[Screening for Dehydration in Outpatient Cancer Chemotherapy-Use of Serum Osmolality and Hidden Dehydration Check Sheet].

Weight loss during cancer chemotherapy affects the continuation of treatment; therefore, it is important to maintain and improve nutritional status. Additionally, appropriate fluid and electrolyte replacement is essential for maintaining life. This study included 100 patients who underwent outpatient chemotherapy in April 2021. The degree of dehydration was assessed based on serum osmolality, and the possibility of screening was examined by a hidden dehydration check sheet. Hidden dehydration was noted in 38 patients and dehydration in 6 patients. The incidence of pancreatic cancer was significantly lower than that of lung cancer. In the hidden dehydration check sheet, 51 patients were found to present with high possibility of hidden dehydration and required consultation to a medical professional. The serum osmolality of the results was not significantly different. During outpatient cancer chemotherapy, a certain percentage of patients present with hidden dehydration. To detect dehydration at an early stage, serum osmolality should be actively measured and continuous diet counseling, including confirmation of food and fluid intake, is required.

Hepatectomy Followed by Adjuvant Chemotherapy with 3-Month Capecitabine Plus Oxaliplatin for Colorectal Cancer Liver Metastases.

LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver metastases (CLM). Recurrence in patients who underwent the 3-month adjuvant CAPOX after resection of CLM was most commonly at extrahepatic sites. BACKGROUND: The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable colorectal cancer liver metastases (CLM) is still unclear. We evaluated the feasibility of 3-month adjuvant treatment with capecitabine plus oxaliplatin in combination (CAPOX) for postcurative resection of CLM. METHODS: Patients received one cycle of capecitabine followed by four cycles of CAPOX as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given as 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CAPOX consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. Primary endpoint was the completion rate of adjuvant chemotherapy. Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), dose intensity, and safety. RESULTS: Twenty-eight patients were enrolled. Median age was 69.5 years, 54% of patients had synchronous metastases, and 29% were bilobar. Mean number of lesions resected was two, and mean size of the largest lesion was 31 mm. Among patients, 20 (71.4%; 95% confidence interval, 53.6%-89.3%) completed the protocol treatment and met its primary endpoint. The most common grade 3 or higher toxicity was neutropenia (29%). Five-year recurrence-free survival and overall survival were 65.2% and 87.2%, respectively. CONCLUSION: Three-month adjuvant treatment with CAPOX is tolerable and might be a promising strategy for postcurative resection of CLM.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Feasibility of International Proposed Standardized Enteral Connector for Semi-Solid Formula Feeding.

BACKGROUND/AIMS: The current study was undertaken to assess if the semi-solid formulas could be used with a new ENFit connector with similar force to current percutaneous endoscopic gastrostomy (PEG) tubes. METHODS: Experiment 1: We measured the applied pressure (force) needed to compress the syringe containing 7 viscous semi-solid formulas with a 20 Fr PEG tube and low-profile tube through the ENFit connector or the current connector. Experiment 2: This experiment was conducted to evaluate the compression force through 2 connectors in 3 infusion velocity, 7 PEG tube types with 2 semi-solid formulas. RESULTS: Experiment 1: The force needed to compress the syringe through the ENFit connector was higher in 3 semi-solid formulas with a 20 Fr low-profile tube; otherwise, there were no significant differences. Experiment 2: Each formula required a higher force in the ENFit connector in 6 settings out of 21. CONCLUSIONS: The ENFit connector will likely not show any remarkable change in the force to administer the semi-solid formula. However, a higher force was required under some conditions in the prototype ENFit connector. Further investigation of sensory test is needed to confirm the feasibility of the ENFit connector for using the semi-solid formulas.

Association between left ventricular hypertrophy and changes in arterial stiffness during hypertensive treatment.

Cardio-ankle vascular index (CAVI) has been demonstrated as a parameter of arterial stiffness, which antihypertensive therapy may improve. However, little information is available about the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. We performed a study to examine the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. Eighty treated hypertensive patients (71 ± 10 years) were divided into two groups: 50 patients showing a decrease in CAVI (Group 1) and 30 patients showing an increase (Group 2) during observation (24 ± 11 months) of antihypertensive therapy. The groups did not differ in the rates of use of angiotensin II receptor blockers or calcium channel blockers. Age (Group 1: 67 ± 11 versus Group 2: 74 ± 8 years), left ventricular mass index (LVMI) (Group 1: 103 ± 19 versus Group 2: 120 ± 24 g/m(2)) and systolic blood pressure (Group 1: 133 ± 17 versus Group 2: 144 ± 23 mm Hg) at the start of observation were significantly higher in Group 2 than in Group 1 (p = 0.003, p = 0.001 and p = 0.027, respectively). The changes in CAVI during observation were correlated only with LVMI (r = 0.289, p = 0.009) at the start of observation for all 80 patients. It may be difficult to improve arterial stiffness assessed by CAVI during antihypertensive therapy in hypertensive patients with left ventricular hypertrophy.

Association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine and the cardiac function in hypertensive patients without overt heart disease.

Although increased oxidative stress is known to be associated with worsened cardiac function in chronic heart failure, consensus is still lacking regarding the association between oxidative stress and cardiac function in hypertensive patients without overt heart disease. This study aimed to evaluate the association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine (8-OHdG) and cardiac function in hypertensive patients without overt heart disease. We enrolled a total of 80 hypertensive patients (70 ± 11 y) who had been taking antihypertensive medications for at least 1 year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001, Selista Inc., Tokyo, Japan). Echocardiography was performed to assess the left ventricular (LV) diastolic function by measuring early diastolic mitral annular velocity (e') and the ratio of early transmitral flow velocity (E) to e' (E/e'). Urinary 8-OHdG was correlated with E/e' (r = 0.346, P = .002), e' (r = -0.310, P = .005), and HbA1c (r = 0.276, P = .013). Multiple linear regression analysis revealed that only e' (ß = -0.343, P = .004) was an independent determinant of urinary 8-OHdG. In conclusion, decreased e' is independently associated with elevated urinary 8-OHdG, a marker of oxidative stress, in hypertensive patients. Therefore, an elevated urinary 8-OHdG level may be useful in detecting subclinical LV diastolic dysfunction in hypertensive patients without overt heart disease.

Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases.

BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. METHODS: Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. RESULTS: Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION: The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.

Clinical relevance of antibodies to cardiolipin in patients with chronic hepatitis C.

The significance of antibodies to cardiolipin (anti-CL) remains uncertain in patients with chronic hepatitis C (CH-C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH-C seropositive for anti-CL. The prevalence of anti-CL and clinical parameters associated with anti-CL in those patients were examined. Six of the 45 (13%) patients with CH-C had anti-CL. However, none of these six CH-C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH-C patients with anti-CL were significantly higher than those in CH-C patients without anti-CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH-C patients with anti-CL had significantly more progressive hepatic fibrosis than those without anti-CL. The degree of 8-hydroxy 2'-deoxyguanosine (8-OHdG) expression in the liver tissue was more severe in CH-C patients with anti-CL than in those without it. However, the emergence of anti-CL in CH-C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti-CL is associated with oxidative stress and that CH-C patients seropositive for anti-CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis.

Reduced bone mineral density in hypertensive patients is associated with left ventricular diastolic dysfunction, not left ventricular hypertrophy.

Left ventricular (LV) hypertrophy and diastolic dysfunction are commonly observed in hypertensive patients, and have been demonstrated to be risk factors of chronic heart failure due to LV diastolic dysfunction. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. However, relationships between bone mineral density and LV hypertrophy and diastolic dysfunction have not been fully assessed. We examined relationships between bone mineral density and both LV hypertrophy and diastolic dysfunction in 38 hypertensive patients (23 males, 15 females; mean age 71 ± 8 y) who had been treated with antihypertensive drugs for at least 1 year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device (A-1000 EXPRESS/InSight, GE Healthcare, Horten, Norway), and the stiffness index was determined as a parameter of bone mineral density. Echocardiography was performed to measure the left ventricular mass index as a parameter of LV hypertrophy. Left ventricular diastolic dysfunction was also assessed by early diastolic mitral annular velocity (e'), and the ratio of early transmitral flow velocity (E) to e' (E/e'). The bone mineral density did not correlate with left ventricular mass index, but did correlate with e' (r = 0.453, P < .01) and E/e' (r = -0.359, P < .05). Thus, reduced bone mineral density in hypertensive patients is not associated with LV hypertrophy but with LV diastolic dysfunction. Hypertensive patients with reduced bone mineral density may have a high risk of chronic heart failure due to LV diastolic dysfunction as well as bone fractures due to osteoporosis.

Association between echocardiographic parameters and brain natriuretic peptide levels in treated hypertensive patients.

We examined which echocardiographic parameter correlated best with plasma brain natriuteric peptide (BNP) levels in treated hypertensive patients. Enrolled in the study were 122 treated hypertensive patients (70 ± 9 y). The left ventricular mass index and left atrial dimension (LAD) were measured using echocardiography as indexes of left ventricular hypertrophy and left atrial enlargement, respectively. Among all the echocardiographic parameters, LAD correlated best with BNP (r = 0.343, p < 0.001). Stepwise regression analysis showed that LAD (ß coefficient = 0.513, p < 0.001) was independently associated with BNP. Left atrial enlargement, rather than left ventricular hypertrophy, may be clinically useful for predicting elevated BNP levels in treated hypertensive patients.

Seasonal variation in estimated glomerular filtration rate based on serum creatinine levels in hypertensive patients.

Seasonal variations in blood pressures should be kept in mind when controlling blood pressure in hypertensive patients. Seasonal variations in glomerular filtration rate (GFR) also may have a clinical significance. However, it is time-consuming to measure GFR directly. We therefore examined the seasonal variation in estimated glomerular filtration rate (eGFR) based on serum creatinine levels in hypertensive patients without CKD (eGFR ≥ 60 mL/min/1.73 m(2)) and those with chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). This study included 47 hypertensive patients without CKD (69 ± 11 yrs) and 55 hypertensive patients with CKD (76 ± 8 yrs). The eGFR was determined from the equation: eGFR = 194 × age(-0.287) × (serum creatinine)(-1.094) (× 0.739 if female). Overall, both groups of hypertensive patients demonstrated similar seasonal variations in eGFR. Importantly, hypertensive patients without CKD and those with CKD showed the lower eGFR in summer (June-August) (71.8 ± 13.2 and 37.2 ± 13.0 mL/min/1.73 m(2), respectively) compared with the eGFR in spring (March-May) (77.9 ± 13.0 and 43.0 ± 14.0 mL/min/1.73 m(2), respectively) (p < 0.05). The decrease in eGFR from spring to summer was similar for both types of hypertensive patients (without CKD, -6.1 ± 7.0; with CKD, -5.8 ± 5.2 mL/min/1.73 m(2)). However, the percent change in eGFR from spring to summer was greater in hypertensive patients with CKD (-13.8 ± 9.4 %) than in those without CKD (-7.7 ± 8.3 %) (p = 0.001). In conclusion, careful observation regarding renal function is needed for hypertensive patients with CKD during summer.

Association between bone mineral density and arterial stiffness in hypertensive patients.

Hypertension and osteoporosis are two common diseases in the elderly population. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. Reduced bone mineral density is associated with increased arterial stiffness in chronic dialysis patients and healthy postmenopausal women. However, relationships between bone mineral density and arterial stiffness in hypertensive patients have not been fully assessed. We examined the relationships between bone mineral density and both arterial stiffness and nutritional status in 52 hypertensive patients (27 male and 25 female subjects; mean age 71±8 years) who had been treated with antihypertensive drugs for at least one year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device, and the stiffness index was determined as a parameter of the bone mineral density. We measured the cardio-ankle vascular index (CAVI) to assess arterial stiffness and used the serum albumin to assess nutritional status. Increased arterial stiffness as assessed with CAVI is associated with reduced bone mineral density (r=-0.289, p=0.038). However, the correlation between CAVI and bone mineral density is not as strong as the correlation between serum albumin and bone mineral density (r=0.501, p<0.001). In conclusion, nutritional status is an important indicator of bone mineral density in hypertensive patients. Moreover, increased arterial stiffness is associated with reduced bone mineral density in hypertensive patients. Therefore, hypertensive patients with increased arterial stiffness may have a high risk of bone fracture due to osteoporosis.

Association between high-sensitivity C-reactive protein and left ventricular diastolic function assessed by echocardiography in patients with cardiovascular risk factors.

High-sensitivity C-reactive protein (hsCRP) has been demonstrated to play a causal role in atherosclerosis and to predict cardiovascular events in the general population. On the other hand, left ventricular (LV) hypertrophy and diastolic dysfunction assessed by echocardiography can also predict cardiovascular events in patients with cardiovascular risk factors. However, there are few data regarding the relationships among hsCRP, LV hypertrophy, and diastolic function. We examined the relationships among hsCRP, LV hypertrophy, and diastolic function in 185 patients (65±11 years), who had no overt heart disease, but had cardiovascular risk factors, including hypertension, diabetes, and dyslipidemia. Echocardiography was performed to measure the left ventricular mass index (LVMI) as a parameter of LV hypertrophy. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (E'), and the ratio (E/E') of E to E' using Doppler echocardiography. The hsCRP was correlated with LVMI (r=0.228, p=0.002), E' (r=-0.276, p<0.001), and E/E' (r=0.419, p<0.001). The E/E' as a parameter of LV diastolic function showed the closest correlation to hsCRP. These results indicate that elevated hsCRP reflects LV diastolic dysfunction rather than LV hypertrophy. We therefore suggest that hsCRP may be a marker of subclinical LV diastolic dysfunction in patients with cardiovascular risk factors.

Correlation of arterial stiffness to left ventricular function in patients with reduced ejection fraction.

Heart failure has been divided into heart failure with preserved left ventricular (LV) ejection fraction (EF) and heart failure with reduced EF, because the pathophysiologies of the two conditions are different. Cardio-ankle vascular index (CAVI) is a new indicator of arterial stiffness, and the most conspicuous feature of CAVI is its independence of blood pressure at the time of measurement. Arterial stiffness has been considered to increase LV afterload, which requires special care to avoid the onset of heart failure. We compared the correlation of arterial stiffness as assessed by CAVI to LV function in 44 hypertensive patients with preserved EF (EF: 71 ± 7%) and 31 patients with reduced EF (48 ± 8%). All of patients with reduced EF had history of both hypertension and myocardial infarction. Using Doppler echocardiography, LV diastolic and systolic function was evaluated by measuring peak early diastolic mitral annular velocity (e') and global LV peak systolic longitudinal strain (GPSLS), respectively. In patients with preserved EF, CAVI was correlated with e' (r = -0.313, p = 0.038), but not with GPSLS (r = 0.207). By contrast, CAVI was correlated with GPSLS (r = 0.604, p < 0.001) as well as e' (r = -0.393, p = 0.029) in patients with reduced EF. Thus, patients with reduced EF showed a closer correlation of arterial stiffness to LV function compared with patients with preserved EF. Therefore, hypertensive patients with reduced EF require a stricter regimen for treating arterial stiffness than their counterparts with preserved EF.

Differences between hypertensive and atherosclerotic lesions in retinal arteries assessed by Scheie's classification in hypertensive patients following stroke.

Scheie's classification regarding hypertensive and atherosclerotic lesions in retinal arteries is generally used to assess the severity of hypertensive retinopathy and the risks of cardiovascular events in hypertensive patients. However, the differences between these two types of retinal artery lesions have not been fully examined. Both arterial stiffness and aortic root diameter are increased in hypertensive patients. The aim of this study was to elucidate differences in the two types of lesions by comparing their relationships to arterial stiffness and aortic root diameter in hypertensive patients following stroke. Fifty-two hypertensive patients following stroke were divided into five stages according to Scheie's classification of hypertensive (H stage 0-4) and atherosclerotic (S stage 0-4) lesions by ophthalmologists. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV) using an automatic waveform analyzer. Aortic root diameter was measured using M-mode echocardiography. The H and S stages in retinal arteries correlated with each other (ρ = 0.443, p < 0.001). However, the S stage correlated with baPWV (ρ = 0.385, p = 0.005) and the aortic root diameter (ρ = 0.285, p = 0.043), while the H stage did not correlate with these parameters. Multiple stepwise regression analysis demonstrated that the aortic root diameter was independently associated with S stage (ß = 0.373, p = 0.006), even though baPWV was independently associated with neither S stage nor H stage. In conclusion, hypertensive lesions (H stage) in retinal arteries are associated with atherosclerotic lesions (S stage) in retinal arteries. However, S stage may reflect arterial stiffening and aortic root dilatation better than H stage in hypertensive patients following stroke. This difference between H and S stages of Scheie's classification should be kept in mind when considering the association between retinal microcirculation and large vessel arteriosclerosis.

Aortic annular velocity assessed by tissue Doppler echocardiography as a potential parameter of arterial stiffness.

Although mitral annular velocity assessed by tissue Doppler echocardiography has been established as a parameter of left ventricular (LV) diastolic function, aortic annular velocity has never been investigated as a parameter of cardiovascular function. We investigated whether aortic annular velocity can be measured using the same tissue Doppler echocardiographic method that is used for measuring mitral annular velocity, as well as the correlation between the aortic annular velocity thus measured and arterial stiffness that was assessed by the cardio-ankle vascular index (CAVI). Sixty-three patients (69 +/- 13 years) with hypertension, diabetes, or dyslipidemia, who had no overt heart disease, were enrolled. The mitral and aortic annular velocities were measured at the mitral and aortic annuluses, respectively, using tissue Doppler echocardiography. Aortic annular velocity was successfully obtained in all patients. The correlation between the peak early diastolic aortic annular velocity (r = -0.803, p < 0.001) and CAVI as an index of arterial stiffness was greater than that of the peak early diastolic mitral velocity and CAVI (r = -0.649, p < 0.001). Stepwise regression analysis showed that the age (beta coefficient = 0.488, p = 0.002) and the peak early diastolic aortic annular velocity (beta coefficient = -0.405, p = 0.008) were independent determinants of the CAVI. The strong inter-relationship was found between left ventricular diastolic function assessed by the aortic annular velocity and arterial stiffness assessed by CAVI. In conclusion, the aortic annular velocity may be helpful for assessing arterial stiffness in patients with cardiovascular risk factors.

Cardio-ankle vascular index for evaluating immunosuppressive therapy in a patient with aortitis syndrome.

Aortitis syndrome is a chronic vasculitis that leads to arterial wall thickening and stiffening in large elastic arteries. However, there are no established markers for assessing arterial stiffening in aortitis syndrome. The cardio-ankle vascular index (CAVI) has recently been utilized to assess arterial stiffening that is associated with atherosclerosis-related diseases. We hypothesized that CAVI can be applicable for assessing alterations in arterial stiffness during immunosuppressive therapy for aortitis syndrome. A 69-year-old woman with a 2-month history of recurrent fever, fatigue, and malaise, showed intense 18F-fluorodeoxyglucose (18F-FDG) uptake in the thoracic aorta and common carotid arteries in 18F-FDG-positron emission tomography. These clinical and imaging findings resulted in the diagnosis of aortitis syndrome. The patient also showed the elevated CAVIs on both sides (right, 10.3; left, 10.4) (normal value for her age, 9.1 +/- 0.8), indicating the arterial stiffness due to aortitis syndrome. The patient was treated for 34 weeks with immunosuppressive therapy, which included oral prednisolone and methotrexate. C-reactive protein (from 4.24 to 0.49 mg/dL) and immunoglobulin G (from 2,627 to 1,524 mg/dL) were decreased by 7 weeks after initiation of the treatment. The decrease in these inflammatory parameters suggests the effectiveness of the immunosuppressive therapy. In addition, after the 34-week treatment, the CAVIs on both sides (right, 9.3; left, 9.2) were within the normal range. These data indicate that the immunosuppressive therapy ameliorates the degree of arterial stiffness. In conclusion, CAVI may be a promising marker for evaluating the effectiveness of immunosuppressive therapy in patients with aortitis syndrome.

Age-related decrease in inferior vena cava diameter measured with echocardiography.

The diameter of the inferior vena cava (IVC) measured with echocardiography is clinically used as a parameter to estimate right atrial pressure, which reflects dehydration or overhydration. Because elderly patients fall easily into dehydration, normal values for IVC diameters in elderly patients may be helpful for geriatric medicine. However, normal values of IVC diameter in relation to age have not been investigated. The purpose of this study was to elucidate age-related changes in IVC diameter using echocardiography. Enrolled in the study were 200 patients (67 ± 15 yrs: range 17-94 yrs) with cardiovascular risk factors but no overt cardiac diseases. IVC diameters throughout the respiratory cycle were measured as maximum and minimum IVC diameters (IVC(max), IVC(min)) using M-mode echocardiography. To assess IVC collapsibility, the respirophasic variation of IVC diameter was calculated as (IVC(max) - IVC(min))/(IVC(max)) ×100. Maximum IVC diameter was decreased with advancing age (r = -0.221, p = 0.002). The respirophasic variation of the IVC diameter was increased with advancing age (r = 0.244, p = 0.001). Stepwise multiple regression analysis showed that age was an independent determinant for both maximum IVC diameter (ß coefficient = -0.249, p < 0.001) and respirophasic variation of the IVC diameter (ß coefficient = 0.268, p < 0.001). Age-related decrease in maximum IVC diameter and increase in the respirophasic IVC collapsibility may indicate the decrease in right atrial pressure in some elderly patients. Therefore, elderly patients with decreased maximum IVC and increased respirophasic IVC collapsibility may need prevention for dehydration.

Elevated brachial-ankle pulse wave velocity is associated with left ventricular hypertrophy in hypertensive patients after stroke.

Brachial-ankle pulse wave velocity (baPWV) is widely used as a marker of arterial stiffness, but there are no data regarding the usefulness of measuring baPWV in hypertensive patients after stroke. The purpose of this study was to examine the clinical significance of baPWV by assessing its correlation with echocardiographic parameters in hypertensive patients after stroke. The study enrolled 61 hypertensives after stroke (24 patients with cerebral infarction and 37 with cerebral hemorrhage) and 61 age-matched hypertensives without stroke. Left ventricular (LV) hypertrophy was evaluated by measuring LV mass index (LVMI) and relative wall thickness (RWT), and LV diastolic function was evaluated by measuring peak early mitral annular velocities (E') using echocardiography. Concentric LV hypertrophy showing increased RWT (0.50 +/- 0.12) was observed in hypertensives after stroke, but not in hypertensives without stroke. In hypertensives after stroke, elevated baPWV correlated with age (r = 0.60, p < 0.001), systolic blood pressure (r = 0.56, p < 0.001), increased LVMI (r = 0.47, p < 0.001), and decreased E' (r = -0.40, p = 0.002). Multiple regression analysis showed that age (beta coefficient = 0.43, p < 0.001), systolic blood pressure (beta coefficient = 0.40, p < 0.001), and LVMI (beta coefficient = 0.25, p = 0.008) were independent determinants of elevated baPWV. In conclusion, elevated baPWV is more closely associated with LV hypertrophy than with LV diastolic dysfunction. Elevated baPWV is independently associated with the severity of LV hypertrophy adjusted with systolic blood pressure and age in hypertensive patients after stroke.

Early detection of hypertension in a patient treated with sunitinib by measuring cardio-ankle vascular index.

Cardio-ankle vascular index (CAVI) has been established as a marker of arterial stiffness, which is increased in hypertensive patients. CAVI reflects the stiffness of the aorta, femoral artery, and tibial artery. Sunitinib, multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activities, has been proved effective in patients with gastrointestinal stromal tumors. However, the treatment with sunitinib is often complicated by side effects such as hypertension. We describe an 84-year-old woman with gastrointestinal stromal tumor, who showed changes in arterial stiffness preceding the appearance of hypertension in the early phase after sunitinib initiation. The patient received sunitinib (50 mg given daily) for gastrointestinal stromal tumor. We assessed the influence of sunitinib on arterial stiffness every 7 days by measuring CAVI. The CAVI, which reflects arterial stiffness, was increased from 9.95 at baseline to 11.65 at 7 days after the initiation of sunitinib, whereas the blood pressure remained unchanged (117/72 and 119/76 mmHg). At 14 days after sunitinib initiation, the blood pressure was increased to 159/89 mmHg, indicating the occurrence of hypertension, while the CAVI was 11.90, the similar level detected at 7 days. Subsequently, sunitinib treatment was discontinued, because of the marked decrease in blood platelets. Both blood pressure and CAVI, together with blood platelets, were restored to the baseline values at 12 days after cessation of sunitinib. In conclusion, the increase in the CAVI preceded the appearance of sunitinib-induced hypertension. Arterial stiffness assessed by CAVI may be useful for early detection of sunitinib-induced hypertension.