1.Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody
Takeshi SAINOH ; Takeshi SAINOH ; Sumihisa ORITA ; Sumihisa ORITA ; Masayuki MIYAGI ; Masayuki MIYAGI ; Miyako SUZUKI-NARITA ; Miyako SUZUKI-NARITA ; Yoshihiro SAKUMA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Yasuhiro OIKAWA ; Go KUBOTA ; Go KUBOTA ; Jun SATO ; Jun SATO ; Yasuhiro SHIGA ; Yasuhiro SHIGA ; Kazuki FUJIMOTO ; Kazuki FUJIMOTO ; Yawara EGUCHI ; Yawara EGUCHI ; Masao KODA ; Masao KODA ; Yasuchika AOKI ; Yasuchika AOKI ; Tsutomu AKAZAWA ; Tsutomu AKAZAWA ; Takeo FURUYA ; Takeo FURUYA ; Junichi NAKAMURA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Hiroshi TAKAHASHI ; Satoshi MAKI ; Satoshi MAKI ; Masahiro INOUE ; Masahiro INOUE ; Hideyuki KINOSHITA ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Masaki NORIMOTO ; Takashi SATO ; Takashi SATO ; Masashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Masahiro SUZUKI ; Keigo ENOMOTO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Norichika MIZUKI ; Takashi HOZUMI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Ryuto TSUCHIYA ; Geundong KIM ; Geundong KIM ; Takuma OTAGIRI ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Takahisa HISHIYA ; Seiji OHTORI ; Seiji OHTORI ; Kazuhide INAGE ; Kazuhide INAGE
Asian Spine Journal 2022;16(1):99-106
Methods:
This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events.
Results:
Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events.
Conclusions
Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.
2.Diffusion Tensor Imaging of the Spinal Canal in Quantitative Assessment of Patients with Lumbar Spinal Canal Stenosis
Masaki NORIMOTO ; Yawara EGUCHI ; Hirohito KANAMOTO ; Yasuhiro OIKAWA ; Koji MATSUMOTO ; Yoshitada MASUDA ; Takeo FURUYA ; Sumihisa ORITA ; Kazuhide INAGE ; Satoshi MAKI ; Yasuhiro SHIGA ; Hideyuki KINOSHITA ; Koki ABE ; Masahiro INOUE ; Tomotaka UMIMURA ; Takashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Keigo ENOMOTO ; Seiji OHTORI
Asian Spine Journal 2021;15(2):207-215
Methods:
Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD).
Results:
Compared to healthy individuals, LSS patients had significantly lower ADC (
3.Diffusion Tensor Imaging of the Spinal Canal in Quantitative Assessment of Patients with Lumbar Spinal Canal Stenosis
Masaki NORIMOTO ; Yawara EGUCHI ; Hirohito KANAMOTO ; Yasuhiro OIKAWA ; Koji MATSUMOTO ; Yoshitada MASUDA ; Takeo FURUYA ; Sumihisa ORITA ; Kazuhide INAGE ; Satoshi MAKI ; Yasuhiro SHIGA ; Hideyuki KINOSHITA ; Koki ABE ; Masahiro INOUE ; Tomotaka UMIMURA ; Takashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Keigo ENOMOTO ; Seiji OHTORI
Asian Spine Journal 2021;15(2):207-215
Methods:
Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD).
Results:
Compared to healthy individuals, LSS patients had significantly lower ADC (
4.Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study
Kazuhide INAGE ; Sumihisa ORITA ; Yawara EGUCHI ; Yasuhiro SHIGA ; Masao KODA ; Yasuchika AOKI ; Toshiaki KOTANI ; Tsutomu AKAZAWA ; Takeo FURUYA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Miyako SUZUKI-NARITA ; Satoshi MAKI ; Shigeo HAGIWARA ; Masahiro INOUE ; Masaki NORIMOTO ; Hideyuki KINOSHITA ; Takashi SATO ; Masashi SATO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Geundong KIM ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Seiji OHTORI
Yonsei Medical Journal 2021;62(9):829-835
Purpose:
In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects.
Materials and Methods:
Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab.
Results:
A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine.
Conclusion
Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.
5.Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study
Kazuhide INAGE ; Sumihisa ORITA ; Yawara EGUCHI ; Yasuhiro SHIGA ; Masao KODA ; Yasuchika AOKI ; Toshiaki KOTANI ; Tsutomu AKAZAWA ; Takeo FURUYA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Miyako SUZUKI-NARITA ; Satoshi MAKI ; Shigeo HAGIWARA ; Masahiro INOUE ; Masaki NORIMOTO ; Hideyuki KINOSHITA ; Takashi SATO ; Masashi SATO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Geundong KIM ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Seiji OHTORI
Yonsei Medical Journal 2021;62(9):829-835
Purpose:
In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects.
Materials and Methods:
Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1–2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5–7 months after the administration of romosozumab.
Results:
A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1–2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5–7 months after romosozumab administration;and a significant increase only observed in the lumbar spine.
Conclusion
Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.
6.Evaluating Spinal Canal Lesions Using Apparent Diffusion Coefficient Maps with Diffusion-Weighted Imaging
Hirohito KANAMOTO ; Masaki NORIMOTO ; Yawara EGUCHI ; Yasuhiro OIKAWA ; Sumihisa ORITA ; Kazuhide INAGE ; Koki ABE ; Masahiro INOUE ; Hideyuki KINOSHITA ; Tomotaka UMIMURA ; Koji MATSUMOTO ; Yoshitada MASUDA ; Takeo FURUYA ; Masao KODA ; Yasuchika AOKI ; Atsuya WATANABE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2020;14(3):312-319
Methods:
We performed 3T MRI in 10 healthy volunteers and 13 patients with LSS. The ADC values in the spinal canal were evaluated at 46 vertebrae (L4/5 and L5/S1 for each participant), and the reduced and conventional fields of view were compared.
Results:
The ADC values were 2.72±0.12 at L4/5 in healthy volunteers, 2.76±0.19 at L5/S1 in healthy volunteers, 1.77±0.58 at L4/5 in patients with LSS, and 2.35±0.29 at L5/S1 in patients with LSS. The ADC value at L4/5 in patients with LSS was significantly lower than that at L5/S1 in patients with LSS and that at L4/5 and L5/S1 in healthy volunteers (p <0.05). With an ADC cutoff value of 2.46 to identify LSS, this approach provided an area under the curve of 0.81, sensitivity of 0.92, and specificity of 0.76 (p <0.05).
Conclusions
Preoperative examination using ADC maps permits visualization and quantification of spinal canal lesions, thus proving the utility of ADC maps in the selection of decompression surgery for LSS.
7.Correlation Between Walking Ability and Monthly Care Costs in Elderly Patients After Surgical Treatments for Hip Fractures.
Koki ABE ; Kazuhide INAGE ; Keishi YAMASHITA ; Masaomi YAMASHITA ; Akiyoshi YAMAMAOKA ; Masaki NORIMOTO ; Yoshinori NAKATA ; Takeshi MITSUKA ; Kaoru SUSEKI ; Sumihisa ORITA ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Tomotaka UMIMURA ; Yawara EGUCHI ; Takeo FURUYA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Annals of Rehabilitation Medicine 2018;42(4):569-574
OBJECTIVE: To validate the relationship between residual walking ability and monthly care cost as well as long-term care insurance (LTCI) certification level in elderly patients after surgical treatment for hip fractures in Japan. METHODS: Elderly patients aged >75 years who underwent surgical treatment for hip fractures in our hospital were included. The preand post-surgical (6-month) walking ability and LTCI certification and the presence or absence of dementia was determined from medical records and questionnaires. Walking ability was classified into 6 levels used in our daily medical practice. Based on these data, we correlated the relationship between walking ability and the LTCI certification level. Further, based on the official statistics pertaining to the average monthly costs per person at each LTCI certification level, we evaluated the relationship between walking ability and monthly care cost. RESULTS: A total of 105 cases (mean age, 80.2 years; 16 men; 39 patients with dementia) were included. The correlation between walking ability and average monthly cost per person as well as LTCI certification level at 6 months postoperatively (r=0.58) was demonstrated. The correlation was found in both groups with and without dementia. CONCLUSION: The ability to walk reduced the cost of care in elderly patients who experienced hip fracture, regardless of the presence of dementia.
Aged*
;
Certification
;
Cost-Benefit Analysis
;
Dementia
;
Hip Fractures*
;
Hip*
;
Humans
;
Insurance, Long-Term Care
;
Japan
;
Long-Term Care
;
Male
;
Medical Records
;
Mobility Limitation
;
Walking*
8.Inhibiting Vascular Endothelial Growth Factor in Injured Intervertebral Discs Attenuates Pain-Related Neuropeptide Expression in Dorsal Root Ganglia in Rats.
Jun SATO ; Kazuhide INAGE ; Masayuki MIYAGI ; Yoshihiro SAKUMA ; Kazuyo YAMAUCHI ; Masao KODA ; Takeo FURUYA ; Junichi NAKAMURA ; Miyako SUZUKI ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI ; Sumihisa ORITA
Asian Spine Journal 2017;11(4):556-561
STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. METHODS: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. RESULTS: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). CONCLUSIONS: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.
Animals
;
Back Pain
;
Calcitonin Gene-Related Peptide
;
Cytokines
;
Diagnosis-Related Groups
;
Endothelial Growth Factors
;
Ganglia
;
Ganglia, Spinal*
;
Humans
;
Intervertebral Disc*
;
Low Back Pain
;
Models, Animal
;
Needles
;
Neuropeptides*
;
Punctures
;
Rats*
;
Rats, Sprague-Dawley
;
Sodium
;
Sodium Chloride
;
Spinal Nerve Roots*
;
Vascular Endothelial Growth Factor A*
9.Correlation among Inflammatory Cytokine Expression Levels, Degree of Disk Degeneration, and Predominant Clinical Symptoms in Patients with Degenerated Intervertebral Discs.
Takeshi SAINOH ; Kazuhide INAGE ; Sumihisa ORITA ; Masao KODA ; Takeo FURUYA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(3):472-477
STUDY DESIGN: Observational study. PURPOSE: To assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD). OVERVIEW OF LITERATURE: Low back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial. METHODS: Using the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels. RESULTS: A gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002). CONCLUSIONS: These results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.
Dichlorodiphenyldichloroethane
;
Disease Progression
;
Enzyme-Linked Immunosorbent Assay
;
Humans
;
Interleukin-6
;
Intervertebral Disc Degeneration*
;
Intervertebral Disc*
;
Leg
;
Low Back Pain
;
Magnetic Resonance Imaging
;
Nerve Growth Factor
;
Observational Study
;
Tumor Necrosis Factor-alpha
10.Response to: “Long-term Outcomes of In Situ Fusion for Treating Dysplastic Spondylolisthesis”.
Kazuhide INAGE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(5):845-846
No abstract available.
Spondylolisthesis*

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