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The addition of elotuzumab (a monoclonal antibody against SLAMF7) to lenalidomide plus dexamethasone produced a significant increase in progression-free survival as compared with lenalidomide plus dexamethasone alone. Multiple myeloma, a malignant disease of monoclonal plasma cells, has a median overall survival of approximately 5 years. 1 Despite improvements in treatment outcomes with proteasome inhibitors and immunomodulatory drugs, most patients continue to have a relapse, and new treatment approaches are needed. Combination therapy may be key to overcoming drug resistance and improving long-term treatment outcomes. Lenalidomide, an immunomodulatory drug, in combination with dexamethasone is a standard regimen in patients with relapsed or refractory disease. 2 , 3 Three-drug combinations are emerging for patients with previously treated multiple myeloma 3 but may be limited by toxic effects. Agents with new mechanisms of action . . .

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.

Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival. Sarcomas are rare malignant tumours of bone and soft tissue whose diagnosis remain difficult. Here, the authors analyse serum samples from over 1000 patients and using separate discovery, training and validation cohorts, identify and validate a 7-microRNA index that distinguishes malignant sarcomas from benign disease.

Pain is an undesirable sensory experience that can induce depression and limit individuals’ activities of daily living, in turn negatively impacting the labor force. Affected people frequently feel pain during activity; however, pain is subjective and difficult to judge objectively, particularly during activity. Here, we developed a system to objectively judge pain levels in walking subjects by recording their quantitative electroencephalography (qEEG) and analyzing data by machine learning. To do so, we enrolled 23 patients who had undergone total hip replacement for pain, and recorded their qEEG during a five-minute walk via a wearable device with a single electrode placed over the Fp1 region, based on the 10–20 Electrode Placement System, before and three months after surgery. We also assessed subject hip pain using a numerical rating scale. Brain wave amplitude differed significantly among subjects with different levels of hip pain at frequencies ranging from 1 to 35 Hz. qEEG data were also analyzed by a support vector machine using the Radial Basis Functional Kernel, a function used in machine learning. That approach showed that an individual’s hip pain during walking can be recognized and subdivided into pain quartiles with 79.6% recognition Accuracy. Overall, we have devised an objective and non-invasive tool to monitor an individual’s pain during walking.

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 μg·mL−1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 μg·mL−1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Little is known about the effects of posterior tethers on the development of proximal junctional kyphosis (PJK). We evaluated the ability of posterior tethers to the proximal motion segment stiffness in long instrumented spinal instrumentation and fusion using a whole body human FE model. A series of finite element (FE) analysis of long segmental spinal fusion (SF) from the upper thoracic vertebra (T1) or lower thoracic vertebra (T9) to the sacrum with pedicle screws and rods were performed using an entire human body FE model (includes 234,910 elements), and compressive stresses (CS) on the anterior column, and tensile stresses (TS) on the posterior ligamentous complex (PLC) in the upper-instrumented vertebra (UIV) and the vertebra adjacent to the UIV (UIV + 1) were evaluated with posterior tethers or without posterior tethers. The models were tested at three T1 tilts (0, 20, 40 deg.), with 20% muscle contraction. Deformable material models were assigned to all body parts. Muscle-tendon complexes were modeled by truss elements with a Hill-type muscle material model. The CS of anterior column decreased with increasing T1 slope with tethers in both models, while the CS remained relatively large in T9 model compared with T1 model (T1 UIV; 0.96 to 1.56 MPa, T9 UIV; 4.79 to 5.61 MPa). The TS of the supraspinous ligament was markedly reduced in both T1 and T9 models with posterior tethers (11–35%). High vertebral CS on UIV and UIV + 1 were seen in the T9 UIV model, and the TS on the PLC were increased in both UIV models. Posterior tethers may decrease PJK development after SF with a proximal thoracic UIV, while both posterior tethers and vertebral augmentation may be necessary to reduce PJK development with a lower thoracic UIV.

Prolonged computer work and smartphone use can cause stiffness of the neck and shoulder muscles, including the trapezius muscle. Hence, muscle hardness quantification is clinically beneficial. The present study aimed to examine the reliability of trapezius muscle hardness measurement using a portable muscle hardness meter and ultrasound strain elastography. Overall, 20 healthy young men participated in this study. Prior to measurement, the participant’s subjective symptoms, particularly shoulder muscle stiffness, were rated using an 11-point verbal scale. Furthermore, hardness of the right and left upper trapezius muscles was assessed. In the strain elastography assessment, muscle hardness was evaluated using strain ratio. Results showed that, in quantifying upper trapezius muscle hardness, both portable muscle hardness meter and strain elastography had an excellent intra-tester reliability (>0.9). However, the correlation coefficients between muscle hardness values assessed using a muscle hardness meter and those evaluated with strain elastography did not significantly differ, and the scores for subjective shoulder stiffness did not correspond to muscle hardness values. Therefore, the hardness of the trapezius muscle does not directly reflect the subjective shoulder stiffness. Future studies should thoroughly examine the location of the shoulder stiffness, and check whether it is accompanied by local pain or tenderness.

BackgroundMyxofibrosarcoma is a common sarcoma among older patients, with locally infiltrative behavior and a predilection for local postoperative recurrence. Some studies have reported the factors affecting prognosis, although only a few have mentioned the previous staging classification systems. This study investigated the clinical overview and prognosis of myxofibrosarcoma to determine the optimal treatment.MethodsThis retrospective study analyzed the records of 349 patients with myxofibrosarcoma in the nationwide Bone and Soft Tissue Tumor Registry in Japan from 2006 to 2015. Clinical features, treatment options, and patient outcomes were investigated.ResultsUltimately, 349 patients were identified. The overall survival rates were 93.1% at 2 years and 84.3% at 5 years. A multivariate analysis was performed using the Cox proportional hazards model. The study identified four significant prognostic factors for survival: tumor size, depth, compartment status, and location. The prognostic score was calculated by summing the scores of all the factors. The overall survival rate was 69.3% at 5 years for the patients with prognostic scores of 6 or higher. Conversely, the patients with prognostic scores of 2 or lower had a survival rate of 95.6% at 5 years.ConclusionsAmong myxofibrosarcomas, those larger than 5 cm, deep-seated, invaded into the external compartment, or in axial body parts were associated with a significantly worse prognosis. Adjuvant radiotherapy and chemotherapy did not contribute significantly to a better prognosis. Previous staging classification systems are impractical for prognosis prediction. Therefore, new classifications are needed. Further research on new treatment methods for patients with a poor prognosis will be crucial in the future.

Study designRetrospective cohort study.ObjectivesAlthough intramedullary astrocytoma is associated with a high mortality rate, the optimal treatment has not reached a consensus. This study aimed at evaluating neurologic function and overall survival rate (OSR) in the treatment of this tumor.SettingThe single institution in Japan.MethodsThis study enrolled 67 subjects who underwent surgical treatment for intramedullary astrocytoma. Demographic, imaging, and surgical information were collected from each participant. Tumors were histologically categorized using the World Health Organization classification, and subjects were divided into low-grade (I and II; n = 40) and high-grade (III and IV; n = 27) groups. Neurologic status was evaluated using the modified McCormick scale (MMS). OSR was assessed using Kaplan–Meier methods.ResultsThe OSR decreased when the pathological grade increased (p < 0.01). Regarding the therapeutic efficacy for low-grade astrocytomas, subjects who underwent gross total resection (GTR) showed a higher OSR than those who did not (p = 0.02). GTR prevented worsening of MMS score, while non-GTR increased the MMS score (p < 0.01). In the high-grade group, 19 and 10 underwent radiation therapy and chemotherapy, respectively. However, both treatments did not improve OSR. Cordotomy was performed for subjects whose lesional area was at the thoracic level, but the OSR did not significantly increase.ConclusionsThe most beneficial therapeutic strategy for low-grade astrocytomas was GTR, whereas that for the high-grade tumors was unclear. Further studies with a larger sample size are warranted to validate the effective treatment for malignant astrocytomas.

Vitamin D deficiency is a recognized risk factor for sarcopenia development, but mechanisms underlying this outcome are unclear. Here, we show that low vitamin D status worsens immobilization-induced muscle atrophy in mice. Mice globally lacking vitamin D receptor (VDR) exhibited more severe muscle atrophy following limb immobilization than controls. Moreover, immobilization-induced muscle atrophy was worse in neural crest-specific than in skeletal muscle-specific VDR-deficient mice. Tnfα expression was significantly higher in immobilized muscle of VDR-deficient relative to control mice, and was significantly elevated in neural crest-specific but not muscle-specific VDR-deficient mice. Furthermore, muscle atrophy induced by limb immobilization in low vitamin D mice was significantly inhibited in Tnfα-deficient mice. We conclude that vitamin D antagonizes immobilization-induced muscle atrophy via VDR expressed in neural crest-derived cells.