Bone metastatic lesions are classified as osteoblastic or osteolytic lesions. Prostate and breast cancer patients frequently exhibit osteoblastic-type and osteolytic-type bone metastasis, ...respectively. In metastatic lesions, tumor cells interact with many different cell types, including osteoblasts, osteoclasts, and mesenchymal stem cells, resulting in an osteoblastic or osteolytic phenotype. However, the mechanisms responsible for the modification of bone remodeling have not been fully elucidated. MicroRNAs (miRNAs) are transferred between cells via exosomes and serve as intercellular communication tools, and numerous studies have demonstrated that cancer-secreted miRNAs are capable of modifying the tumor microenvironment. Thus, cancer-secreted miRNAs can induce an osteoblastic or osteolytic phenotype in the bone metastatic microenvironment. In this study, we performed a comprehensive expression analysis of exosomal miRNAs secreted by several human cancer cell lines and identified eight types of human miRNAs that were highly expressed in exosomes from osteoblastic phenotype-inducing prostate cancer cell lines. One of these miRNAs, hsa-miR-940, significantly promoted the osteogenic differentiation of human mesenchymal stem cells in vitro by targeting ARHGAP1 and FAM134A. Interestingly, although MDA-MB-231 breast cancer cells are commonly known as an osteolytic phenotype-inducing cancer cell line, the implantation of miR-940–overexpressing MDA-MB-231 cells induced extensive osteoblastic lesions in the resulting tumors by facilitating the osteogenic differentiation of host mesenchymal cells. Our results suggest that the phenotypes of bone metastases can be induced by miRNAs secreted by cancer cells in the bone microenvironment.
A retrospective cohort study.
The aim of this study is to investigate the preoperative factors for postlaminoplasty kyphotic deformity in cervical spondylotic myelopathy (CSM) patients without ...preoperative kyphotic alignment focused on the cervical sagittal balance.
After laminoplasty (LAMP), appropriate decompression may be obtained when cervical lordosis is maintained to allow the posterior shift of the spinal cord. Therefore, LAMP is not suitable for patients with preoperative cervical kyphosis. However, we sometimes encounter patients who developed postoperative kyphosis despite normal preoperative alignment. The risk factors of postlaminoplasty kyphotic deformity for the patients without preoperative kyphotic alignment are not well known.
A total of 174 consecutive patients who received a double-door LAMP for CSM without preoperative kyphotic alignment and completed a 1-year follow-up were enrolled. Cervical lateral X-ray images obtained in the standing position were measured at the preoperative stage and during a 1-year follow-up visit. The radiographic measurements included the following: (1) C2-7 lordotic angle (C2-7 angle), (2) C2-7 range of motion (C2-7 ROM), (3) CGH (center of gravity of the head)-C7 SVA, and (4) C7 slope. The clinical results were evaluated using the Japanese Orthopedic Association score system for cervical myelopathy (C-JOA score).
Postoperative kyphotic deformity was observed in 9 patients (5.2%). The recovery rates of the C-JOA scores at the 1-year follow-up period in the kyphotic deformity (+) group were inferior to those of the kyphotic deformity (-) group. The CGH-C7 SVA and advanced age were detected as preoperative risk factors using multivariate analysis. Cutoff values for predicting postlaminoplasty kyphotic deformity were a CGH-C7 SVA = 42 mm and an age of 75 years.
Cervical sagittal imbalance and advanced age were the preoperative risk factors for kyphotic deformity after LAMP for CSM in patients without preoperative cervical kyphotic alignment.
4.
Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O
content in tissues through ...increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO
, VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3-7 days and muscle healing at 5-7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.
To describe the effectiveness and risk management of remote rehabilitation for coronavirus disease (COVID-19) patients.
Single-centre, retrospective, observational study.
COVID-19 patients undergoing ...rehabilitation (24 April to 24 May 2020).
All COVID-19 inpatients undergoing rehabilitation in the general ward were assessed. Data were collected on age, sex, physical ability, rehabilitation modality (remote/direct), need for intubation or extracorporeal membrane oxygenation, degree of pneumonia, oxygen therapy from the start of rehabilitation, D-dimer and C-reactive protein levels, and rehabilitation-related complications. Activities of daily living were measured using the Barthel Index.
Out of a total of 43 patients, 14 were initially provided with remote rehabilitation and 29 with direct rehabilitation. Four patients were switched from direct to remote rehabilitation during the study, thus at the end of the study there were 18 in the remote rehabilitation group and 25 in the direct rehabilitation group. Patients in remote rehabilitation were significantly younger than those in direct rehabilitation. Of 12 patients who required intubation, 3 were given remote rehabilitation. One extracorporeal membrane oxygenation survivor underwent direct rehabilitation. All patients on remote rehabilitation were discharged home or to a hotel. Twelve out of 29 patients were transferred to a rehabilitation hospital due to delayed recovery of activities of daily living. No serious adverse events occurred.
Effective and safe remote rehabilitation was performed in 41.9% of COVID-19 patients in this study, which resulted in improved rehabilitation in COVID-19 zones.
This was a retrospective observational study.
To assess the diagnostic value of procalcitonin (PCT) and neutrophil lymphocyte ratio (NLR) for predicting surgical site infection (SSI) in patients ...undergoing spinal instrumentation surgery, we analyzed a large consecutive cohort of patients who had undergone spinal instrumentation surgery.
Although PCT and NLR are commonly used as markers for bacterial infection, the diagnostic value of these factors for predicting SSI in the context of spinal instrumentation surgery has not been extensively investigated.
We retrospectively investigated 242 patients who underwent spinal instrumentation surgery and evaluated the significance of various postoperative measures for predicting SSI, including PCT and NLR. We then determined the diagnostic cut-off values for these markers in the prediction of SSI using receiver operating characteristic curve analysis.
Among the 242 patients analyzed, 10 were diagnosed with infection. Even though univariate analysis showed that neutrophil percentage and NLR at 6 to 7 days postoperatively were significant predictors for SSI, PCT at 6 to 7 days postoperatively did not differ significantly between the SSI and non-SSI groups. The cut-off value used for neutrophil percentage at 6 to 7 days postoperatively was more than 69.0% sensitivity, 80.0%; specificity, 70.0%; area under the curve, 0.737. The cut-off value used for NLR at 6 to 7 days postoperatively was 3.87 (sensitivity, 70.0%; specificity, 73.2%; area under the curve, 0.688).
Neutrophil percentage and NLR at 6 to 7 days postoperatively were more useful markers than PCT at 6 to 7 days postoperatively for early prediction of SSI in patients who had undergone spinal instrumentation surgery. Therefore, routine use of PCT as a predictor of postoperative infection is not supported by the results of this study.
4.
Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis.
The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, ...CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study.
Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL.
Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain.
Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples.
Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL.
N/A.
This study aimed to determine differences in the hip abductor muscle activity during clam exercise at different hip flexion and femoral anteversion angles. Thirty healthy females were divided into ...two groups based on the femoral anteversion angle: the excessive femoral anteversion group and the normal group. Clam exercise was performed at three different hip flexion angles (60°, 45°, and 30°). Tensor fascia latae, gluteus medius, and superior portion of gluteus maximus activities were measured during the exercise, and the results were normalized to the activity during maximum voluntary isometric contraction to calculate the gluteal-to-tensor fascia latae muscle activation index. The superior portion of gluteus maximus activities at a hip flexion of 60° and 45° were greater than that at 30°. The excessive femoral anteversion group had a lower gluteal-to-tensor fascia latae muscle activation index than the normal group; the gluteal-to-tensor fascia latae muscle activation index for hip flexion at 60° was higher than that at 45°, and the gluteal-to-tensor fascia latae muscle activation index for hip flexion at 60° and 45° were higher than that at 30°. Therefore, the femoral anteversion angle and hip joint position were related to the activity of the hip abductor muscles during clam exercise. These findings may provide a rationale for instructing exercises to maximize the activity of the hip abductor muscles in individuals with an excessive femoral anteversion angle.
Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue injuries. However, the healing mechanism is unclear. Here we assessed the effects of HBO on contused calf muscles in a rat ...skeletal muscle injury model. An experimental HBO chamber was developed and rats were treated with 100% oxygen, 2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb volume and muscle wet weight in contused muscles, and promoted muscle isometric strength 7 days after injury. HBO suppressed the elevation of circulating macrophages in the acute phase and then accelerated macrophage invasion into the contused muscle. This environment also increased the number of proliferating and differentiating satellite cells and the amount of regenerated muscle fibers. In the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused muscles. Our results demonstrate that HBO has a dual role in decreasing inflammation and accelerating myogenesis in muscle contusion injuries.
Prospective, comparative clinical study.
To compare the clinical outcome of anterior decompression and fusion with floating method and laminoplasty in the treatment of cervical myelopathy caused by ...ossification of the posterior longitudinal ligament (OPLL).
There have been no reports that have accurately and prospectively compared surgical outcomes after anterior decompression and posterior decompression.
For cervical myelopathy caused by OPLL, we performed anterior decompression and fusion with floating method (ADF) in 1997, 1999, 2001, 2003, and 2004 and French-door laminoplasty (LAMP) in 1996, 1998, 2000, and 2002 at one institution. Twenty patients in the ADF group and 22 patients in the LAMP group were evaluated for 5 years' follow-up. The following criteria were evaluated: operation time, blood loss, complications, and Japanese Orthopedic Association score. For radiographic evaluation, canal narrowing ratio of OPLL, lordotic angle at C2-C7, and postoperative progression of the ossified lesion were measured.
The operation time in the ADF group was longer than that in the LAMP group. The average blood loss showed no statistical difference between the 2 groups. Complications occurred in 5 cases in the ADF group, but none occurred in the LAMP group. The mean Japanese Orthopedic Association score system for cervical myelopathy and the recovery rate in the ADF group were superior to those in the LAMP group, especially for cases with greater than 50% of the spinal canal compromised by OPLL or kyphotic alignment of the cervical spine, preoperatively. Postoperative progression of OPLL was observed in 5% of the ADF group and 50% of the LAMP group.
ADF is considered especially suitable for cases with massive OPLL and preoperative kyphotic alignment of the cervical spine, although it leads to a higher incidence of surgery-related complications compared with LAMP.