Ryo Yoshikawa

Background: Locomotive syndrome (LS) is a clinical condition used to describe reduced mobility caused by musculoskeletal dysfunction and is highly prevalent among patients with cancer. The fat-free mass index (FFMI) is an indicator of nutritional status and muscle mass, and has been associated with malnutrition and prognosis in this population. This study investigated the relationship between FFMI and LS in patients with cancer and determined sex-specific FFMI cutoff values associated with severe LS. Methods: This study included patients hospitalized for cancer treatment who were referred for rehabilitation therapy. Patient characteristics, laboratory data, body composition, and grip strength were collected. LS was assessed using the stand-up test, two-step test, and 25-Geriatric Locomotive Function Scale. FFMI was measured using bioelectrical impedance analysis. Results: Overall, 144 patients (102 men and 42 women; mean age, 63.9 ± 15.8 years) were analyzed. Ordinal logistic regression analysis demonstrated that FFMI was independently associated with LS severity (odds ratio [OR], 0.597; 95% confidence interval [CI], 0.434–0.821). The optimal FFMI cutoff values associated with severe LS (grade ≥ 2) were 16.99 kg/m² in men and 15.25 kg/m² in women, with areas under the curves of 0.806 (95% CI, 0.720–0.890) and 0.760 (95% CI, 0.596–0.925), respectively. Conclusions: FFMI was associated with mobility function in patients with cancer. The proposed sex-specific cutoff values may help identify patients with impaired mobility who could be considered for referral to rehabilitation therapy.

PurposeExercise capacity in patients with non-small cell lung cancer (NSCLC) has been reported to be a prognostic factor. This study aimed to clarify the associations of preoperative and postoperative exercise capacity with cancer recurrence and survival.MethodsThis single-center retrospective cohort study included 133 patients with NSCLC who underwent pulmonary resection and completed a six-minute walk test either preoperatively or at discharge. Patients were stratified into long- and short-distance groups using cohort-specific six-minute walk distance (6MWD) cutoffs derived from receiver operating characteristic analyses. Outcomes were relapse-free survival (RFS), overall survival (OS), and time to recurrence (TTR).ResultsThe preoperative cohort included 75 patients, and the postoperative cohort included 123 patients. Shorter 6MWD (≤485 m preoperatively and ≤432 m postoperatively) was associated with significantly worse 5-year RFS, OS, and TTR. These associations remained significant after multivariable adjustment.ConclusionsPerioperative exercise capacity assessed by the 6MWD was associated with postoperative recurrence and survival in patients with NSCLC. Assessment of exercise capacity may provide valuable prognostic information in lung cancer management.

CT has evolved into a complementary tool for three-dimensional (3-D) structural assessment in OA research. This review highlights advances across key domains of CT-based OA imaging: structural features, shape modeling, alignment, contact stress modeling, bone morphometry and BMD, articular cartilage, meniscus, and combination with other modalities. CT’s high-resolution bone visualization enables accurate quantification of osteophytes, subchondral bone cysts, and sclerosis, as well as precise measurement of joint space width (JSW). The high geometric fidelity of CT also facilitates 3-D bone shape modeling. Additionally, CT supports dynamic evaluation of joint mechanics, including articular contact stress estimates. Weight-bearing CT enables functional assessment of joint alignment and JSW under physiologic loads. QCT, HR-pQCT, and micro-CT support detailed analysis of periarticular bone morphometry and BMD, capturing microarchitectural changes linked to OA severity. CT arthrography provides high-contrast visualization of articular cartilage and has shown superior sensitivity over MRI for detecting cartilage and meniscal defects. Dual-energy CT enables material differentiation, offering a noninvasive alternative to arthrocentesis. Spectral photon-counting CT combines ultra-high spatial resolution with multi-energy tissue characterization, improving the accuracy of compositional and structural assessment. Moreover, CT provides the anatomical framework for hybrid imaging modalities, such as PET CT and SPECT CT, which can assess bone metabolic activity. Together, these emerging CT modalities allow detailed 3-D analysis of bone geometry and subchondral changes, as well as evaluation of cartilage thickness and meniscal integrity, alongside accurate 3-D alignment measurements. These advances establish CT as a versatile platform for developing OA imaging biomarkers, monitoring disease progression, and enhancing clinical trial outcomes. Insights gained from these technologies will continue to inform future OA research and guide clinical decision-making.

Transcutaneous CO₂ application promotes fracture healing and osteogenesis via angiogenesis. However, its molecular mechanism remains unclear. This therapy transiently decreases intra-tissue pH in the affected area to approximately 7.0 for 20 min, followed by recovery. We hypothesized that such intermittent pH changes activate endothelial cells similarly to acidic preconditioning. We aimed to investigate the response of human umbilical vein endothelial cells (HUVECs) to daily intermittent low-pH stimulation. HUVECs were cultured under three conditions: daily 20-min exposure to a low-pH medium (approximately 7.0), followed by a return to a control medium (approximately 7.4) (Change group); continuous exposure to a low-pH medium (Low pH group); constant culturing in a control medium (Control group). Cell proliferation, tube formation, migration, and protein/gene expression were assessed. Tube formation and migration were significantly enhanced in the Change group compared with those in the Control group, and tube formation was also increased in the Low pH group. Western blotting revealed upregulated expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in the Change group. CD31 gene expression was elevated in the Low pH and Change groups on Days 1 and 7, respectively. Phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (AKT) levels in the Low pH and Change groups were significantly increased compared with those in the Control, except for ERK2 in the Low pH group. The suppression of ERK1/2 or AKT by their inhibitors (U0126 and LY294002, respectively) during low-pH exposure inhibited proliferation and tube formation, indicating that the ERK1/2 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT pathways mediate endothelial cell activation in response to intermittent acidic stimulation. Intermittent low-pH exposure enhanced HUVEC activity, mediated by the ERK1/2 MAPK and PI3K/AKT pathways. Our findings provide insights into the mechanism by which transcutaneous CO₂ application promotes angiogenesis and tissue repair.

Rationale: Hereditary spastic paraplegia (HSP), a rare neurodegenerative disorder in Japan, is characterized by insidiously progressive lower extremity spasticity and muscle weakness. Current management is primarily symptomatic, including physical therapy and spasticity modulation with botulinum toxin or intrathecal baclofen. Recent studies have suggested that extracorporeal shock wave therapy (ESWT) may be effective for treating spasticity in patients recovering from stroke. We report a case exploring the use of radial ESWT (rESWT) combined with physiotherapy in a patient with HSP. Patient concerns: A 31-year-old man diagnosed with HSP in his 20s had been receiving physical therapy and orthotics but experienced progressive bilateral lower extremity spasticity, leading to deterioration in gait function and mobility. Diagnoses: Progressive HSP with exacerbated bilateral lower extremity spasticity manifesting as impaired gait efficiency and reduced functional mobility. Interventions: The patient was treated with rESWT focusing bilaterally on the calf muscles. Outcomes: Posttreatment, the patient’s visual analog scale score for ease of walking improved significantly from 40 to 85, reflecting enhanced walking ability. The timed up and go test results improved from 15.08 to 12.59 seconds and 11.51 to 10.43 seconds at comfortable and maximum speeds, respectively. The 10-meter walk test time decreased from 10.48 to 7.24 seconds, and the step count improved from 20 to 14. Despite the modified Ashworth scale scores and dorsiflexion measurements showing minimal changes, no adverse effects were observed. Lessons: This case report provides preliminary evidence that rESWT combined with physical therapy may improve gait disturbances, as well as the ease of walking and ambulatory ability, associated with spasticity in HSP. However, due to the limitations of a single-case study and the potential influence of confounding factors, further research – including randomized, placebo-controlled trials – is necessary to confirm its efficacy and determine optimal treatment parameters.