Posterior Ligamentous Complex Injuries Are Related to Fracture Severity and Neurological Damage in Patients with Acute Thoracic and Lumbar Burst Fractures

Masaaki Machino,Yasutsugu Yukawa,Keigo Ito,Shunsuke Kanbara,Daigo Morita,Fumihiko Kato 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.4

Purpose: The proposed the thoracolumbar injury classification system (TLICS) for thoracolumbar injury cites the integrity of the posterior ligamentous complex (PLC). However, no report has elucidated the severity of damage in thoracic and lumbar injury with classification schemes by presence of the PLC injury. The purpose of this study was to accurately assess the severity of damage in thoracic and lumbar burst fractures with the PLC injuries. Materials and Methods: One hundred consecutive patients treated surgically for thoracic and lumbar burst fractures were enrolled in this study. There were 71 men and 29 women whose mean age was 36 years. Clinical and radiologic data were investigated, and the thoracolumbar injury classification schemes were also evaluated. All patients were divided into two groups (the P group with PLC injuries and the C group without PLC injuries)for comparative examination. Results: Fourth-one of 100 cases showed PLC injuries in MRI study. The load sharing classification score was significantly higher in the P group [7.8±0.2 points for the P group and 6.9±1.1 points for the C group (p<0.001)]. The TLICS (excluded PLC score) score was also significantly higher in the P group [6.2±1.1 points for the P group and 4.0±1.4 points for the C group (p<0.001)]. Conclusion: The presence of PLC injury significantly influenced the severity of damage. In management of thoracic lumbar burst fractures, evaluation of PLC injury is important to accurately assess the severity of damage.

Integrative analysis reveals early epigenetic alterations in high-grade serous ovarian carcinomas

Machino Hidenori,Dozen Ai,Konaka Mariko,Komatsu Masaaki,Nakamura Kohei,Ikawa Noriko,Shozu Kanto,Asada Ken,Kaneko Syuzo,Yoshida Hiroshi,Kato Tomoyasu,Nakayama Kentaro,Saloura Vassiliki,Kyo Satoru,Hamam 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. To date, the profiles of gene mutations and copy number alterations in HGSOC have been well characterized. However, the patterns of epigenetic alterations and transcription factor dysregulation in HGSOC have not yet been fully elucidated. In this study, we performed integrative omics analyses of a series of stepwise HGSOC model cells originating from human fallopian tube secretory epithelial cells (HFTSECs) to investigate early epigenetic alterations in HGSOC tumorigenesis. Assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA sequencing (RNA-seq) methods were used to analyze HGSOC samples. Additionally, protein expression changes in target genes were confirmed using normal HFTSECs, serous tubal intraepithelial carcinomas (STICs), and HGSOC tissues. Transcription factor motif analysis revealed that the DNA-binding activity of the AP-1 complex and GATA family proteins was dysregulated during early tumorigenesis. The protein expression levels of JUN and FOSL2 were increased, and those of GATA6 and DAB2 were decreased in STIC lesions, which were associated with epithelial-mesenchymal transition (EMT) and proteasome downregulation. The genomic region around the FRA16D site, containing a cadherin cluster region, was epigenetically suppressed by oncogenic signaling. Proteasome inhibition caused the upregulation of chemokine genes, which may facilitate immune evasion during HGSOC tumorigenesis. Importantly, MEK inhibitor treatment reversed these oncogenic alterations, indicating its clinical effectiveness in a subgroup of patients with HGSOC. This result suggests that MEK inhibitor therapy may be an effective treatment option for chemotherapy-resistant HGSOC.

Persistence of Denosumab Therapy among Patients with Osteoporosis

Kobayashi Kazuyoshi,Ando Kei,Machino Masaaki,Morozumi Masayoshi,Kanbara Shunsuke,Ito Sadayuki,Inoue Taro,Yamaguchi Hidetoshi,Ishiguro Naoki,Imagama Shiro 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.4

Study Design: Retrospective study in a single center.Purpose: To examine denosumab persistence in patients of different ages with severe osteoporosis in Japan.Overview of Literature: Denosumab is an antibody drug used for the treatment of osteoporosis. It is mainly used in patients with severe osteoporosis who might have high motivation for treatment, and the need for only semi-annual subcutaneous injection might improve the continuation rate. However, no English-language articles have reported on denosumab persistence in the Japanese population, including young people, despite the importance of this issue in a super-aging society. Methods: The subjects started treatment with subcutaneous denosumab in our department from July 2013 until December 2017. Persistence rates were calculated using Kaplan-Meier curves. Patients were defined as “persistent” or “non-persistent” according to the use of therapy after 60 months.Results: The study included 101 patients (84 females) with a median follow-up period of 23.6±14.2 months. The persistence rate declined to 85.3%, 78.3%, 74.1%, 71.3%, and 69.3% at 12, 24, 36, 48, and 60 months, respectively. Age at the initiation of denosumab therapy differed significantly between non-persistent (n=31) and persistent (n=70) patients (81.3 vs. 72.8 years, <i>p</i> <0.01). Persistence was significantly lower in patients aged ≥80 years than in those aged <60 and 60–79 years (both <i>p</i> <0.01). The reasons for non-persistence of denosumab therapy were transfer to another hospital (n=13), interruption of outpatient visits (n=11), dental treatment (n=4), adverse events (n=2), and patient request (n=1).Conclusions: Persistence was significantly lower in patients aged ≥80 years than in patients of other ages, and strategies promoting persistence are needed for these elderly patients.

Scoliosis Caused by Limb-Length Discrepancy in Children

Kobayashi Kazuyoshi,Ando Kei,Nakashima Hiroaki,Machino Masaaki,Morozumi Masayoshi,Kanbara Shunsuke,Ito Sadayuki,Inoue Taro,Yamaguchi Hidetoshi,Mishima Kenichi,Ishiguro Naoki,Imagama Shiro 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.6

Study Design: Single-center retrospective study in pediatric patients.Purpose: The purpose of the study was to investigate the effects of the presence and severity of leg-length discrepancy (LLD) on scoliosis in children.Overview of Literature: LLD is a common orthopedic problem that can result in standing imbalance, low back pain, and stress fractures. It may cause structural changes in the spine over time, but the exact effect of LLD on scoliosis is unknown.Methods: The subjects were 23 children with LLD ≥20 mm (range, 27–65 mm) treated at Nagoya University Hospital between 2007 and 2017. Whole spine posteroanterior standing radiographs and whole lower limb radiographs in a supine position were recorded. Data were collected for demographics, LLD, Cobb angle, pelvic obliquity, and Nash/Moe index. Scoliosis was defined as a Cobb angle ≥10°. Leg length was measured from the top of the femoral head to the middle of the tibial plafond, and LLD was defined as the difference between the left and right leg lengths.Results: The patients (nine males and 14 females) had a mean age of 14.0 years (range, 5–18 years). The average LLD was 44.3±17.2 mm, with LLDs of 20 to 39 mm, 40 to 59 mm, and ≥60 mm in 13, five, and five subjects, respectively. The average Cobb angle was 13.0°±7.0°, and 15 subjects (65%) had scoliosis. Convexity of the scoliosis was to the short leg side in all cases. The Cobb angle was significantly related to the severity of the LLD (<i>R</i>=0.736, <i>p</i><0.01), pelvic obliquity (<i>R</i>=0.966, <i>p</i><0.01), and Nash/Moe index (<i>p</i><0.05).Conclusions: LLD is a common pediatric condition that can cause scoliosis of the spine. Severe scoliosis may develop if the LLD is ≥30 mm. Long-term studies are needed to examine the effect of LLD resolution on the elimination of scoliosis.

Evaluation of the Association between Neck Pain and the Trapezius Muscles in Patients with Cervical Myelopathy Using Motor Evoked Potential: A Retrospective Study

Ito Sadayuki,Sakai Yoshihito,Harada Atsushi,Ando Kei,Kobayashi Kazuyoshi,Nakashima Hiroaki,Machino Masaaki,Kambara Shunsuke,Inoue Taro,Hida Tetsuro,Ito Kenyu,Ishiguro Naoki,Imagama Shiro 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.5

Study Design: Retrospective study. Purpose: We aimed to use motor evoked potentials (MEPs) to examine the association of electrophysiological assessment of the trapezius muscle with neck pain. Overview of Literature: Previous reports on the association of neck pain with the trapezius muscle have focused on surface electromyograms and muscle oxygenation; however, to our knowledge, none of these studies included detailed data on MEPs. Methods: The study included 100 patients with cervical myelopathy who underwent surgery at the National Center for Geriatrics and Gerontology in Obu, Japan from June 2010 to March 2013. Before the surgery, neck pain was evaluated using a Visual Analog Scale (a score ≥50 indicated neck pain and a score <50 indicated no neck pain). The preoperative cross-sectional areas of the trapezius muscles were measured with cervical magnetic resonance imaging sagittal T2-weighted images. Cranial stimulation under general anesthesia was used to derive the MEPs, enabling the measurement of latency and amplitude, using preoperative MEPs of the trapezius muscles. Results: The MEP of the trapezius muscle in patients with neck pain had significantly shorter latencies than those in patients who did not have neck pain. However, there was no significant difference in the amplitude between patients with and without neck pain. However, this tended to be greater in patients with neck pain as compared to that in those without neck pain. The cross-sectional area of the trapezius muscle in patients with neck pain was significantly smaller than that in those who did not have neck pain. Conclusions: MEPs revealed electrophysiological abnormalities of the trapezius muscles in patients with neck pain, supporting a relationship of neck pain with the trapezius muscles.

Association between Postoperative Neck Pain and Intraoperative Transcranial Motor-Evoked Potential Waveforms of the Trapezius Muscles in Patients with Cervical Myelopathy Who Underwent Cervical Laminoplasty

Ito Sadayuki,Sakai Yoshihito,Ando Kei,Nakashima Hiroaki,Machino Masaaki,Segi Naoki,Tomita Hiroyuki,Koshimizu Hiroyuki,Hida Tetsuro,Ito Kenyu,Harada Atsushi,Imagama Shiro 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.2

Study Design: Retrospective study.Purpose: Cervical laminoplasty is safe and effective for treating cervical myelopathy but has a higher frequency of postoperative axial pain compared to other methods. Several studies have reported on the causes of postoperative axial pain, but none have fully elucidated them. This study aimed to investigate the association between postoperative neck pain and intraoperative transcranial motor-evoked potential (MEP) waveforms of the trapezius muscles using transcranial MEPs.Overview of Literature: Few studies have investigated the association between postoperative neck pain and intraoperative transcranial MEP waveforms of the trapezius muscles in patients with cervical laminoplasty.Methods: A total of 79 patients with cervical myelopathy who underwent cervical laminoplasty at our facility between June 2010 and March 2013 were included in this study. Intraoperative control and final waveform were evaluated based on the trapezius muscle MEPs by measuring the latency and amplitude. A neck pain group comprised patients with higher neck pain Visual Analog Scale scores from preoperative value to 1 year postoperatively. The cross-sectional areas of the trapezius muscles and the MEP latencies and amplitudes were compared between patients with and without neck pain.Results: The latency and amplitude of the control waveforms were not significantly different between groups. The neck pain group had a significantly shorter final waveform latency (neck pain: 23.6±2.5, no neck pain: 25.8±4.5; p =0.019) and significantly larger amplitude (neck pain: 2,125±1,077, no neck pain: 1,630±966; p =0.041) than the no neck pain group.Conclusions: Postoperative neck pain was associated with the final waveform latency and amplitude of the trapezius muscle MEPs during cervical laminoplasty. Intraoperative electrophysiological trapezius muscle abnormalities could cause postoperative neck pain.

Advances in cancer DNA methylation analysis with methPLIER: use of non-negative matrix factorization and knowledge-based constraints to enhance biological interpretability

Takasawa Ken,Asada Ken,Kaneko Syuzo,Shiraishi Kouya,Machino Hidenori,Takahashi Satoshi,Shinkai Norio,Kouno Nobuji,Kobayashi Kazuma,Komatsu Masaaki,Mizuno Takaaki,Okubo Yu,Mukai Masami,Yoshida Tatsuya 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

DNA methylation is an epigenetic modification that results in dynamic changes during ontogenesis and cell differentiation. DNA methylation patterns regulate gene expression and have been widely researched. While tools for DNA methylation analysis have been developed, most of them have focused on intergroup comparative analysis within a dataset; therefore, it is difficult to conduct cross-dataset studies, such as rare disease studies or cross-institutional studies. This study describes a novel method for DNA methylation analysis, namely, methPLIER, which enables interdataset comparative analyses. methPLIER combines Pathway Level Information Extractor (PLIER), which is a non-negative matrix factorization (NMF) method, with regularization by a knowledge matrix and transfer learning. methPLIER can be used to perform intersample and interdataset comparative analysis based on latent feature matrices, which are obtained via matrix factorization of large-scale data, and factor-loading matrices, which are obtained through matrix factorization of the data to be analyzed. We used methPLIER to analyze a lung cancer dataset and confirmed that the data decomposition reflected sample characteristics for recurrence-free survival. Moreover, methPLIER can analyze data obtained via different preprocessing methods, thereby reducing distributional bias among datasets due to preprocessing. Furthermore, methPLIER can be employed for comparative analyses of methylation data obtained from different platforms, thereby reducing bias in data distribution due to platform differences. methPLIER is expected to facilitate cross-sectional DNA methylation data analysis and enhance DNA methylation data resources.

Efficacy of Anal Needle Electrodes for Intraoperative Spinal Cord Monitoring with Transcranial Muscle Action Potentials

Kazuyoshi Kobayashi,Kei Ando,Hideki Yagi,Kenyu Ito,Mikito Tsushima,Masayoshi Morozumi,Satoshi Tanaka,Masaaki Machino,Kyotaro Ota,Yukihiro Matsuyama,Naoki Ishiguro,Shiro Imagama 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.4

Study Design: Retrospective study. Purpose: To examine the relationship between postoperative bowel bladder disorder (BBD) and the efficacy of needle electrodes for the external anal sphincter (EAS) in intraoperative spinal cord monitoring with transcranial muscle action potentials (Tc-MsEP). Overview of Literature: Spinal surgery for spina bifida, spinal cord tumor, and spinal tethered cord syndrome has a high rate of postoperative BBD. Monitoring of the EAS with Tc-MsEP is frequently performed during spinal surgery. We initially used plug-surface electrodes for this purpose, but have more recently switched to needle electrodes for the monitoring of the EAS. To date, there has been no comparison between the utility of these electrodes. Methods: Waveform derivation, exacerbation of postoperative BBD, and sensitivity and specificity for prediction of BBD by 70% amplitude reduction of EAS activity using needle and plug-surface electrodes were investigated in 239 spine surgeries. The cut-off for the % drop in amplitude for BBD prediction was determined for EAS monitoring using a needle electrode. Results: The overall rate of postoperative BBD aggravation was 7.1% (17/239 cases), with the individual rates using needle and plug-surface electrodes being 6.9% (8/116) and 7.3% (9/123), respectively. The waveform derivation rate was significantly higher using needle electrodes (91.3% [106/116] vs. 76.4% [94/123], p <0.01). In patients with baseline waveform detection, the sensitivity and specificity for postoperative BBD were similar in the two groups. With needle electrodes, a cutoff amplitude of Tc-MsEP for the EAS at the end of surgery of 25% of the baseline amplitude had a sensitivity of 89% and specificity of 82% for the prediction of postoperative BBD aggravation. Conclusions: The significantly higher waveform derivation rate using needle electrodes suggests that these electrodes are effective for monitoring the EAS in spinal surgery in cases with preoperative BBD.

Perioperative Management of Patients with Hemophilia during Spinal Surgery

Kazuyoshi Kobayashi,Shiro Imagama,Kei Ando,Kenyu Ito,Mikito Tsushima,Masayoshi Morozumi,Satoshi Tanaka,Masaaki Machino,Kyotaro Ota,Yoshihiro Nishida,Naoki Ishiguro 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.3

Study Design: Single-center retrospective study. Purpose: To optimize the perioperative management of patients with hemophilia who are undergoing spinal surgery. Overview of Literature: Hemophilia is a rare disease in which there is a tendency of bleeding because of a congenital deficiency in blood coagulation factor activity. There has been no previous report on spinal surgery in patients with hemophilia. Methods: The subjects were five patients (all males) with hemophilia who underwent spinal surgery at Nagoya University Hospital. Two patients had hemophilia A (deficiency of factor VIII) and three had hemophilia B (deficiency of factor IX). The mean age at the time of surgery was 63 years (range, 46–73 years). The following surgeries were performed: posterior lumbar interbody fusion (PLIF) in two patients, and lumbar fenestration, cervical laminoplasty and lumbar fenestration, and cervical laminoplasty and PLIF in one patient each. Results: Coagulation factor at a mean dose of 4.8 ×103 U (range, 3–6 ×103 U) was intravenously injected before surgery, and a mean dose of 5.2 ×103 U (rang, 4–6 ×103 U) was continuously administered for 24 hours after surgery. Factor activity was maintained at ≥80% until postoperative day 14 and at ≥50% thereafter. The average duration of surgery was 178 minutes (range, 133–233 minutes), the estimated blood loss was 661 mL (range, 272–1,344 mL), and a drain tube was left subfascially in place for 2 days in all patients. Reoperation due to postoperative surgical site infection was required in one patient, but there were no complications due to hemorrhagic diathesis. The total dose of coagulation factor administered during hospitalization was 102 ×103 U (range, 46–198 ×103 U). Conclusions: Coordination with a hematologist and dose adjustment of the coagulation factor preparation to maintain a target level of coagulation factor activity facilitated a smooth postoperative course with perioperative control of bleeding during spinal surgery for patients with hemophilia.