Yoshinari Matsumoto

Physical inactivity and insufficient dietary intake are associated with the frequency of sarcopenia in patients with compensated viral liver cirrhosis.

The association between sarcopenia and nutritional status is thought to be an important problem in patients with cirrhosis. In this study, we investigated whether nutritional factors were related to sarcopenia in patients with liver cirrhosis.

Cytoglobin deficiency promotes liver cancer development from hepatosteatosis through activation of the oxidative stress pathway.

This study was conducted to clarify the role of cytoglobin (Cygb), a globin expressed in hepatic stellate cells (HSCs), in the development of liver fibrosis and cancer in nonalcoholic steatohepatitis (NASH). Cygb expression was assessed in patients with NASH and hepatocellular carcinoma. Mouse NASH model was generated in Cygb-deficient (Cygb(-/-)) or wild-type (WT) mice by giving a choline-deficient amino acid-defined diet and, in some of them, macrophage deletion and N-acetyl cysteine treatment were used. Primary-cultured mouse HSCs isolated from WT (HSCs(Cygb-wild)) or Cygb(-/-) (HSCs(Cygb-null)) mice were characterized. As results, the expression of CYGB was reduced in patients with NASH and hepatocellular carcinoma. Choline-deficient amino acid treatment for 8 weeks induced prominent inflammation and fibrosis in Cygb(-/-) mice, which was inhibited by macrophage deletion. Surprisingly, at 32 weeks, despite no tumor formation in the WT mice, all Cygb(-/-) mice developed liver cancer, which was ameliorated by N-acetyl cysteine treatment. Altered expression of 31 genes involved in the metabolism of reactive oxygen species was notable in Cygb(-/-) mice. Both HSCs(Cygb-null) and Cygb siRNA-transfected-HSCs(Cygb-wild) exhibited the preactivation condition. Our findings provide important insights into the role that Cygb, expressed in HSCs during liver fibrosis, plays in cancer development with NASH.

Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in patients with rheumatoid arthritis –TOMORROW study

Abstract Objectives. The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level. Methods. A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay. Results. Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate. Conclusions. Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.

Absence of cytoglobin promotes multiple organ abnormalities in aged mice

Cytoglobin (Cygb) was identified in hepatic stellate cells (HSCs) and pericytes of all organs; however, the effects of Cygb on cellular functions remain unclear. Here, we report spontaneous and age-dependent malformations in multiple organs of Cygb−/− mice. Twenty-six percent of young Cygb−/− mice (<1 year old) showed heart hypertrophy, cystic disease in the kidney or ovary, loss of balance, liver fibrosis and lymphoma. Furthermore, 71.3% (82/115) of aged Cygb−/− mice (1–2 years old) exhibited abnormalities, such as heart hypertrophy and cancer development in multiple organs; by contrast, 5.8% (4/68) of aged wild-type (WT) mice had abnormalities (pu2009<u20090.0001). Interestingly, serum and urine analysis demonstrated that the concentration of nitric oxide metabolites increased significantly in Cygb−/− mice, resulting in an imbalance in the oxidative stress and antioxidant defence system that was reversed by NG-monomethyl-L-arginine treatment. A senescent phenotype and evidence of DNA damage were found in primary HSCs and the liver of aged Cygb−/− mice. Moreover, compared with HSC+/+, HSC−/− showed high expression of Il-6 and chemokine mRNA when cocultured with mouse Hepa 1–6 cells. Thus, the absence of Cygb in pericytes provokes organ abnormalities, possibly via derangement of the nitric oxide and antioxidant defence system and through accelerated cellular senescence.

Body composition analysis of cachectic rabbits by total body electrical conductivity

A simple formula (1.536 x TOBEC + 475.146 = LBM, where TOBEC is total body electrical conductivity and LBM is lean body mass) to estimate LBM in grams was developed on the basis of the total body fat data obtained by ether extraction and TOBEC in normal rabbits. The formula was also applicable to rabbits with cachexia induced by inoculation of VX2 carcinoma or by starvation. We were able to assess the losses of body fat in the rabbits with cachexia at 10-day intervals by using TOBEC.

Expression of the mitotic-arrest deficiency 2 is associated with chemotherapy resistance in ovarian serous adenocarcinoma

Mitotic-arrest deficiencyxa02 (MAD2) is a key component of spindle assembly checkpoint (SAC) function; SAC mediates spindle microtubule attachment to kinetochores on chromosomes and chromosomal segregation during mitosis. To determine whether MAD2 expression is associated with chemotherapy resistance in ovarian serous adenocarcinoma, we reviewed tumor samples from 41xa0cases of ovarian serous adenocarcinoma at Osaka City University Medical School Hospital (Osaka, Japan), 2000-2007. Of the 41xa0cases, 24 were recurrent and 17 were not recurrent. Expression of MAD2 was investigated in paraffin-embedded sections using a MAD2 antibody. Quantitative analysis of MAD2 expression gave mean weighted scores of 4.3 for the relapsed group and 7.2 for the relapse-free group; the expression was, thus, significantly greater in the relapse-free group compared to the relapsed group (P=0.023). When the 41xa0cases were classified into low- and high-expression, these classifications showed no significant difference in terms of progression-free survival (P=0.0685), however, overall survival for the low-expression group was significantly shorter than that of the high-expression group (P=0.0188). The present study implies that MAD2 expression levels can indicate sensitivity to anticancer agents, and risk for recurrence.

Nutritional changes and factors contributing to postoperative weight recovery after esophagectomy

BackgroundIn patients treated surgically for esophageal cancer, time-dependent data on nutritional status from the perioperative to postoperative period are questionable. We investigated time-dependent data on weight, body composition, and nutritional indices of patients with esophageal cancer from the preoperative period through the 12-month postoperative period.MethodsEighty patients with esophageal cancer were enrolled and subsequently underwent esophagectomy. Forty out of eighty patients were completed the 12-month follow-up survey period and analyzed. We assessed clinical, anthropometric measurement, laboratory data, and nutritional status data preoperatively and at 1, 3, 6, and 12xa0months postoperatively.ResultsPatients with esophageal cancer had 7.2% weight loss in the preoperative period compared with the usual body weight (UBW) before morbidity and 9.3% weight loss from preoperative to 12-month postoperative period. Weight gain in the postoperative survey period was not significant. Conversely, there was a time lag in the time-dependent changes in the postoperative nutritional status; this was considered to coincide with internal organ protein, body protein, and body fat levels, in that order. Multivariate analysis identified axa0≥xa010% preoperative weight loss compared with UBW as the only independent factor negatively contributing toxa0≥xa085% weight recovery at 12xa0months postoperatively (OR 6.54, 95% CI 1.14–37.60, pxa0=xa00.036).ConclusionsFor sufficient nutritional status recovery in patients treated with esophagectomy, minimizing weight loss preoperatively is important. Regardless of neoadjuvant therapy or age, preoperative nutritional treatment should be promptly administered for all patients.

Factors Related to Body Mass Index in Women with Rheumatoid Arthritis - TOMORROW study

Objectives : This study aimed to clarify the relationship between body mass index (BMI) and patient characteristics, lifestyle factors, and cardiovascular disease (CVD)-related clinical data in women with rheumatoid arthritis (RA). Methods : A total of 171 female outpatients with RA and 170 age-matched females without RA (controls) from the TOMORROW study (UMIN: 000003876) were included in this cross-sectional study. We divided subjects into 3 groups based on BMI: underweight (BMI < 18.5 kg/m 2 ), normal weight (BMI ≥ 18.5 kg/m 2 and < 25 kg/m 2 ), and overweight (BMI ≥25 kg/m 2 ), and compared RA disease activity, activities of daily living (ADL) assessed by modified health assessment questionnaire (mHAQ) score, energy and nutrient intake, and CVD risk-related clinical data. Results : In patients with RA, mHAQ scores were lower in the normal weight group compared with the underweight and overweight groups ( p < 0.05). Disease activity showed a similar trend. Energy, protein, and carbohydrate intake showed a positive correlation with BMI ( p < 0.05). Blood pressure, C-reactive protein, uric acid, triglyceride, fasting plasma glucose, immune reactive insulin, HbA1c, and leptin showed a positive correlation with BMI, and adiponectin showed a negative correlation with BMI ( p < 0.05). Control subjects showed similar trends. Conclusions : BMI is related to ADL, disease activity, energy, protein and carbohydrate intake, and CVD risk-related clinical data, and might be an indicator of total health status in female patients with RA.

Utility of a web-based weight loss program with auto-extraction of behavioural objectives and recording of daily weight and steps in pre-obese outpatients.

The epidemic of obesity is now a major public health concern in many parts of the world. Face-to-face tailored lifestyle modification therapy is one of the major approaches used for weight loss. However, the lack of time for multiple visits and the lack of resources for administering therapy hinder its implementation. We administered a web-based weight loss program for obese patients from July 2010 to January 2012 that required only 2 personal interviews over 6 months. The program used a system of auto-extraction of behavioural objectives and auto recording of daily weight and number of steps taken. The subjects included 3 obese men (mean age, 35.7 ± 2.3 years; mean body mass index (BMI), 30.4 ± 0.8 kg/m²) and 17 obese women (mean age, 39.3 ± 9.5 years; mean BMI, 28.1 ± 1.8 kg/m2) who volunteered to participate in this weight loss program. Weight loss achieved through this program was significant (mean, 2.7%, p=0.047). Abdominal visceral fat area (VFA) decreased significantly (mean, 12.6%, p=0.017), and the serum cholinesterase and alanine aminotransferase levels improved (mean, 33 U/L, p=0.003; mean, 7 IU/L, p=0.033 respectively). Metabolic syndrome criteria number had a tendency to decrease. Dietary and nutrient intake levels on the food frequency questionnaire improved. Weight loss ratio after 6 months and initial weight loss ratio were strongly significantly correlated. A web-based weight loss program with auto-extraction of behavioural objectives and recording of daily weight and steps can achieve weight loss, as determined by VFA reduction, on low manpower.

OP0010-HPR Intake of Monounsaturated Fatty Acids as Components of A Mediterranean Diet Suppresses Rheumatoid Arthritis Disease Activity – the Tomorrow Study

Background The Mediterranean diet suppresses the disease activity of rheumatoid arthritis (RA). However, the key elements involved in this effect have not been assessed. Objectives To clarify the relationship between disease activity in patients with RA and Mediterranean diet scores calculated from daily food and specific nutrient components. Methods Data from 208 consecutive patients with RA and 205 age- and gender-matched healthy volunteers participating in a 10-year-prospective cohort study (TOMORROW) that started in 2010 were assessed (UMIN000003876). We performed a cross-sectional, retrospective analysis of baseline and 2011 data. Daily food and nutrient intake status were assessed using a brief-type self-administered diet history questionnaire (BDHQ) and Mediterranean diet scores were calculated from reference results from the control group. Disease activity was calculated using disease activity scores in 28 joints based on erythrocyte sedimentation rates (DAS28-ESR). Results The intake of monounsaturated fatty acids (MUFA) and of Mediterranean diet components was significantly lower in the RA than in the control group (p =0.003). The ratio of MUFA to saturated FA (SFA) was significantly lower; and intake of fruits, tubers and roots were significantly higher in patients with RA with high disease activity than in those in remission and with low disease activity (p =0.033, 0.010, 0.047, respectively). The DAS28-ESR and MUFA/SFA values revealed a significant correlation, even after age adjustment (R = -0.228, p <0.01). We clarified these findings using logistic regression analysis. Components of Mediterranean diet scores were categorized according to the median intake based on control food and nutrient intake status, and the DAS28-ESR values were categorized as remission or active disease. Intake of MUFA was an independent predictor of remission in patients with RA (Odds: 0.51; 95% CI =0.25–1.02, p=0.057). Annual changes in DAS28-ESR values between 2010 and 2011 significantly correlated with the MUFA/SFA ratio during 2011 even after age adjustment (R =0.180, p =0.01). Conclusions The daily intake of MUFA, a component of the Mediterranean diet, might suppress disease activity in patients with RA. Disclosure of Interest Y. Matsumoto: None declared, Y. Sugioka: None declared, M. Tada: None declared, T. Okano: None declared, K. Mamoto: None declared, K. Inui: None declared, D. Habu: None declared, T. Koike Grant/research support: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbvie, Teijin Pharma, MSD and Ono Pharmaceutical, Speakers bureau: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbvie, Teijin Pharma, MSD and Ono Pharmaceutical DOI 10.1136/annrheumdis-2014-eular.3937