Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4–not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3–1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4–26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better than previously reported data of TRS. These facts suggest that trabectedin become an important choice of treatment for patients with advanced EMCS or MCS who failed or were intolerable to standard chemotherapy. The randomized phase 2 study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121850 (May 31, 2012).

Background: Treatment for patients with locally recurrent soft tissue sarcomas after wide resection is challenging, and few studies have examined the results of treating these patients. In treatment of recurrent tumors, it has been reported that positive margins are correlated to local rerecurrence, but the relationship between surgical margin and survival remains controversial and risk factors for local recurrences after wide resection of soft tissue sarcomas are not well established. This study examined clinical outcomes and factors associated with survival and local rerecurrence in patients with local recurrence after initial surgical treatment who underwent another resection with a goal of negative margins. Questions/purposes: The purpose of this study was to determine (1) oncologic outcomes (survival rates and local rerecurrence-free rates) of surgical treatment for patients with local recurrence after wide resection; (2) whether factors associated with survival and local rerecurrence-free rates can be determined; and (3) the proportion of patients treated by amputation at final followup. Methods: Between 1992 and 2013, we treated 530 patients with soft tissue sarcoma without metastasis. Of those, 26 (5%) were lost before 3 years of followup but were not known to have died. Of the remainder, 59 have had a local recurrence. Of those with a local recurrence, 34 (58%) were treated with wide resection, whereas 25 (42%) were treated with nonsurgical treatment including chemotherapy and radiotherapy. During that period, our general indications for wide resection were patients (1) without distant metastasis; or (2) without distant lymph node metastasis, and contraindications were distant organ metastasis and/or distant lymph node metastasis. Of those treated with wide resection, 30 (88%) were available for followup. We conducted a retrospective analysis of these 30 patients with local recurrence (17 men, 13 women) who had previously undergone wide resection. Patient followup ranged from 1 to 12 years (median, 5 years). Survivorship (including overall survival and survival free from repeat recurrence) was ascertained by the Kaplan-Meier method. Factors associated with survival were evaluated by the log-rank test. Amputations were performed when limb-sparing surgery was deemed unsuitable because of extensive involvement of the limb by tumor, including invasion of multiple muscle compartments and neurovascular components. Survivorship free from amputation was ascertained by the Kaplan-Meier method. Results: Overall 5- and 10-year Kaplan-Meier survival rates after resection were 70% (95% confidence interval [CI], 50%-91%) and 44% (95% CI, 12%-76%), respectively, and 12 patients (40%) developed distant metastases after the second operation. Ten patients (33%) had additional local recurrences, and overall 5- and 10-year local rerecurrence-free rates were 66% (95% CI, 48%-85%) and 50% (95% CI, 18%-81%), respectively. A positive margin was associated with further recurrence (5-year local rerecurrence-free rates of positive margin: 20% [95% CI, 0%-52%], negative margin: 89% [95% CI, 74%-100%], p < 0.01) and with survival (5-year survival rates of positive margin: 36% [95% CI, 0%-75%], negative margin: 91% [95% CI, 74%-100%], p < 0.01). The survival rate was lower in patients with recurrence developing after 2 years (5-year survival rates of within 2 years: 46% [95% CI, 2%-90%], after 2 years: 83% [95% CI, 62%-100%], p = 0.01). The overall 5- and 10-year amputation-free rates were 86% (95% CI, 74%-99%) and 81% (95% CI, 67%-96%), respectively. Conclusions: A surgical procedure with negative margins appears to be important for reducing the likelihood of local recurrences and improving survival of patients with rerecurrence after wide resection of soft tissue sarcomas. Although these findings need to be confirmed in larger studies, it appears that when tumor recurrence is evident within 2 years from the primary surgery, it is associated with a poor prognosis. Local recurrence within 2 years after wide resection may also be an indicator of aggressive tumor biology. Level of Evidence: Level IV, therapeutic study.

There is evidence that social relationships may modify cognitive decline in older people. We examined the prospective association between social support and cognitive function among community-dwelling older people. Japanese adults recruited at health checkups in suburban towns were surveyed at baseline and one-year follow-up. Cognitive function was assessed using the Montreal Cognitive Assessment, Japanese version (MoCA-J). Social support from coresiding family, non-coresiding family, and neighbors/friends was assessed using self-administered questionnaires. Multivariable linear regression analysis was conducted to examine the effects of social support on MoCA-J scores at follow-up. Data were analyzed from 121 older people (mean age (standard deviation): 73.86 (4.95) years). There was a positive association between social support exchanges with neighbors and friends and MoCA-J scores at follow-up after covariate adjustment (unstandardized β = 1.23, p = 0.006). Social support exchanges with coresiding family and non-coresiding family and relatives were not associated with MoCA-J scores at follow-up (coresiding family: Unstandardized β = 0.28, p = 0.813, non-coresiding family and relatives: Unstandardized β = 0.51, p = 0.238). The provision of emotional support to neighbors and friends had the largest effect on MoCA-J scores. Our findings suggest that social support exchanges with neighbors and friends are protective against cognitive decline.

In April 2020, the Japanese government declared a state of emergency due to the novel coronavirus disease (COVID-19). Schools were closed and a stay-at-home order was issued in April and May 2020. This before-and-after study aimed to measure the effects of these COVID-19-related restrictions on physical function among Japanese children. The study included children aged 6–7 years, enrolled before and after the emergency declaration. Their body fat percentage, single-leg standing time, Gait Deviation Index score, and history of falls were compared. There were 56 and 54 children in the before and after groups, respectively. Children in the after group had a higher body fat percentage (p = 0.037), shorter single-leg standing time (p = 0.003), and a larger number of falls per month (p < 0.001) than those in the before group. In the logistic regression analysis, children in the after group had a significantly shorter single-leg standing time (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.972−0.997, p = 0.013), a greater number of falls per month (OR: 1.899, 95% CI: 1.123−3.210, p = 0.017), and a higher body fat percentage (OR: 1.111, 95% CI: 1.016−1.215, p = 0.020) than those in the before group. The COVID-19 emergency restrictions had a negative effect on children’s physical function, especially on balance.

This study examined the association between Gait Deviation Index (GDI) and the five-times-sit-to-stand test (FTSST) or gait speed results, which represent mobility and muscle strength of the lower extremities in ambulatory children with Gross Motor Function Classification System (GMFCS) level I and II spastic cerebral palsy. In this cross-sectional, observational study, three-dimensional gait analysis data were obtained during gait trials to evaluate the GDI in 35 children (age 5–16 years) with spastic palsy. Motor function was evaluated using FTSST and gait speed. Gross motor function was evaluated using GMFCS. Children with GMFCS level II spastic cerebral palsy demonstrated lower GDI (p < 0.001) and poorer FTSST (p = 0.031) than those with GMFCS level I spastic cerebral palsy. Correlation analysis showed that FTSST results were significantly correlated with GDI (r = −0.624; p < 0.001). Motor function may be important for the maintenance of gait quality in patients with GMFCS level I and II spastic cerebral palsy and should not be ignored. In conclusion, reduction in gait impairment may affect the values of FTSST and GDI in patients with spastic cerebral palsy who can ambulate without an assistive device.

Cachexia is a multifactorial syndrome characterized by muscle loss that cannot be reversed by conventional nutritional support. To uncover the molecular basis underlying the onset of cancer cachectic muscle wasting and establish an effective intervention against muscle loss, we used a cancer cachectic mouse model and examined the effects of aerobic exercise. Aerobic exercise successfully suppressed muscle atrophy and activated adiponectin signaling. Next, a cellular model for cancer cachectic muscle atrophy using C2C12 myotubes was prepared by treating myotubes with a conditioned medium from a culture of colon-26 cancer cells. Treatment of the atrophic myotubes with recombinant adiponectin was protective against the thinning of cells through the increased production of p-mTOR and suppression of LC3-II. Altogether, these findings suggest that the activation of adiponectin signaling could be part of the molecular mechanisms by which aerobic exercise ameliorates cancer cachexia-induced muscle wasting.