CAN WE DIAGNOSE SARCOPENIA USING ANTERIOR FEMORAL MUSCLE THICKNESS IN PATIENTS WITH CARDIOVASCULAR DISEASE?

Objective: Making the diagnosis of sarcopenia is not always easy and this is especially true for those with cardiovascular disease. The purpose of this study is to investigate whether it is possible to diagnose sarcopenia by using ultrasound-guided measurements of anterior femoral muscle thickness. Methods: We investigated the utility of ultrasound-guided measurements of anterior femoral muscle thickness in 1075 hospitalized patients with cardiovascular disease (675 men). As a comparison, sarcopenia was assessed by skeletal muscle mass index using bioelectrical impedance analysis and the Asia Working Group for Sarcopenia criteria. Results: When the receiver operating characteristic curve using muscle thickness was examined, we found this could be used to make the diagnosis of sarcopenia (men: cutoff value 2.425 cm, area under the curve 0.796; women: cutoff value 1.995 cm, area under the curve 0.746). The prevalence of sarcopenia according to the criteria with skeletal muscle mass index was 34.2% in men and 51.8% in women, while its prevalence according to the cutoff value of muscle thickness was 29.2% in men and 36.7% in women. Conclusion: Ultrasound-guided measurement of the anterior femoral muscle thickness is a simple and useful method to help make the diagnosis of sarcopenia in patients with cardiovascular disease.

Clinical usefulness of phase angle as an indicator of muscle wasting and malnutrition in inpatients with cardiovascular diseases.

Background and Objectives: Extracellular water is increased in patients with edema, such as those with chronic heart failure, and it is difficult to assess skeletal muscle mass with the skeletal muscle mass index when extracellular water is high. We investigated the relationship between phase angle and physical function, nutritional indices, and sarcopenia in patients with cardiovascular diseases, including chronic heart failure. Methods and Study Design: In 590 patients with cardiovascular diseases (372 men), handgrip strength, gait speed, and anterior mid-thigh muscle thickness by ultrasound were measured, and the skeletal muscle mass index, phase angle, and the extracellular water: total body water ratio were measured with a bioelectrical impedance analyzer, and presence of sarcopenia was evaluated. Results: Phase angle, but not the skeletal muscle mass index, was correlated with serum albumin (r = 0.377, p < 0.001) and hemoglobin values in women. Multivariate regression analysis showed that at the extracellular water: total body water ratio below 0.4, both phase angle and skeletal muscle mass index were independent determinants of handgrip strength and log mid-thigh muscle thickness in men, after adjustment for age and presence of chronic heart failure. In contrast, for the ratio of 0.4 or greater, after adjustment for age and presence of chronic heart failure, phase angle was a stronger independent determinant of handgrip strength and log mid-thigh muscle thickness than the skeletal muscle mass index in men. Conclusions: Phase angle is a good marker of muscle wasting and malnutrition in patients with cardiovascular disease, including chronic heart failure.

Optimal uric acid reduction to improve vascular endothelial function in patients with chronic heart failure complicated by hyperuricemia.

Although an association of serum uric acid levels with endothelial function has been shown in various clinical settings, the optimal treatment target that would benefit vascular endothelial function has not been established. We, therefore, conducted a post hoc analysis of the Excited-UA study to identify an optimal target. Patients (N = 133) with chronic heart failure and comorbid hyperuricemia who enrolled in the Excited-UA study were divided into three tertiles based on their serum uric acid level 24 weeks after initiating xanthine oxidase inhibitor treatment with topiroxostat or allopurinol (i.e., groups with low, moderate, and high uric acid levels). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) values measured by reactive hyperemia peripheral arterial tonometry (RH-PAT) were compared among groups. The change from baseline in the FMD value 24 weeks after treatment was comparable among the three groups. In contrast, the change from baseline in the RHI was significantly different among the three groups (-0.153 ± 0.073, 0.141 ± 0.081 and -0.103 ± 0.104 in the low, moderate, and high uric acid level groups, respectively, P = 0.032). After adjustment for age, body mass index, and concomitant use of diuretics, which differed among the three groups, the change in the RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group (P = 0.057) and was significantly higher than that in the low uric acid level group (P = 0.020). These results indicate that targeting excessively low uric acid levels by treatment with xanthine oxidase inhibitors might be less beneficial for improving microvascular endothelial function in patients with chronic heart failure. Comparisons of the changes from baseline in vascular endothelial function parameters at 24 weeks among the 3 groups of low, moderae and high uric acid levels achieved with xanthine oxidase inhibitors. After adjustment for confounding factors, such as age, body mass index and concomitant diuretic use, which showed differences among the 3 groups, the change in RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group and was significantly higher than that in the low uric acid level group.

Relationship between the serum GDF-15 concentration and muscle function in female patients receiving aortic valve replacement (TAVR, SAVR): Comparison with healthy elderly female subjects.

Purpose: Sarcopenia is closely associated with postoperative prognosis in patients undergoing cardiovascular surgery. Growth differentiation factor (GDF)-15 is involved in the pathogenesis of cardiovascular disease. We examined the relationship between the serum GDF-15 concentration and muscle function in patients receiving aortic valve replacement and healthy elderly subjects. Methods: Forty-three female patients undergoing aortic valve surgery (79.9 ± 6.4 years; transcatheter aortic valve replacement [TAVR] n = 19, conventional surgical aortic valve replacement [SAVR] n = 24) and 64 healthy elderly female subjects (75.9 ± 6.1 years) were included. Walking speed, grip strength, and skeletal muscle mass index (SMI) by a multifrequency bioelectrical impedance analyzer were measured to determine the presence of sarcopenia. Preoperative serum GDF-15 concentration was measured by enzyme-linked immunosorbent assay. Results: The GDF-15 level was higher in patients receiving aortic valve replacement than in healthy elderly subjects (aortic valve replacement: 1624 ± 1186 pg/mL vs. healthy: 955 ± 368 pg/mL, p < 0.001). Multivariate linear regression analysis showed that the serum GDF-15 level determined grip strength independently of the high-sensitivity C-reactive protein level and eGFR, even after adjusting for age (ß = -0.318, p = 0.025). Sarcopenia was found in 12.5% of healthy elderly subjects, 83.3% of patients with TAVR, and 64.3% of patients with SAVR. The GDF-15 concentration that defined sarcopenia was 1109 pg/mL in subjects including patients receiving aortic valve replacement. Conclusions: The preoperative serum GDF-15 concentration, which was higher in female patients receiving aortic valve replacement than in healthy elderly subjects, may be a serum marker of sarcopenia.

Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats.

BACKGROUND: Surgical stresses, including hepatic ischemia-reperfusion (I/R), promote cancer growth and metastasis. We have reported that continuous hepatic I/R increases liver damage and promoted liver metastasis from colon cancer, whereas intermittent I/R causes less liver damage. We therefore examined whether intermittent I/R could reduce liver metastasis in a rat model. MATERIALS AND METHODS: Adult male Fischer rats was divided between three groups: group A (control), which received laparotomy for 120 min with no liver ischemia; group B (continuous I/R), which received 60 min of 70% partial liver ischemia followed by 60 min of reperfusion; and group C (intermittent I/R), which received 15 min of 70% ischemia and 15 min of reperfusion, repeated four times. Just before closing the abdomen, all animals were inoculated intrasplenically with rat colon adenocarcinoma cells (RCN-H4). Tumor nodules on the liver surface were counted 3 weeks later. In addition, expression of E-selectin mRNA in liver was examined at 1, 3, and 6 h after completing I/R by a reverse transcription-polymerase chain reaction. RESULTS: Continuous I/R (B) greatly promoted liver metastasis in both ischemic and nonischemic liver lobes, whereas intermittent I/R (C) showed significantly fewer metastasis than group B in both lobes. Significantly less E-selectin mRNA was expressed in group C than in group B. CONCLUSIONS: Intermittent I/R limits expression of E-selectin mRNA and liver metastasis. Intermittent hepatic I/R is less stressful than continuous I/R, minimizing liver metastasis by colon cancer cells through avoidance of E-selectin up-regulation.

Hepatic ischemia-reperfusion promotes liver metastasis of colon cancer.

BACKGROUND: The effects of hepatic ischemia/reperfusion (I/R) on liver metastasis have not been fully examined. We examined hepatic I/R and liver metastasis of colorectal cancer in a rat model; we also quantitated expression of E-selectin (ELAM-1) mRNA after I/R. MATERIALS AND METHODS: Rats underwent 30 or 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. The number of tumor nodules on the liver surface was determined 3 weeks later. Expression of E-selectin mRNA was determined at 1, 3, and 6 h after ischemia by quantitative RT-PCR. RESULTS: Hepatic I/R promoted liver metastasis of RCN-H4 and induced the expression of E-selectin mRNA in both clamped and unclamped liver lobes. The number of tumor nodules and the expression of E-selectin mRNA after 60 min of ischemia was greater than that after 30 min. CONCLUSIONS: Hepatic I/R, especially with a long duration of ischemia, induces expression of E-selectin and promotes liver metastasis of colon cancer in rats.

[A gastric cancer patient with marked para-aortic lymph node metastasis surviving more than 10 years after aggressive operation and repeated EAP chemotherapy].

The high incidence of side effects for EAP (etoposide, adriamycin, cisplatin) combination chemotherapy led to the recent decline in its use. However, we report herein the long-term disease-free survival of a woman following postoperative EAP therapy. A 57-year-old woman was referred to our hospital because of general malaise. X-ray and endoscopic examination revealed a Borrmann type 3 gastric cancer. Preoperative computed tomography and ultrasonography revealed multiple para-aortic lymph node swellings. The patient simultaneously underwent subtotal gastrectomy and splenectomy, and complete para-aortic lymph node dissection. Histopathological tests revealed that the tumor was a poorly differentiated adenocarcinoma with 35 metastatic para-aortic lymph nodes. The patient was treated with 2 cycles of EAP therapy. After discharge, swelling in one para-aortic lymph node was detected. Following three subsequent cycles of EAP therapy, the swollen lymph node disappeared and the patient has remained disease free for 10 years. This case illustrates that aggressive surgery followed by repeated courses of EAP therapy can produce excellent clinical outcomes.

Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.

OBJECTIVE: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN: Laboratory experimental study. SETTING: Research laboratory, Japan. SUBJECTS: Male Fischer rats. INTERVENTIONS: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.