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Abstract Background Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. Methods We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. Results A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11–1.44] and 1.12 [CI: 1.00–1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14–56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05–1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. Conclusions More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. The objective of this study was to characterize the safety and efficacy of romidepsin as consolidation therapy after gemcitabine, dexamethasone, and cisplatin (GDP) therapy (GDPR). This study of patients treated between March 2019 and March 2021 was registered with the Japan Registry of Clinical Trials (registration number: jRCT0000000519). If complete response, partial response, or stable disease was confirmed after 2–4 GDP cycles, romidepsin was administered every 4 weeks for 1 year. Seven patients with relapsed/refractory (R/R) PTCL (T-follicular helper phenotype [n = 1] and angioimmunoblastic T-cell lymphoma [n = 6]) were included in this prospective study (PTCL-GDPR). After a median follow-up of 34 months of patients in PTCL-GDPR, the 2-year overall survival rate was 71%, and the overall response rate after treatment was 57%. Common adverse events in patients with PTCL-GDPR included hematological toxicities such as neutropenia, which improved with supportive treatment. There were no treatment-related mortalities. GDPR might be safe and effective in elderly transplant-ineligible patients with R/R PTCL; however, further investigation is required.

Introduction: Precise prediction of hospital stay duration is essential for maximizing resource utilization during surgery. Existing lumbar spinal stenosis (LSS) surgery prediction models lack accuracy and generalizability. Machine learning can improve accuracy by considering preoperative factors. This study aimed to develop and validate a machine learning-based model for estimating hospital stay duration following decompression surgery for LSS. Methods: Data from 848 patients who underwent decompression surgery for LSS at three hospitals were examined. Twelve prediction models, using 79 preoperative variables, were developed for postoperative hospital stay estimation. The top five models were chosen. Fourteen models predicted prolonged hospital stay (14 days), and the most accurate model was chosen. Models were validated using a randomly divided training sample (70%) and testing cohort (30%). Results: The top five models showed moderate linear correlations (0.576-0.624) between predicted and measured values in the testing sample. The ensemble of these models had moderate prediction accuracy for final length of stay (linear correlation 0.626, absolute mean error 2.26 days, standard deviation 3.45 days). The c5.0 decision tree model was the top predictor for prolonged hospital stay, with accuracies of 89.63% (training) and 87.2% (testing). Key predictors for longer stay included JOABPEQ social life domain, facility, history of vertebral fracture, diagnosis, and Visual Analogue Scale (VAS) of low back pain. Conclusions: A machine learning-based model was developed to predict postoperative hospital stay after LSS decompression surgery, using data from multiple hospital settings. Numerical prediction of length of stay was not very accurate, although favorable prediction of prolonged stay was accomplished using preoperative factors. The JOABPEQ social life domain score was the most important predictor.

Abstract Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = − 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p

Abstract Muscle atrophy due to fragility fractures or frailty worsens not only activity of daily living and healthy life expectancy, but decreases life expectancy. Although several therapeutic agents for muscle atrophy have been investigated, none is yet in clinical use. Here we report that bezafibrate, a drug used to treat hyperlipidemia, can reduce immobilization-induced muscle atrophy in mice. Specifically, we used a drug repositioning approach to screen 144 drugs already utilized clinically for their ability to inhibit serum starvation-induced elevation of Atrogin-1, a factor related to muscle atrophy, in myotubes in vitro. Two candidates were selected, and here we demonstrate that one of them, bezafibrate, significantly reduced muscle atrophy in an in vivo model of muscle atrophy induced by leg immobilization. In gastrocnemius muscle, immobilization reduced muscle weight by an average of ~ 17.2%, and bezafibrate treatment prevented ~ 40.5% of that atrophy. In vitro, bezafibrate significantly inhibited expression of the inflammatory cytokine Tnfa in lipopolysaccharide-stimulated RAW264.7 cells, a murine macrophage line. Finally, we show that expression of Tnfa and IL-1b is induced in gastrocnemius muscle in the leg immobilization model, an activity significantly antagonized by bezafibrate administration in vivo. We conclude that bezafibrate could serve as a therapeutic agent for immobilization-induced muscle atrophy.

Leuprorelin acetate is a common anticancer medication used for prostate cancer treatment. One of the local adverse reactions after leuprorelin injection is the development of reactive granulomas, typically presenting as subcutaneous nodules. In this case report, we describe a 73-year-old patient with prostate cancer who developed unusually large sized intramuscular reactive granulomas, which mimicked malignant soft tissue tumors. The patient, who had been receiving leuprorelin acetate treatment for the past 12 months, noticed painful masses in both upper arms. Based on the findings of magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography, a diagnosis of malignant soft tissue tumor was strongly suggested. However, further investigation through needle biopsy ultimately led us to the final diagnosis of reactive granuloma. The masses spontaneously resolved after discontinuation of leuprorelin injection. While reactive granulomas after leuprorelin injections are not rare, intramuscular cases are relatively uncommon. Despite using imaging studies as a rational initial approach in the diagnostic process, as we did in our case, their results turned out to be indistinguishable from those of malignant soft tissue tumors, thus highlighting the importance of pathological examination in confirming diagnosis, especially when a patient presents with atypical clinical manifestations.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is usually a solitary adipocytic tumor. ALT/WDLPS shows no potential for metastasis unless it undergoes dedifferentiation. No case of multiple ALT/WDLPS has been reported in recent years. We present a rare case of multiple recurrent liposarcomas. A 71-year-old man with a history of scrotal ALT/WDLPS at 61 years presented with multiple large tumors spread throughout the body. The patient was bedridden and severely limited in his activities of daily living (ADL) due to multiple large tumors in the trunk and lower extremities. Radiological examination revealed multiple adipocytic tumors, mainly in the soft tissues of the trunk and extremities, with several visceral lesions. Tumors were resected in stages, starting with large tumors directly related to disability. Repeated palliative resections improved the patient’s ADL; he regained ambulation and was discharged 18 months after admission. Twelve surgeries were performed to remove 44 adipocytic tumors from the testis, left chest wall, perigastric area, ileum, left inguinal region, both buttocks, thighs, and lower legs. Histological examination revealed dedifferentiated components in five tumors, while 39 tumors were diagnosed as ALT/WDLPS. At the age of 76 years, the patient developed an unresectable dedifferentiated liposarcoma between the heart and aorta, leading to fatality at 79 years. The patient’s clinical course suggested multiple metastases of ALT/WDLPS of scrotal origin or ALT/WDLPS of multicentric origin. Although multicentric ALT/WDLPS or ALT/WDLPS metastases are rare, they should be considered when multiple large adipocytic tumors are found throughout the body. Despite the presence of numerous large malignant tumors, surgical treatments of the lesions can improve ADL and prolong life if the tumors are of low-grade malignancy.

Abstract Background Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). Methods Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. Results The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups. Conclusions We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.

Introduction: Adolescent idiopathic scoliosis (AIS) with a major curve at the main thoracic (MT) area is classified as Lenke type 1, 2, or 3 depending on the flexibility of the proximal thoracic (PT) curve and lumbar curve. No definite classification has been established for a major curve at the PT spine. The purpose of this study is to investigate the radiographic characteristics before and after correction surgery for AIS with a major curve at the PT area. Methods: This is a retrospective cohort study at a single academic institution. Twelve patients with a major curve at the PT spine participated in our study and followed for at least two years after surgery. We evaluated the pre- and postoperative Cobb angles of the curve, curve range, location of the apex, sagittal parameters, and shoulder balance-related parameters. All patients were treated by posterior correction and fusion surgery using pedicle screw constructs. Results: The patients were classified as having a double-curve (DC) type, in which the MT curve was structural, or a single-curve (SC) type, in which the MT curve was corrected to less than 25° on supine side-bending films. The mean correction rates for the PT curve were favorable in both groups (DC, 65.7%±9.6%; SC, 39.2%±4.9%). The mean Cobb angle of the lumbar curve improved in the DC group (preoperative, 17.1°±4.0°; postoperative, 5.0°±4.2°) but deteriorated in the SC group (preoperative, 7.1°±1.2°; postoperative, 12.4°±4.4°) after surgery. Conclusions: We illustrated the postoperative radiographical changes of 12 consecutive patients with the major curve at the PT curve. Although posterior correction and fusion surgery corrected the PT curve satisfactorily in both DC and SC patients, the Cobb angle of the lumbar curve deteriorated after surgery in all SC patients. Surgeons need to pay attention to the fusion area, especially LIV, when operating the SC curve type.

Abstract Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN−), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN− and silicone+ groups. Meanwhile, the CCN− and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive intermediate soft tissue neoplasm that occurs in the dermis. DFSP generally occurs in young to middle-aged adults and rarely in infancy. Because of its extreme rarity, DFSP is difficult to diagnose and treat, especially when it occurs in infancy. In this paper, we reported a case of infantile DFSP in which we performed additional wide resection with a 3-cm horizontal margin for a mass that had previously undergone unplanned excision. No tumor recurrence has been seen for 3 years postoperatively. We suggest that the possibility of DFSP should always be considered when an enlarging superficial mass is identified on the trunk, even in an infant. Additionally, radical local treatment is as important for DFSP in infancy as it is for DFSP in adults, even after unplanned excision.

Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has a potential risk for postoperative pleural effusion. Although pleural effusion at an early period after PSF for AIS occurs with a relatively high frequency and occasionally requires some treatments, the impact of postoperative pleural effusion on future pulmonary function or lung volume (LV) has not been clarified to date. The aim of this study was to evaluate the effect of pleural effusion after PSF for AIS on the postoperative pulmonary function and LV. Methods: A total of 114 consecutive patients who underwent PSF for AIS followed up greater than 2 years at our institute were retrospectively reviewed. We evaluated postoperative pleural effusion by computed tomography (CT) at the 1-week follow-up and divided patients into the pleural effusion (PF) and non-pleural effusion (NP) groups. We investigated spirometry parameters recorded for testing included vital capacity (VC), forced expiratory volume in the first second (FEV1), %VC, and FEV1% and measured the LV using CT images and a workstation at baseline and 2 years after surgery. Results: A total of 87 (76.3%) patients with postoperative pleural effusion were identified, but all patients were asymptomatic and did not require additional treatment for postoperative pleural effusion. All pulmonary function parameters at the 2-year follow-up exhibited no significant differences between the two groups. Although preoperative left LV (1.21±0.30 L vs. 1.36±0.34 L; p=.022) and total LV (2.68±0.62 L vs. 2.99±0.73 L; p=.031) were significantly lower in the PF group than in the NP group, all postoperative LV parameters were similar between the two groups. Conclusions: Pleural effusion at an early period after PSF for AIS was a postoperative occurrence without an impact on future pulmonary function and LV.

Background: The choice of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial. The purpose of this study was to identify the preoperative factors affecting the 2-year postoperative patient-reported outcome in Meyerding grade I degenerative spondylolisthesis. Methods: Seventy-two consecutive patients who had minimally invasive decompression alone (D group; 28) or with fusion (DF group; 44) were enrolled. The parameters investigated were the Japanese Orthopaedic Association back pain evaluation questionnaire as patient-reported assessment, and L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment for radiological evaluation. Data collected prospectively at 2 years postoperatively were examined by statistical analysis. Results: Sixty-two cases (D group; 25, DF group; 37) were finally evaluated. In multiple logistic regression analysis, preoperative L4S and LASD were extracted as significant preoperative factors affecting the 2-year postoperative outcome. Patients with preoperative L4S of 6 mm or more have a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio=0.188, p=.043). Patients with a preoperative LASD of 30 mm or more have a higher rate of improvement in lumbar dysfunction due to low back pain (risk ratio=11.48, p=.021). The results of multiple logistic analysis by operative method showed that there was a higher rate of improvement in lumbar spine dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more in DF group (risk ratio=172.028, p=.01). Conclusions: Preoperative L4S and LASD were extracted as significant preoperative factors affecting patient-reported outcomes at 2 years postoperatively. Multiple logistic analyses by the operative method suggested that DF may be advantageous in improving lumbar dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more.

Introduction: Only a few reports have described the clinical features of recurrent spinal cord tumors. This study aimed to report the recurrence rates (RRs), radiographic imaging, and pathological features of various histopathological recurrent spinal cord tumors using a large sample size. Methods: This study adopted the retrospective observational study design using a single-center study setting. We retrospectively reviewed 818 consecutive individuals operated for spinal cord and cauda equina tumors between 2009 and 2018 in a university hospital. We first determined the number of surgeries and then the histopathology, duration to reoperation, number of surgeries, location, degree of tumor resection, and tumor configuration of the recurrent cases. Results: A total of 99 patients (46 men and 53 women) who underwent multiple surgeries were identified. The mean duration between the primary and second surgeries was 94.8 months. A total of 74 patients underwent surgery twice, 18 patients thrice, and 7 patients 4 or more times. The recurrence sites were broadly distributed over the spine, with mainly intramedullary (47.5%) and dumbbell-shaped (31.3%) tumors. The RRs for each histopathology were as follows: schwannoma, 6.8%; meningioma and ependymoma, 15.9%; hemangioblastoma, 15.8%; and astrocytoma, 38.9%. The RRs after total resection were significantly lower (4.4%) than that after partial resection. Neurofibromatosis-associated schwannomas had a higher RR than sporadic schwannomas (p

Abstract Background Occult proximal femoral fractures do not appear as fracture lines in radiographs, causing misdiagnosis and delayed diagnosis unless additional imaging studies, such as computed tomography or magnetic resonance imaging, are performed. Here, we present a 51-year-old male with an occult proximal femoral fracture who experienced radiating unilateral leg pain that took 3 months to be diagnosed because his symptoms mimicked lumbar spine disease. Case presentation A 51-year-old Japanese male experienced persistent lower back and left thigh pain after falling off a bicycle, and was referred to our hospital 3 months thereafter. Whole-spine computed tomography and magnetic resonance imaging revealed minute ossification of the ligamentum flavum at T5/6 without spinal nerve compression, but this did not explain his leg pain. Additional magnetic resonance imaging of the hip joint revealed a fresh left proximal femoral fracture without displacement. He underwent surgery for in situ fixation using a compression hip screw. Post-surgical pain relief was immediate. Conclusions Misdiagnosis of occult femoral fractures as lumbar spinal disease may occur if distally radiating referred pain is present. Hip joint disease should be considered as a differential diagnosis in cases of sciatica-like pain with an unknown spinal origin and no specific findings on spinal computed tomography or magnetic resonance imaging accounting for the leg pain, especially following trauma.

Study Design This is a single-center retrospective cohort study with a university hospital setting. Purpose This study aims to evaluate the short-term course of physical function and walking ability after intramedullary spinal cord tumor (ISCT) resection and predict walking independence 1 year after surgery. Overview of Literature Although several reports have shown the postoperative functional prognosis of spinal intramedullary tumors with long-term follow-up, no reports have identified the predictors associated with the functional outcome at an early stage. Methods A total of 79 individuals who underwent ISCT resection at our institute between 2014 and 2019 were enrolled in the study, whose preoperative walking state was independent ambulator regardless of cane support with the Functional Independence Measure Locomotor Scale (FIM-L) score of ≥6. The FIM-L, the American Spinal Injury Association (ASIA) motor and sensory scores in the lower extremities, and the Walking Index for Spinal Cord Injury II (WISCI II) were assessed for walking independence, lower-limb function, and walking ability, respectively. These evaluations were performed at 4 time points: preoperatively, 1 week (1W), 2 weeks (2W), and 1 year after surgery. Results In the early phase after surgery, 71% and 43% of the participants were nonindependent ambulators at 1W and 2W, respectively. Histopathology indicated that patients with solid tumors (ependymoma, astrocytoma, or lipoma) showed significantly lower indices at 1W and 2W than those with vascular tumors (hemangioblastoma or cavernous hemangioma). Regarding tumor location, thoracic cases exhibited poorer lower-limb function at 1W and 2W and poorer walking ability at 2W than cervical cases. According to the receiver operating characteristic (ROC) analysis, 2 WISCI II points at 2W had the highest sensitivity (100%) and specificity (92.2%) in predicting the level of walking independence at 1 year postoperatively (the area under the ROC curve was 0.99 (95% confidence interval, 0.93–1.00). Conclusions The higher the lower-limb function scores in the early phase, the better the improvement in walking ability is predicted 1 year after ISCT resection.

Abstract Real haptics is a technology that reproduces the sense of force and touch by transmitting contact information with real objects by converting human movements and the feel of the objects into data. In recent years, real haptics technology has been installed in several surgical devices. A custom-made surgical drill was used to drill into the posterior lamina to verify the time required for penetration detection and the distance the drill advanced after penetration. A surgeon operated with the drill and the same aspects were measured and verified. All experiments were performed on female miniature pigs at 9 months of age with a mean body weight of 23.6 kg (range 9–10 months and 22.5–25.8 kg, n = 12). There were statistically significant differences in the average reaction time and the distance travelled after penetration between a handheld drill and the drill with the penetration detection function (p

Abstract Background Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (−) C-OPLL. Methods From January 2010 to December 2015, 202 patients with K-line (+) or (−) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors. Results Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36–54 months) were included. The postoperative JOA score significantly improved in both groups (P 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (−) C-OPLL in both groups. Conclusions Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or −) in patients with C-OPLL.

Abstract Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria.

Osteoid osteoma (OO) is a benign osteoblastic tumor characterized by nocturnal pain that responds well to non-steroidal anti-inflammatory drugs. This condition commonly affects adolescents and young adults, and patients between 5 and 24 years of age account for 85% of all OO cases; it occurs very rarely in patients under 5 years old. Tumors often occur in the cortical bone in the diaphysis and metaphysis of the appendicular skeleton and are more common in the lower extremities than upper extremities. Here, we present an extremely rare case of intramedullary OO that arose in the proximal metaphysis of the humerus in a 2-year-old boy, which mimicked subacute osteomyelitis on imaging studies. We also conducted a retrospective literature review and found that the intramedullary location was fairly common in very young patients (

The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Abstract Autologous stem cell transplantation (ASCT) remains an important therapeutic strategy for multiple myeloma; however, a proportion of patients fail to mobilize a sufficient number of peripheral blood stem cells (PBSCs) to proceed to ASCT. In the present study, we aimed to clarify the characteristics and outcomes of poor mobilizers. Clinical data on poorly mobilized patients who underwent PBSC harvest for almost 10 years were retrospectively collected from 44 institutions in the Japanese Society of Myeloma (JSM). Poor mobilizers were defined as patients with less than 2 × 106/kg of CD34+ cells harvested at the first mobilization. The proportion of poor mobilization was 15.1%. A sufficient dataset including overall survival (OS) was evaluable in 258 poor mobilizers. Overall, 92 out of 258 (35.7%) poor mobilizers did not subsequently undergo ASCT, mainly due to an insufficient number of PBSCs. Median OS from apheresis was longer for poor mobilizers who underwent ASCT than for those who did not (86.0 vs. 61.9 mon., p = 0.02). OS from the diagnosis of poor mobilizers who underwent ASCT in our cohort was similar to those who underwent ASCT in the JSM database (3y OS rate, 86.8% vs. 85.9%). In this cohort, one‐third of poor mobilizers who did not undergo ASCT had relatively poor survival. In contrast, the OS improved in poor mobilizers who underwent ASCT. However, the OS of extremely poor mobilizers was short irrespective of ASCT.

Visualisation of the activity of neural grafts using engineered luciferase provides insights into the integration between the graft and host.

Abstract Age-related changes in the posterior extensor muscles of the cervical and lumbar spine have been reported in some studies; however, longitudinal changes in the thoracic spine of healthy subjects are rarely reported. Therefore, this study aimed to evaluate changes in the cross-sectional areas (CSAs) of posterior extensor muscles in the thoracic spine over 10 years and identify related factors. The subjects of this study were 85 volunteers (mean age: 44.7 ± 11.5) and the average follow-up period was about 10 years. The CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles from T1/2 to T11/12 were measured on magnetic resonance imaging. The extent of muscle fat infiltration was assessed by the signal intensity (luminance) of the extensor muscles’ total cross-section compared to a section of pure muscle. We applied a Poisson regression model, which is included in the generalized linear model, and first examined the univariate (crude) association between each relevant factor (age, sex, body mass index, lifestyle, back pain, neck pain, neck stiffness, and intervertebral disc degeneration) and CSA changes. Then, we constructed a multivariate model, which included age, sex, and related factors in the univariate analysis. The mean CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles significantly increased over 10 years. Exercise habit was associated with increased CSAs of the erector spinae muscles and the total area of the extensor muscles. The cross-section mean luminance significantly increased from baseline, indicating a significant increase of fat infiltration in the posterior extensor muscles. Progression of disc degeneration was inversely associated with increased fat infiltration in the total extensor muscles.

Abstract Background A small, wearable thermo device that uses Peltier elements for programmed heat and cold stimulation has been developed recently and is expected to be applied in conventional contrast bath therapy. This study was aimed to examine improvements in trapezius muscle hardness and subjective symptoms resulting from alternating heat and cold stimulation, with different rates of cooling. Methods This cross-over study included four conditions. Twenty healthy young male individuals (age, 22.3 ± 4.5 years) participated in this study. These four interventions targeted the unilateral trapezius muscle of the dominant arm after a 15-min typing task. Specifically, heat and cold stimulations were applied at different ratios (the heating/cooling rate of 3:1, 3:2, and 3:3) or not applied. Each intervention was separated by at least one week. Skin temperature at the stimulation area was recorded using a data logger. Outcome measures included muscle hardness (measured using a portable tester) and subjective symptoms (muscle stiffness and fatigue). Each item was assessed at three time points: baseline, after typing, and after the intervention. Results Two-way analysis of variance with repeated measures found an interaction effect for muscle hardness between four conditions (3:1, 3:2, 3:3, and no) and three time points (p

Study Design This is a retrospective study. Purpose This study aims to evaluate the risk factor associated with pseudoarthrosis after placement of lateral interbody fusion (LIF) cages for adult spinal deformity (ASD) treatment. Overview of Literature LIF technique is widely used for ASD correction. Furthermore, pseudoarthrosis is a major complication of fusion surgery required for revision surgery. Methods This study included 42 patients with ASD (two men and 40 women; 112 segments; mean, 68.5±8.4 years; and mean follow-up, 31.6±17.0 months) who underwent LIF and posterior correction surgery. The concave slot of the LIF cage was filled with an autologous iliac crest bone graft (IBG), and the convex slot with a porous hydroxyapatite/collagen (HAp/Col) composite was soaked with bone marrow aspirate. Endplate injury, the gap between vertebral endplate and cage in the coronal or sagittal plane, and fusion status were evaluated using computed tomography multiplanar reconstruction at 12 months after surgery. Moreover, the associated risk factors for pseudoarthrosis were analyzed. Results Fusion at LIF segments were observed in 71.4% segments at 12 months after surgery. Fusion on the concave slot (autologous IBG side), convex slot (porous HAp/Col composite side), and both concave and convex slots were observed in 66.1%, 37.5%, and 36.6% of patients, respectively. Moreover, pseudoarthrosis was observed in 28.6% at 12 months after surgery. Consequently, logistic regression analysis of the fusion at the LIF segment revealed that the gap between the LIF cage and endplate in the coronal plane (p=0.030; odds ratio, 0.183; 95% confidence interval, 0.030–0.183) was significantly associated with pseudoarthrosis at the LIF segments. Conclusions ASD surgery fusion rate using LIF cages was 71.4% at 12 months after surgery. The fusion rate was higher on the concave slot filled with autologous IBG than on the convex slot filled with a porous HAp/Col composite. The gap in the coronal plane was a risk factor for pseudoarthrosis at the LIF segment.

Abstract Positive association between ossification of the posterior longitudinal ligament of the spine (OPLL) and obesity is widely recognized; however, few studies focused on the effects of obesity on treatment of cervical OPLL. The effects of obesity on surgical treatment of cervical OPLL were investigated by a Japanese nationwide, prospective study. Overall, 478 patients with cervical myelopathy due to OPLL were prospectively enrolled. To clarify the effects of obesity on the surgical treatment for cervical OPLL, patients were stratified into two groups, non-obese (

Abstract Background Limited chondrocyte migration and impaired cartilage-to-cartilage healing is a barrier in cartilage regenerative therapy. Collagenase treatment and delivery of a chemotactic agent may play a positive role in chondrocyte repopulation at the site of cartilage damage. This study evaluated chondrocyte migratory activity after enzymatic treatment in cultured cartilage explant. Differential effects of platelet-derived growth factor (PDGF) dimeric isoforms on the migratory activity were investigated to define major chemotactic factors for cartilage. Methods Full-thickness cartilage (4-mm3 blocks) were harvested from porcine femoral condyles and subjected to explant culture. After 15 min or 60 min of actinase and collagenase treatments, chondrocyte migration and infiltration into a 0.5-mm cartilage gap was investigated. Cell morphology and lubricin, keratan sulfate, and chondroitin 4 sulfate expression in superficial- and deep-zone chondrocytes were assessed. The chemotactic activities of PDGF-AA, −AB, and -BB were measured in each zone of chondrocytes, using a modified Boyden chamber assay. The protein and mRNA expression and histological localization of PDGF-β were analyzed by western blot analysis, real-time reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry, and results in each cartilage zone were compared. Results Superficial-zone chondrocytes had higher migratory activity than deep-zone chondrocytes and actively bridged the cartilage gap, while metachromatic staining by toluidine blue and immunoreactivities of keratan sulfate and chondroitin 4 sulfate were detected around the cells migrating from the superficial zone. These superficial-zone cells with weak immunoreactivity for lubricin tended to enter the cartilage gap and possessed higher migratory activity, while the deep-zone chondrocytes remained in the lacuna and exhibited less migratory activity. Among PDGF isoforms, PDGF-AB maximized the degree of chemotactic activity of superficial zone chondrocytes. Increased expression of PDGF receptor-β was associated with higher migratory activity of the superficial-zone chondrocytes. Conclusions In enzymatically treated cartilage explant culture, chondrocyte migration and infiltration into the cartilage gap was higher in the superficial zone than in the deep zone. Preferential expression of PDGF receptor-β combined with the PDGF-AB dimeric isoform may explain the increased migratory activity of the superficial-zone chondrocytes. Cells migrating from superficial zone may contribute to cartilage regeneration.

Objective The purpose of our study was to investigate the risk factors of remnant tumor growth after incomplete resection (IR) of cervical dumbbell-shaped schwannomas (DS). Methods Twenty-one patients with IR of cervical DS with at least 2 years of follow-up were included and were divided into 2 groups: the remnant tumor growth (G) (n = 10) and no growth (NG) (n = 11) groups. The tumor location in the axial plane according to Toyama classification, the location of the remnant tumor margin, and the tumor growth rate (MIB-1 index) index were compared. Results No significant differences in Toyama classification and MIB-1 index were found. Age was significantly higher in the G group (61.4 years vs. 47.6 years; p=0.030), but univariate logistic regression analysis revealed little correlation to the growth (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.001–1.166; p=0.047). Seventeen patients (9 in the G and 8 in the NG group) underwent the posterior one-way approach, and significant differences in the location of the remnant tumor margin were confirmed: within the spinal canal in 1 and 0 case, at the entrance of the intervertebral foramen in 7 and 1 cases, and in the foramen distal from the entrance in 1 and 7 cases, in the G and NG groups, respectively (p=0.007). The proximal margin was identified as a significant predictor of the growth (OR, 56.0; 95% CI, 2.93–1,072; p=0.008). Conclusion Remnant tumors with margins distally away from the entrance of the foramen were less likely to grow after IR of cervical DS.

Study Design Cross-sectional study. Purpose To examine whether the number of continuous vertebral bone bridges and bone mineral density (BMD) influence the fracture risk in diffuse idiopathic skeletal hyperostosis (DISH) patients. Overview of Literature Bone bridges connecting through the intervertebral body in DISH create long lever arms that can increase the risk of fractures from minor trauma. DISH patients have a BMD that is higher than or comparable to those of age-matched healthy subjects. Methods We examined the computed tomography scans from the thoracic vertebra to the sacrum used to diagnose DISH in 140 patients (98 men and 42 women; average age, 78.6 years). We compared patients who did (n=52) and did not have (n=88) fractures at the continuous vertebral bodies fused by bone bridges. The relationship between the vertebral fractures and the maximum number of vertebrae that are bony cross-linked with contiguous adjacent vertebrae (max VB) from the thoracic vertebra to the sacrum or from the lumbar vertebra to the sacrum and proximal femur BMD were analyzed using a logistic regression model. Results We found that after adjusting for the confounding factors, higher max VB, both from the thoracic vertebrae to the sacrum and the lumbar vertebrae to the sacrum, was associated with a higher risk of vertebral fractures. This difference was statistically significant. The risk was higher when only the lumbar vertebrae to the sacrum was considered (thoracic vertebrae to the sacrum: odds ratio, 1.21; p

Body weight-supported treadmill training with the voluntary driven exoskeleton (VDE-BWSTT) has been shown to improve the gait function of patients with chronic spinal cord injury. However, little is known whether VDE-BWSTT can effectively improve the trunk function of patients with chronic spinal cord injury. In this open-label, single-arm study, nine patients with chronic spinal cord injury at the cervical or thoracic level (six males and three females, aged 37.8 ± 15.6 years, and time since injury 51.1 ± 31.8 months) who underwent outpatient VDE-BWSTT training program at Keio University Hospital, Japan from September 2017 to March 2019 were included. All patients underwent twenty 60-minute gait training sessions using VDE. Trunk muscular strength, i.e., the maximum force against which patient could maintain a sitting posture without any support, was evaluated in four directions: anterior, posterior, and lateral (right and left) after 10 and 20 training sessions. After intervention, lateral muscular strength significantly improved. In addition, a significant positive correlation was detected between the change in lateral trunk muscular strength after 20 training sessions relative to baseline and gait speed. The change in trunk muscular strength after 20 training sessions relative to baseline was greatly correlated with patient age. This suggests that older adult patients with chronic spinal cord injury achieved a greater improvement in trunk muscle strength following VDE-BWSTT. All these findings suggest that VDE-BWSTT can improve the trunk function of patients with chronic spinal cord injury and the effect might be greater in older adult patients. The study was approved by the Keio University of Medicine Ethics Committee (IRB No. 20150355-3) on September 26, 2017.

Abstract Background Technological innovations have allowed the use of miniature apparatus that can easily control and program heat and cold stimulations using Peltier elements. The wearable thermo-device has a potential to be applied to conventional contrast bath therapy. This study aimed to examine the effects of alternating heat and cold stimulation (HC) using a wearable thermo-device on subjective and objective improvement of shoulder stiffness. Methods Twenty healthy young male individuals (20.3 ± 0.6 years) participated in this study. The interventions were randomly conducted under four conditions, including HC, heat stimulation, cold stimulation, and no stimulation on their bilateral trapezius muscle, after a 30-min typing task. Each intervention was administered at least 1 week apart. The analyzed limb was the dominant arm. Muscle hardness was assessed using a portable muscle hardness meter, as well as the skin temperature over the stimulated area. After each condition, the participants were asked for feedback regarding subjective improvement in refreshed feelings, muscle stiffness, and muscle fatigue using an 11-point numerical rating scale. Results With regard to muscle hardness, only the HC condition significantly decreased from 1.43 N to 1.37 N (d = 0.44, p < 0.05). Additionally, reduced muscle hardness in HC condition was associated with the degree of skin cooling during the intervention (cold max: r = 0.634, p < 0.01; cold change: r = −0.548, p < 0.05). Subjective improvement in refreshed feelings, muscle stiffness, and muscle fatigue was determined in the HC and heat stimulation conditions compared with the no stimulation condition (p < 0.01 and p < 0.05, respectively). Moreover, the HC condition showed significantly greater improvements in muscle stiffness and fatigue compared to the cold stimulation condition (p < 0.05). Conclusions The current study demonstrated that HC promoted not only better subjective symptoms, such as muscle stiffness and fatigue, but also lesser muscle hardness. Furthermore, an association was observed between the degree of skin temperature cooling and reduced muscle hardness during HC. Further investigations on the ratio and intensity of cooling should be conducted in the future to establish the optimal HC protocol for muscle stiffness or fatigue. Trial registration UMIN000040620 . Registered 1 June 2020

Abstract Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH)2D3 or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment. 1,25(OH)2D3 or ED71 administration also significantly inhibited osteocyte apoptosis induced by tooth extraction and bisphosphonate treatment. Administration of either active vitamin D analogue significantly inhibited elevation of serum inflammatory cytokine levels in mice in response to injection of lipopolysaccharide, an infection mimetic. Furthermore, administration of either anti-inflammatory or antibiotic reagents significantly blocked ONJ development following tooth extraction and zoledronate treatment. These findings suggest that administration of active vitamin D, anti-inflammatory agents or antibiotics could prevent ONJ development induced by tooth extraction in patients treated with zoledronate.

Abstract This prospective multicenter study, established by the Japanese Ministry of Health, Labour and Welfare and involving 27 institutions, aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL), in order to address the controversy surrounding the role of instrumented fusion in cases of posterior surgical decompression for OPLL. 478 patients were considered for participation in the study; from among them, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, there were no significant differences among the participants in terms of patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments. The overall risk of perioperative complications was found to be lower with LM (odds ratio [OR] 0.40, p = 0.006), and the rate of C5 palsy occurrence was significantly lower with LM (OR 0.11, p = 0.0002) than with PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p

Objective To evaluate the cervical dynamics, neurological function, pain, and quality of life in patients with mild cervical kyphotic alignment who underwent expansive unilateral open-door laminoplasty (ELAP). Methods In this retrospective single-center study, we reviewed the surgical outcomes of 80 patients with cervical spondylotic myelopathy who were followed for at least 2 years. The patients were categorized into the preoperative kyphotic group (C2–7 angle < 0°) and nonkyphotic group (angle ≥ 0°). We compared clinical information, radiographic parameters, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) scores, and cervical Japanese Orthopaedic Association (JOA) scores between the groups. Results The kyphotic and nonkyphotic groups comprised 17 and 63 patients, respectively. The preoperative C2–7 angles were -3.7° in the kyphotic group and 15.4° in the nonkyphotic group (p

Background: Few studies have examined the changes in cervical sagittal alignment (CSA) and its relationship with other sagittal alignments in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent correction surgery. This study investigated the radiographical changes in CSA after correction surgery in patients with Lenke type 6 adolescent idiopathic scoliosis (AIS) and assess any possible factors affecting postoperative CSA. Methods: Forty-four patients with Lenke type 6 AIS (3 males and 41 females, mean age at surgery of 15.6 ± 2.8 years) who could be followed up for 3 years after correction surgery were included in this study. Variations of outcome variables were analyzed in various spinal sagittal parameters using radiographic outcomes. Univariate correlation analyses were used to evaluate possible factors influencing the postoperative CSA. The Scoliosis Research Society (SRS)-22 questionnaires and the Oswestry Disability Index (ODI) were used for clinical evaluation, and the changes between pre- and 3-year post-operation were compared. Results: The Cobb angle of the major and minor curve was significantly improved after correction surgery. Furthermore, CSA, such as C2-7 angle and T1 slope, changed significantly postoperatively. The magnitude of coronal curve correction did not affect CSA postoperatively, while the postoperative TK, T10-L2 kyphosis and LL were significantly correlated with the postoperative C2-7 angle, respectively. None of the patients in this study complained of neck or low back pain during the period up 3 years after the operation. Comparing each domain of SRS-22 or ODI score, these were unchanged between pre-, 1-year, and 3-year post-operation, with no statistically significant differences. Conclusions: CSA changed significantly after correction surgery, and cervical kyphosis indicated a tendency to decrease in Lenke type 6 AIS patients, which was associated with an improvement in thoracic and lumbar sagittal alignment, not correction for coronal deformity.

Objective: Although syringomyelia is considered a risk factor for neurological complications of correction surgery for scoliosis, only a few reports on the surgical results of the correction surgery complicated with associated syringomyelia are available. The purpose of this study is to verify the potential risk of neurological complications due to the presence of syringomyelia and explore the factors affecting the surgical outcomes of posterior correction surgery for scoliosis associated with syringomyelia. Methods: This is a retrospective observational study in a single university hospital setting. Among 754 consecutive patients who underwent posterior correction and fusion surgery for scoliosis from 2009 through 2018 in our institution, we identified 28 patients presenting with spinal syringomyelia on preoperative whole spine MRI. The identified cases comprised 14 males and 14 females aged 11 years to 23 years (14.0 ± 2.9 years), and those with wide-type syrinx within fused spinal levels had undergone surgery for syringomyelia beforehand. First, we investigated the occurrence rate of peri- and postoperative neurological complications. Then we explored the factors affecting the correction rate of the Cobb angle and the incidence of coronal decompensation. Results: Neurological complication (transient sensory deficits in bilateral legs) occurred in one case with thoracic single curve and narrow-type syrinx, disappearing spontaneously within several weeks postoperatively. The cases with an L4 long curve (n = 3, including L4 in thoracolumbar long C-shaped curve) showed a significantly poor correction rate (38.7%, p = 0.003) and developed postoperative coronal decompensation. Conclusions: Prior treatment for wide-type syrinx located within the spinal fusion level effectively prevented severe neurological complications, and when treating cases with long-curve L4 scoliosis associated with syringomyelia, the surgeons should note the occurrence of postoperative coronal decompensation.

Introduction: In 2018, the first Mobi-CⓇ total disk replacement (TDR) case was performed in Japan. In this study, we examined the preliminary clinical outcome of Mobi-CⓇ for degenerative cervical spine disease. Methods: We examined 24 consecutive patients who underwent 1-level TDR after 2018 and followed up for more than 6 months after surgery. The evaluation criteria included age, gender, diagnosis, follow-up period, surgical level, implant size, surgery time, intraoperative bleeding volume, complications, revision surgery, imaging findings, JOA score, and various questionnaires. Results: The mean age was 52.7 years, 13 males and 11 females. There were 15 cases of cervical disk herniation and 9 cases of cervical spondylosis. The mean follow-up period was 17.4 months. Surgical levels were C3/4 in 4 cases, C4/5 in 2 cases, C5/6 in 16 cases, and C6/7 in 2 cases. The mean operation time was 138.5 minutes, the amount of intraoperative bleeding was 32.1 ml, and there were no serious intraoperative complications. The range of motion of the affected level increased significantly, from 6.6 degrees preoperatively to 12.2 degrees at final follow-up. No patients required revision surgery at final follow-up, and there were no cases of heterotopic ossification or adjacent segment disease. One patient exhibited radiculopathy due to mild subsidence 1 year after surgery, and 1 had asymptomatic contact of device plates. Preoperative and final JOA scores improved from 11.7 to 15.8 points, and NRS improved from 4.3 to 1.3 points for neck pain and 4.3 to 1.7 points for arm pain. Preoperative and final NDI improved from 39.7% to 14.0%, and EQ-5D improved from 0.602 to 0.801. Conclusions: The short-term treatment outcomes of Mobi-CⓇ TDR were generally favorable. Spine surgeons should comply with guidelines when introducing this procedure and strive to adopt this new technology in Japan.

Study Design This is a retrospective observational study with an outpatient setting. Purpose This study aimed to describe the effects of duloxetine (DLX) administration for postsurgical chronic neuropathic disorders (both pain and numbness) following spinal surgery in patients without depression. Overview of Literature Although several reports indicated the potential of DLX to effectively treat postoperative symptoms as a perioperative intervention, there have been no reports of its positive effect on postsurgical chronic neuropathic disorders. Methods A total of 24 patients with postsurgical chronic pain and/or numbness Numeric Rating Scale (NRS) scores of ≥4 were enrolled. All patients underwent spine or spinal cord surgery at Keio University Hospital and received daily administration of DLX for more than 3 months. The mean postoperative period before the first administration of DLX was 35.5±57.0 months. DLX was administered for more than 3 months at a dose of 20, 40, or 60 mg/day, and the degree of pain and numbness was evaluated using the NRS before administration and 3 months after administration. Effectiveness was defined as more than a 2-point decrease in the NRS score following administration. Results In terms of the type of symptoms, 15 patients experienced only numbness, eight experienced both pain and numbness, and one experienced only pain. Of the 24 patients, 19 achieved effective relief with DLX. DLX was effective for all patients with postsurgical chronic pain (n=9), and it reduced postsurgical chronic numbness in 18 of 23 patients. No significant difference was observed in background spinal disorders. DLX was not effective for five patients who complained only of postsurgical chronic numbness. Conclusions This study reports the effectiveness of DLX for postsurgical chronic neuropathic disorders. Although DLX reduced postsurgical chronic pain (efficacy rate=100%) and numbness (78.3%) in certain patients, further investigation is needed to determine its optimal use.

Abstract Background Standing whole spinal radiographs are used to evaluate spinal alignment in adult spinal deformity (ASD), yet some studies have reported that pelvic incidence, pelvic tilt, and thoracic kyphosis (TK) intra- and inter-observer reliability is low. This study aimed to evaluate the accuracy of spinopelvic parameters through comparing standing whole spinal radiographs and upright CT images. Methods We enrolled 26 patients with ASD. All standing whole spinal posterior/anterior and lateral radiographs and upright whole spinal CT had been obtained in a natural standing position. Two examiners independently measured 13 radiographic parameters. Interclass correlation coefficients (ICCs) were used to analyze measurement intra- and inter-observer reliability. Paired t- and Pearson’s correlation tests were used to analyze validity of the standing whole spinal radiographs. Results ICCs of upright CT were excellent in both intra- and inter-observer reliability. However, intra-observer ICCs for TK2–12, TK1–5, TK2–5, and TK5–12 on standing lateral radiographs were relatively low, as were inter-observer ICCs for TK2–12, TK1–5, TK2–5, and TK5–12. Concerning TK values, the difference between the radiographs and CT in TK1–12 and TK2–12 were 4.4 ± 3.1 and 6.6 ± 4.6, respectively, and TK values from T2 showed greater measurement error (p

To prevent pedicle screw implant failure, a diagnostic technique that allows surgeons to evaluate implant stability easily, quickly, and quantitatively in clinical orthopedic situations is required. This study aimed to predict the insertion torque equivalent to laboratory-level evaluation accuracy. This serves as an index of the implant stability of pedicle screws placed in cadaveric bone, which relies on laser resonance frequency analyses (L-RFA) when irradiating with two types of lasers. The machine learning analysis was optimized using a dataset with artificial bone as teaching data. In this analysis, many explanatory variables extracted from the laser-induced vibration spectra obtained during an analysis/RFA evaluation were predicted by selecting important variables using the least absolute shrinkage and selection operator and performing a non-linear approximation using support vector regression. It was found that combining both artificial and cadaveric bone data with the bone densities as teaching data dramatically improved the determination coefficient from R2 = −0.144 to R2 = 0.858 as the prediction accuracy and reduced the influence of differences between artificial and cadaveric bones. This technology will contribute to the development of preventive diagnostic technologies that can be used during surgery, which is necessary in order to further advance treatment technologies.

Abstract Background Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. Methods Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. Results There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0–0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1–0.4) and slightly decreased years with activity limitation (0.1–0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3–1.5 years) and decreased years with activity limitation (0.3–1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0–0.8 years) and non-ADL limitations (0.0–0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7–1.1 years) and non-ADL limitations (0.3–0.4). Conclusions These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.

Osteosarcoma is the most common malignant primary bone tumor that occurs most frequently in the second decade of life but rarely in patients over 40 years of age. The most common primary sites of osteosarcoma are the distal femur followed by proximal tibia and proximal humerus, and involvement of the wrist is extremely rare. Moreover, dedifferentiated osteosarcoma is also a rare condition that progresses to high-grade osteosarcoma from low-grade osteosarcoma, usually central low-grade osteosarcoma or parosteal osteosarcoma that bears MDM2 and/or CDK4 gene amplifications. We herein report an extremely rare case of dedifferentiated osteosarcoma arising in the distal ulna of an adult over 40 years of age. The patient was a 46-year-old man with a 2-month history of pain in his left swollen wrist. The initial radiological findings suggested a benign bone tumor in the distal ulna, and the lesion was marginally excised at the nearby hospital. Although the pathological diagnosis at the nearby hospital suggested a benign cartilaginous tumor, the tumor recurred in an aggressive manner 8 months after the initial surgery. The patient was referred to our hospital, and an incisional biopsy showed a high-grade osteosarcoma. The primary tumor was retrospectively re-evaluated at our hospital and diagnosed as low-grade osteosarcoma. Since neoadjuvant chemotherapy failed to shrink the tumor, the patient had to undergo below the elbow amputation to cure the disease. Although the tumor was negative for MDM2 nor CDK4, the definitive diagnosis of dedifferentiated osteosarcoma was made according to the clinical course and the histological findings. Lung metastases were found 10 months after the amputation, which were successfully treated by neoadjuvant chemotherapy and surgery. The patient has been doing well with no evidence of disease for 1 year and 6 months. Surprisingly, the literature review revealed that many low-grade osteosarcomas of the distal ulna progressed to high-grade dedifferentiated osteosarcomas. One should bear in mind that the diagnosis and treatment for bone-forming tumors of the distal ulna should be made very carefully because, although rare, it is possible that the tumor may initially appear as a benign or low-grade malignant tumor and may progress to high-grade osteosarcoma.

Abstract Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. The bridging of ossified lesions to the vertebral body gradually increases, thereby decreasing the mobility of the cervical spine; thus, cervical spine function may decrease over time. However, cervical spine function in patients with cervical OPLL has not been evaluated in large prospective studies. Therefore, we conducted a prospective multicenter study to clarify whether ossification spread can influence cervical spine function and quality of life (QOL) in patients with cervical OPLL. In total, 238 patients (162 men, 76 women; mean age, 63.9 years) were enrolled from 16 institutions. Each patient underwent whole spine computed tomography and was evaluated for cervical spine function and QOL using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). In the multivariate regression analysis, a higher neck VAS score and a larger number of bridge formations of OPLL in the whole spine were significant predictors of adverse outcomes related to cervical spine function. This is the first prospective multicenter study to reveal the impact of ossification spread on cervical spine function. These findings are important to understand the natural course of OPLL and can serve as controls when evaluating postoperative cervical spine function.

Abstract Although favourable surgical outcomes for myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) have been reported, factors significantly associated with post-operative neck pain attenuation still remain unclear. The primary aim of the present study was to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL. Significant postoperative neck pain reduction (50% reduction of neck pain) was achieved in 31.3% of patients. There was no significant difference in neck pain attenuation between surgical procedures. Statistical analyses with univariate analyses followed by stepwise logistic regression revealed neurological recovery as a factor having a significant positive association with post-operative neck pain attenuation (p = 0.04, odds ratio 5.68 (95% confidence interval: 1.27–22.2)). In conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.