferior outcomes, and alternative treatment strategies are needed to help improve outcomes in this patient population. Recognition and optimization of modifiable risk factors, such as physical function and mental health, and reduced SAEs may improve overall clinical outcomes of ASLD surgery.Level of Evidence: 3.

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Spontaneous reduction of chiari malformation and syringomyelia after posterior spinal fusion for scoliosis

Iwami T., Watanabe K., Suzuki S., Nori S., Tsuji O., Nagoshi N., Okada E., Yagi M., Fujita N., Nakamura M., Matsumoto M.

JBJS Case Connector （JBJS Case Connector）  11 （ 2 ）  2021年06月

ISSN  21603251

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Case: A 22-year-old skeletally mature man with scoliosis accompanied by syringomyelia associated with Chiari malformation type 1 was presented to our hospital. Because the maximal syrinx/cord ratio was small, and he had no neurological deficit, he underwent corrective surgery without the treatment of the syringomyelia. Conclusion: The scoliosis was corrected without any neurological complications. Magnetic resonance imaging taken 8 days after the surgery showed the reduction of the size of the syringomyelia. The syringomyelia almost disappeared at the 8-year follow-up.

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The Long-term Impact of Whiplash Injuries on Patient Symptoms and the Associated Degenerative Changes Detected Using MRI: A Prospective 20-year Follow-up Study Comparing Patients with Whiplash-associated Disorders with Asymptomatic Subjects

Watanabe K., Daimon K., Fujiwara H., Nishiwaki Y., Okada E., Nojiri K., Watanabe M., Katoh H., Shimizu K., Ishihama H., Fujita N., Ichihara D., Tsuji T., Nakamura M., Matsumoto M.

Spine （Spine）  46 （ 11 ） 710 - 716 2021年06月

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STUDY DESIGN: A longitudinal, 20-year comparative study of patients with whiplash-associated disorders (WAD). OBJECTIVE: The aim of this study was to clarify the long-term impact of WAD on patient symptoms and on magnetic resonance imaging (MRI) findings of the cervical spine, in comparison with asymptomatic volunteers. SUMMARY OF BACKGROUND DATA: The long-term impact of WAD has not been fully elucidated. METHODS: Between 1993 and 1996, we conducted a cross-sectional comparative study of 508 acute WAD patients and 497 asymptomatic volunteers, all of whom underwent MRI on cervical spine and physical examinations. For this 20-year follow-up comparative study, 75 WAD patients and 181 control subjects aged <60 years were recruited from the original cohort. The MRI findings, including discs' signal intensities, posterior disc protrusions, anterior dural compressions, spinal cord disc space narrowing, and foraminal stenoses, were evaluated using two to four numerical grades. The results of the WAD patients and control subjects were compared. RESULTS: In this follow-up, the prevalence of shoulder stiffness (72.0% vs. 45.9%), headache (24.0% vs. 12.2%), and arm pain (13.3% vs. 3.9%) were significantly greater in WAD patients than in control subjects. The multiregression analysis revealed that a history of WAD was associated with shoulder stiffness (odds ratio [OR]: 3.36), headache (OR: 2.39), and arm pain (OR: 3.82). Although MRI findings in WAD patients were more degenerated than in control subjects in the initial study, all MRI findings were similar at the 20-year follow-up. There were no significant correlations between clinical cervical symptoms and progression in each MR finding in either group. CONCLUSION: After 20 years, whiplash injuries significantly impacted the residual symptoms of shoulder stiffness, headache, and arm pain when compared with initially asymptomatic volunteers. The progression of degenerative changes in the cervical intervertebral discs after 20 years revealed no association with existing whiplash injuries, neither did the residual cervical-related symptoms.Level of Evidence: 3.

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Baseline severity of myelopathy predicts neurological outcomes after posterior decompression surgery for cervical spondylotic myelopathy: a retrospective study

Nori S., Nagoshi N., Kono H., Kobayashi Y., Isogai N., Ninomiya K., Tsuji T., Horiuchi Y., Takemura R., Kimura R., Tsuji O., Suzuki S., Okada E., Yagi M., Nakamura M., Matsumoto M., Watanabe K., Ishii K., Yamane J.

Spinal Cord （Spinal Cord）  59 （ 5 ） 547 - 553 2021年05月

ISSN  13624393

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Study design: Retrospective multicenter study. Objectives: To identify the usefulness of the baseline severity of myelopathy for predicting surgical outcomes for cervical spondylotic myelopathy (CSM). Setting: Seventeen institutions in Japan. Methods: This study included 675 persons with CSM who underwent posterior decompression. According to baseline severity, the individuals were divided into the mild (Japanese Orthopaedic Association [JOA] score ≥ 14.5), moderate (JOA score = 10.5–14), and severe (JOA score ≤ 10) groups. Surgical outcomes and clinical variables were compared between the groups. Logistic regression analysis was used to develop a prediction model for unsatisfactory symptom state (postoperative JOA score ≤ 14, residual moderate or severe myelopathy). Results: The mean (±standard deviation) age was 67 ± 12 years. The participants in the severe group were older than those in the mild group. Postoperative JOA scores were higher in the mild group than in the severe group. According to multivariate logistic regression analysis, the prediction model included preoperative JOA scores (odds ratio [OR] 0.60; 95% confidence interval [CI] 0.55–0.67) and age (OR 1.06, 95% CI 1.04–1.08). On the basis of the model, a representative combination of the thresholds to maximize the value of “sensitivity − (1 − specificity)” demonstrated a preoperative JOA score of 11.5 as a predictor of postoperative unsatisfactory symptom state in people around the mean age of the study cohort (67 years). Conclusions: The combination of the baseline severity of myelopathy and age can predict postoperative symptom states after posterior decompression surgery for CSM.

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Predictors of neurologic outcome after surgery for cervical ossification of the posterior longitudinal ligament differ based on myelopathy severity: A multicenter study

Shin J.J., Jeon H., Lee J.J., Kim H.C., Kim T.W., An S.B., Shin D.A., Yi S., Kim K.N., Yoon D.H., Nagoshi N., Watanabe K., Nakamura M., Matsumoto M., Li N., Ma S., He D., Tian W., Kwan K.Y.H., Cheung K.M.C., Riew K.D., Hoh D.J., Ha Y.

Journal of Neurosurgery: Spine （Journal of Neurosurgery: Spine）  34 （ 5 ） 749 - 758 2021年05月

ISSN  15475654

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OBJECTIVE The purpose of this retrospective multicenter study was to compare prognostic factors for neurological recovery in patients undergoing surgery for cervical ossification of the posterior longitudinal ligament (OPLL) based on their presenting mild, moderate, or severe myelopathy. METHODS The study included 372 consecutive patients with OPLL who underwent surgery for cervical myelopathy between 2006 and 2016 in East Asian countries with a high OPLL prevalence. Baseline and postoperative clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) myelopathy score and recovery ratio. Radiographic assessment included occupying ratio, cervical range of motion, and sagittal alignment parameters. Patient myelopathy was classified as mild, moderate, or severe based on the preoperative JOA score. Linear and multivariate regression analyses were performed to identify patient and surgical factors associated with neurological recovery stratified by baseline myelopathy severity. RESULTS The mean follow-up period was 45.4 months (range 25-140 months). The mean preoperative and postoperative JOA scores and recovery ratios for the total cohort were 11.7 ± 3.0, 14.5 ± 2.7, and 55.2% ± 39.3%, respectively. In patients with mild myelopathy, only age and diabetes correlated with recovery. In patients with moderate to severe myelopathy, older age and preoperative increased signal intensity on T2-weighted imaging were significantly correlated with a lower likelihood of recovery, while female sex and anterior decompression with fusion (ADF) were associated with better recovery. CONCLUSIONS Various patient and surgical factors are correlated with likelihood of neurological recovery after surgical treatment for cervical OPLL, depending on the severity of presenting myelopathy. Older age, male sex, intramedullary high signal intensity, and posterior decompression are associated with less myelopathy improvement in patients with predomiworse baseline function. Therefore, myelopathy-specific preoperative counseling regarding prognosis for postoperative long-term neurological improvement should include consideration of these individual and surgical factors.

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Residual lumbar curvature that developed during adolescence accelerates intervertebral disc degeneration in adulthood

Suzuki S., Fujiwara H., Nori S., Tsuji O., Nagoshi N., Okada E., Fujita N., Yagi M., Nohara A., Kawakami N., Michikawa T., Nakamura M., Matsumoto M., Watanabe K.

Spine Deformity （Spine Deformity）  9 （ 3 ） 711 - 720 2021年05月

ISSN  2212134X

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Purpose: To elucidate the influence of spinal deformity in adolescent idiopathic scoliosis (AIS) on lumbar intervertebral disc (IVD) degeneration in adulthood using magnetic resonance imaging (MRI). Methods: A total of 102 patients (8 men, 94 women; mean age, 31.4 years) who had developed idiopathic scoliosis at the age of 10–18 years and underwent preoperative lumbar spine MRI at the age of ≥ 20 were included in the study. Twenty volunteers (3 men, 17 women; mean age, 33.6 years) without scoliosis were assessed as controls. We divided the adult scoliosis patients into two groups: Group A consisted of patients with lumbar modifier A, and Group BC consisted of those with modifiers B and C. IVD degeneration from L1/2 to L5/S1 was assessed by MRI. The Scoliosis Research Society-22 (SRS-22) patient questionnaire was used in the patients’ clinical assessment. Results: There were 40 patients in the Group A and 62 in the Group BC. Compared to the control groups, significant IVD degeneration was observed at L2/3 and L3/4 in Group A, and at all levels except for L5/S1 in Group BC. The proportion of degenerated IVDs patients (Grades 1c and 2) was significantly higher in Group BC than those in Group A at L3/L4 and L4/L5. Furthermore, the severity of IVD degeneration was significantly greater in the group BC than in the group A at all levels, except for L5/S1, especially in patients aged > 30 years. The mean scores of all subdomains in the SRS-22 questionnaire were comparable between the two groups. Conclusion: Our study showed that the residual lumbar curvature from AIS may have accelerated IVD degeneration in adulthood, especially in patients aged > 30 years. Level of evidence: III.

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Incidence and Risk Factors for Unplanned Return to the Operating Room Following Primary Definitive Fusion for Pediatric Spinal Deformity: A Multicenter Study with Minimum 2-year Follow-Up

Taniguchi Y., Ohara T., Suzuki S., Watanabe K., Suzuki T., Uno K., Yamaguchi T., Yanagida H., Nakayama K., Kotani T., Watanabe K., Hirano T., Yamamoto T., Kawamura I., Sugawara R., Takeshita K., Demura S., Oku N., Sato T., Fujiwara K., Akazawa T., Murakami H., Kakutani K., Matsubayashi Y., Kawakami N.

Spine （Spine）  46 （ 8 ） E498 - E504 2021年04月

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STUDY DESIGN: A retrospective multicenter cohort study. OBJECTIVE: The aim of this study was to identify the incidence and risk factors for UPROR within minimum 2-year follow-up in primary definitive fusion for pediatric spinal deformity. SUMMARY OF BACKGROUND DATA: Several previous reports have elucidated the incidence of complications after pediatric scoliosis surgery; however, there has been no study that described the incidence and risk factors for unplanned return to the operating room (UPROR) with long-term follow-up in surgery for pediatric scoliosis with every etiology. METHODS: We retrospectively extracted data of patients aged <19 years, from 14 institutes in Japan, who underwent primary definitive fusion surgery for spinal deformity between January 1, 2015 and December 31, 2017. The primary outcomes were the incidence of UPROR within the minimum 2-year follow-up period for any reason. Univariate and multivariate logistical analyses were conducted to identify potential risk factors associated with UPROR. RESULTS: We identified 1417 eligible patients (287 males and 1130 females) with a mean age of 13.9 years. UPROR for any reason within minimum 2-year follow-up was identified in 68 patients (4.8%). The most frequent cause for UPROR was implant failure found in 29 patients, followed by surgical site infection in 14 patients, junctional problems in 10 patients, and neurological complications in six patients. The multivariate logistic regression analysis revealed that a diagnosis of kyphosis (odds ratio [OR], 2.65; 95% confidence interval [CI] 1.16-6.04), etiology of congenital or structural type (OR 2.21; 95% CI 1.08-4.53), etiology of syndromic type (OR 2.67; 95% CI 1.27-5.64), and increased operation time of ≥300 minutes (OR 1.81; 95% CI 1.07-3.07) were the risk factors for the incidence of UPROR. CONCLUSION: The present multicenter study identified for the first time the incidence and risk factors for UPROR with minimum 2-year follow-up after primary definitive fusion surgery for pediatric spinal deformity with every etiology.Level of Evidence: 3.

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Diabetes Does Not Adversely Affect Neurological Recovery and Reduction of Neck Pain After Posterior Decompression Surgery for Cervical Spondylotic Myelopathy: Results From a Retrospective Multicenter Study of 675 Patients

Nori S., Nagoshi N., Yoshioka K., Nojiri K., Takahashi Y., Fukuda K., Ikegami T., Yoshida H., Iga T., Tsuji O., Suzuki S., Okada E., Yagi M., Nakamura M., Matsumoto M., Watanabe K., Ishii K., Yamane J.

Spine （Spine）  46 （ 7 ） 433 - 439 2021年04月

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STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: The aim of this study was to identify the impact of diabetes on surgical outcomes of posterior decompression for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Although some previous studies have reported surgical outcomes of posterior decompression for CSM in diabetic patients, their results were inconsistent. METHODS: We included 675 patients with CSM who underwent posterior decompression. Patients were divided into diabetic (n = 140) and nondiabetic (n = 535) groups according to the diabetic criteria for glucose intolerance. Surgical outcomes as assessed by the Japanese Orthopedic Association (JOA) scores and visual analog scale (VAS) for neck pain were compared between groups. Subsequently, the functional outcomes of diabetic patients were compared between the mild (n = 131) and moderately severe (n = 9) groups. All patients were followed up for at least 1 year after surgery. RESULTS: Compared with the nondiabetic group, the diabetic group showed lower pre- and postoperative JOA scores (P = 0.025 and P = 0.001, respectively) and a lower JOA score recovery rate (RR) (P = 0.009). However, the preoperative-to-postoperative changes in JOA scores in the diabetic and nondiabetic groups were not significantly different (P = 0.988). Pre- and postoperative VAS for neck pain and postoperative reduction of neck pain were comparable between groups (P = 0.976, P = 0.913 and P = 0.688, respectively). Although statistical analysis was not performed due to the small underpowered sample size, functional outcomes assessed by the JOA score RR (43.3 ± 37.1% vs. 45.3 ± 33.9%) and preoperative-to-postoperative changes in JOA scores (3.0 ± 2.2 vs. 2.7 ± 2.5) were similar between the mild and moderately severe diabetes groups. CONCLUSION: CSM patients with diabetes experienced improvements in neurological function and neck pain as a result of posterior decompression to the same extent seen in patients without diabetes.Level of Evidence: 3.

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