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Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression., (© 2023 Wiley Periodicals LLC.)

Background: Our purpose was to quantify the postoperative rotation deformity (RD) after osteosynthesis of unstable intertrochanteric fractures (ITFx) using 3D-CT / image processing software, and to clarify the clinical meaning of RD., Methods: Forty-six consecutive patients with unstable intertrochanteric fractures were enrolled in this study. All were fixed with Gamma 3 Trochanteric nail and RC Lag Screw ® (Stryker). We performed 3D-CT evaluations for the rotational deformity of head-neck fragments, the medial cortex support (MCS) between main fragments and bone healing at 3 months postoperatively., Results: The RD was significantly larger in the patients without the MCS (5.1 ± 4.0°, N = 9) than those with the MCS (2.4 ± 2.6°, N = 37) (P = 0.006*). Delayed healing (N=3) was observed in patients without the MCS, and the association between RD and delayed healing was significant (P = 0.003*, cut-off value 6.4°, sensitivity 100% and specificity 90.7%, AUC 0.91)., Conclusions: This study proposed a novel method of measuring postoperative RD. Lack of MCS may lead to RD and consequent delayed healing in unstable ITFx fixed with intramedullary nails.

We retrospectively evaluated spinal surgeries performed using the high-definition three-dimensional exoscopic system, which became available at our institution in August 2020. Eleven patients (4 with cervical disease and 7 with lumbar disease) underwent surgery with the system. There were no surgical complications related to the system, and the results were satisfactory. The small, flexible camera of the exoscope allows the surgeon to view the surgical field from various angles, facilitating both the approach and technique. In addition, it allows the surgeon to operate in an upright position without strain on the head and neck. Although further surgical experience is needed, this system has the potential to improve the visualization of the surgical field in spinal surgery.

Background: Locomotive syndrome (LS) is characterized by reduced mobility. Clinical decision limit (CDL) stage 3 in LS indicates physical frailty. Lumbar spinal canal stenosis (LSS) is one of the causes of LS, for which lumbar surgery is considered to improve the CDL stage. This study aimed to investigate the efficacy of lumbar surgery and independent factors for improving the CDL stage in patients with LSS., Methods: This retrospective study was conducted at the Department of Orthopaedic Surgery at our University Hospital. A total of 157 patients aged ≥ 65 years with LSS underwent lumbar surgery. The 25-Question Geriatric Locomotive Function scale (GLFS-25) was used to test for LS, and the Timed Up and Go test (TUG) was used to evaluate functional ability. Lower limb pain was evaluated using a visual analog scale. Patients with at least one improvement in the CDL stage following lumbar surgery were included in the improvement group. Differences in lower limb pain intensity between the groups were evaluated using the Wilcoxon rank-sum test. The Spearman's rank correlation coefficient was used to determine correlations between Δ lower limb pain and Δ GLFS-25. Logistic regression analysis was used to identify factors associated with improvement in LS., Results: The proportion of patients with improved CDL stage was 45.1% (improvement/non-improvement: 32/39). Δ Lower limb pain was significantly reduced in the improvement group compared with that in the non-improvement group (51.0 [36.3-71.0] vs 40.0 [4.0-53.5]; p = 0.0107). Δ GLFS-25 was significantly correlated with Δ lower limb pain (r = 0.3774, p = 0.0031). Multiple logistic regression analysis revealed that TUG and age were significantly associated with improvement in LS (odds ratio, 1.22; 95% confidence interval: 1.07-1.47)., Conclusions: Lumbar surgery effectively improved the CDL stage in patients with LSS. In addition, TUG was an independent factor associated with improvement in the CDL., (© 2023. The Author(s).)

Study Design: A prospective multicenter observational cohort study., Objective: This study aimed to investigate the role of transcranial motor evoked potential (TcMEP) monitoring during traumatic spinal injury surgery, the timing of TcMEP alerts, and intervention strategies to avoid intraoperative neurological complications., Summary of Background Data: Intraoperative neuromonitoring, including TcMEP monitoring, is commonly used in high-risk spinal surgery to predict intraoperative spinal cord injury; however, little information is available on its use in traumatic spinal injury surgery., Methods: The TcMEP monitoring data of 350 consecutive patients who underwent traumatic spinal injury surgery (mean age, 69.3 y) between 2017 and 2021 were prospectively reviewed. In this study, a TcMEP amplitude reduction ≥70% was established as a TcMEP alert. A rescue case was defined as a case with the recovery of TcMEP amplitudes after certain procedures and without postoperative neurological complications., Results: Among the 350 patients who underwent traumatic spinal injury surgery (TcMEP derivation rate 94%), TcMEP monitoring revealed seven true-positive (TP) (2.0%), three rescues (0.9%; rescue rate 30%), 31 false-positive, one false-negative, and 287 true-negative cases, resulting in 88% sensitivity, 90% specificity, 18% positive predictive value, and 99% negative predictive value. The TP rate in patients with preoperative motor deficits was 2.9%, which was higher than that in patients without preoperative motor deficits (1.1%). The most common timing of TcMEP alerts was during decompression (40%). During decompression, suspension of surgery with intravenous steroid injection was ineffective (rescue rate, 0%), and additional decompression was effective., Conclusion: Given the low prevalence of neurological complications (2.3%) and the low positive predictive value (18.4%), single usage of TcMEP monitoring during traumatic spinal injury surgery is not recommended. Further efforts should be made to reduce FP alert rates through better interpretation of multimodal Intraoperative neuromonitorings and the incorporation of anesthesiology to improve the positive predictive value., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Retrospective multicenter cohort study., Objectives: We aimed to clarify the efficacy of multimodal intraoperative neuromonitoring (IONM), especially in transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) with spinal cord-evoked potentials after transcranial stimulation of the brain (D-wave) in the detection of reversible spinal cord injury in high-risk spinal surgery., Methods: We reviewed 1310 patients who underwent TES-MEPs during spinal surgery at 14 spine centers. We compared the monitoring results of TES-MEPs with D-wave vs TES-MEPs without D-wave in high-risk spinal surgery., Results: There were 40 cases that used TES-MEPs with D-wave and 1270 cases that used TES-MEPs without D-wave. Before patients were matched, there were significant differences between groups in terms of sex and spinal disease category. Although there was no significant difference in the rescue rate between TES-MEPs with D-wave (2.0%) and TES-MEPs (2.5%), the false-positivity rate was significantly lower (0%) in the TES-MEPs-with-D-wave group. Using a one-to-one propensity score-matched analysis, 40 pairs of patients from the two groups were selected. Baseline characteristics did not significantly differ between the matched groups. In the score-matched analysis, one case (2.5%) in both groups was a case of rescue ( P = 1), five (12.5%) cases in the TES-MEPs group were false positives, and there were no false positives in the TES-MEPs-with-D-wave group ( P = .02)., Conclusions: TES-MEPs with D-wave in high-risk spine surgeries did not affect rescue case rates. However, it helped reduce the false-positivity rate.

Background: Surgical site infection following spinal surgery causes prolonged delay in recovery after surgery, increases cost, and sometimes leads to additional surgical procedures. We investigated risk factors for the occurrence of surgical site infection events in terms of patient-related, surgery-related, and postoperative factors., Methods: This retrospective study included 1000 patients who underwent spinal surgery in our hospital between April 2016 and March 2019., Results: Patient-related factors were dementia, length of preoperative hospital stay (≥ 14 days), and diagnosis at the time of surgery (traumatic injury or deformity). The one surgery-related factor was multilevel surgery (≥ 9 intervertebral levels), and the one postoperative factor was time to ambulation (≥ 7 days) were statistically significant risk factors for spinal surgical site infection., Conclusion: One risk factor identified in this study that is amenable to intervention is time to ambulation. As delayed ambulation is a risk factor for postoperative surgical site infection, how medical staff can intervene in postoperative ambulation to further reduce the incidence of surgical site infection is a topic for future research.

Lumbar spinal stenosis (LSS) can interfere with daily life and quality of life (QOL). Evaluating physical function and QOL and helping patients to improve is the focus of rehabilitation. Phase angle (PhA) assessment is widely used to measure body composition and is considered an indicator of physical function and QOL. This study investigated the relationship between PhA and physical function, physical activity, and QOL in patients with LSS. PhA, handgrip strength, walking speed, Timed Up and Go test (TUG), Life Space Assessment (LSA), Prognostic Nutritional Index (PNI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and EQ-5D were assessed and statistically analyzed. The study included 133 patients with LSS. Multiple regression analysis of PhA adjusted for age, sex, and body mass index (Model 1) and for Model 1 + PNI (Model 2) showed significant correlations (P < 0.05) with handgrip strength, walking speed, TUG, and LSA. Regarding QOL, PhA was significantly correlated (P < 0.05) with lumbar function in JOABPEQ. PhA was associated with physical function and QOL in patients with LSS and might be a new clinical indicator in this population., (© 2023. Springer Nature Limited.)

Study Design: Prospective multicenter study., Objective: To investigate the validity of transcranial motor-evoked potentials (Tc-MEP) in thoracic spine surgery and evaluate the impact of specific factors associated with positive predictive value (PPV)., Methods: One thousand hundred and fifty-six cases of thoracic spine surgeries were examined by comparing patient backgrounds, disease type, preoperative motor status, and Tc-MEP alert timing. Tc-MEP alerts were defined as an amplitude decrease of more than 70% from the baseline waveform. Factors were compared according to preoperative motor status and the result of Tc-MEP alerts. Factors that showed significant differences were identified by univariate and multivariate analysis., Results: Overall sensitivity was 91.9% and specificity was 88.4%. The PPV was significantly higher in the preoperative motor deficits group than in the preoperative no-motor deficits group for both high-risk (60.3% vs 38.3%) and non-high-risk surgery groups (35.1% vs 12.8%). In multivariate logistic analysis, the significant factors associated with true positive were surgical maneuvers related to ossification of the posterior longitudinal ligament (odds ratio = 11.88; 95% CI: 3.17-44.55), resection of intradural intramedullary spinal cord tumor (odds ratio = 8.83; 95% CI: 2.89-27), preoperative motor deficit (odds ratio = 3.46; 95% CI: 1.64-7.3) and resection of intradural extramedullary spinal cord tumor (odds ratio = 3.0; 95% CI: 1.16-7.8). The significant factor associated with false positive was non-attributable alerts (odds ratio = .28; 95% CI: .09-.85)., Conclusion: Surgeons are strongly encouraged to use Tc-MEP in patients with preoperative motor deficits, regardless of whether they are undergoing high-risk spine surgery or not. Knowledge of PPV characteristics will greatly assist in effective Tc-MEP enforcement and minimize neurological complications with appropriate interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Intraoperative neurophysiologic monitoring (IONM) reportedly helps prevent postoperative neurological complications following high-risk spinal cord surgeries. There are negative and positive reports about using IONM for intradural extramedullary (IDEM) tumors. We investigated factors affecting alerts of IONM in IDEM tumor surgery., Methods: We analyzed 39 patients with IDEM tumors who underwent surgery using IONM at our hospital between January 2014 and March 2021. Neurological symptoms were evaluated pre- and postoperatively using the manual muscle test (MMT). All patients were evaluated to ascertain the tumor level and location in the axial view, the operative time, intraoperative bleeding volume, and histological type. Additionally, the intraoperative procedure associated with significant IONM changes in transcranial electrical stimulation muscle-evoked potential was investigated., Results: There were 11 false-positive and 16 true-negative cases. There was one true-positive case and one false-negative case; the monitoring accuracy achieved a sensitivity of 50%, a specificity of 59%, a positive predictive value of 8%, and a negative predictive value of 94%. In the 22 alert cases, if the tumor was located anterolateral in the axial view, alerts were triggered with a significant difference (p = 0.02) during tumor resection. Alerts were generated for fifteen patients during tumor resection; nine (60%) showed waveform improvement by intervention and were classified as rescue cases., Conclusion: Alert is probably triggered during tumor resection for anterolaterally located tumors. Alerts during tumor resection procedures were more likely to be rescued than other procedures in IDEM tumor surgery., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Study Design: Multicenter prospective study., Objectives: Although intramedullary spinal cord tumor (IMSCT) and extramedullary SCT (EMSCT) surgeries carry high risk of intraoperative motor deficits (MDs), the benefits of transcranial motor evoked potential (TcMEP) monitoring are well-accepted; however, comparisons have not yet been conducted. This study aimed to clarify the efficacy of TcMEP monitoring during IMSCT and EMSCT resection surgeries., Methods: We prospectively reviewed TcMEP monitoring data of 81 consecutive IMSCT and 347 EMSCT patients. We compared the efficacy of interventions based on TcMEP alerts in the IMSCT and EMSCT groups. We defined our alert point as a TcMEP amplitude reduction of ≥70% from baseline., Results: In the IMSCT group, TcMEP monitoring revealed 20 true-positive (25%), 8 rescue (10%; rescue rate 29%), 10 false-positive, a false-negative, and 41 true-negative patients, resulting in a sensitivity of 95% and a specificity of 80%. In the EMSCT group, TcMEP monitoring revealed 20 true-positive (6%), 24 rescue (7%; rescue rate 55%), 29 false-positive, 2 false-negative, and 263 true-negative patients, resulting in a sensitivity of 91% and specificity of 90%. The most common TcMEP alert timing was during tumor resection (96% vs. 91%), and suspension surgeries with or without intravenous steroid administration were performed as intervention techniques., Conclusions: Postoperative MD rates in IMSCT and EMSCT surgeries using TcMEP monitoring were 25% and 6%, and rescue rates were 29% and 55%. We believe that the usage of TcMEP monitoring and appropriate intervention techniques during SCT surgeries might have predicted and prevented the occurrence of intraoperative MDs.

The importance of the microenvironment is widely recognized as it regulates not only malignant cell behavior but also drug sensitivity. The cancer cell microenvironment is composed of biological, physical and chemical elements, and simultaneous reproduction of these three elements are important conditions investigated in cancer research. In the present study, we focused on the epidemiological and anatomical specificities of endometrioid carcinoma, obesity (biological), fluid flow (physical) and anticancer agents (chemical) to target the specific microenvironmental elements of endometrioid carcinoma. To elucidate the individual effects of these elements on endometrioid carcinoma and to investigate the relationships between these factors, we developed an adipose tissue fragments (ATFs)-embedded cell disc under a rotational culture method to generate carcinoma-stroma interactions and to create fluid flow. ATFs and fluid flow individually or synergistically influenced proliferative cellular behavior and the morphological changes underlying endometrioid carcinoma. ATFs and fluid flow also governed the expression of extracellular signal-regulated kinase and p38 signaling synergistically or individually, depending on the endometrioid carcinoma cell type. Adipose tissue induced chemoresistance to cis-diamminedichloro-platinum (CDDP) in endometrioid cancer, but the resistance effect was abolished by fluid flow. Thus, a simple reconstructed model was established to investigate three elements of the microenvironment of endometrioid carcinoma in vitro. This culture model unequivocally demonstrated the individual and synergistic effects of the three elements on endometrioid carcinoma. This new culture model is a promising tool for elucidating the mechanisms underlying endometrioid carcinoma and for developing further treatment strategies., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Squamous cell carcinoma (SCC) is the most major malignant tumor of the tongue. The tongue exists at the air-liquid interface and is covered with saliva. In addition, the tongue constituent cells and tongue cancer are present under fluid flow stimulation due to the abundant capillary network and contraction of muscle tissue. Therefore, replicating both cell-cell interactions (the cellular microenvironment) and the aforementioned physical microenvironment is very important for understanding the kinetics of tongue SCC. To elucidate the effects of the cellular and physical microenvironment on tongue SCC and to investigate the relationships between these factors, we developed a collagen cell disc, with double dish under a rotational culture method to generate cancer-stroma interactions and to create fluid flow stimulation. Mesenchymal cells, NIH-3T3 cells and tongue-derived fibroblasts influenced the proliferative potential. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by cellular interactions and fluid flow stimulation, depending on the SCC cell type. The cell-cell interactions and fluid flow stimulation independently, synergistically or contradictorily affected the behavior of tongue SCC. Fluid flow stimulation synergistically enhanced the antiproliferative effect of cis-diamminedichloroplatinum on tongue SCC cells, but mesenchymal cells abolished the synergistic antiproliferative effect related to fluid flow stimulation. In conclusion, a reconstructed model was established to investigate the cellular and physical microenvironments of tongue SCC in vitro. The newly established system is a promising model for the development of further regimes to treat general oral cancer., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

A prospective multicenter cohort study. To clarify the differences in the accuracy of transcranial motor-evoked potentials (TcE-MEPs) and procedures associated with the alarms between cervical anterior spinal fusion (ASF) and posterior spinal fusion (PSF). Neurological complications after TcE-MEP alarms have been prevented by appropriate interventions for cervical degenerative disorders. The differences in the accuracy of TcE-MEPs and the timing of alarms between cervical ASF and PSF noted in the existing literature remain unclear. Patients (n = 415) who underwent cervical ASF (n = 171) or PSF (n = 244) at multiple institutions for cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, spinal injury, and others were analyzed. Neurological complications, TcE-MEP alarms defined as a decreased amplitude of ≤70% compared to the control waveform, interventions after alarms, and TcE-MEP results were compared between the 2 surgeries. The incidence of neurological complications was 1.2% in the ASF group and 2.0% in the PSF group, with no significant intergroup differences (P-value was .493). Sensitivity, specificity, negative predictive value, and rate of rescue were 50.0%, 95.2%, 99.4%, and 1.8%, respectively, in the ASF group, and 80.0%, 90.9%, 99.5%, and 2.9%, respectively, in the PSF group. The accuracy of TcE-MEPs was not significantly different between the 2 groups (P-value was .427 in sensitivity, .109 in specificity, and .674 in negative predictive value). The procedures associated with the alarms were decompression in 3 cases and distraction in 1 patient in the ASF group. The PSF group showed Tc-MEPs decreased during decompression, mounting rods, turning positions, and others. Most alarms went off during decompression in ASF, whereas various stages of the surgical procedures were associated with the alarms in PSF. There were no significant differences in the accuracy of TcE-MEPs between the 2 surgeries., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: A prospective multicenter observational study., Objective: The aim was to investigate the validity of transcranial motor-evoked potentials (Tc-MEP) in cervical spine surgery and identify factors associated with positive predictive value when Tc-MEP alerts are occurred., Summary of Background Data: The sensitivity and specificity of Tc-MEP for detecting motor paralysis are high; however, false-positives sometimes occur., Materials and Methods: The authors examined Tc-MEP in 2476 cases of cervical spine surgeries and compared patient backgrounds, type of spinal disorders, preoperative motor status, surgical factors, and the types of Tc-MEP alerts. Tc-MEP alerts were defined as an amplitude reduction of more than 70% from the control waveform. Tc-MEP results were classified into two groups: false-positive and true-positive, and items that showed significant differences were extracted by univariate analysis and detected by multivariate analysis., Results: Overall sensitivity was 66% (segmental paralysis: 33% and lower limb paralysis: 95.8%) and specificity was 91.5%. Tc-MEP outcomes were 33 true-positives and 233 false-positives. Positive predictive value of general spine surgery was significantly higher in cases with a severe motor status than in a nonsevere motor status (19.5% vs . 6.7%, P =0.02), but not different in high-risk spine surgery (20.8% vs . 19.4%). However, rescue rates did not significantly differ regardless of motor status (48% vs . 50%). In a multivariate logistic analysis, a preoperative severe motor status [ P =0.041, odds ratio (OR): 2.46, 95% confidence interval (95% CI): 1.03-5.86] and Tc-MEP alerts during intradural tumor resection ( P <0.001, OR: 7.44, 95% CI: 2.64-20.96) associated with true-positives, while Tc-MEP alerts that could not be identified with surgical maneuvers ( P =0.011, OR: 0.23, 95% CI: 0.073-0.71) were associated with false-positives., Conclusion: The utility of Tc-MEP in patients with a preoperative severe motor status was enhanced, even in those without high-risk spine surgery. Regardless of the motor status, appropriate interventions following Tc-MEP alerts may prevent postoperative paralysis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: A prospective, multicenter study., Objective: This study clarified the uses and limitations of transcranial motor-evoked potentials (Tc-MEPs) for nerve root monitoring during adult spinal deformity (ASD) surgeries., Summary of Background Data: Whether Tc-MEPs can detect nerve root injuries (NRIs) in ASD surgeries remains controversial., Materials and Methods: We prospectively analyzed neuromonitoring data from 14 institutions between 2017 and 2020. The subjects were ASD patients surgically treated with posterior corrective fusion using multichannel Tc-MEPs. An alert was defined as a decrease of ≥70% in the Tc-MEP's waveform amplitude from baseline, and NRI was considered as meeting the focal Tc-MEP alerts shortly following surgical procedures with postoperative nerve root symptoms in the selected muscles., Results: A total of 311 patients with ASD (262 women and 49 men) and a mean age of 65.5 years were analyzed. Tc-MEP results revealed 47 cases (15.1%) of alerts, including 25 alerts after 10 deformity corrections, six three-column osteotomies, four interbody fusions, three pedicle screw placements or two decompressions, and 22 alerts regardless of surgical maneuvers. Postoperatively, 14 patients (4.5%) had neurological deterioration considered to be all NRI, 11 true positives, and three false negatives (FN). Two FN did not reach a 70% loss of baseline (46% and 65% loss of baseline) and one was not monitored at target muscles. Multivariate logistic regression analysis revealed that risk factors of NRI were preexisting motor weakness ( P <0.001, odds ratio=10.41) and three-column osteotomies ( P =0.008, odds ratio=7.397)., Conclusions: Nerve root injuries in our ASD cohort were partially predictable using multichannel Tc-MEPs with a 70% decrease in amplitude as an alarm threshold. We propose that future research should evaluate the efficacy of an idealized warning threshold (e.g., 50%) and a more detailed evoked muscle selection, in reducing false negatives., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although intraoperative spinal neuromonitoring (IONM) is recommended for spine surgeries, there are no guidelines regarding its use in Japan, and its usage is mainly based on the surgeon's preferences. Therefore, this study aimed to provide an overview of the current trends in IONM usage in Japan., Methods: In this web-based survey, expert spine surgeons belonging to the Japanese Society for Spine Surgery and Related Research were asked to respond to a questionnaire regarding IONM management. The questionnaire covered various aspects of IONM usage, including the preferred modality, operation of IONM, details regarding muscle-evoked potential after electrical stimulation of the brain (Br(E)-MsEP), and need for consistent use of IONM in major spine surgeries., Results: Responses were received from 134 of 186 expert spine surgeons (response rate, 72%). Of these, 124 respondents used IONM routinely. Medical staff rarely performed IONM without a medical doctor. Br(E)-MsEP was predominantly used for IONM. One-third of the respondents reported complications, such as bite injuries caused by Br(E)-MsEP. Interestingly, two-thirds of the respondents did not plan responses to alarm points. Intramedullary spinal cord tumor, scoliosis (idiopathic, congenital, or neuromuscular in pediatric), and thoracic ossification of the posterior longitudinal ligament were representative diseases that require IONM., Conclusions: IONM has become an essential tool in Japan, and Br(E)-MsEP is a predominant modality for IONM at present. Although we investigated spine surgeries for which consistent use of IONM is supported, a cost-benefit analysis may be required., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2023 The Japanese Society for Spine Surgery and Related Research.)

Study Design: A prospective, multicenter study., Objective: To evaluate the usefulness of transcranial motor-evoked potentials (Tc-MEPs) during supine-to-prone position change for thoracic ossification of the posterior longitudinal ligament (T-OPLL)., Summary of Background Data: Supine-to-prone position change might be a risk of spinal cord injury in posterior decompression and fusion surgeries for T-OPLL., Methods: The subjects were 145 patients with T-OPLL surgically treated with posterior decompression and fusion using Tc-MEPs in 14 institutes. Tc-MEPs were monitored before surgery from supine-to-prone position and intraoperatively in seven institutes and only intraoperatively in the other seven institutes because of disapproval of the anesthesia department. In cases of Tc-MEP alert after position change, we adjusted the cervicothoracic posture. When the MEP did not recover, we reverted the position to supine and monitored the Tc-MEPs in supine position., Results: There were 83 and 62 patients with/without Tc-MEP before position change to prone (group A and B). The true-positive rate was lower in group A than group B, but without statistical significance (8.4% vs. 16.1%, P = 0.12). In group A, five patients who had Tc-MEP alert during supine-to-prone position change were all female and had larger body mass index values and upper thoracic lesions. Among the patients, three underwent surgeries after cervicothoracic alignment adjustment, and two had postponed operations to 1 week later with halo-vest fixation because of repeated Tc-MEP alerts during position change to prone. The Tc-MEP alert at exposure was statistically more frequent in group B than in group A ( P = 0.033)., Conclusion: Tc-MEP alert during position change is an important sign of spinal cord injury due to alignment change at the upper thoracic spine. Tc-MEP monitoring before supine-to-prone position change was necessary to prevent spinal cord injury in surgeries for T-OPLL., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This study was conducted to analyze the findings and benefits of computed tomography (CT) epidurography in patients with low back and leg pain and compare these findings with those of magnetic resonance imaging (MRI) images. In total, 495 intervertebral discs from 99 patients with low back and leg pain who underwent percutaneous epidural adhesiolysis (epidural neuroplasty or percutaneous adhesiolysis) were examined. The axial views of CT epidurography were classified into six types to examine each intervertebral disc: round type, ellipse type, spike type, Benz mark, incomplete block, complete block, and non-contrast. MRI images were graded from A to D using the Schizas classification. Notably, 176 images were round-type and ellipse-type axial views, and 138 were spike-type and Benz-mark views; Schizas classification Grades A and B were observed in 272 and 47 MRI images, respectively. The incomplete block and complete block axial images did not significantly differ in CT epidurography and Schizas classification Grades C and D. The images showing Benz marks existed only at the L4/5 and L5/S intervertebral levels and only in 14.7% of patients. The ratio of normal shadows differed between MRI images and CT epidurography. Therefore, CT epidurography may enable a detailed evaluation of the epidural space.

Study Design: Prospective multicenter study., Objective: To examine transcranial motor-evoked potential (Tc-MEP) waveforms in intraoperative neurophysiological monitoring in surgery for intradural extramedullary (IDEM) tumors, focused on the characteristics for cervical, thoracic, and conus lesions., Summary of Background Data: IDEM tumors are normally curable after resection, but neurological deterioration may occur after surgery. Intraoperative neurophysiological monitoring using Tc-MEPs during surgery is important for timely detection of possible neurological injury., Methods: The subjects were 233 patients with IDEM tumors treated surgically with Tc-MEP monitoring at 9 centers. The alarm threshold was ≥70% waveform deterioration from baseline. A case with a Tc-MEP alert that normalized and had no new motor deficits postoperatively was defined as a rescue case. A deterioration of manual muscle test score ≥1 compared to the preoperative value was defined as postoperative worsening of motor status., Results: The 233 patients (92 males, 39%) had a mean age of 58.1 ± 18.1 years, and 185 (79%), 46 (20%), and 2 (1%) had schwannoma, meningioma, and neurofibroma. These lesions had cervical (C1-7), thoracic (Th1-10), and conus (Th11-L2) locations in 82 (35%), 96 (41%), and 55 (24%) cases. There were no significant differences in preoperative motor deficit among the lesion levels. Thoracic lesions had a significantly higher rate of poor baseline waveform derivation (0% cervical, 6% thoracic, 0% conus, P < 0.05) and significantly more frequent intraoperative alarms (20%, 31%, 15%, P < 0.05). Use of Tc-MEPs for predicting neurological deficits after IDEM surgery had sensitivity of 87% and specificity of 89%; however, the positive predictive value was low., Conclusion: Poor derivation of waveforms, appearance of alarms, and worse final waveforms were all significantly more frequent for thoracic lesions. Thus, amplification of the waveform amplitude, using multimodal monitoring, and more appropriate interventions after an alarm may be particularly important in surgery for thoracic IDEM tumors.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: A prospective multicenter observational study., Objective: To elucidate the efficacy of transcranial motor-evoked potentials (Tc(E)-MEPs) in degenerative cervical myelopathy (DCM) surgery by comparing cervical spondylotic myelopathy (CSM) to cervical ossification of the posterior longitudinal ligament (OPLL) and investigate the timing of Tc(E)-MEPs alerts and types of interventions affecting surgical outcomes., Summary of Background Data: Although CSM and OPLL are the most commonly encountered diseases of DCM, the benefits of Tc(E)-MEPs for DCM remain unclear and comparisons of these two diseases have not yet been conducted., Methods: We examined the results of Tc(E)-MEPs from 1176 DCM cases (840 CSM /336 OPLL) and compared patients background by disease, preoperative motor deficits, and the type of surgical procedure. We also assessed the efficacy of interventions based on Tc(E)-MEPs alerts. Tc(E)-MEPs alerts were defined as an amplitude reduction of more than 70% below the control waveform. Rescue cases were defined as those in which waveform recovery was achieved after interventions in response to alerts and no postoperative paralysis., Results: Overall sensitivity was 57.1%, and sensitivity was higher with OPLL (71.4%) than with CSM (42.9%). The sensitivity of acute onset segmental palsy including C5 palsy was 40% (OPLL/CSM: 66.7%/0%) whereas that of lower limb palsy was 100%. The most common timing of Tc(E)-MEPs alerts was during decompression (63.16%), followed by screw insertion (15.79%). The overall rescue rate was 57.9% (OPLL/CSM: 58.3%/57.1%)., Conclusion: Since Tc(E)-MEPs are excellent for detecting long tract injuries, surgeons need to consider appropriate interventions in response to alerts. The detection of acute onset segmental palsy by Tc(E)-MEPs was partially possible with OPLL, but may still be difficult with CSM. The rescue rate was higher than 50% and appropriate interventions may have prevented postoperative neurological complications.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective multicenter study., Objective: The aim of this study was to evaluate transcranial motor evoked potential (Tc-MEP) waveform monitoring in spinal surgery for patients with severe obesity., Summary of Background Data: Spine surgeries in obese patients are associated with increased morbidity and mortality. Intraoperative Tc-MEP monitoring can identify neurologic deterioration during surgery, but has not been examined for obese patients., Methods: The subjects were 3560 patients who underwent Tc-MEP monitoring during spine surgery at 16 centers. Tc-MEPs were recorded from multiple muscles via needle or disc electrodes. A decrease in Tc-MEP amplitude of ≥70% from baseline was used as an alarm during surgery. Preoperative muscle weakness with manual muscle test (MMT) grade ≤4 was defined as a motor deficit, and a reduction of one or more MMT grade postoperatively was defined as deterioration., Results: The 3560 patients (1698 males, 47.7%) had a mean age of 60.0 ± 20.3 years. Patients with body mass index >35 kg/m2 (n = 60, 1.7%) were defined as severely obese. Compared with all other patients (controls), the rates of preoperative motor deficit (41.0% vs. 29.6%, P < 0.05) and undetectable baseline waveforms in all muscles were significantly higher in the severely obese group (20.0% vs. 1.7%, P < 0.01). Postoperative motor deterioration did not differ significantly between the groups. The sensitivity and specificity of the alarm criterion for prediction of postoperative neurologic complications were 75.0% and 83.9% in severely obese patients and 76.4% and 89.6% in controls, with no significant difference between the groups., Conclusion: Tc-MEPs can be used in spine surgery for severely obese cases to predict postoperative motor deficits, but the rate of undetectable waveforms is significantly higher in such cases. Use of a multichannel waveform approach or multiple modalities may facilitate safe completion of surgery. Waveforms should be carefully evaluated and an appropriate rescue procedure is required if the alarm criterion occurs.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cervical stenosis is a postoperative complication of conization for uterine cervical malignancy, but a standard method of preventing this complication has yet to be established. Collagen vitrigel is a collagen-based biomaterial that has antifibrotic and epithelization promoting actions. We evaluated the antistenotic effect of an indwelling collagen vitrigel membrane-coated nylon line (CVNL) after cervical conization in rabbits. In one group of rabbits, a CVNL was placed in the cervical canal after conization. In another group, a nylon line without a collagen coating was placed in the cervical canal after conization. The control group underwent cervical conization without placement of a device. The control (conization alone) and nylon (conization plus indwelling nylon line) groups exhibited cervical swelling. Rabbits in the CVNL group (cervical conization plus indwelling CVNL in the xerogel state) had a normal cervical surface. The cervical canal in the control group was enlarged and showed cystic changes attributed to cervical stenosis. The nylon group exhibited a trend toward cervical canal dilatation. In the CVNL group, the cervical canal was normal and did not show cystic dilatation. Fibrosis occurred to a lesser degree in the nylon group than in the control group, and the CVNL group exhibited minimal interstitial fibrosis. The control and nylon groups showed increased numbers of myofibroblasts in the regenerated cervix, but few myofibroblasts were observed in the CVNL group. Abundant collagen type III was observed in regenerated cervical tissue in the control and nylon groups but not in the CVNL group. The number of proliferative mesenchymal cells in the regenerated cervix was lowest in the CVNL group. The expressions of connective tissue growth factor (CTGF, a regulator of fibroblast growth and extracellular matrix secretion), extracellular signal-regulated protein kinases 1 and 2, and c-Jun N-terminal kinase (which are involved in the induction of CTGF by transforming growth factor-β) were lower in the CVNL group than in the control or nylon groups. This study describes an indwelling CVNL that prevents cervical stenosis and cystic changes after conization. These effects were likely mediated by inhibition of fibrosis, myofibroblast emergence, CTGF expression, and collagen type III deposition in regenerating cervix. Impact statement Collagen vitrigel is a high-density collagen material that promotes epithelization, inhibits fibrosis, and suppresses inflammation in regenerating tissue. We evaluated whether a collagen vitrigel membrane-coated nylon line would prevent cervical stenosis after conization in the rabbit. We found that an indwelling collagen vitrigel membrane-coated nylon line prevented cervical canal stenosis and cystic changes after cervical conization by inhibiting fibrosis, myofibroblast emergence, connective tissue growth factor expression, and collagen type III deposition in the regenerating cervix. Our device has potential as a new method of preventing cervical canal fibrosis and stenosis after conization for cervical cancer.

Study Design: Prospective multicenter study., Objective: The purpose of the study is to examine cases with poor baseline waveform derivation for all muscles in multichannel monitoring of transcranial motor-evoked potentials (Tc-MEPs) in spine surgery., Summary of Background Data: Intraoperative neuromonitoring (IONM) is useful for identifying neurologic deterioration during spinal surgery. Tc-MEPs are widely used for IONM, but some cases have poor waveform derivation, even in multichannel Tc-MEP monitoring., Methods: The subjects were 3625 patients (mean age 60.1 years, range 4-95; 1886 females, 1739 males) who underwent Tc-MEP monitoring during spinal surgery at 16 spine centers between April 2017 and March 2020. Baseline Tc-MEPs were recorded from the deltoid, abductor pollicis brevis, adductor longus, quadriceps femoris, hamstrings, tibialis anterior, gastrocnemius, and abductor hallucis (AH) muscles after surgical exposure of the spine., Results: The 3625 cases included cervical, thoracic, and lumbar lesions (50%, 33% and 17%, respectively) and had preoperative motor status of no motor deficit, and motor deficit with manual muscle testing (MMT) ≥3 and MMT <3 (70%, 24% and 6%, respectively). High-risk surgery was performed in 1540 cases (43%). There were 73 cases with poor baseline waveform derivation (2%), and this was significantly associated with higher body weight, body mass index, thoracic lesions, motor deficit of MMT <3, high-risk surgery (42/1540 [2.7%] vs. 31/2085 [1.5%], P < 0.05), and surgery for ossification of the posterior longitudinal ligament (OPLL). Intraoperative waveform derivation occurred in 25 poor derivation cases (34%) and the AH had the highest rate., Conclusion: The rate of poor baseline waveform derivation in spine surgery was 2% in our series. This was significantly more likely in high-risk surgery for thoracic lesions and OPLL, and in cases with preoperative severe motor deficit. In such cases, it may be preferable to use multiple modalities for IONM to derive multichannel waveforms from distal limb muscles, including the AH.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective multicenter cohort study., Objective: The aim of this study was to validate an alarm point of intraoperative neurophysiological monitoring () formulated by the Monitoring Working Group (WG) of the Japanese Society for Spine Surgery and Related Research (JSSR)., Summary of Background Data: The Monitoring WG of the JSSR formulated an alarm point of IONM using transcranial electrical stimulation-muscle motor evoked potentials (Tc(E)-MEPs) and has conducted a prospective multicenter study. The validity of the JSSR alarm point of ≥ 70% decreased in Tc(E)-MEPs for each high-risk surgery and any other spine surgeries has not been verified., Methods: Patients who underwent spine and spinal cord surgery with IONM in 16 Japanese spine centers in the Monitoring WG of the JSSR from 2017 to 2018 were enrolled. The patients were divided into the high-risk surgery group (Group HR) and the common surgery group (Group C). Group HR was defined by ossification of the posterior longitudinal ligament (OPLL), spinal deformity, and spinal cord tumor. Group C was classified as other spine surgeries. The alarm point was defined as a ≥70% decrease in the Tc(E)-MEPs., Results: In Group HR, the sensitivity and specificity were 94.4% and 87.0%, respectively. In Group C, the sensitivity and specificity were 63.6% and 91.9%. The sensitivity in Group C was statistically lower than that in Group HR (P < 0.05). In Group HR, the sensitivity and specificity in OPLL were 100% and 86.9%, respectively. The sensitivity and specificity in spinal deformity were 87.5% and 84.8%, respectively, and the sensitivity and specificity in spinal cord tumors were 92.9% and 89.9%, respectively. The sensitivity and specificity in each high-risk surgery showed no significant difference., Conclusion: The alarm point of IONM by the Monitoring WG of the JSSR appeared to be valid for each disease in Group HR. Meanwhile, applying the JSSR alarm point for Group C potentially needed attention.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)