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Current treatment options for osteoporosis primarily involve pharmacotherapies, but they are often accompanied by undesirable side effects. Utilization of mechanical stress which can noninvasively induce bone formation has been suggested as an alternative to conventional treatments. Here, we examined the efficacy of mechanical stress induced by electrical stimulation, radial extracorporeal shock waves, and ultrasound for estrogen-deficient osteoporosis. Female Wistar rats were divided into following five groups: sham-operated group, untreated after ovariectomy, and treated with electrical stimulation, radial extracorporeal shock wave, or ultrasound starting at 8 weeks after ovariectomy for 4 weeks. Trabecular bone architecture of the femur was assessed by micro-CT and its biomechanical properties were obtained by mechanical testing. The femurs were further evaluated by histochemical, immunohistochemical, and real-time PCR analyses. Radial extracorporeal shock wave and ultrasound treatment improved trabecular bone microarchitecture and bone strength in osteoporotic rats, but not electrical stimulation. The shock wave decreased osteoclast activity and RANKL expression. The exposure of ultrasound increased osteoblast activity and β-catenin-positive cells, and they decreased sclerostin-positive osteocytes. These findings suggest that mechanical stress induced by radial extracorporeal shock wave and ultrasound can improve estrogen-deficient bone loss and bone fragility through promoted bone formation or attenuated bone resorption.

Background Gait–balance disturbances are core symptoms of idiopathic normal pressure hydrocephalus (iNPH). However, the rehabilitation effects of cerebrospinal fluid (CSF) shunting along with other treatment or no further treatment (natural course [NC]) for iNPH are unknown. Objectives This study evaluated whether dynamic equilibrium gait training (DEGT) can improve gait–balance functions after CSF shunting of patients with iNPH compared to standard exercise (SE) and NC. Furthermore, it investigated the incidence of falls. Methods A total of 70 patients with iNPH who underwent CSF shunting were randomly assigned to 6 weeks of DEGT ( n  = 23), 6 weeks of SE ( n  = 23), or NC ( n  = 24). Evaluation was performed at baseline (preoperatively) and at 1 week, 7 weeks (postintervention), and 6 months postoperatively (follow-up). Outcomes were measured using the functional gait assessment (FGA), 10-m walk test, timed up-and-go test, life-space assessment (LSA), and fall incidence. Results A total of 65 participants completed the study. During the intention-to-treat analysis, the DEGT group demonstrated significant recovery of gait–balance functions according to only the FGA at postintervention and follow-up compared to the SE and NC groups; however, recovery of the SE group did not differ from that of the NC group. The DEGT group had a significantly lower fall incidence than the other groups at follow-up. Significantly better LSA results were observed for all groups at follow-up compared to baseline; however, no difference in LSA results were observed between groups. Conclusions DEGT in addtion to CSF shunting can facilitate the recovery of gait–balance function and reduce the fall incidence of iNPH patients.

Background Older adults are more likely to experience loneliness than younger people. Moreover, greater loneliness in older adults is associated with poor mental health and increased risk of cardiovascular disease and mortality. Physical activity is an effective intervention for reducing loneliness among older adults. Among physical activities, walking is suitable for older adults, because it is easy and safe to incorporate into daily life. We hypothesized that the association between walking and loneliness depends on the presence of others and the number of people present. The aim of this study is to investigate the association between the context of walking (the number of walkers) and loneliness among community-dwelling older adults. Methods This cross-sectional study included 173 community-dwelling older adults aged 65 or older. Context of walking was classified as non-walking, walking alone (days of walking alone > days of walking with someone), and walking with someone (days of walking alone ≤ days of walking with someone). Loneliness was measured using the Japanese version of the University of California Los Angeles Loneliness Scale. A linear regression model was used to investigate the relationship between context of walking and loneliness, adjusted for age, sex, living situation, social participation, and physical activity excluding walking. Results Data from 171 community-dwelling older adults (mean age = 78.0 years, 59.6% women) were analyzed. After adjustment, walking with someone was associated with lower loneliness than non-walking (adjusted β: -0.51, 95% confidence interval: -1.00, -0.01). Conclusions The study’s findings suggest that walking with a companion may effectively prevent or reduce loneliness among older adults.

A correction to this paper has been published: https://doi.org/10.1007/s00223-021-00867-8

•iNPH-associated gait and balance disturbances can increase the risk of falling.•The factors influencing falls in patients with iNPH remain unclear.•Advanced age and gait-balance instability increased the risk of falling.•Our findings may help identify patients who are at high risk of falling.•This will allow the implementation of suitable prevention strategies. The factors influencing falls in idiopathic normal pressure hydrocephalus (iNPH) remain unclear, although iNPH-associated gait and balance disturbances can lead to an increased risk of falls. This study aimed to investigate the associations among fall status, gait variability, balance function in iNPH, and to identify fall-related factors in iNPH. Sixty-three patients with iNPH with a positive cerebrospinal fluid tap test result according to the iNPH diagnosis criteria participated in this prospective cross-sectional study. Patients were assessed using the 10-meter walk test (10MWT), the Functional Gait Assessment (FGA), the Berg Balance Scale (BBS), and the isometric quadriceps strength (QS). We also investigated each patient’s history of falls in the past 6 months. Gait variability was measured using a triaxial accelerometer attached to the patient’s torso at the L3 vertebra level during the 10MWT. Fall status correlated significantly with gait variability (measured as the coefficient of variation; CV) in step time and movement trajectory amplitude (i.e., center of mass movement) in the medial/lateral (ML) and vertical (VT) directions, with balance function as assessed by FGA and BBS scores. In contrast, QS was not correlated with fall status. The independent variables associated with the risk of falling were step time CV, FGA score, and age. The factors associated with the risk of falling in iNPH were aging and gait-balance instability, particularly temporal gait variability and dynamic balance dysfunction. Our results may enable physicians to identify the patients with iNPH who are at risk of falling and implement suitable prevention strategies.

Soft tissue sarcomas (STSs) are rare heterogeneous malignancies of mesenchymal origin. Pulmonary metastases develop in approximately 50% of the patients with high-grade STS, being the major cause of mortality in patients with metastatic STS. Pulmonary metastasectomy has been reported to contribute to long-term survival; however, an appropriate treatment has not been established. We aimed to identify factors associated with post-metastasis survival in STS patients with pulmonary metastasis and determine the appropriate treatment for each patient. We retrospectively reviewed the records of metastatic STS patients treated between 2000 and 2017 and analyzed the clinico-pathologic variables to identify factors associated with the survival. The median survival after pulmonary metastasis was 20.6 months, and the 1-, 3-, and 5-year survival rates were 68.6%, 36.0%, and 25.1%, respectively. The survival was significantly greater in patients who underwent pulmonary metastasectomy than in those without surgery (38.9 months vs. 10.5 months; p < 0.0001). Among those who did not undergo surgery, the survival was significantly greater in patients who received chemotherapy than in those without chemotherapy (19.1 months vs. 6.3 months, p = 0.037). Multivariate analysis identified pulmonary metastasectomy as the most important prognostic factor for post-metastasis survival (Hazard ratio 5.623; 95% Confidence Interval 2.733–11.572; p < 0.0001). In conclusion, pulmonary metastasectomy was the most important prognostic factor for post-metastasis survival in patients with metastatic STS. In addition, chemotherapy could prolong survival in patients who were not eligible for pulmonary resection. Although we should carefully weigh the risks and benefits, appropriate treatment for pulmonary metastases could contribute to long-time survival.

The purpose of the present study was to determine the effects of transcutaneous CO2 application on the blood flow and capillary architecture of the soleus muscle in rats with streptozotocin (STZ)-induced hyperglycemia. Wistar rats were randomly divided into four groups: control, control + CO2-treated, STZ-induced hyperglycemia, and STZ-induced hyperglycemia + CO2-treated groups. Blood flow in soleus muscle increased during the transcutaneous CO2 exposure, and continued to increase for 30 min after the treatment. In addition, the transcutaneous CO2 attenuated a decrease in capillary and the expression level of eNOS and VEGF protein, and an increase in the expression level of MDM-2 and TSP-1 protein of soleus muscle due to STZ-induced hyperglycemia. These results indicate that the application of transcutaneous CO2 could improve capillary regression via the change of pro- and anti-angiogenesis factors, which might be induced by an increase in blood flow.

We herein describe soft tissue tumor arising in the lower extremity of a pediatric patient. The tumor displayed a unique and wide range of histological features, sheet-like and cohesive growth pattern consisting of enlarged round to epithelioid atypical cells with a large alveolar and pseudopapillary histological architecture, focally mimicking alveolar soft part sarcoma and MiT family translocation renal cell carcinoma. Tumor cells were focally immunoreactive for cytokeratin, S-100, and EMA. RNA sequencing identified a novel in-frame NR1D1 (exon 5)-MAML1 (exon 2) gene rearrangement resulting in the formation of a putative chimeric protein containing the N-terminal C4-type zing finger domains of NR1D1 and the C-terminal MAML1 protein, which was confirmed by subsequent RT-PCR, Sanger sequencing, and FISH assay. To the best of our knowledge, NR1D1-MAML1 fusion has not yet been described in any neoplasms, suggesting the emergence of a novel tumor entity.

Background and Objectives: Bone metastasis cancer boards (BMCBs) focusing on the management of bone metastases have been gathering much attention. However, the association of BMCBs with spinal surgery in patients with spinal metastases remains unclear. In this retrospective single-center observational study, we aimed to clarify the effect of a BMCB on spinal metastasis treatment. Materials and Methods: We reviewed consecutive cases of posterior decompression and/or instrumentation surgery for metastatic spinal tumors from 2008 to 2019. The BMCB involved a team of specialists in orthopedics, rehabilitation medicine, radiation oncology, radiology, palliative supportive care, oncology, and hematology. We compared demographics, eastern cooperative oncology group performance status (ECOGPS), Barthel index (BI), number of overall versus emergency surgeries, and primary tumors between patients before (2008–2012) and after (2013–2019) BMCB establishment. Results: A total of 226 patients including 33 patients before BMCB started were enrolled; lung cancer was the most common primary tumor. After BMCB establishment, the mean patient age was 5 years older (p = 0.028), the mean operating time was 34 min shorter (p = 0.025), the mean hospital stay was 34.5 days shorter (p < 0.001), and the mean BI before surgery was 12 points higher (p = 0.049) than before. Moreover, the mean number of surgeries per year increased more than fourfold to 27.6 per year (p < 0.01) and emergency surgery rates decreased from 48.5% to 29.0% (p = 0.041). Patients with an unknown primary tumor before surgery decreased from 24.2% to 9.3% (p = 0.033). Postoperative deterioration rates from 1 to 6 months after surgery of ECOGPS and BI after BMCB started were lower than before (p = 0.045 and p = 0.027, respectively). Conclusion: The BMCB decreased the emergency surgery and unknown primary tumor rate despite an increase in the overall number of spinal surgeries. The BMCB also contributed to shorter operation times, shorter hospital stays, and lower postoperative deterioration rates of ECOGPS and BI.

Background The prognosis of patients with metastatic or advanced sarcomas is poor and there are few options for treatment. Several studies have shown that gemcitabine and docetaxel (GD) combination chemotherapy has antitumor activity against various subtypes of sarcoma. Recently, some studies have shown a favourable outcome for GD combination chemotherapy for relapsed high-grade osteosarcoma and spindle cell sarcoma of bone. If the effectiveness of GD is proven, this will result in new treatment options for advanced bone and soft tissue sarcomas (STS). The aim of this prospective Phase 2 study is to evaluate the efficacy and toxicity of the GD combination in patients with advanced bone sarcomas and STS. Methods This is a Phase 2, single-arm, open-label study to investigate the efficacy and safety of combination chemotherapy with GD for advanced bone sarcomas and STS and will enrol 20 patients. The patients will receive gemcitabine 900 mg/m 2 on Days 1 and 8, and docetaxel 70 mg/m 2 on Day 8 in 3-week cycles until disease progression or other evidence of treatment failure. The primary aim of this study is to analyse GD’s effect on progression-free survival (PFS). The secondary objectives are to analyse treatment efficacy and safety in terms of response rate, tumour control rate, overall survival, and adverse event rate. The length of follow-up will be 5 years. Discussion This study will evaluate the efficacy and safety of combination therapy with gemcitabine and docetaxel for bone sarcomas and STS. If this combination proves to be acceptable, it could be used for as second, third, or later line therapy for patients with sarcomas (especially bone sarcomas). In the future, the role of various treatments, including GD therapy, will be clarified for specific subtypes of sarcoma. Trial registration This study was registered as UMIN000031004 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 1 March 1 2018 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs051180042 on 30 January 2019. The posted information will be updated as needed to reflect protocol amendments and study progress.