Extracellular water to total body water ratio may mediate the association between phase angle and mortality in patients with cancer cachexia: A single-center, retrospective study.

Recently, prognostic factors for cancer cachexia patients have been reported. We hypothesized that phase angle (PhA), which is measured by bioelectrical impedance analysis (BIA), might be a promising marker for assessing the nutritional status and prognosis of cancer patients. This study aimed to evaluate the predictive utility of PhA, which is mediated by several BIA factors and other anthropometric parameters, such as calf circumference, for the prognosis of cancer cachexia patients. Consecutive patients (114, both outpatients and inpatients) with an unselected stage of cancer cachexia were recruited between July 2018 and December 2019 in Fujita Health University Hospital for this retrospective cohort study. Their mean age was 74.0 years (standard deviation, 8.5); among the total, 70 were men and 44 women. A time-dependent Cox proportional-hazards regression analysis (adjusted for age and sex) was performed to assess the following: 1) the association between potential mediators and mortality; 2) the association between five PhAs and statistically significant mediators from 1); and 3) the association between the five PhAs and mortality. Finally, Kaplan-Meier survival curves were constructed and compared between the two groups based on the patients' median baseline ratio of extracellular water (ECW) to total body water (TBW) using a log-rank test. The ECW/TBW ratio (hazard ratio [HR] per 1-interquartile range [IQR] increase: 2.87; 95% confidence interval [CI]: 1.46, 5.46; p < 0.001) and skeletal muscle mass index (HR per 1-IQR increase: 0.67; 95% CI: 0.51, 0.89; p = 0.001) were associated with mortality. All five PhAs were associated with the ECW/TBW ratio (p < 0.001). Before adjustment for the ECW/TBW ratio, all five PhAs were associated with mortality (p < 0.001); only the association of the PhAs of the left arm and the trunk retained the statistical significance after adjusting for confounders (p < 0.05). The median survival times in the low (370 days; 95% CI: 168, not calculated) and high ECW/TBW groups (101 days; 95% CI: 61, 219) differed significantly (p < 0.001). The association between PhA and mortality in cancer cachexia patients was largely mediated by the ECW/TBW ratio. We believe that adjusting PhA for the ECW/TBW ratio may improve the prognostication of cancer patients with cachexia, ultimately improving their palliative care.

Katsura N ，Yamashita M ，Ishihara T 《Clinical Nutrition ESPEN》

Phase angle and extracellular water-to-total body water ratio estimated by bioelectrical impedance analysis are associated with levels of hemoglobin and hematocrit in patients with diabetes.

Anemia is one of the common complications of diabetes and is associated with mortality. Phase angle (PhA), ratio of extracellular water to total body water (ECW/TBW) and skeletal muscle mass index (SMI) estimated by bioelectrical impedance analysis (BIA) have been used as prognostic indicators for various chronic diseases and frailty. We aimed to clarify the clinical significance of PhA, ECW/TBW and SMI for anemia in patients with diabetes. The values of PhA, ECW/TBW and SMI were estimated by a portable BIA device and blood samples were collected in 371 Japanese patients with diabetes. The relationships of PhA, ECW/TBW and SMI with hemoglobin (Hgb) and hematocrit (Hct) were statistically evaluated. In simple linear regression analysis, PhA and SMI were positively correlated with Hgb and Hct levels in total subjects, male subjects and female subjects. In contrast, ECW/TBW was negatively correlated with Hgb and Hct levels regardless of sex. Multivariate regression analysis showed that both PhA and ECW/TBW but not SMI independently contributed to Hgb and Hct levels after adjustment of clinical confounding factors in both males and females. PhA and ECW/TBW but not SMI were associated with levels of Hgb and Hct in patients with diabetes. Therefore, aberrant values of PhA and ECW/TBW suggest a risk of anemia in diabetic patients.

Hori T ，Nakamura S ，Yamagami H ，Yasui S ，Hosoki M ，Hara T ，Mitsui Y ，Masuda S ，Kurahashi K ，Yoshida S ，Harada T ，Kuroda A ，Otoda T ，Yuasa T ，Endo I ，Matsuhisa M ，Abe M ，Aihara KI ... -  《Heliyon》

The extracellular-to-total body water ratio reflects improvement in the activities of daily living in patients who experienced acute stroke.

To determine the relationship between bioelectrical impedance analysis (BIA) parameters, including the extracellular water-to-total body water ratio (ECW/TBW), and the activities of daily living (ADL) improvement, in patients who experienced acute stroke. This retrospective cohort study included 307 patients (mean age, 72 years; 39 % female) who experienced acute stroke and were admitted to the stroke unit of the Nippon Medical School Hospital (Bunkyo-ku, Tokyo, Japan) between April 2021 and March 2022. The Functional Independence Measure (FIM) was assessed at initial rehabilitation and discharge, and FIM effectiveness was calculated as ADL improvement in the participating acute care hospitals. BIA markers included the skeletal muscle mass index (SMI), phase angle (PhA), and ECW/TBW. Multiple linear regression models were used to estimate the relationship between the FIM effectiveness and each BIA marker. The mean (±SD) FIM effectiveness was 0.45 ± 0.36. The proportions of low SMI (male, <7.0 kg/m2; female, <5.7 kg/m2) and low PhA (male <5.36 degrees, female <3.85 degrees), were 48.9 % and 43.3 %, respectively. In addition, the proportions of of low (<0.36), normal (0.36-0.40), and high (>0.4) ECW/TBW ratios were 1.3 %, 78.5 %, and 20.2 %, respectively. After adjustments for demographic and clinical variables, low PhA, low ECW/TBW, and high ECW/TBW were all significantly associated with FIM effectiveness (P < 0.05), with β coefficients of -0.126, -0.089, and -0.117, respectively. Low and High ECW/TBW and low PhA levels were negatively correlated with improvements in ADL. The ECW/TBW ratio may be an additional indicator of rehabilitation trainability in patients who experience acute stroke.

Ishiyama D ，Toi K ，Aoyagi Y ，Suzuki K ，Takayama T ，Yazu H ，Yoshida M ，Kimura K ... -  《-》

Prognostic value of overhydration and bioelectrical impedance vector on short- and long-term outcomes in hospitalized patients with cancer.

Water, an essential component of body composition, appears to be a significant predictor of adverse outcomes in clinical populations, despite being frequently underexplored. Bioelectrical impedance analysis (BIA) and vector analysis (BIVA) are easy and cost-effective bedside tools for estimating body composition, particularly water content. Therefore, our study aimed to assess the impact of hydration and fluid status using both BIA and BIVA on outcomes in hospitalized patients with cancer. A prospective cohort study involving hospitalized individuals with cancer was conducted. Total body water (TBW) was estimated using BIA. Extracellular-water/TBW (ECW/TBW) and ECW/intracellular-water (ECW/ICW) ratios were calculated. BIVA ellipses vectors were constructed to enhance our analysis of hydration status. Participants were followed during their hospital stay and up to six months after discharge to assess outcomes, including in-hospital mortality, 6-month non-elective rehospitalization, and 6-month mortality. TBW, ECW/TBW, ECW/ICW ratios, and BIVA plots were not associated with non-elective rehospitalization during the follow-up period. However, TBW and an elevated ECW/ICW ratio were independent predictors of in-hospital mortality [hazard ratio (HR): 1.07 (1.01; 1.13) p = 0.020; HR: 4.23 (1.69; 10.58) p = 0.002]. Elevated ratios ECW/TBW and ECW/ICW were independent predictors of 6-month mortality [HR: 1.87 (1.10; 3.21) p = 0.022; HR: 2.49 (1.37; 4.51) p = 0.003]. BIVA vectors for in-hospital and 6-month mortality shifted significantly to the right, leading to cachexia and overhydration quadrants (p < 0.05). Abnormalities related to overhydration were important predictors of short- and long-term mortality in hospitalized patients with cancer.

Pedro da Costa Pereira J ，Santana Costa JH ，Gomes de Miranda BL ，de Sousa Rebouças A ，Denise de Lima Bezerra A ，Gomes Dantas Lopes MM ，Trussardi Fayh AP ... -  《-》

The clinical application value of the extracellular-water-to-total-body-water ratio obtained by bioelectrical impedance analysis in people with advanced cancer.

Body-composition analysis using bioelectrical impedance analysis is gradually becoming more widely used in clinical practice. The ratio of extracellular water (ECW) to total body water (TBW) is thought to be related to the prognosis of a variety of diseases. However, its performance in people with advanced cancer deserves further discussion. A retrospective analysis was performed on 784 people with advanced cancer. Anthropometric indicators, serologic indicators, nutritional status, health-related quality of life, and body composition were analyzed. Participants were grouped into two groups according to ECW/TBW ratio. We used t tests and χ2 tests to analyze differences between the groups. Univariate and multivariate Cox regressions were conducted to analyze the factors influencing overall survival. Logistic regression was used to analyze the related factors of malnutrition, and linear regression for factors of health-related quality of life. Age, body mass index, Patient-Generated Subjective Global Assessment score, Karnofsky Performance Status questionnaire score, skeletal muscle mass index, and fat-free mass index were statistically different between the non-overhydrated and overhydrated groups. Univariate and multivariate Cox regression models showed that an ECW/TBW ≥ 0.40 is a risk factor for poor prognosis in people with advanced cancer (hazard ratio = 1.511; 95% confidence interval, 1.103-2.070; P = 0.010). Subgroup analyses were next conducted according to tumor type, with ECW/TBW ≥ 0.40 emerging as a risk factor for poor prognosis for people with advanced breast cancer and advanced gastric cancer. Logistic regression showed that ECW/TBW ≥ 0.40 is a risk factor for malnutrition in people with advanced cancer (odds ratio = 1.988; 95% confidence interval, 1.049-3.767; P = 0.035). The univariate and multivariate linear regression models showed that the ECW/TBW ratio is an influencing factor for health-related quality of life in the domains of physical functioning, role functioning, and constipation. We found that in people with cancer, an ECW/TBW ≥ 0.40 was a risk factor for malnutrition and lower health-related quality of life, and in people with advanced cancer, it was a risk factor for poor prognosis.

Zheng K ，Lu J ，Liu X ，Ji W ，Liu P ，Cui J ，Li W ... -  《-》