Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer

Objectives: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings.

Methods: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed.

Results: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = ?0.22), performance status (ρ = ?0.30), functional well-being (ρ?=?0.20), anorexia/cachexia subscale (ρ?=?0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ?=?0.26). PA was also correlated with fluid retention (ρ = ?0.34) and albumin (ρ?=?0.32), C-reactive protein (ρ = ?0.31), and hemoglobin (ρ?=?0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = ?0.43).

Conclusions: PA was correlated with physical condition, but not with psychological well-being.     

Long-term skeletal stability in the treatment of mandibular prognathism with a physiological positioning strategy

Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.     

Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti‐CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc‐ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc‐ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti‐topoisomerase I‐positive SSc‐ILD patients. At the 24‐month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX‐treated group were significantly higher than those in the CYC‐treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs ?1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc‐ILD patients than CYC treatment. In the future, it is expected that large‐scale clinical trials will show the usefulness of RTX treatment for SSc‐ILD.     

Association of Red Meat Intake with the Risk of Cardiovascular Mortality in General Japanese Stratified by Kidney Function: NIPPON DATA80

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m². Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46–0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function.     

YES1 activation induces acquired resistance to neratinib in HER2‐amplified breast and lung cancers

Molecular‐targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan‐HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2‐positive breast cancer. However, acquired resistance of various cancers to molecular‐targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib‐resistant cell lines from HER2‐amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib‐resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1‐amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2‐targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome.