Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis.

OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.

Body composition and motor function in children born large for gestational age at term.

BACKGROUND: This cross-sectional study compared body composition and motor function between children who were born large for gestational age (LGA) and those born appropriate for gestational age (AGA) and to investigate the association between gait quality and other variables. METHODS: Body composition was determined using a bioelectrical impedance analyzer. Motor functions were assessed using one-leg standing time, timed up-and-go test, five times sit-to-stand test, and three-dimensional gait analysis. We compared the results between two groups. We performed multiple regression analysis to evaluate the association between gait deviation index and variables of LGA, fat mass index, and motor functions (adjusted for age and sex). RESULTS: Children aged 6-12 years who were born LGA at term (n = 23) and those who were born AGA at term (n = 147) were enrolled. The LGA group had a higher fat mass index (2.9 vs. 2.2, p = 0.006) and lower gait deviation index (91.4 vs. 95.4, p = 0.011) than the AGA group. On multiple regression analysis, gait deviation index was associated with being LGA and fat mass index. CONCLUSIONS: In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function. IMPACT: Children aged 6-12 years who were born large for gestational age (LGA) at term showed a higher fat mass index and lower gait deviation index than those who were born appropriate for gestational age at term. No significant differences in balance function or muscle strength were observed between groups. On multiple regression analysis, gait deviation index was associated with being LGA at birth and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function.

Responsiveness and minimal clinically important difference of the 6-minute walk distance in patients undergoing colorectal cancer surgery.

PURPOSE: This study aimed to clarify the responsiveness and minimal clinically important difference (MCID) of the 6-minute walk distance (6MWD) from before and 1 week after surgery in patients with colorectal cancer (CRC). METHODS: This retrospective cohort study enrolled 97 patients with primary CRC scheduled for surgery. An anchor-based approach estimated the MCID of the 6MWD, with postoperative physical recovery and EuroQol 5-dimension 5L questionnaire assessments serving as anchors. Effect size (ES) and standardized response mean (SRM) of the 6MWD were calculated to evaluate responsiveness, and the receiver operating characteristic (ROC) curve was used to estimate the MCID of the 6MWD. RESULTS: Of the 97 patients, 72 were included in the analysis. The absolute value of ES and SRM of the 6MWD were 0.69 and 0.91, respectively. The ROC curve indicated that the optimal cut-off values for estimating the MCID of the 6MWD were -60 m (area under the curve [AUC] = 0.753 [95% CI: 0.640-0.866]) and -75 m (AUC = 0.870 [95% CI: 0.779-0.961]) at each anchor. CONCLUSION: From before to 1 week after surgery, the responsiveness of the 6MWD was favorable, and the MCID of the 6MWD was -75 to -60 m in patients with CRC.

Recovery of the Japanese orthopedic association back pain evaluation questionnaire score and walking ability following lumbar spinal stenosis surgery.

PURPOSE: We investigated the recovery of the Japanese orthopedic association back pain evaluation questionnaire (JOABPEQ) scores and 6 min walk distance (6MWD) in patients after surgery for lumbar spinal stenosis and identified the items among 25 questions of JOABPEQ that showed recovery. METHODS: A total of 227 patients (average age 71.5 years; SD: 7.5; 121 men) were included from a single center. The outcome measures were JOABPEQ, visual analog scale (VAS), and 6MWD and obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Mixed-model repeated measures were used to compare the variables at each time point between the surgery groups. RESULTS: The JOABPEQ, VAS, and 6MWD scores generally improved at 1 month postoperatively compared with those obtained preoperatively, and some parameters further improved at 3 months. However, improvement in the lumbar spine dysfunction item of JOABPEQ was delayed, showing improvement at 3 months postoperatively for decompression surgery (average score: pre, 64.6; 3 months, 78.5) and 6 months postoperatively for fusion surgery (average score: Pre, 64.3; 6 months, 77.1). Responses to the individual JOABPEQ questions generally improved after surgery. No significant changes in lumbar spine dysfunction occurred in the fusion group. CONCLUSION: Our results demonstrated the early postoperative recovery course of JOABPEQ and 6MWD. In the fusion group, significant changes in lumbar spine dysfunction started at 6 months postoperatively. These findings could help medical staff explain postoperative recovery to patients after lumbar spinal stenosis surgery and in their decision making regarding surgery.

Factors associated with physical activity following total knee arthroplasty for knee osteoarthritis: a longitudinal study.

BACKGROUND: After total knee arthroplasty (TKA), patients' physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data. METHODS: Eighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus. RESULTS: A higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (ß = 0.155, p = 0.028) as well as a higher preoperative average daily step count (ß = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (ß = 0.723, p < 0.001). CONCLUSION: These findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.

Hand Grip Strength Assessment Based on Sarcopenia Diagnostic Criteria Predicts Swallowing Function.

The purpose of this study is to clarify whether swallowing function can be inferred from grip strength. Based on the diagnostic criteria of sarcopenia, patients were divided into two groups according to grip strength, and it was analyzed whether there was a difference in the evaluation index for swallowing function between the two groups. Among the cases requesting evaluation of swallowing function from June 10, 2020 to October 28, 2020, 83 cases (mean age: 71.7 years, 59 males and 24 females) who received assessment tests and swallowing endoscopy were included. According to the diagnostic criteria for grip strength in the Asian working group in Sarcopenia, less than 28 kgf and 18 kgf were defined as the weak group for men and women, respectively. Hyodo scores, repeated salivary swallowing tests (RSST), maximum vocalization time (MPT), and dysphagia severity classification (DSS) were compared between the two groups. Of the 83 patients, 29 and 54 were in the normal group and weak group, respectively. In all indicators, the normal group showed significantly better results than the weak group: Hyodo score (2.4 vs. 4.0, p < 0.01), RSST (4.1 times vs. 2.4 times, p < 0.01), MPT (12.1 s vs. 5.9 s, p < 0.001), DSS (4.5 vs. 5.9, p < 0.001), respectively. In multiple regression analysis with DSS as the dependent variable, grip strength was a significant independent variable of DSS even after adjusting for age, gender, and body mass index. Grip strength assessment based on sarcopenia criteria can be a useful tool for estimating swallowing function.

The association between objectively measured preoperative light-intensity physical activity and postoperative ambulation in patients with gastrointestinal cancer.

[Purpose] To clarify the association between preoperative physical activity and postoperative ambulation based on physical activity intensity, and independent of functional capacity and depression, in patients with gastrointestinal cancer. [Participants and Methods] Seventy patients who underwent surgery for primary colorectal or gastric cancer were enrolled. Preoperative moderate-to-vigorous-intensity physical activity, light-intensity physical activity, and sedentary behavior were assessed using an accelerometer. The primary outcome was the days to postoperative first ambulation (capable of independently and continuously walking 150 m). Functional capacity and depression, as confounders, were evaluated by measuring the 6-minute walk distance and using the Hospital Anxiety and Depression Scale. [Results] Of the 70 patients, 28 had insufficient accelerometer data, and 42 were included in the analysis. Preoperative light-intensity physical activity, but not moderate-to-vigorous-intensity physical activity and sedentary behavior, was negatively associated with the days to postoperative first ambulation, after adjusting for age, preoperative functional capacity, and preoperative depression. [Conclusion] Preoperative light-intensity physical activity was associated with the days to postoperative ambulation independently of age, functional capacity, and depression. Hence, predicting delayed ambulation by preoperative light-intensity physical activity in patients with gastrointestinal cancer may be useful.

Prolonged preoperative sedentary time is a risk factor for postoperative ileus in patients with colorectal cancer: a propensity score-matched retrospective study.

PURPOSE: This study aimed to investigate the association between prolonged preoperative sedentary time (ST) and postoperative ileus (POI) after adjusting for confounders in patients with colorectal cancer (CRC). METHODS: This single-center retrospective study enrolled 155 consecutive patients who underwent surgery for primary CRC. A diagnosis of POI was made by the surgeons if the Clavien-Dindo classification (CD) grade is ≥ 2 within 30 days after surgery. Preoperative ST was assessed using the International Physical Activity Questionnaire usual week short version (Japanese version). Patients were classified into two groups (ST < 6 h/day and ST ≥ 6 h/day) based on results from the questionnaire, and data were analyzed using a propensity score-matching strategy to adjust for confounders. In addition, receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff value of preoperative ST for predicting POI. RESULTS: Of the 155 patients, 134 were included in the analysis. POI occurred in 16 (11.9%) patients of overall patients and 11 (12.5%) of the 88 matched patients. The logistic regression analysis after propensity score-matching showed that prolonged preoperative ST (ST ≥ 6 h/day) was associated with POI (odds ratio 5.40 (95% confidence interval: 1.09 - 26.60), p = 0.038). The ROC curve analysis indicated that the optimal cutoff value of preoperative ST for predicting POI was 6 h/day. CONCLUSION: Prolonged preoperative ST is a risk factor for POI in patients with CRC. Therefore, reducing preoperative ST may play an important role in preventing POI.

Decreased walking efficiency in elementary school children with developmental coordination disorder trait.

OBJECTIVE: To compare walking efficiency, and associated physical function, between children, with and without developmental coordination disorder trait. DESIGN: Cross-sectional study. SETTING: The study was conducted in a Medical and Rehabilitation Center for Developmental Disabilities in Okazaki, Japan. SUBJECTS: The study included 286 children, 6-12 years of age, with and without developmental coordination disorder trait. Developmental coordination disorder trait was defined by a score below the -1 standard deviation on the Japanese version of the Developmental Coordination Disorder Questionnaire. Based on this criterion, 45 children (28 boys) were classified into the developmental coordination disorder trait group and the other 241 (115 boys) in the control group. MEASURES: The following physical function outcomes were measured: single leg stance test; step length variability; and walking efficiency, measured using the 2-min walk test. Logistic regression analysis was used to determine the association between developmental coordination disorder trait and lower walking efficiency and physical function. RESULTS: Compared to the control group, the developmental coordination disorder group showed lower walking efficiency (P = 0.026), higher step length variability (P = 0.047), and shorter single leg stance test (P = 0.001). Developmental coordination disorder was independently associated with walking efficiency (odds ratio, 1.03; 95% confidence interval [CI], 1.001-1.061; P = 0.041) and single leg stance test (odds ratio, 0.99; 95% CI, 0.978-0.996; P = 0.006), but not to step length variability, age, and sex. CONCLUSIONS: Lower walking efficiency increases energy expenditure in children with developmental coordination disorder trait. Interventions to improve walking efficiency could improve the physical function and participation of these children.

Gap between the prevalence of and consultation rate for lumbopelvic pain in postnatal Japanese women.

BACKGROUND: We aimed to assess the prevalence of lumbopelvic pain (LPP), including low back pain (LBP) and/or pelvic girdle pain (PGP), consultation rate, and desire for treatment of postnatal Japanese women. METHODS: We performed a cross-sectional study of 98 postnatal Japanese women within 1 year of childbirth. We retrospectively evaluated the prevalence of LBP before and during pregnancy and the prevalence of LPP after childbirth using a self-administered questionnaire. We used the distribution of pain to differentiate LBP and/or PGP after childbirth and its intensity was assessed using a visual analogue scale. The effects of LPP on daily life were assessed using the Oswestry disability index (ODI). In addition, we assessed the consultation rate for LPP and the desire to consult a healthcare professional, using self-administered questionnaires. RESULTS: The prevalence of LPP after childbirth was 66%. Women with a history of LBP before and during pregnancy were more likely to have LPP following childbirth (both P < 0.001). The consultation rate among the postnatal women with LPP was 9%, but 56% of the women wished to consult a healthcare professional. The ODI score was significantly higher in postnatal women who wanted to consult a healthcare professional than in those who did not (P < 0.01). CONCLUSIONS: Two thirds of the postnatal Japanese women who participated in this study had LPP, but the consultation rate was low. However, more than half of these women had the desire to consult a healthcare professional.

Aerobic Exercise Ameliorates Cancer Cachexia-Induced Muscle Wasting through Adiponectin Signaling.

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.

Magnification of visual feedback modulates corticomuscular and intermuscular coherences differently in young and elderly adults.

Beta-band (15-30 â€‹Hz) corticomuscular and intermuscular coherences are important markers of the corticospinal interaction. The purpose of this study was to investigate whether amount of visual feedback during an isometric pinch grip contraction would influence these coherences in young and elderly adults. Thirty-three healthy young and elderly subjects performed pinch grip force-matching task with right thumb and index finger, while scalp electroencephalogram (EEG) and electromyogram (EMG) from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles were recorded. The amount of visual feedback was altered by manipulation of visual gain (low and high). Beta-band corticomuscular coherence was computed between EEG over the sensorimotor cortex and EMG from the FDI muscle and between EEG and EMG from the APB muscle (EEG-FDI and EEG-APB coherences). Also, beta-band intermuscular coherence was computed between EMG signals from the FDI and APB muscles (EMG-EMG coherence). Task performance was quantified as standard deviation (SD) of force and mean force error (MFE). EEG-FDI coherence was larger at high than low visual gain in the elderly but not in the young subjects, whereas there was no effect of age or visual gain on EEG-APB coherence. EMG-EMG coherence was smaller at high than low visual gain in the young and elderly subjects. The MFE was smaller at high than low visual gain in the young and elderly subjects, but the SD of force was smaller at high than low visual gain only in the young subjects. These results suggest that the effect of aging on beta-band coherence depends on the amount of visual feedback and further that visual feedback modulates beta-band corticomuscular and intermuscular coherences differently.

Gait characteristics of children with Williams syndrome with impaired visuospatial recognition: a three-dimensional gait analysis study.

Williams syndrome (WS) is a genetically based neurodevelopmental disorder characterized by intellectual disability and impaired visuospatial recognition. The aim of this study was to analyze the gait characteristics of WS children with impaired visuospatial recognition using a three-dimensional gait analysis (3DGA) to clarify the gait adaptation needed to compensate for it. 3DGA was performed in 8 WS children with impaired visuospatial recognition (mean age, 11.8 years) and 9 age-, sex-, height-, and weight-matched controls. Clinical data, fundamental motor tests, and gait variables while walking on a flat surface and walking up a mat were compared between the two groups, and the correlations between variables were analyzed in the WS children. WS children showed impairment of balance function without muscle weakness. In walking on a flat surface, the WS group showed reduced walking speed, short step length, increased variability of step length, increased knee flexion throughout the stance phase, increased horizontal pelvic range of motion (ROM), and a low Gait Deviation Index and a high Gait Profile Score, which are indices of gait quality. In walking up a mat, the WS group showed further reduced walking speed and decreased sagittal hip flexion and ankle dorsiflexion ROM in the swing phase. Impaired balance function was significantly correlated with increased variability of step length and decreased sagittal ankle dorsiflexion ROM in the swing phase. The detailed gait pattern of WS children with impaired visuospatial recognition was presented. These findings show that impaired visuospatial recognition and balance function contribute to gait adaptation.

Predictors of complications in heat-treated autograft reconstruction after intercalary resection for malignant musculoskeletal tumors of the extremity.

BACKGROUND: Biological reconstruction with recycled heat-treated autografts has been an option for a segmental skeletal defect after intercalary resection for malignant musculoskeletal tumors in the extremity. This study was undertaken to evaluate the clinical outcomes in patients treated with this procedure and identify factors affecting the incidence of complications. METHODS: We retrospectively reviewed 24 patients treated with heat-treated autografts after intercalary resection at our institution between 1992 and 2015. RESULTS: The survival rate of the heat-treated autografts was 70.1% at 10 years. Of the 48 host-graft junctions in the 24 patients, nonunion occurred in 18 junctions (38%). In the univariate analysis, location in the upper extremity, intercalary grafts without vascularized fibula autografts (VFG), and junction at the diaphysis significantly increased the rate of nonunion (P = 0.003, P = 0.003, and P = 0.031, respectively). Location in the upper extremity was an independent factor associated with nonunion in the multivariate analysis (P = 0.006). Upper extremity location and intercalary grafts without VFG were also significant factors for bone absorption (P = 0.042 and P < 0.001, respectively). CONCLUSIONS: Our results can provide useful information to devise possibly novel clinical approaches to patients requiring intercalary reconstruction of the extremity.

What Is the Success of Repeat Surgical Treatment of a Local Recurrence After Initial Wide Resection of Soft Tissue Sarcomas?

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.

Correlation between the Gait Deviation Index and skeletal muscle mass in children with spastic cerebral palsy.

[Purpose] This study aimed to identify a simple and useful muscle parameter for use with the Gait Deviation Index in assessment of ambulatory children with unilateral and bilateral spastic cerebral palsy. [Participants and Methods] Twenty-eight patients (aged 6 to 18 years; 16 females and 12 males) participated in this cross-sectional study. Outcome measurements included the Gait Deviation Index, grip strength, 5-repetition chair stand test, upper limb skeletal muscle mass index, and lower limb skeletal muscle mass index. [Results] By multiple regression analysis, significant independent correlations were observed between the Gait Deviation Index and 5-repetition chair stand test and the Gait Deviation Index and lower limb skeletal muscle mass index, but not between the Gait Deviation Index and grip strength or upper limb skeletal muscle mass index. [Conclusion] The Gait Deviation Index was correlated with lower limb muscle mass in children with spastic cerebral palsy. Determination of lower limb muscle mass may be useful gait evaluation.

Efficacy of Trabectedin in Patients with Advanced Translocation-Related Sarcomas: Pooled Analysis of Two Phase II Studies.

BACKGROUND: Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS). METHODS: Trabectedin was administered on day one of a 21-day cycle. Efficacy was assessed using progression-free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (<1,000/µL, ≥1,000/µL) or number of previous chemotherapy regimens (0, 1, 2, ≥3 regimens), and a Weibull parametric model was used to estimate the numerical relationship between lymphocyte count and PFS and OS. RESULTS: Median PFS and OS in overall patients were 5.6 (95% confidence interval [CI]: 4.1-7.3) and 17.5 months (95% CI: 12.6-23.6), respectively. PFS in the myxoid and round-cell liposarcoma (MRCL) group (7.4 months [95% CI: 5.6-11.1]) was longer than in the other subtypes. The response rate was also highest in the MRCL group. Median OS was longer in patients with baseline lymphocyte counts ≥1,000/µL than in those with counts of <1,000/µL, but median PFS was not different between the two subgroups. CONCLUSION: Our updated and pooled data showed that trabectedin exerted prolonged disease control and antitumor effects in patients with advanced TRS, especially in MRCL. We consider that the subgroup analyses also provide important information for trabectedin treatment in patients with TRS. IMPLICATIONS FOR PRACTICE: The progression-free survival (PFS) for the integrated data of 66 patients with translocation-related sarcomas (TRSs) in two phase II studies of trabectedin 1.2 mg/m2 was 5.6 months (95% confidence interval: 4.1-7.3). PFS and response rate in myxoid/round-cell liposarcoma was longer than that of other subtypes. The overall survival (OS) in all TRS subtypes was similar to previous data of TRS patients. In subgroup analysis, the patients with baseline lymphocyte count ≥1,000/µL exhibited better OS, although PFS was not different by baseline lymphocyte count. Our data are considered important information for trabectedin treatment in TRS patients.

Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma.

Objective: Eribulin, a microtubule dynamics inhibitor, is approved for the treatment of patients with breast cancer and soft tissue sarcoma. We investigated the efficacy and safety of eribulin in Japanese patients with soft tissue sarcoma. Methods: This open-label, multicenter, nonrandomized, Phase 2 study enrolled Japanese patients with measurable, advanced/metastatic soft tissue sarcoma of high/intermediate grade and ≥1 prior chemotherapy for advanced disease. Patients received eribulin mesilate 1.4 mg/m2 intravenously over 2­5 minutes on Days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free rate at 12 weeks. Secondary endpoints included overall survival, progression-free survival and safety. Efficacy analyses were stratified by histology (liposarcoma or leiomyosarcoma, and other subtypes). Results: Overall, 52 patients were enrolled and 51 patients were treated. Patients with liposarcoma/leiomyosarcoma (n = 35) had similar characteristics to those with other subtypes (n = 16), except for a higher proportion of women (63% vs 38%, respectively) and patients with Eastern Cooperative Oncology Group performance status 0 (57% vs 44%). Progression-free rate at 12 weeks was 60% in liposarcoma/leiomyosarcoma patients, 31% in other subtypes and 51% overall. Median progression-free survival was 5.5 months in liposarcoma/leiomyosarcoma patients, 2.0 months in other subtypes and 4.1 months overall. Median overall survival was 17.0 months in liposarcoma/leiomyosarcoma patients, 7.6 months in other subtypes and 13.2 months overall. The most common Grade 3­4 adverse events were neutropenia (86%), leukopenia (75%), lymphopenia (33%), anemia (14%) and febrile neutropenia (8%). Conclusion: Eribulin showed clinical activity with a manageable safety profile in previously treated Japanese patients with advanced/metastatic soft tissue sarcoma.

Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group.

BACKGROUND: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG). METHODS: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions. RESULTS: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment. CONCLUSIONS: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study.

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study.

BACKGROUND: Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data. METHODS: Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS. RESULTS: The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively. CONCLUSIONS: There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.