Validation of Assaying Carcinoembryonic Antigen in Human Serum by Using Immunomagnetic Reduction.

Immunomagnetic reduction (IMR) is a method to assay biomolecules by utilizing antibody functionalized magnetic nanoparticles. For clinical validation, important analytic performances of assaying carcinoembryonic antigen (CEA) using IMR are characterized. Furthermore, IMR is applied to assay carcinoembryonic antigen (CEA) in human serum for clinical validation. A total of 118 healthy controls and 79 patients with colorectal cancer (CRC) are recruited in this study. For comparison, assays using chemiluminometric immunoassay (CLIA) are also done for quantizing CEA in these serum samples. The results reveal a high correlation in terms of serum CEA concentration detected via IMR and CLIA is found (r = 0.963). However, IMR shows higher clinical sensitivity and specificity than those of CLIA. Moreover, the rate of false positives for smoking subjects is clearly reduced through the use of IMR. All the results demonstrate IMR is a promising alternative assay for serum CEA to diagnose CRC.

High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance.

OBJECTIVE: Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. RESEARCH DESIGN AND METHODS: This was a hospital-based case-control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. RESULTS: After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). CONCLUSIONS: We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation.

Association of Non-alcoholic Fatty Liver Disease with Metabolic Syndrome Independently of Central Obesity and Insulin Resistance.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease that may lead to liver cirrhosis and hepatocellular carcinoma. We aimed to determine the association between the prevalence of metabolic syndrome (MetS) and NAFLD severity using semi-quantitative ultrasonography (US). A total of 614 participants were recruited from the community. NAFLD was evaluated according to the ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Insulin resistance was estimated with the homeostasis model assessment index for insulin resistance (HOMA-IR). NAFLD and MetS were found in 53.7 and 17.3% of the participants, respectively. Linear relationships were found between the severity of NAFLD and waist circumference, fasting glucose, HOMA-IR, triglycerides, HDL-C and blood pressure. After adjusting for confounding factors, i.e., body mass index and HOMA-IR, the odds ratios for MetS were 3.64 (95% confidence interval (CI): 1.5-8.83) for those with mild NAFLD and 9.4 (95% CI: 3.54-24.98) for those with moderate-to-severe NAFLD compared to those without NAFLD. The combination of the HOMA-IR and US-FLI scores better differentiated MetS than the HOMA-IR alone. In addition to obesity, the severity of NAFLD and the HOMA-IR both play important roles in MetS. Whether NAFLD is a component of MetS warrants further research.

Cancer incidence in the vicinity of nuclear power plants in Taiwan: a population-based study.

Numerous antinuclear demonstrations reveal that the public is anxious about the potential health effects caused by nuclear power plants. The purpose of this study is to address the question "Is there a higher cancer incidence rate in the vicinity of nuclear power plants in Taiwan?" The Taiwan Cancer Registry database from 1979 to 2003 was used to compare the standardized incidence rate of the top four cancers with strong evidence for radiation risks between the "plant-vicinity" with those "non-plant-vicinity" groups. All cancer sites, five-leading cancers in Taiwan, and gender-specific cancers were also studied. We also adopted different observation time to compare the incidence rate of cancers between two groups to explore the impact of the observation period. The incidences of leukemia, thyroid, lung, and breast cancer were not significantly different between two groups, but cervix uteri cancer showed higher incidence rates in the plant-vicinity group. The incidence of cervical cancer was not consistently associated with the duration of plant operation, according to a multiyear period comparison. Although there was higher incidence in cervix cancer in the plant-vicinity group, our findings did not provide the crucial evidence that nuclear power plants were the causal factor for some cancers with strong evidence for radiation risks.

Plasma zinc α2-glycoprotein levels are elevated in smokers and correlated with metabolic syndrome.

BACKGROUND: Smoking is a strong risk factor of metabolic syndrome. Zinc α2-glycoprotein (ZAG) is a protein involved in metabolic syndrome. This study aims to investigate the effect of smoking on plasma ZAG levels and its relations to metabolic syndrome. MATERIALS AND METHODS: A group of 41 cigarette smokers and 47 non-smokers were enrolled. ZAG levels were measured to correlate to participants' demographic and metabolic parameters. RESULTS: Plasma ZAG levels of smokers were higher than those of controls (P < 0.0001). Plasma ZAG levels were positively correlated with male gender (P = 0.0002), number of cigarettes smoked per day (P < 0.0001), smoking duration in years (P < 0.0001), smoking index (P < 0.0001) and nicotine dependence score (P < 0.0001). In the multiple regression analysis, smoking was a strong independent factor affecting plasma ZAG levels (P = 0.0034). Plasma ZAG levels elevated progressively with the number of metabolic syndrome components (P = 0.0143). In the multiple regression analysis, plasma ZAG was an independent factor for metabolic syndrome. CONCLUSIONS: Plasma ZAG levels are high in smokers and correlate with metabolic syndrome. Our results indicate ZAG is an independent risk factor, but also interacted with smoking, for the metabolic syndrome.

Wishes of Patients With Terminal Cancer and Influencing Factors Toward the Use of Antibiotics in Taiwan.

CONTEXT: The use of antibiotics is a common ethical dilemma in palliative care, thus identifying the concerns of patients with terminal cancer and respecting their wishes are important in making an ethically justified decision. OBJECTIVES: The aim of this study was to understand wishes of patients with terminal cancer and determine influencing factors toward the use of antibiotics. METHODS: Two hundred and one patients with terminal cancer, admitted to a palliative care unit in Taiwan, completed a structured questionnaire interview, including demographic characteristics, knowledge and attitudes on antibiotics, the health locus of control, subjective norms, and the wishes to use antibiotics. RESULTS: The most common misconception was "Antibiotics use is helpful to all terminal patients with infection," which only 13.4% respondents disagreed. Of the 201patients, 92 (45.8%) expressed their wishes to use antibiotics even in the very terminal stage, and around one-fourth (26.4%) of patients wished not to use antibiotics, the remaining 27.8% were unclear. The most influential persons were medical professionals. The results of logistic regression analysis that showed familiarity with antibiotics, subjective norms, and the attitude toward burdens of antibiotics were the most significant predicting variables for those wishing to use antibiotics (odds ratio [OR] = 4.133, 95% confidence interval [CI] = 1.012-16.880; OR = 1.890, 95% CI = 1.077-3.317; and OR = 1.255, 95% CI = 1.047-1.503). CONCLUSION: This study indicated the responsibility of medical professionals to convey burdens of using antibiotics to patients and family. Otherwise, by enhancing professional training and performing effective communication with patients, we can reach a more appropriate decision in the use of antibiotics.

Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly.

UNLABELLED: Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. CONCLUSION: Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality.

Is it appropriate to withdraw antibiotics in terminal patients with cancer with infection?

BACKGROUND: Antibiotic administration is frequent in terminal patients with cancer, yet the effects on survival are still under debate. OBJECTIVE: The aim of this study was to examine the status of infection and the benefit/burden of antibiotic administration on the survival of terminal patients with cancer with infection. DESIGN: A prospective observational study. SETTING/SUBJECTS: We studied 799 patients with terminal cancer who were admitted to a palliative care unit in Taiwan between January 2008 and the end of April 2010. Survival was calculated from the first day of admission to the day of death in the palliative care unit or under home care. MEASUREMENTS: A specially designed assessment tool was used daily to evaluate clinical conditions. Afterwards, it was analyzed at different time points in a weekly team meeting. Multivariate Cox proportional hazard analyses were used to examine the benefit/burden of antibiotic administration on survival. RESULTS: Four hundred fifty-five patients were diagnosed as having at least one episode of infection after first admission. A total of 295 of the 378 (78.0%) with infection received antibiotic treatment upon admission. Multivariate Cox proportional hazard analyses showed that antibiotic administration was related to improved survival for patients who were still alive 1 week after admission (hazard ratio: 0.66, 95% confidence interfal [CI]: 0.46-0.95). However, antibiotics would be a hazard to patients' survival if used in the time 2 days prior to death (hazard ratio: 1.54, 95% CI: 1.22-1.94). CONCLUSIONS: The results suggest that with good communication between patients, families, and medical staff, withdrawal of antibiotics should be considered if signs of death appear, in order to avoid unnecessary risks. The possible benefit of prolonged survival should be in line with the goal of care, and also take into account preparing the patient for a dignified death.

Effect of a compassion-focused training program in palliative care education for medical students.

BACKGROUND: Compassion is the key value of humanities perspective. Little is known, however, concerning the impact of enhancing compassion on ethical decision making in end-of-life care. METHODS: A total of 251 preclinical medical students were enrolled in a palliative care training course. A structured self-report questionnaire was administered before and after training. RESULTS: Experience with caring for patients with terminal cancer was positively related to improvement in the decision of "truth telling is helpful to a good death." In addition, improvement in the perception of "compassionate care" was correlated with higher improvement in the decision of "discharge planning and home care." CONCLUSION: Compassion-focused training program can be helpful to improve medical students' competence in making more appropriate ethical decisions in end-of-life care.

Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase expression by endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress is induced in infectious and inflammatory conditions, but its role in inflammatory responses still remains elusive. In this study we found tunicamycin (TM) and brefeldin A (BFA), two ER stressors, could attenuate lipopolysaccharide (LPS)-elicited inducible nitric oxide synthase (iNOS) gene expression in murine RAW264.7 macrophages, and this effect was not resulting from the effects on IKK or MAPKs activation. However, ER stressors could block NF-κB binding to the iNOS promoter in late-phase signaling evoked by LPS. Results indicated that inhibition of RelB nuclear translocation and p300 expression are involved in the anti-inflammatory actions of ER stressors. We also found that ER stressors could block LPS- and IFN (α, ß, and γ)-mediated STAT1 phosphorylation. Our results suggest that activation of MKP-1 via a Ca/calmodulin/calcineurin pathway accounts for the inhibitory effect of ER stressors on IFN signaling. MKP-1 was downregulated by IFN-γ and is a newly identified protein phosphatase targeting STAT1. Taken together, these results indicate that multiple mechanisms are involved in the inhibition of LPS-induced iNOS gene expression by ER stressors. These include downregulation of RelB and p300, upregulation of MKP-1, and inhibition of the JAK/STAT signaling pathway.

Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults.

OBJECTIVES: This study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. BACKGROUND: SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. METHODS: A baseline cohort of 115,746 participants without a history of thyroid disease, ≥20 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. RESULTS: There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. CONCLUSIONS: Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death.

Changes of serum adiponectin and soluble intercellular adhesion molecule-1 concentrations after smoking cessation.

BACKGROUND: This study aims to investigate the effect of increased serum adiponectin concentration during smoking cessation on soluble intercellular adhesion molecule-1 (sICAM-1) concentration. METHODS: One hundred and sixty-six eligible smokers were assessed at baseline and were followed up at the 1st, 5th, and 9th weeks after smoking cessation. Demographic data, body weight and blood pressure of these participants were obtained; serum glucose biochemical data, sICAM-1 and adiponectin concentrations were measured. Repeated measures analysis paired t-tests and generalized estimating equations for balanced repeated measures were used for statistical analyses. RESULTS: Forty-one individuals completed the 2-month smoking cessation program. The mean cigarette consumption dramatically decreased (p<0.0001) and the cotinine concentration also decreased significantly (p<0.0001) among the quitters. Serum adiponectin concentration significantly increased (p=0.0186) and sICAM-1 significantly decreased (p<0.0001) in quitters after smoking cessation. The elevation of serum adiponectin concentration significantly correlated with lowering of sICAM-1 (p=0.0001) concentration. Body weight changes at the end of 2-month smoking cessation was inversely correlated with adiponectin increment from baseline (p=0.0003). CONCLUSIONS: An increase in serum adiponectin concentration is an independent factor correlated with lowering of sICAM-1 concentration during smoking cessation.

Family experience with difficult decisions in end-of-life care.

OBJECTIVE: The difficult decisions encountered by family caregivers in the process of care for patients with terminal cancer are seldom studied. Investigating their experiences with difficult decisions may help relieve their psychological distress. The purpose of this study was to determine the frequency and difficulty of decisions experienced in end-of-life care and to identify related factors. METHODS: A cross-sectional study using questionnaires was conducted with family caregivers of patients who died of cancer in a university hospital. Difficulty of decisions and relevant influencing variables including demographic data, knowledge in palliative care and the Natural Death Act, and beliefs on the Natural Death Act were measured. RESULTS: A total of 302 bereaved family caregivers were included in the final analysis. The most difficult decisions commonly encountered in both hospice and non-hospice wards related to truth telling, place of care, and alternative treatments. Logistic regression analysis demonstrated that older age (odds ratio = 0.92, 95% confidence interval = 0.89-0.95), not being the main family caregiver (0.20, 0.06-0.62), and less perception of burdens regarding the Natural Death Act (0.61, 0.37-0.99) were negatively correlated with the difficulty of decisions. CONCLUSIONS: Families frequently encountered difficult decisions while caring for terminally ill loved ones. Better communication with family members, particularly the main caregiver, to diminish negative perceptions of the Natural Death Act could help to decrease psychological distress.

What factors are important in increasing junior doctors' willingness to provide palliative care in Taiwan? An educational intervention study.

PURPOSE: To explore the factors that influence the willingness of junior doctors to provide palliative care in future clinical practice and to evaluate the effect of palliative care education in ameliorating these factors. METHODS: A 2-week clinical training course consisting of clinical patient care, multidisciplinary team meetings, home visits, and lecture series was conducted for interns in a palliative care unit of a university hospital. A structured self-report questionnaire was administered before and after the training. RESULTS: One hundred forty-seven interns were enrolled and completed the questionnaire, which demonstrated significant improvements in knowledge and beliefs toward palliative care after the training (p < 0.001). Although the interns' willingness to provide palliative medical care was influenced by relatives' support before the training (odds ratio [OR] = 3.861, 95% confidence interval [CI] = 1.217-12.243), this relationship vanished after training. A higher willingness to provide home visits was noted in participants who received palliative care education at medical school. In contrast, information received from mass media was shown to be negatively correlated with willingness. After the training, the only independent variable that was positively correlated with interns' willingness to provide home visits was their own beliefs on palliative care (OR = 1.074, 95% CI = 1.058-8.089). CONCLUSIONS: Educating junior doctors to build positive beliefs toward palliative care is strongly encouraged. Palliative care education contributes to increased junior doctors' willingness toward providing palliative care, which suggests that this kind of training course should be emphasized in medical education.

Age-period-cohort analysis of hepatocellular carcinoma mortality in Taiwan, 1976-2005.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant primary liver tumors worldwide. A previous study showed a decline in pediatric HCC in Taiwan after the universal vaccination program was initiated in 1984. We investigated whether the recent change in HCC mortality in Taiwan represented a short-term fluctuation or an emerging long-term decline trend. METHODS: An age-period-cohort analysis was conducted to show HCC mortality trends between 1976 and 2005. A total of 121,643 HCC mortality cases (92,926 males and 28,717 females) of individuals older than 40 years of age was used in the analyses. RESULTS: Results indicate an increasing secular trend in HCC mortality over the last three decades in people aged 60 years and above. In the age group of >85 years old, the mortality rate for males and females was 7.47 (95% confidence interval [95% CI]: 6.24-8.94) and 25.0 (95% CI: 15.5-40.2) times greater than in the youngest age group (40-44), respectively. The relative risk of dying from HCC in the period 2001-2005 was 1.36 (95% CI: 1.23-1.50) for males compared to the 1976-1980 time period, and 1.42 (95% CI: 1.17-1.72) for females compared to the 1986-1990 time period. A strong birth-cohort effect was also found. Individuals born around 1936 had the highest risk of dying from HCC. CONCLUSION: These findings imply that important determinants of HCC may occur early in life, with their effects only becoming apparent much later.

Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men.

BACKGROUND: Betel nut chewing is related to several kinds of cancer, metabolic syndrome, and type 2 diabetes. Whether it is associated with a greater risk of cardiovascular disease (CVD) and all-cause mortality, however, remains unclear. OBJECTIVE: We aimed to investigate the association between betel nut chewing and CVD and all-cause mortality. DESIGN: A baseline cohort of 56,116 male participants > or = 20 y old were recruited from 4 nationwide health screening centers in Taiwan in 1998 and 1999. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of CVD and all-cause mortality for betel nut chewers during an 8-y follow-up period. RESULTS: There were 1549 deaths during the follow-up period, 309 of which were due to CVD. After adjustment for age, body mass index, diabetes, hypertension, lipids, smoking, alcohol consumption, physical activity, income, and education level, the RRs (95% CI) of CVD and all-cause mortality among the former betel nut chewers were 1.56 (1.02, 2.38) and 1.40 (1.17, 1.68), respectively, and those among current chewers were 2.02 (1.31, 3.13) and 1.40 (1.16, 1.70), respectively, compared with persons who had never chewed betel quid. Current and former betel nut chewers had a higher risk of CVD mortality (RR: 2.10; P < 0.05) than did current and former smokers. Greater frequency of betel nut chewing was associated with greater CVD and all-cause mortality. CONCLUSIONS: Betel nut chewing was independently associated with a greater risk of CVD and all-cause mortality in Taiwanese men. Regular screening for betel nut chewing history may help prevent excess deaths in the future. An anti-betel nut chewing program is urgently warranted for current chewers.

Metabolic syndrome is related to nonalcoholic steatohepatitis in severely obese subjects.

BACKGROUND: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to steatohepatitis (NASH), have become important health issues in obese subjects. In this study, we investigated the relationship between MetS and NASH in severely obese subjects. METHODS: A total of 111 non-alcoholic obese patients who underwent laparoscopic bariatric surgery (BMI 45.4 +/- 5.7 kg/m2) were enrolled from February to September 2004 in a referral center in North Taiwan. MetS and its individual components were defined using the American Heart Association/National Heart, Lung, and Blood Institute criteria. Based on liver biopsy during surgery, subjects were classified into either having NASH or not. The relationship among NASH, adiponectin, insulin resistance, MetS and its individual components was examined using a multivariate logistic regression analysis. RESULTS: The prevalence of NASH and MetS in these subjects was 79.3% and 68.5%, respectively. Using a multivariate logistic regression analysis with NASH as the outcome variable, odds ratio (OR) of NASH for subjects with MetS versus without MetS was 2.96 (95% CI = 1.14-7.68) adjusted for age, gender, and BMI. Also, high blood pressure (OR = 2.97, 1.31-6.73) and high fasting glucose (OR = 2.94, 1.13-7.67) were independently associated with NASH after adjustment for age, gender, and BMI. Insulin resistance measured as HOMA-IR and serum adiponectin level were not significantly different between the NASH and non-NASH group. CONCLUSION: MetS and NASH were common in severely obese Taiwanese adults. Presence of MetS, high blood pressure, and high fasting glucose was independently related to increased risk of NASH. The underlying mechanism deserves to be explored in the future.