Case-control study of IL23R rs76418789 polymorphism, smoking, and ulcerative colitis in Japan.

BACKGROUND: Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population. METHODS: The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking. RESULTS: The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44-0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype. CONCLUSION: IL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC.

Prospective multicenter surveillance study of branch-duct intraductal papillary mucinous neoplasm of the pancreas; risk of dual carcinogenesis.

BACKGROUND: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). METHODS: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. RESULTS: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. CONCLUSION: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

High-sensitivity C-reactive protein is a predictor of all-cause mortality in a rural Japanese population.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of inflammation. This study aimed to determine whether increased hsCRP levels are associated with all-cause mortality rate. METHODS: We examined data for participants from the 2002 Nomura Cohort Study who attended follow-ups for 20 years (follow-up rate: 93.3%). Of these, 793 were male (aged 61 ± 14 years) and 1040 were female (aged 63 ± 11 years). The Japanese Basic Resident Registry provided data on adjusted relative hazards for all-cause mortality. The data were subjected to a Cox regression analysis using a time variable of age and confounding risk factors. RESULTS: The median (interquartile range) follow-up period was 6548 days (6094-7452 days). The follow-up confirmed that there were 632 (34.8%) deaths, of which 319 were male (40.2% of all males) and 313 were female (30.6% of all females). Multivariable-adjusted hazard ratio (1.27; 95% confidence interval, 1.01-1.59) in the highest hsCRP category was also significantly higher compared with reference. A higher hsCRP was associated with a greater risk of all-cause mortality in male participants aged ≥65 years, a BMI < 25 kg/m2 , and no history of CVD or diabetes, and this association was particularly significant among participants with both of the latter two risk factors (p = 0.004 and 0.022 for interaction, respectively). CONCLUSIONS: Our results indicate a significant association between hsCRP levels and all-cause mortality in a rural Japanese population. Specifically, hsCRP appears to be a crucial biomarker for predicting long-term survival, particularly among older persons.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Association between alanine aminotransferase and all-cause mortality rate: Findings from a study on Japanese community-dwelling individuals.

BACKGROUND: This study examined the relationship between survival prognosis and alanine aminotransferase (ALT), a critical factor contributing to aging-related health and mortality. The research is based on a follow-up study with 6- and 10-year intervals. METHODS: The participants included 1,610 males (63 ± 14 years old) and 2,074 females (65 ± 12 years old) who were part of the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort). The multivariable-adjusted hazard ratios (HRs) of death between the baseline health checkup and the end of the follow-up periods were estimated using a Cox proportional hazards model, controlling for potential confounding factors. RESULTS: The follow-up survey revealed 180 male deaths (11.2% of male participants) and 146 female deaths (7.0% of female participants). The univariate Cox regression analysis showed a significant increase in the HRs of all-cause mortality with decreasing ALT levels (p < 0.001). Furthermore, compared with individuals with ALT levels of 20-29 IU/L, the multivariable-adjusted HRs (95% confidence interval) for all-cause mortality were 2.73 (1.59-4.70) for those with ALT levels <10 IU/L, 1.45 (1.05-2.00) for those with ALT levels of 10-19 IU/L, and 1.63 (1.05-2.53) for those with ALT levels ≥30 IU/L. CONCLUSIONS: Our findings show that abnormally low ALT levels and high within the normal range were related to all-cause mortality in Japan's community-dwelling individuals. Especially, ALT activity may be an important biomarker for predicting the long-term survival of older adults.

Relationship between rural self-efficacy and rural career intent after rural clinical training: a study on medical students in Japan.

BACKGROUND: In Japan, community medicine clerkships facilitate positive attitudes toward rural medical practice and encourage rural recruitment. Rural self-efficacy has been shown to influence rural career intent following a rural clinical placement. However, the impact of subjective difficulties of living in a rural area on future rural career intent is also important. This study aims to explore whether rural self-efficacy influences the relationship between difficulty with living in a rural area and rural career intent.  METHODS: The subjects included 308 male and 255 female participants aged 20-41 [median (interquartile range): 22 (21-22)] years. Rural self-efficacy was based on a validated scale consisting of 15 questions. Difficulty with living in a rural area was measured asking students. A cohort survey was conducted to evaluate the effect of the rural self-efficacy score on the rural career intent of Japanese medical students after they completed their rural clinical training. RESULTS: The following variables were significantly associated with a higher rural self-efficacy score: female sex (p = 0.003), age < 21 years (p = 0.013), having a doctor as a role model (p < 0.001), gaining admission through a school recommendation (p = 0.016), living in a rural or remote area until the age of 18 years (p = 0.018), and orientation towards general medicine (p < 0.001). In addition, baseline difficulty with living in a rural area was significantly associated with a lower self-efficacy score (p < 0.001). Participants with a stronger intent to practice in a rural area before rural clinical training had higher rural self-efficacy and showed a stronger positive rural career intent after rural clinical training (p < 0.001). A multivariable logistic regression analysis demonstrated that difficulty with living in a rural area [odds ratio (OR): 0.61; 95% confidence interval (CI), 0.39-0.84] was still associated with lower rural career intent after rural clinical training, independent of all confounders such as gender, age, scholarship for regional duty, rural background, and orientation towards general medicine. However, when rural self-efficacy (OR, 1.12; 95% CI, 1.07-1.16) was added as a factor for rural career intent, difficulty with living in a rural area (OR, 0.68; 95% CI, 0.43-1.06) was no longer observed as an associated factor. CONCLUSION: Subjective difficulty with living in a rural area was shown to reduce future rural career intent, but high rural self-efficacy ameliorated this decline.

Relationship between body composition and the histology of non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. METHODS: This cross-sectional study comprised 149 patients (55 men; age, 20-76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. RESULTS: Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. CONCLUSIONS: Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression.

Pancreas stiffness in liver cirrhosis is an indicator of insulin secretion caused by portal hypertension and pancreatic congestion.

AIM: Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. METHODS: Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples. RESULTS: Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. CONCLUSIONS: In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.

Low density lipoprotein cholesterol and all-cause mortality rate: findings from a study on Japanese community-dwelling persons.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up. METHODS: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD. RESULTS: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015). CONCLUSIONS: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant.

Alcohol consumption and serum uric acid are synergistically associated with renal dysfunction among community-dwelling persons.

BACKGROUND: Serum uric acid (SUA) is a key risk factor contributing to renal failure, a serious public health problem. However, few studies have examined whether the interactive relationship between alcohol consumption and SUA is independently associated with the estimated glomerular filtration rate (eGFR). METHODS: Our sample comprised 742 men aged 69 ± 11 years (mean ± standard deviation) and 977 women aged 69 ± 10 years from a rural area. We cross-sectionally examined the relationships between the confounding factors of alcohol consumption and SUA with renal function denoted by eGFR estimated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations modified by a Japanese coefficient. RESULTS: In both genders, eGFR increased with a rise in alcohol consumption. This tendency was more pronounced in participants with hyperuricemia, where SUA was greater than 7.0 mg/dL in men and greater than 6.0 mg/dl in women (men: F = 41.98, p < 0.001; women: F = 41.98, p < 0.001). A multiple linear regression analysis showed that alcohol consumption (men: ß = 0.112, p < 0.001; women: ß = 0.060, p = 0.011) and SUA (men: ß = -0.282, p < 0.001; women: ß = 0.317, p < 0.001) were significantly and independently related to eGFR. Further, the interactive relationship between alcohol consumption and SUA (men: F = 6.388, p < 0.001; women: F = 5.368, p < 0.001) was a significant and independent indicator of eGFR. CONCLUSIONS: These results suggested that alcohol consumption and SUA were synergistically associated with renal dysfunction among community-dwelling persons.

Endoscopic stent placement above the sphincter of Oddi for biliary strictures after living donor liver transplantation.

BACKGROUND: Endoscopic balloon dilation and/or plastic stent placement has been a standard method for treating biliary strictures complicated post living donor liver transplantation (LDLT). The strictures may be refractory to endoscopic treatment and require long-term stent placement. However, consensus on the optimal period of the stent indwelling and usefulness of the inside stent does not exist. METHODS: We evaluated the long-term efficacy of stent treatment in patients with biliary stricture post LDLT. In addition, we compared the stent patency between inside stent and conventional outside stent. RESULTS: A total of 98 ERC sessions (median 6: range 1-14) performed on 16 patients receiving endoscopic treatment for biliary strictures post LDLT with duct-to-duct biliary reconstruction were analyzed. Biliary strictures successfully treated in 14 patients (88%) included 7 patients (44%) showing improvement of biliary strictures with repeated endoscopic stent placement. Stent replacement was carried out every 6 to 12 months for the remainder 7 patients (44%). Biliary stents were placed in 87 sessions (77 inside sessions and 10 outside sessions). Stent migration occurred 13 times (16%) and none of the inside stent sessions and the outside stent sessions, respectively. Median patency of inside stent and outside stent were 222 days (range; 8-1736) and 99 days (range; 7-356), respectively. The stent occlusion was significantly less in inside stent than in outside stent (p < 0.001). Stone formation was observed in 14 (18%) of the inside stent and 3 (30%) of the outside stent. Biliary stones were small and successfully removed endoscopically. CONCLUSIONS: The endoscopic treatment using inside stent was useful in the management of biliary strictures after LDLT.

Interactive association of baseline and changes in serum uric acid on renal dysfunction among community-dwelling persons.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. Baseline serum uric acid (SUA) levels were independently associated with incident renal dysfunction, but whether baseline and changes in SUA produce an interactive effect on renal dysfunction remains unclear. METHODS: The subjects comprised 460 men aged 68 ± 10 (mean ± standard deviation) years and 635 women aged 68 ± 9 years from a rural village. We have found participants who underwent a similar examination 3 years later, and analyzed the relationship between baseline SUA, changes in SUA, and a 3-year follow-up renal function evaluated by estimated glomerular filtration rate (eGFR). RESULTS: A total of 93 (20.2%) men and 76 (12.0%) women had hyperuricemia (men: SUA ≥ 7.0 mg/dL and women: SUA ≥ 6.0 mg/dL) at baseline. Multiple regression analysis using changes in eGFR as objective variable, adjusted for risk factors as explanatory variables, showed that the baseline SUA and changes in SUA were linearly associated with changes in eGFR (ß = ï¼0.115, P < .001 and ß = ï¼0.431, P < .001, respectively). In both normal SUA group and hyperuricemia group, changes in SUA significantly associated with changes in eGFR (ß = ï¼0.473, P < .001 and ß = ï¼0.197, P = .009, respectively). Participants with increased SUA from normal to hyperuricemia group had greater eGFR decline over the follow-up period, and their multivariate-adjusted 3-year follow-up eGFR was significantly lower than in other groups (P < .001). CONCLUSION: Our data demonstrated that baseline and longitudinal changes in SUA were independently and interactively associated with the renal function decline among community-dwelling persons.

Efficacy of chemotherapy in elderly patients with unresectable pancreatic cancer: a multicenter review of 895 patients.

BACKGROUND: The efficacy of chemotherapy for unresectable pancreatic cancer has improved. However, it is occasionally difficult to make treatment decisions for elderly patients. We reviewed the outcomes of elderly patients with unresectable pancreatic cancer by using a large cohort and evaluated whether they had received chemotherapy and the reason why. METHODS: Data for 895 pancreatic cancer patients who were treated using chemotherapy or best supportive care were analyzed considering demographics, clinical stage, treatment, and outcome. Data were analyzed using the chi-square test, Student t-test, or Mann-Whitney U-test, as appropriate. Outcomes were analyzed using the Kaplan-Meier method. Differences in survival were analyzed using the log-rank test. RESULTS: The median survival time was significantly shorter in elderly patients (≥65 years) than in younger patients (<65 years) (181 vs. 263 days, P = 0.0001). The median survival time of patients treated with chemotherapy was not significantly different between the elderly and the younger group (274 days vs. 333 days, P = 0.09), and nor was that of patients choosing best supportive care (84 days vs. 78 days, P = 0.83). These results held true even when the age cut-off between younger and elder patients was increased to 70, 75, and 80 years. Elderly patients treated with chemotherapy had a significantly longer median survival time than those choosing best supportive care (274 vs. 86 days, P < 0.0001); a significantly greater proportion of elderly patients chose best supportive care compared to younger patients (47.8 vs. 25.8%, P < 0.0001). The reason for choosing best supportive care was established in 261 elderly patients (82.9%); 133 (51.0%) met the eligibility criteria for chemotherapy, but of these, 78 (58.6%) were not informed about their disease. The treatment preferences of elderly patients were not always considered; they often received only best supportive care per family members preference (N = 65, 48.8%) or because the physician based their treatment decision only on the patient's age (N = 68, 51.1%). CONCLUSIONS: Chemotherapy appears effective for elderly pancreatic cancer patients with unresectable disease, but treatment needs to be optimized to improve prognosis.

Comparison between real-time tissue elastography and vibration-controlled transient elastography for the assessment of liver fibrosis and disease progression in patients with primary biliary cholangitis.

AIM: Assessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real-time tissue elastography (RTE) and vibration-controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC. METHODS: The study participants were 44 patients with PBC. We assessed hepatic and splenic elasticity using RTE and VCTE and measured serum markers related to fibrosis and hepatic and splenic blood flow using Doppler ultrasonography. We then compared RTE and VCTE for diagnostic accuracy. Patients with asymptomatic PBC were followed every 1-3 months. RESULTS: Both RTE and VCTE performed well and had superior diagnostic accuracy compared with biochemical markers. The areas under the receiver operating characteristic curve for RTE and VCTE were 0.92 and 0.92, 0.95 and 0.91, and 0.97 and 0.91 for F ≥ 2, F ≥ 3, and F = 4, respectively. During follow-up, nine patients (25.0%) developed liver-related symptoms. Multivariate analysis revealed that splenic elasticity assessed using RTE was a significant independent factor for the development of liver-related symptoms (odds ratio, 2.19; P = 0.024). CONCLUSIONS: Real-time tissue elastography offered better diagnostic accuracy for severe fibrosis and cholangitis than VCTE. Splenic elasticity determined using RTE is a useful parameter for evaluating liver-related symptoms and an effective predictive marker of disease progression in patients with asymptomatic PBC.

Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy.

BACKGROUND & AIMS: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. METHODS: We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of ursodeoxycholic acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. RESULTS: Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04-1.06; P < .0001); levels of bilirubin (hazard ratio = 2.56; 95% CI: 2.22-2.95; P < .0001), albumin (hazard ratio = 0.10; 95% CI: 0.05-0.24; P < .0001), and alkaline phosphatase (hazard ratio = 1.40; 95% CI: 1.18-1.67; P = .0002); and platelet count (hazard ratio/10 units decrease = 0.97; 95% CI: 0.96-0.99; P < .0001) were all independently associated with death or liver transplantation (C-statistic derivation, 0.81; 95% CI: 0.79-0.83, and validation cohort, 0.82; 95% CI: 0.79-0.84). Patients with risk scores >0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P < .0001). The GLOBE score identified patients who would survive for 5 years and 10 years (responders) with positive predictive values of 98% and 88%, respectively. Up to 22% and 21% of events and nonevents, respectively, 10 years after initiation of treatment were correctly reclassified in comparison with earlier proposed criteria. In subgroups of patients aged <45, 45-52, 52-58, 58-66, and ≥66 years, age-specific GLOBE-score thresholds beyond which survival significantly deviated from matched healthy individuals were -0.52, 0.01, 0.60, 1.01 and 1.69, respectively. Transplant-free survival could still be accurately calculated by the GLOBE score with laboratory values collected at 2-5 years after treatment. CONCLUSIONS: We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of ursodeoxycholic acid-treated patients with PBC. This score might be used to select strategies for treatment and care.

Handgrip strength is associated with metabolic syndrome among middle-aged and elderly community-dwelling persons.

The association of low muscle strength with cardio-metabolic risks remains controversial. The present study included 742 men aged 70 ± 9 years and 937 women aged 70 ± 8 years from a rural village. We examined the cross-sectional relationship between relative muscle strength defined by handgrip strength (HGS)/body weight (BW) ratio, and metabolic syndrome (MetS) based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report and its components. Of these, 203 men (27.4%) and 448 women (47.8%) had MetS. In men, increasing quartile of HGS/BW ratio was significantly and independently associated with high waist circumference {odds ratio, 0.31; 95% confidence interval (CI), 0.24-0.41} and elevated triglyceridemia (0.71, 0.59-0.86). In women, it was also significantly and independently associated with high waist circumference (0.41; 0.36-0.48), high blood pressure (0.78; 0.66-0.92), Low HDL-cholesterolemia (0.84; 0.73-0.98) and elevated triglyceridemia (0.65; 0.53-0.79). In both genders, the prevalence of MetS significantly decreased in relation to increasing HGS/BW ratio. After adjustment for age, smoking status, drinking status, LDL-C, estimated glomerular filtration ratio (eGFR), and medication, the respective odds ratio (95% CI) for the quartile of HGS/BW ratio for MetS was 1.00, 0.54 (0.34-0.85), 0.32 (0.19-0.53), and 0.16 (0.09-0.29) in men, and 1.00, 0.76 (0.50-1.16), 0.33 (0.22-0.51), and 0.16 (0.10-0.25) in women. These results suggest that HGS/BW ratio was significantly and negatively associated with an increased risk of cardio-metabolic disorders in Japanese-community dwelling persons.

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes.

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (ß = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.