Search

Background Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by heterotopic bone formation in the posterior longitudinal ligament of the spine. Although the patients with OPLL are more common in the 60s and 70s, we know that there are markedly young patients (e.g., early 40s). However, to the best of our knowledge, there is few reports characterize young patients with cervical OPLL in terms of the imaging features, subjective symptoms, and ADL problems. Methods This is the multicenter cross-sectional study. Two hundred and thirty-seven Japanese symptomatic patients with cervical OPLL confirmed by standard X-rays collected from 16 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament formed by the Japanese Ministry of Health, Labor and Welfare were recruited. Whole spine CT data as well as demographic data such as age, gender, patients-based evaluations, and the 36-item Short Form Health Survey (SF-36) were evaluated. Results Young group (≦ 45 years old) consisted of 23 patients (8 females and 15 males), accounting for 9.7% of the total. Their characteristics were high body mass index (BMI), significant involvement of trauma in the onset and deterioration of symptoms, and the predominance of thoracic OPLL. The patient-based evaluations did not show a significant difference between the young and non-young groups, or between the genders in the young group except for bodily pain (BP) of SF-36. Female patients in young group had significantly lower BP score of SF-36 than that of male in young group. Conclusions Characteristics of young patients with cervical OPLL were high BMI, significant involvement of trauma in the onset and deterioration of symptoms, lower BP score of SF-36 in female, and the predominance of thoracic OPLL.

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.

Abnormalities in cerebrospinal fluid (CSF) dynamics cause diverse conditions, such as hydrocephalus and scoliosis, but the underlying mechanism is still unknown. Methods to study CSF dynamics in small animals have not been established due to the lack of an evaluation system. Therefore, the purpose of this research is to to establish the time-spatial labelling inversion pulse (Time-SLIP) MRI technique for the evaluation of CSF dynamics in mice. We performed the Time-SLIP technique on 10 wild-type mice and 20 Tiptoe walking Yoshimura (TWY) mice, a mouse model of ossification of the posterior longitudinal ligament (OPLL). We defined the Stir Distance as the distance of CSF stirring and calculated the mean ± standard deviation. The intraclass correlation coefficient of the intraobserver reliabilities was also calculated. Furthermore, in TWY mice, the correlation coefficient between Stir Distance and Canal Stenosis Ratio (CSR) was calculated. The Stir Distance was significantly lower in TWY mice (p0.90) and there was a strongly negative correlation between Stir Distance and CSR in TWY mice (>-0.80). In this study, we established the Time-SLIP technique in experimental mice. This technique allows a better understanding of CSF dynamics in small laboratory animals.

We report the case of a 61-year-old woman with right-sided flexor pollicis longus (FPL) tendon ruptured a month after volar locking plate fixation. Five months after the initial operation, hardware removal and reconstruction of the FPL tendon with the ipsilateral palmaris longus were performed. The proximal stump of the ruptured FPL tendon was found in the space between the distal radius and plate.

Background: Recently, mesenchymal stem cell therapy has emerged as an option for osteoarthritis (OA) treatment. Intra-articular injection of adipose-derived stem cells (ADSCs) is growing in popularity in clinical practice as conservative treatment for OA. The adipose-derived mesenchymal stem cell line (ASCL) established in our institute provides allogeneic ADSCs that are more purified than conventional ADSCs. This study evaluated the therapeutic efficacy of intra-articular injection of the ASCL using the low-dose monoiodoacetate-OA (MIA-OA) model in rats. Methods: Expression of cell surface markers for ADSCs and the ASCL was examined by flow cytometry. Low-dose MIA-OA model was created in 8-week-old male immunodeficient rats by intra-articular injection of 0.2 mg of MIA on day 0. After MIA injection, treatment group rats underwent intra-articular injection of the ASCL, and control group rats underwent intra-articular injection of ADSCs or vehicle on day 1. All rats subsequently underwent nociception analysis, gait analysis, immunoserological analysis and histopathological analysis. Results: Flow cytometric analysis suggested that the ASCL consists of a homogeneously stem cell population than ADSCs. Nociception analysis revealed that the ASCL rats had higher pain thresholds than ADSCs control rats. Gait analysis revealed that mean swing duration, swing speed and duty cycle were significantly better in the ASCL rats than in vehicle control rats on day 56. Interleukin-6 (IL-6) levels in synovial fluid were significantly lower in the ASCL rats than in vehicle control rats on days 5 and 56. Histopathological scores for infrapatellar synovitis and cartilage erosion were significantly improved in the ASCL rats than in vehicle control rats on days 5 and 56. Conclusions: Intra-articular injection of the ASCL providing allogeneic ADSCs attenuated pain, synovitis and cartilage degeneration both in the early inflammatory phase and in a later less-inflammatory phase in low-dose MIA-OA model. The ASCL injection did not induce any adverse reactions, potentially representing an effective and safe therapeutic option for OA.

Background The K-line in the neck-flexed position (FK-line) on radiography reflects dynamic factors and cervical alignment. Although the FK-line has been reported to affect the neurological recovery after muscle-preserving selective laminectomy for cervical spondylotic myelopathy (CSM), its influence on surgical outcomes after expansive open-door laminoplasty (ELAP) has not been investigated. Methods We reviewed the surgical outcomes in 81 patients with multilevel CSM who underwent C4–C6 ELAP combined with C3 and C7 partial laminectomy using a laminoplasty plate and were followed up for at least 2 years. We defined the K-line (−) as some portion of a bony spur or the vertebral body crossing the FK-line, whereas the FK-line (+) was defined as that never crossing the FK-line. Patients were divided into the FK-line (+) (n = 61) and FK-line (−) groups (n = 20), and the surgical outcomes were compared between the groups. A multivariate analysis was performed to identify the factors that influenced the neurological outcomes. Results The FK-line (−) group had a smaller C2–C7 angle, smaller C7 slope, greater postoperative increase in the C2–C7 sagittal vertical axis, greater kyphosis in cervical flexion and less lordosis in cervical extension, and higher incidence of postoperative residual spinal cord compression. The preoperative-to-postoperative changes in the Japanese Orthopedic Association (JOA) score and JOA score recovery rate (RR) were lower in the FK-line (−) group. The multiple linear regression analysis revealed that the K-line (−) (β = −0.327, P = 0.011) and high signal intensity (SI) changes on T2-weighted imaging (WI) combined with the low SI changes on T1-WI in the spinal cord (β = −0.320, P = 0.013) negatively affected the JOA score RR. Conclusions The FK-line can be used for patients with CSM as a simple indicator of neurological outcomes after ELAP.

Background Patients with diffuse idiopathic skeletal hyperostosis (DISH) are susceptible to spinal column injuries with neurological deterioration. Previous studies indicated that the prevalence of diabetes mellitus (DM) in patients with DISH was higher than that in patients without DISH. This study investigates the impact of DM on surgical outcomes for spinal fractures in patients with DISH. Methods We retrospectively evaluated 177 spinal fractures in patients with DISH (132 men and 45 women; mean age, 75 ± 10 years) who underwent surgery from a multicenter database. The subjects were classified into two groups according to the presence of DM. Perioperative complications, neurological status by Frankel grade, mortality rate, and status of surgical site infection (SSI) were compared between the two groups. Results DM was present in 28.2% (50/177) of the patients. The proportion of men was significantly higher in the DM group (DM group: 86.0% vs. non-DM group: 70.1%) (p = 0.03). The overall complication rate was 22.0% in the DM group and 19.7% in the non-DM group (p = 0.60). Poisson regression model revealed that SSI was significantly associated with DM (DM group: 10.0% vs. non-DM group: 2.4%, Relative risk: 4.5) (p = 0.048). Change in neurological status, mortality rate, instrumentation failure, and nonunion were similar between both groups. HbA1c and fasting blood glucose level (SSI group: 7.2% ± 1.2%, 201 ± 67 mg/dL vs. non-SSI group: 6.6% ± 1.1%, 167 ± 47 mg/dL) tended to be higher in patients with SSI; however, there was no significant difference. Conclusions In spinal fracture in patients with DISH, although DM was an associated factor for SSI with a relative risk of 4.5, DM did not negatively impact neurological recovery. Perioperative glycemic control may be useful for preventing SSI because fasting blood glucose level was high in patients with SSI.

In cohort C of the phase 2 MM-014 trial, the efficacy and safety of pomalidomide, dexamethasone, and daratumumab therapy were investigated in 18 Japanese patients with relapsed/refractory multiple myeloma (RRMM) after their most recent regimen of lenalidomide-based therapy (NCT01946477). Patients received oral pomalidomide (4 mg daily), oral dexamethasone (20-40 mg weekly), and intravenously infused daratumumab (16 mg/kg). Median age was 67.5 years. All patients received prior lenalidomide per protocol; 89% received prior bortezomib. Twelve patients (67%) had lenalidomide-refractory disease, and 6 (33%) had lenalidomide-relapsed disease. Ten patients (56%) had only 1 prior treatment line. As of August 3, 2020, 15 patients (83%) were still on treatment; median follow-up was 8.1 months. Three patients (17%) discontinued treatment (2 for adverse events; 1 for major protocol deviation). Overall response rate (primary endpoint) was 83% (very good partial response or better, 61%). All patients had ≥ 1 grade 3/4 treatment-emergent adverse events, most commonly neutropenia (78%; febrile, 6%), leukopenia (28%), and lymphopenia (22%). Grade 3/4 infections occurred in 17%; 11% had pneumonia. In Japanese patients with RRMM, a triplet regimen of pomalidomide, dexamethasone, and daratumumab after early-line lenalidomide treatment failure showed high efficacy and safety consistent with the known safety profile.

This was a retrospective case series of prospectively collected data.The present study first described the effect of sublaminar tethering (SLT) on proximal junctional failure (PJF) in adult spinal deformity (ASD) surgery.PJF is a devastating complication following ASD surgery. Teriparatide administration and spinous process tethering have been reported as alternatives for the prevention of PJF, but a clinically effective prevention strategy is still a matter of debate.We used data from an ASD database that included 381 patients with ASD (minimum 2-y follow-up). Among them, the data of patients who had a severe sagittal deformity and had surgery from the lower thoracic spine (T9-T11) to the pelvis were extracted and propensity score matched by age, sex, body mass index, bone mineral density, curve type, sagittal alignment, and fused level to clarify whether SLT prevented the development of PJF [SLT vs. control (CTR); age: 67±7 vs. 66±8 y, T-score: -1.4±0.7 vs. -1.3±0.6, body mass index: 22±4 vs. 22±5 kg/m2, C7 sagittal vertical axis (C7SVA): 12±7 vs. 11±5 cm, pelvic incidence-lumbar lordosis (PI-LL): 51±22 vs. 49±21 degrees, pelvic tilt (PT): 36±10 vs. 34±10 degrees, level fused: 11±2 vs. 11±2]. Sixty-four patients were matched into 32 pairs and compared in terms of the postoperative alignment and frequency of PJF.Two years postoperatively, C7SVA and PT were significantly larger in the CTR group, while no significant difference in PI-LL was found (C7SVA: 3±3 vs. 6±4 cm, P0.01, PT: 16±6 vs. 24±9 degrees, P0.01, PI-LL: 7±9 vs. 11±11 degrees, P=0.22). The proximal junctional angle was significantly greater in the CTR group (proximal junctional kyphosis: 8±8 vs. 17±13 degrees, P0.01). The incidence of PJF was significantly lower in the SLT group (3% vs. 25%, P=0.03), with an odds ratio of 0.1 (95% confidence interval: 0.0-0.8, P=0.03).In the propensity score-matched cohort, the incidence of PJF was significantly lower in the SLT group. SLT is a promising procedure that may reduce the risk of PJF in severe ASD surgery.

Introduction: Posterior radiocapitellar synovial plica excision is sometimes performed for lateral epicondylitis after debridement of the extensor carpi radialis brevis (ECRB) tendon. We describe a rare intra-articular abnormality of the posterior radiocapitellar joint diagnosed on posterior arthroscopic observation. Case Report: A 48-year-old man presented with posterolateral pain and discomfort in his left elbow. A diagnosis of lateral epicondylitis was made, and arthroscopic debridement of the ECRB tendon was performed. Posterior arthroscopic examination revealed a tendon-like abnormality running longitudinally along the articular surface of the capitulum of the humerus. The abnormality was resected using a shaver, and symptoms improved postoperatively. Conclusion: In patients with posterolateral pain and discomfort or catching of the elbow, posterior arthroscopic confirmation of the intra-articular structure is recommended after debridement of the ECRB tendon.

Summary Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI., Highlights • The neuronal activity of hM4Di-NS/PCs was controlled by CNO administration • Inhibiting the neuronal activity of grafted NS/PCs led to functional decline • Grafted neurons derived from hiPSC-NS/PCs integrated into host motor circuits, This study by Okano, Nagoshi, and colleagues demonstrated decreased locomotor function in hiPSC-NS/PC-transplanted SCI mice induced by inhibition of graft-derived neuronal activity using a DREADD. Locomotor changes caused by the graft neuronal activity inhibition were observed exclusively in the chronic phase. These results suggested the significance of engrafting functionally mature neurons via hiPSC-NS/PC transplantation for behavioral improvement following SCI.

The maximum number of vertebral bodies with bony bridges between adjacent vertebrae (max VB) helps assess the risk of fracture in diffuse idiopathic skeletal hyperostosis (DISH). In addition to max VB, the maximum thickness of bone cross-bridges (max TB) may be an index of bone mineral density (BMD). Therefore, this study investigated the relationship among max VB, max TB, and BMD. The participants in this cross-sectional study were male patients (n = 123) with various max VB from the thoracic vertebrae to the sacrum without sacroiliac ankylosis. The participants were grouped by max VB. For example, a group with max VB from 4 to 8 would be listed as max VB (4–8). The relation between femur proximal BMD and mean max TB and max VB was assessed. Femur proximal BMD was then compared after adjusting for confounding factors. The results indicated that max VB was correlated with femur proximal BMD in max VB (0–8) and max VB (9–18) groups. The mean max TB was correlated only with femur proximal BMD in max VB (0–8). After adjusting, max VB (4–8) showed a significantly higher femur proximal BMD than max VB (0–3) and max VB (9–18). Femur proximal BMD and mean max TB showed different trends after max VB = 9, which suggests that max VB is an index of BMD, and that DISH has at least two possible populations in terms of BMD and bone cross-link thickness.

BACKGROUND A novel biocompatible sealant composed of Alaska pollock-derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model. METHODS Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure. RESULTS The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant. CONCLUSION The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.

Summary Functional recovery is still limited mainly due to several mechanisms, such as the activation of Nogo receptor-1 (NgR1) signaling, when human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PC) are transplanted for subacute spinal cord injury (SCI). We previously reported the neuroprotective and regenerative benefits of overexpression of lateral olfactory tract usher substance (LOTUS), an endogenous NgR1 antagonist, in the injured spinal cord using transgenic mice. Here, we evaluate the effects of lentiviral transduction of LOTUS gene into hiPSC-NS/PCs before transplantation in a mouse model of subacute SCI. The transduced LOTUS contributes to neurite extension, suppression of apoptosis, and secretion of neurotrophic factors in vitro. In vivo, the hiPSC-NS/PCs enhance the survival of grafted cells and enhance axonal extension of the transplanted cells, resulting in significant restoration of motor function following SCI. Therefore, the gene transduction of LOTUS in hiPSC-NS/PCs could be a promising adjunct for transplantation therapy for SCI., Graphical abstract, Highlights • LOTUS-overexpressing hiPSC-NS/PCs induce axonal extension and apoptosis suppression • LOTUS-overexpressing hiPSC-NS/PCs increase secretion of neurotrophic factors • Transplanted LOTUS-overexpressing hiPSC-NS/PCs enhance motor functional recovery • Ex vivo gene therapy delivering LOTUS is beneficial for cell transplantation, In this article, Hideyuki Okano and his colleagues (Ito et al.) show that the transduced LOTUS contributes to neurite extension, apoptosis suppression, and secretion of neurotrophic factors in hiPSC-NS/PCs in vitro. They also show that transplanted LOTUS-overexpressing hiPSC-NS/PCs enhance survival of grafted cells and enhance axonal extension of the transplanted cells, resulting in significant restoration of motor function following SCI.

Patients with DISH are susceptible to spinal fractures and subsequent neurological impairment, including after minor trauma. However, DISH is often asymptomatic and fractures may have minimal symptoms, which may lead to delayed diagnosis. The purpose of this study was to identify risk factors for delayed diagnosis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH).The subjects were 285 patients with DISH surgically treated at 18 medical centers from 2005 to 2015. Cause of injury, imaging findings, neurological status at the times of injury and first hospital examination, and the time from injury to diagnosis were recorded. A delayed diagnosis was defined as that made24 h after injury.Main causes of injury were minor trauma due to a fall from a standing or sitting position (51%) and high-energy trauma due to a fall from a high place (29%) or a traffic accident (12%). Delayed diagnosis occurred in 115 patients (40%; 35 females, 80 males; mean age 76.0 ± 10.4 years), while 170 (60%; 29 females, 141 males; mean age 74.6 ± 12.8 years) had early diagnosis. Delayed group had a significantly higher rate of minor trauma (n = 73, 63% vs. n = 73, 43%), significantly more Frankel grade E (intact neurological status) cases at the time of injury (n = 79, 69% vs. n = 73, 43%), and greater deterioration of Frankel grade from injury to diagnosis (34% vs. 8%, p 0.01). In multivariate analysis, a minor trauma fall (OR 2.08; P 0.05) and Frankel grade E at the time of injury (OR 2.29; P 0.01) were significantly associated with delayed diagnosis.In patients with DISH, it is important to keep in mind the possibility of spinal fracture, even in a situation in which patient sustained only minor trauma and shows no neurological deficit. This is because delayed diagnosis of spinal fracture can cause subsequent neurological deterioration.

MINI A retrospective multicenter study with propensity scoring revealed the impact of the intervertebral level of stenosis on surgical outcomes of posterior decompression for cervical spondylotic myelopathy. Functional recovery was not different between the upper and lower cervical stenosis groups. Posterior decompression is effective, regardless of the intervertebral level of stenosis. STUDY DESIGN Retrospective multicenter study. OBJECTIVE To identify the impact of the intervertebral level of stenosis on surgical outcomes of posterior decompression for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA As the upper affected cervical levels in elderly patients result from degenerative changes in the lower cervical levels with aging, it is usually difficult to determine the influence of the upper affected cervical levels on surgical outcomes after posterior decompression for CSM in older age. METHODS This study involved 636 patients with CSM who underwent posterior decompression. According to the most stenotic intervertebral level, patients were divided into upper (n = 343, the most stenotic intervertebral level was C2/3, C3/4, or C4/5) and lower (n = 293, the most stenotic intervertebral level was C5/6, C6/7, or C7/T1) cervical stenosis groups. Propensity score matching of the baseline factors (characteristics, comorbidities, and neurological function) was performed to compare surgical outcomes, the Japanese Orthopaedic Association (JOA) scores, and visual analog scale (VAS) for neck pain between the upper (n = 135) and lower (n = 135) cervical stenosis groups. RESULTS Before propensity score matching, age at surgery was older and pre- and postoperative JOA scores were lower in the upper cervical stenosis group (P

The aim of this study was to investigate whether body weight-supported treadmill training with voluntary-driven exoskeleton body weight-supported treadmill training (VDE-BWSTT) improves the quality of life (QOL) of persons with chronic spinal cord injury (SCI). Nineteen individuals with chronic SCI with walking limitation underwent a total of 20 sessions of VDE-BWSTT using the hybrid assistant limb. The QOL was measured using the Short Form-36v2 (SF-36v2) questionnaire at preintervention and postintervention. The Walking Index for SCI-II (WISCI-II), Functional Independence Measure (FIM) motor score, and Neuropathic Pain Symptom Inventory (NPSI) self-questionnaire were also administered/completed. In SF-36v2, the mean values of all subscales in our participants were lower than those in healthy individuals. None of the measures showed significant improvement, even in individuals with some residual walking ability (baseline WISCI-II score of 6 or higher). In the correlation analysis between the baselines WISCI-II, FIM, or NPSI values and the mean SF-36v2 subscale changes throughout the training, the baseline FIM motor score was positively correlated with the mean changes in Role Emotional and Mental Health. In addition, NPSI was negatively correlated with the mean change in Vitality and Mental Health. In our protocol, although VDE-BWSTT did not improve the QOL of persons with chronic SCI, those with higher functional independence or lower pain at preintervention likely improved. Further study with combination of task-specific training or pain-targeting treatment with more patients should be considered to more effectively improve their QOL.

The primary analysis of the phase 1/2 ISLANDs study in Japanese individuals with relapsed/refractory multiple myeloma (RRMM) showed that isatuximab monotherapy was well tolerated and effective, even in participants with high-risk cytogenetic abnormalities. Here, we report a prespecified second analysis conducted 20 months after the first dosing of the last participant (ClinicalTrials.gov identifier: NCT02812706). The primary objectives were to evaluate the safety and tolerability of isatuximab in phase 1 and to evaluate the efficacy of isatuximab, including assessment of overall response rate (ORR) at the recommended dose (RD), in phase 2. In phase 1, three participants received isatuximab 10 mg/kg every week (QW) for 4 weeks/cycle followed by every 2 weeks (Q2W) and five participants received 20 mg/kg QW/Q2W. Since no dose-limiting toxicities occurred in phase 1, 20 mg/kg QW/Q2W was identified as the RD for the phase 2 study (n = 28). At the time of data cut-off, three participants (one in phase 1 and two in phase 2) continued to receive isatuximab; disease progression and treatment-related adverse events were the most common reasons for treatment discontinuation. The overall safety profile was consistent with the primary analysis. One death, not related to isatuximab treatment, was reported since the first analysis. The ORR and clinical benefit rate remained unchanged from the primary analysis at 36.4% (95% confidence interval [CI]: 20.4%-54.9%) and 54.5% (95% CI: 36.4%-71.9%), respectively. The median progression-free survival (PFS) was 5.6 months, longer than the median PFS reported in the primary analysis (4.7 months), whereas median overall survival was not reached. Overall, isatuximab 20 mg/kg QW/Q2W had an acceptable safety and tolerability profile and showed promising antitumor activity in Japanese individuals with RRMM.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

In this paper, we report a successful fabrication of a highly nonlinear chalcogenide all-solid hybrid microstructured optical fiber with polarization maintaining properties and a mid-infrared SC generation. Up to 4.5 × 10−4 at 10 µm of the fiber birefringence can be realized by employing a single As2Se3 core and two As2S5 rods horizontally aligned in the AsSe2 cladding. The fiber possesses a near-zero and flattened all-normal chromatic dispersion profile over the wavelength range from 5 to 10 µm. The polarization maintaining properties of the fiber is experimentally confirmed and a broadband supercontinuum spectrum from 2 to 10 µm in the mid-infrared window was experimentally demonstrated.

Study Design Retrospective multicenter study. Objectives Although surgery is frequently selected for the treatment of idiopathic spinal cord herniation (ISCH), its impact on functional outcomes has yet to be fully understood given the limited number of patients in previous studies. This study aims to evaluate the symptomatic history and surgical outcomes of ISCH. Setting Three institutions in Japan. Methods A total of 34 subjects with ISCH were retrospectively enrolled and followed up for at least 2 years. Demographic information, imaging findings, and clinical outcomes were collected. Functional status was assessed using the Japanese Orthopaedic Association score. Results The types of neurologic deficit were monoparesis, Brown–Sequard, and paraparesis in 5, 17, and 12 cases, with their mean disease duration being 1.2, 4.2, and 5.8 years, respectively. Significant differences in disease duration were observed between the monoparesis and Brown–Sequard groups (p

We reported the case of a 65-year-old woman who presented with neuropathic arthropathy of the elbow and had undergone cervical spinal cord tumour resection at 32 years of age. Open synovectomy with free-body resection was performed; however, the instability of the elbow joint rapidly progressed. Therefore, we performed total elbow arthroplasty (TEA) using a linked-type prosthesis. However, the humeral stem became severely loosened 1 year after arthroplasty. Furthermore, a periprosthetic humeral fracture developed due to a minor trauma. A revision TEA using a long-stem prosthesis was performed 4 years after the primary TEA. Radiographs taken 2 years after the revision surgery showed no evidence of implant loosening. In this case, early postoperative loosening occurred despite the use of a linked-type prosthesis and an appropriate cementing technique, suggesting that normal implants may not provide sufficient fixation for neuropathic arthropathy of the elbow. Since surgery for neuropathic arthropathy generally has a poor prognosis, surgical interventions including TEA should be carefully considered.

Background Selection of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial and the preoperative factors affecting the patient-reported postoperative assessment are unknown. The objective of this study was to clarify the preoperative factors affecting the two-year postoperative outcome in Meyerding grade I degenerative spondylolisthesis by using a patient-reported assessment. Methods Seventy-two consecutive patients who had 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, visual analog scales, and radiological evaluation of L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment. The prospectively collected data of postoperative 2 years were examined by statistical analysis. Results Finally, sixty-two cases (D group; 25, DF group; 37) were evaluated. There was no significant difference in JOABPEQ outcome between the two surgical groups. On the other hand, in multiple logistic regression analysis, gender, preoperative L4S, LASD, and LL were extracted as significant preoperative factors affecting the two-year postoperative outcome. Women had a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio = 0.17, p = 0.034) and psychological disability (risk ratio = 0.222, p = 0.045) compared to men. Patients with preoperative L4S greater than 5–6 mm have a lower rate of improvement in low back pain (risk ratio = 0.159, p = 0.049) and lumbar spine dysfunction due to low back pain (risk ratio = 0.188, p = 0.043). Patients with a preoperative LASD greater than 30 mm have a higher rate of improvement in postoperative low back pain (risk ratio = 20.905, p = 0.008) and lumbar dysfunction due to low back pain (risk ratio = 11.48, p = 0.021). Preoperative LL of less than 35 degrees was associated with a lower rate of improvement in gait disturbance due to low back pain (risk ratio of high lordosis to low lordosis = 11.638, p = 0.017). Conclusions In this study, the selection of operative method was not a significant factor affecting the two-year postoperative outcome and gender, preoperative L4S, LASD, and LL were extracted as significant preoperative factors.

Reoperation is usually associated with poor results and increased morbidity and hospital costs. However, the rates, causes, and risk factors for reoperation in patients undergoing lumbar spinal fusion surgery remain controversial. This study aimed to identify the risk factors for early reoperation after posterior lumbar interbody fusion surgery and to compare the clinical outcomes between patients who underwent reoperation and those who did not.We investigated a multicenter medical record database of 1263 patients who underwent posterior lumbar interbody fusion surgery between 2012 and 2015. A total of 72 (5.7%) reoperations within two years after surgery were identified and were propensity-matched for age, sex, number of fusion segments, and surgeon's experience.We analyzed a total of 114 patients (57 who underwent reoperation (R group) and 57 who did not (C group)). The mean age was 62.6 ± 13.4 years, with 78 men and 36 women. The mean number of fused segments was 1.2 ± 0.5. Surgical site infection was the most common cause of reoperation. There were significant differences in the incidence of diabetes mellitus (p = 0.024), preoperative ambulation status (p = 0.046), and ASA grade (p 0.001) between the C and R groups. The recovery rate of the Japanese Orthopaedic Association score was significantly lower in the R group compared to the C group (R: 50.5 ± 28.8%, C: 63.9 ± 33.7%, p = 0.024). There were significant differences in the bone fusion rate (R: 63.2%, C: 96.5%, p 0.001) and incidence of screw loosening (R: 31.6%; C: 10.5%; p = 0.006).Diabetes mellitus, preoperative ambulation status, and ASA grade were significant risk factors for early reoperation following posterior lumbar interbody fusion surgery. The patients who underwent early reoperation had worse clinical outcomes than those who did not.

Study design This was a prospective multicenter study. Objective The aim of this study was to investigate the perioperative complications of posterior surgeries for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL). Summary of background data Surgical treatment for cervical OPLL has a high risk of various complications. Laminoplasty (LAMP) and posterior decompression and instrumented fusion (PDF) are effective for multilevel cervical OPLL; however, few studies have focused on the surgical complications of these 2 procedures. Materials and methods We prospectively included 380 patients undergoing posterior surgeries for cervical OPLL (LAMP: 270 patients, PDF: 110 patients), and investigated the systemic and local complications, including neurological complications. We further evaluated risk factors related to the neurological complications. Results Motor palsy was found in 40 patients (10.5%), and motor palsy in the upper extremity was most frequent (8.9%), especially in patients who received PDF (14.5%). Motor palsies involving the lower extremities was found in 6 patients (1.6%). Regarding local complications, dural tears (3.9%) and surgical site infections (2.6%) were common. In the univariate analysis, body mass index, preoperative cervical alignment, fusion surgery, and the number of operated segments were the factors related to motor palsy. Multivariate analysis revealed that fusion surgery and a small preoperative C2-C7 angle were the independent factors related to motor palsy. Motor palsy involving the lower extremities tended to be found at early time points after the surgery, and all the patients fully recovered. Motor palsy in the upper extremities occurred in a delayed manner, and 68.8% of patients with PDF showed good recovery, whereas 81.3% of patients with LAMP showed good recovery. Conclusions In posterior surgeries for cervical OPLL, segmental motor palsy in the upper extremity was most frequently observed, especially in patients who received PDF. Fusion and a small preoperative C2-C7 angle were the independent risk factors for motor palsy. Level of evidence Level III.

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.

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.

Study design A retrospective study of consecutive collected data. Objective To investigate risk factors for postoperative distal adding-on (DA) in Lenke Type 1B and 1C curves using intraoperative radiographs. Summary of background data In adolescent idiopathic scoliosis (AIS), DA radiographic complication can negatively affect postoperative clinical results. However, few studies have focused on assessing risk factors for DA using intraoperative radiographs. Methods We retrospectively evaluated 69 AIS patients with Lenke Type 1B or 1C curves who underwent posterior selective thoracic fusion. We divided patients into DA and non-DA groups based on radiograph data at 2-year follow-up using Wang et al. (Spine 2011) definition of DA. We compared coronal radiographic parameters, including relative positions of end vertebra (EV), stable vertebra (SV), neutral vertebra (NV), and last touching vertebra (LTV) to lowest instrumented vertebra (LIV), and intraoperative radiographic parameters, between the two groups. Results DA was present in 13 patients (18.8%) at 2-year follow-up. The mean LIV-EV, LIV-NV, LIV-SV, and LIV-LTV relative positions were significantly smaller in the DA group than in the non-DA group. Multivariate analysis showed that LIV-LTV was significantly associated with DA (DA:-0.2 ± 0.7, non-DA: 0.6 ± 0.7). Intraoperative radiographs showed that the mean angulation of the first disc below the LIV after final adjustment was significantly larger in the DA group (2.3° ± 1.1°) than in the non-DA group (0.9° ± 0.7°). Patients whose angulation of the first disc below the LIV was more than 3° were significantly associated with DA. Conclusion The LIV selected at more cranial to the LTV may be a risk factor for postoperative DA in Lenke Type 1B and 1C curves. Moreover, it was suggested that LIV extension might be considered when the first disc's angulation below the LIV is > 3° in intraoperative radiographs.Level of Evidence: 3.

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

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

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.

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.

Introduction: Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd. Methods: We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively. Results: Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1–5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups. Discussion: The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.

Ectopic ossifications often occur in skeletal muscles or tendons following local trauma or internal hemorrhage, and occasionally cause severe pain that limits activities of daily living. However, mechanisms underlying their development remain unknown. Here we show that dissection of the Achilles tendon promotes ectopic ossification at dissection sites in wild-type mice. We observed mTOR activation at dissection sites, and development of ectopic ossification was significantly inhibited by administration of rapamycin, an mTOR inhibitor, to wild-type mice. Moreover, administration of the histamine 2 blocker cimetidine, which reportedly inhibits ectopic ossification in tendons, was not effective in inhibiting ectopic ossification in our models. The inflammatory cytokine TNFα reportedly stimulates mTOR signaling, and we show that TNFα-expressing F4/80-positive macrophages accumulate at dissection sites and that ectopic ossification of the Achilles tendon dissection was significantly inhibited in TNFα-deficient mice in vivo. We also show that ectopic ossification is significantly inhibited by administration of either celecoxib or loxoprofen, both anti-inflammatory agents, in wild-type mice. Finally, we report that mTOR activation by Achilles tendon tenotomy is inhibited in TNFα-deficient mice. Thus, the TNFα-mTOR axis could be targeted therapeutically to prevent trauma-induced ectopic ossification in tendons.

Since osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity.We reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cmAll patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L-L group; preoperative 0.79 ± 0.05 g/cmOf AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis.

LBX1 is a gene located near a single-nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis-like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice.

BackgroundRheumatoid arthritis (RA) is a disease characterized by chronic joint inflammation, pain and joint destruction, leading to alteration in activities of daily living, yet pathological mechanisms underlying the condition are not fully clarified. To date, various therapeutic agents have been developed as RA therapy including DMARDs and/or biological agents that target inflammatory cytokines or inhibit JAK. Here we asked whether inhibiting signal transducer and activator of transcription 3 (Stat3) activity would antagonize RA. MethodsStat3 forms dimers when activated and undergoes nuclear translocalization; thus we screened approximately 4.9 million small compounds as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening. We then tested candidate Stat3-inhibiting activity in vitro by analyzing expression of IL-6, a Stat3 target, in compound-treated fibroblasts. We also analyzed expression of RANKL, a cytokine essential for osteoclastogenesis, in vitro. We then evaluated anti-arthritis effects of candidate compounds in vivo in collagen-induced arthritis model mice. Effects of the candidate compounds on inhibiting Stat3 phosphorylation and nuclear localization following IL-6 stimulation of fibroblasts were analyzed by an immune histocochemical analysis as well as western blotting.ResultsWe identified 15 as strong candidates as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening from approximately 4.9 million small compounds. Four of the 15 significantly inhibited IL-6 as well as RANKL expression induced by IL-6. One compound, F0648-0027, significantly inhibited arthritis development without apparent adverse effects. F0648-0027 also significantly blocked Stat3 phosphorylation and nuclear localization following IL-6 stimulation of fibroblasts. ConclusionsThese data suggest that Stat3 is a target for RA, and that F0648-0027 could serve as a therapeutic reagent against the condition.