[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.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

BACKGROUND: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. PATIENTS AND METHODS: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. RESULTS: Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). CONCLUSION: A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

Protocol of a randomised phase III clinical trial of sequential capecitabine or 5-fluorouracil plus bevacizumab (Cape/5-FU-Bmab) to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab in advanced colorectal cancer: the C-cubed (C3) study.

INTRODUCTION: Results from several randomised trials suggest that the sequential use of cytotoxic agents in patients with metastatic colorectal cancer (mCRC) has the potential to improve overall survival compared with combination chemotherapy. This study is designed to investigate whether sequential treatment with bevacizumab-based first-line treatment with oxaliplatin is superior to combination treatment of mCRC. METHODS AND ANALYSIS: The C-cubed (C(3)) study is a two-arm, multicentre, open-label, randomised phase III trial in Japan comparing the efficacy and safety of sequential capecitabine or 5-fluorouracil plus bevacizumab (Cape/5-FU-Bmab) with escalation to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab as the first-line treatment of mCRC. In the sequential arm (Arm A: oxaliplatin 'wait-and-go'), treatment escalation from Cape/5-FU-Bmab to CapeOX/mFOLFOX6-Bmab is recommended in the case of progressive disease. In the combination arm (Arm B: oxaliplatin 'stop-and-go'), de-escalation from CapeOX/mFOLFOX6-Bmab to Cape/5-FU-Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6-Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin after 12 weeks of treatment not caused by oxaliplatin-associated toxicity. A target sample size of 304 evaluable patients is considered sufficient to validate an expected HR for time to failure of strategy of the sequential approach 'wait-and-go' compared to the combination approach 'stop-and go' with 80% power and 2-sided 5% α in case of a true HR<0.69. ETHICS AND DISSEMINATION: This study is conducted according to the standards of Good Clinical Practice and in compliance with the Declaration of Helsinki 2013 and local regulations, and has been submitted and approved by the Ethical Committee of the Non-Profit Organization MINS Institutional Review Board. The protocol and the trial results, even inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000015405, Pre-results.

Analysis of association between brain natriuretic peptide levels and blood pressure variability.

The present study aimed to investigate the association between plasma brain natriuretic peptide (BNP) levels and systolic blood pressure (SBP) variability over a one-year period. Blood pressure was measured in 44 patients treated for hypertension (73±9 years old) at an outpatient clinic every one to two months over a one-year period. The standard deviation (SD) and the coefficient of variation (CV) were calculated to assess SBP variability. Mean SBP was also calculated over the year. Plasma BNP levels were measured at the end of the one-year period. BNP was found to correlate with mean SBP (r=0.599; P<0.001). However, BNP was not observed to be correlate with either the SD (r=0.219; P=0.153) or the CV (r=0.058; P=0.709) of the SBP. Multiple regression analysis revealed that only the mean values of SBP were independently associated with BNP (ß=0.613; P<0.001). Thus, BNP was found to be correlated with mean SBP, but not SBP variability. In conclusion, plasma BNP levels may reflect the average SBP, but not SBP variability over the one-year period prior to the measurement of BNP in patients with hypertension.

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.

Investigation of the factors associated with circulating soluble CD36 levels in patients with HCV-related chronic liver disease.

BACKGROUND: CD36, a class B scavenger receptor, participates in the pathogenesis of metabolic dysregulation such as insulin resistance, hepatic steatosis, and atherosclerosis. Persistent hepatitis C virus (HCV) infection often evokes these metabolic abnormalities. The primary purpose of this study was to investigate the role of CD36 in the pathogenesis of insulin resistance and hepatic steatosis caused by chronic HCV infection. METHODS: Forty-five patients with HCV-related chronic liver disease (CLD-C) were enrolled in this study. CD36 expression in the liver specimen was examined by an immunohistochemical procedure. The concentrations of circulating soluble form of CD36 (sCD36) and oxLDL were determined by the enzyme-linked innunosorbent assay. Insulin resistance was estimated by the values of HOMA-IR. RESULTS: Moderate to extensive hepatic CD36 expression was observed in the sinusoids of all enrolled CLD-C patients. CD36-positive sinusoids appeared to be identical to Kupffer cells. The severity of CD36 expression in the hepatic sinusoids was significantly correlated with the sCD36 level in sera of patients with CLD-C. The serum sCD36 levels were significantly correlated with body mass index and serum oxLDL levels in those patients. However, the serum sCD36 concentrations were independent of the values of HOMA-IR and the severity of hepatic steatosis. CONCLUSIONS: These data suggest that the serum sCD36 levels reflect the severity of CD36 expression on the Kupffer cells in patients with CLD-C, and that the serum sCD36 levels were associated with obesity, although the levels were independent of insulin resistance and hepatic steatosis in those patients.

Clinical significance of differences between home and clinic systolic blood pressure readings in patients with hypertension.

OBJECTIVES: To elucidate the clinical significance of differences between home- and clinic-measured systolic blood pressure (SBP) in patients with treated hypertension, and to assess the correlations between SBPs and arterial stiffness. METHODS: Patients with treated hypertension measured their blood pressure (BP) themselves once, at home, in the morning (<1 h after awakening) using an automated oscillometric sphygmomanometer. Clinic BP was measured once, at an outpatient clinic on the same day, using a similar instrument. Arterial stiffness was measured by cardio-ankle vascular index (CAVI). Differences between home and clinic SBPs, and the correlations between CAVI and home SBP, clinic SBP, and the difference between home and clinic SBPs, were analysed. RESULTS: Seventy-six patients with treated hypertension (mean age, 71 years) were evaluated. There was no statistically significant difference between home and clinic SBP (mean ± SD 132 ± 14 and 133 ± 16 mmHg, respectively). Home SBP showed no correlation with CAVI, whereas clinic SBP showed a weak correlation. The difference between the home and clinic SBP showed a stronger correlation with CAVI, and was statistically significant. CONCLUSIONS: The difference between home- and clinic-measured SBP showed a better correlation with arterial stiffness than did either home or clinic SBP alone.

Relationship between arterial stiffness and variability in systolic blood pressure during a single clinic visit in patients with hypertension.

OBJECTIVE: To examine factors affecting systolic blood pressure (SBP) variability during a single clinic visit, in treated hypertensive patients. METHODS: Hypertensive patients were recruited to this observational study. Blood pressure was measured using an automated blood pressure monitor when each patient arrived at the outpatient clinic and again when they saw the physician. Mean SBP and SBP variability during a single clinic visit were calculated. The cardio-ankle vascular index (CAVI), as a marker of arterial stiffness, was also measured. RESULTS: A total of 57 treated hypertensive patients (mean age 71 years) were included in the study. The mean SBP was positively correlated with age (r = 0.457), while SBP variability was positively correlated with age (r = 0.383), CAVI (r = 0.330), and glycosylated haemoglobin (r = 0.345) and triglyceride levels (r = 0.299). CONCLUSION: Variability in SBP during a single clinic visit showed better correlations with arterial stiffness and risk factors for atherosclerosis than did mean SBP. Large SBP variability during a single clinic visit may reflect progression of atherosclerosis, in treated hypertensive patients.

The ratio of insulin-like growth factor-I/insulin-like growth factor-binding protein-3 in sera of patients with hepatitis C virus-related chronic liver disease as a predictive marker of insulin resistance.

Recent studies have elucidated a lower level of serum insulin-like growth factor-I (IGF-I) or a decrease in the IGF-I/IGF-binding protein-3 (IGFBP-3) ratio in patients with type 2 diabetes mellitus or hepatic steatosis. Persistent hepatitis C virus (HCV) infection often evokes metabolic abnormalities including hepatic steatosis and insulin resistance. We hypothesized that the relationship between the ratio of IGF-I/IGFBP-3 and the severity of hepatic steatosis or insulin resistance would be observed in patients with HCV-related chronic liver disease (CLD). On the basis of the classifications proposed by Brunt and colleagues (Am J Gastroenterol 1999; 94: 2467-2474), among the 42 enrolled patients with HCV-related CLD, 23 of them had no hepatic steatosis (grade 0), 14 had grade 1 steatosis, and 5 had grade 2 steatosis. The levels of serum IGF-I in the enrolled patients declined in proportion to the severity of hepatic steatosis, whereas serum IGFBP-3 levels did not affect its severity. Therefore, the ratio of IGF-I/IGFBP-3, which corresponds to the circulating free IGF-I status, was significantly lower in those patients with hepatic steatosis (grades 1 and 2) than in those without hepatic steatosis. Serum IGF-I levels significantly correlated with serum zinc levels (r = 0.370, P = .0266), but IGFBP-3 levels did not. However, the linear regression analysis revealed an inverse correlation between the IGF/IGFBP-3 ratio and the value of homeostasis model for assessment of insulin resistance (r =-0.411, P = .0094). These findings suggest that the decline of the circulating free IGF-I level, which derives from zinc deficiency, may contribute to hepatic steatosis and insulin resistance in patients with HCV-related CLD.

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 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.

Association between urinary 8-hydroxydeoxyguanosine, an indicator of oxidative stress, and the cardio-ankle vascular index in hypertensive patients.

AIMS: Oxidative stress has been recently postulated to be an important factor in the pathogenesis and development of arteriosclerosis. Although urinary 8-hydroxydeoxyguanosine (8-OHdG) is clinically used as a marker of oxidative stress, its usefulness in diagnosing arteriosclerosis has not been fully examined. This study aimed to evaluate the association between urinary 8-OHdG and the cardioankle vascular index (CAVI) as a marker of arterial stiffness in hypertensive patients. METHODS: We enrolled 100 hypertensive patients (70 ± 10 years) who had been taking antihypertensive medications for at least one year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001; Selista Inc., Tokyo, Japan). CAVIs were measured at the same visit. RESULTS: Urinary 8-OHdG was correlated with smoking habits (r=0.382, p<0.001) and CAVIs (r= 0.223, p= 0.026). Multiple linear regression analysis revealed two independent determinants of urinary 8-OHdG: smoking habits (ß=0.501, p<0.001) and CAVI (ß=0.325, p=0.001). In addition, CAVIs were correlated with age (r= 0.600, p<0.001), BMI (r=-0.348, p<0.001), systolic blood pressure (r= 0.343, p<0.001), pulse pressure (r= 0.358, p<0.001), serum creatinine level (r=0.408, p<0.001), urinary 8-OHdG level (r= 0.223, p= 0.026), and diabetes (r= 0.210, p=0.036). Multiple linear regression analysis revealed two independent determinants of CAVI: age (ß= 0.568, p<0.001) and 8-OHdG (ß=0.357, p<0.001). CONCLUSION: Elevated CAVI is independently associated with an elevated urinary 8-OHdG level in hypertensive patients.

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.

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 of cardio-ankle vascular index with brain natriuretic peptide levels in hypertension.

AIMS: Plasma brain natriuteric peptide (BNP) is an established marker of cardiovascular events in individuals without heart failure. Although the cardio-ankle vascular index (CAVI) is clinically used as a parameter of arterial stiffness, its usefulness for predicting cardiovascular events has not been fully examined. This study aimed to evaluate the association among CAVIs, plasma BNP levels and left ventricular (LV) hypertrophy and dysfunction in hypertensive patients. METHODS: We enrolled 136 hypertensive patients (69±10 years) who had been taking antihypertensive medications for at least one year. Echocardiography was performed to evaluate LV hypertrophy and function. Plasma BNP levels and CAVIs were also measured simultaneously. RESULTS: CAVI was correlated with plasma BNP (r =0.245, p =0.004). Multiple linear regression analysis revealed three independent determinants of CAVI: age (ß =0.568, p <0.001), diameter of ascending aorta (ß =0.289, p <0.001), and diabetes (ß =0.207, p =0.003). In addition, multiple linear regression analysis revealed two independent determinants of the plasma BNP level: left atrial diameter (ß =0.334, p <0.001) and CAVI (ß =0.256, p =0.002). CONCLUSION: The present study indicates that increased CAVI is independently associated with elevated plasma BNP produced by increased LV afterload, that is, arterial stiffness, in hypertensive patients. Moreover, the present study raises the possibility that CAVI may be as useful as the plasma BNP level for predicting the risk of cardiovascular events in hypertensive patients.

Association between arterial stiffness and pulmonary function in hypertensive patients.

Arterial stiffness, assessed by cardio-ankle vascular index (CAVI), is clinically used to assess arteriosclerosis. Recently, pulmonary age, as determined by pulmonary function test, has been proposed by the Japanese Respiratory Society as a diagnostic measure for chronic obstructive pulmonary disease (COPD). This study aims to examine the association between CAVI and pulmonary function and to elucidate the correlation between vascular stiffness and pulmonary age in hypertensive patients. We enrolled a total of 45 hypertensive patients (70±9 years) who had been taking antihypertensive medications for at least 1 year. Pulmonary function was measured by the percentage of predicted forced vital capacity (FVC) and the ratio of forced expiratory volume in 1 s (FEV(1)) to FVC (FEV(1)/FVC ratio). Pulmonary age was determined by the equation proposed by the Japanese Respiratory Society. CAVI was measured at the same clinic visit. In the simple correlation analysis CAVI correlated with the FEV(1)/FVC ratio (r=-0.399, P=0.007) and pulmonary age (r=0.559, P<0.001). Multiple linear regression analysis revealed that CAVI was independently associated with FEV(1)/FVC ratio (ß=-0.418, P=0.014) and pulmonary age (ß=0.514, P=0.002). In addition, CAVI was significantly higher in patients with increased pulmonary age (9.4±1.4) than in those with normal pulmonary age (8.4±0.9) (P=0.011). The present study indicates that an increased CAVI is independently associated with reduced pulmonary function and increased pulmonary age. Hypertensive patients with high CAVI may need to be monitored for the progression of COPD.

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus-related chronic liver disease.

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.