Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.

Association between coronary artery calcium and all-cause mortality: A large single-center retrospective cohort study.

OBJECTIVE: Previous studies have revealed that coronary artery calcium is related to cardiovascular diseases and mortality. However, most studies have been conducted in Western countries and have excluded patients with pre-existing heart disease. We investigated the association between coronary artery calcium (CAC) and all-cause mortality in an Asian cohort and in subgroups stratified by age, sex, smoking, obesity, diabetes, cardiovascular disease, blood pressure, and biochemical parameters. METHODS: We conducted a retrospective cohort study on 4529 health examinees who underwent multidetector computed tomography in a tertiary medical center in Taiwan between 2011 and 2016. The mean follow-up was 3.5 years. Cox regression was used to estimate the relative hazards of death. Stratified analyses were performed. RESULTS: The all-cause mortality rates were 2.94, 4.88, 17.6, and 33.1 per 1000 person-years for CAC scores of 0, 1-100, 101-400, and >400, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CIs]) for all-cause mortality were 0.95 (0.53, 1.72), 1.87 (0.89, 3.90), and 3.05 (1.46, 6.39) for CAC scores of 1-100, 101-400, and >400, respectively, relative to a CAC score of 0. Compared with CAC ≤ 400, the HRs (95% CIs) for CAC > 400 were 6.46 (2.44, 17.15) and 1.94 (1.00, 3.76) in younger and older adults, respectively, indicating that age was a moderating variable (p = 0.02). CONCLUSION: High CAC scores were associated with increased all-cause mortality. Although older adult patients had higher risks of death, the relative risk of death for patients with CAC > 400 was more prominent in people younger than 65 years.

Rhenium-guanidine complex as photosensitizer: trigger HeLa cell apoptosis through death receptor-mediated, mitochondria-mediated, and cell cycle arrest pathways.

The growing evidence over the past few decades has indicated that the photodynamic antitumor activity of transition metal complexes, and Re(I) compounds are potential candidates for photodynamic therapy. This study reports the synthesis, characterization, and anti-tumor activity of three new Re(I)-guadinium complexes. Cytotoxicity tests reveal that complex Re1 increased cytotoxicity by 145-fold from IC50 > 180 µM in the dark to 1.3 ± 0.7 µM following 10 min of light irradiation (425 nm) in HeLa cells. Further, the mechanism by which Re1 induces apoptosis in the presence or absence of light irradiation was investigated, and results indicate that cell death was caused through different pathways. Upon irradiation, Re1 first accumulates on the cell membrane and interacts with death receptors to activate the extrinsic death receptor-mediated signaling pathway, and then is transported into the cell cytoplasm. Most of the intracellular Re1 locates within mitochondria, improving the reactive oxygen species level, and decreasing mitochondrial membrane potential and ATP levels, and inducing the activation of caspase-9 and, thus, apoptosis. Subsequently, the residual Re1 can translocate into the cell nucleus, and activates the p53 pathway, causing cell cycle arrest and eventually cell death.

Association between the amount of artificial hydration and quality of dying among terminally ill patients with cancer: The East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process.

BACKGROUND: Artificial hydration (AH) is a challenging issue in terminally ill patients with cancer, because it influences patients' symptoms control, quality of life, and quality of dying (QOD). To date, it is not clear how much AH supply is proper for imminently dying patients. This study aimed to investigate the association between the amount of AH and QOD. METHODS: This study is part of the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED) conducted in Japan, Korea, and Taiwan from January 2017 to September 2018. Patients' demographics, symptoms, and managements on admission to palliative care units (PCUs) and before death were recorded. The AH amount was classified into different groups by 250-mL intervals to compare their difference. The Good Death Scale (GDS) was used to measure QOD, with patients classified into higher or lower QOD groups using GDS = 12 as the cutoff point. We used logistic regression analysis to assess the association between AH amount and QOD. RESULTS: In total, 1530 patients were included in the analysis. Country, religion, spiritual well-being, fatigue, delirium, dyspnea, AH, and antibiotics use before death were significantly associated with QOD. After conducting regression analysis, patients administered with 250 to 499 mL AH had significantly better QOD (odds ratio, 2.251; 95% confidence interval, 1.072-4.730; P = .032) than those without AH. CONCLUSIONS: AH use impacts the QOD of terminally ill patients with cancer admitted to PCUs. Communication with patients and their families on appropriate AH use has a positive effect on QOD. LAY SUMMARY: Our prospective cross-cultural multicenter study aims to investigate the relationship between artificial hydration (AH) amount and quality of dying among terminally ill patients with cancer. The findings reveal that country, religion, spiritual well-being, fatigue, delirium, dyspnea, AH, and antibiotics use before death were significantly associated with quality of death (QOD). After multivariable logistic regression, patients administered with AH amount 250 to 499 mL had significantly better QOD (odds ratio, 2.251; 95% confidence interval, 1.072-4.730; P = .032) than those without AH. Communication with patients and their families regarding AH is recommended as it may help them be better prepared for the end-of-life stage and achieve a good death.

The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats.

The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world's population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-ß (TGF-ß)/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5 mg/kg/day) or high (50 mg/kg/day) doses of arecoline for 3 weeks. Results from Masson's trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-ß and p-Smad2/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis.

Derivation and validation of a clinical prediction model for risks of venous thromboembolism in diabetic and general populations.

ABSTRACT: Most studies on the prediction of venous thromboembolism (VTE) focused on hospitalized, surgery, and cancer patients or women receiving hormonal contraceptives or menopausal hormone therapy. No study considered diabetic and general populations to establish a VTE prediction model, especially in Asia. We developed a predictive model for VTE among type 2 diabetic patients and the general population.This study considered 2 nationwide retrospective cohort studies consisting of 52,427 diabetic participants and 508,664 participants from the general population aged 30 to 85 years during 2001 to 2004 in Taiwan. All participants were followed up until VTE event, death, or December 2011. The outcome event was VTE, including deep venous thrombosis and pulmonary embolism. Candidate predictors consisted of socio-demographic factors, diabetes-related factors and biomarkers, comorbidities, and medicine use. Our study followed the procedures proposed by the Framingham Heart Study to develop prediction models by using a Cox regression model. The predictive accuracy and performance characteristics were assessed using the area under curve of receiver operating characteristics curve and calibration of a risk score were performed by Hosmer-Lemeshow goodness-of-fit test.The common factors for persons with type 2 diabetes and general population included age, hospitalization status 1 year before the baseline, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and anti-diabetes medications; the specific factors for persons with type 2 diabetes consisted of body mass index, glycosylated hemoglobin A1C, and creatinine; and the factors for general population included gender, peripheral vascular disease, cancer, hypertension medication, cardiovascular medication, and non-steroidal anti-inflammatory drug. The area under curve of 3-, 5-, and 8-year VTE prediction models were 0.74, 0.71, and 0.69 in the diabetic population and 0.77, 0.76, and 0.75 in the general population, respectively.The new clinical prediction models can help identify a high risk of VTE and provide medical intervention in diabetic and general populations.

Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.

BACKGROUND AND AIM: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.

Arecoline induces heart injure via Fas/Fas ligand apoptotic pathway in heart of Sprague-Dawley rat.

Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague-Dawley rat via intra-peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline-induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline-induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria-dependent apoptotic pathways on heart.

Enhanced home palliative care could reduce emergency department visits due to non-organic dyspnea among cancer patients: a retrospective cohort study.

BACKGROUND: Dyspnea is a common trigger of emergency department visits among terminally ill and cancer patients. Frequent emergency department (ED) visits at the end of life are an indicator of poor-quality care. We examined emergency department visit rates due to dyspnea symptoms among palliative patients under enhanced home palliative care. METHODS: Our home palliative care team is responsible for patient management by palliative care specialists, residents, home care nurses, social workers, and chaplains. We enhanced home palliative care visits from 5 days a week to 7 days a week, corresponding to one to two extra visits per week based on patient needs, to develop team-based medical services and formulate standard operating procedures for dyspnea care. RESULTS: Our team cared for a total of 762 patients who exhibited 512 ED visits, 178 of which were due to dyspnea (mean ± SD age, 70.4 ± 13.0 years; 49.4% male). Dyspnea (27.8%) was the most common reason recorded for ED visits, followed by pain (19.0%), GI symptoms (15.7%), and fever (15.3%). The analysis of Group A versus Group B revealed that the proportion of nonfamily workers (42.9% vs. 19.4%) and family members (57.1% vs. 80.6%) acting as caregivers differed significantly (P < 0.05). Compared to the ED visits of the Group A, the risk was decreased by 30.7% in the Group B (P < 0.05). CONCLUSIONS: This study proves that enhanced home palliative care with two additional days per week and formulated standard operating procedures for dyspnea could significantly reduce the rate of ED visits due to non-organic dyspnea during the last 6 months of life.

To hydrate or not to hydrate? The effect of hydration on survival, symptoms and quality of dying among terminally ill cancer patients.

BACKGROUND: Artificial nutrition and hydration do not prolong survival or improve clinical symptoms of terminally ill cancer patients. Nonetheless, little is known about the effect of artificial hydration (AH) alone on patients' survival, symptoms or quality of dying. This study explored the relationship between AH and survival, symptoms and quality of dying among terminally ill cancer patients. METHODS: A pilot prospective, observational study was conducted in the palliative care units of three tertiary hospitals in Taiwan between October 2016 and December 2017. A total of 100 patients were included and classified into the hydration and non-hydration group using 400 mL of fluid per day as the cut-off point. The quality of dying was measured by the Good Death Scale (GDS). Multivariate analyses using Cox's proportional hazards model were used to assess the survival status of patients, the Wilcoxon rank-sum test for within-group analyses and the Mann-Whitney U test for between-groups analyses to evaluate changes in symptoms between day 0 and 7 in both groups. Logistic regression analysis was used to assess the predictors of a good death. RESULTS: There were no differences in survival (p = 0.337) or symptom improvement between the hydration and non-hydration group, however, patients with AH had higher GDS scores. CONCLUSIONS: AH did not prolong survival nor significantly improve dehydration symptoms of terminally ill cancer patients but it may influence the quality of dying. Communication with patients and their families on the effect of AH may help them better prepared for the end-of-life experience.

Independent associations of urinary albumin-to-creatinine ratio and serum cystatin C with carotid intima-media thickness in community-living Taiwanese adults.

BACKGROUND: Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. METHODS: A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. RESULTS: A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 µm for every one unit of increase in cystatin C level and by 0.07 and 0.14 µm for every one unit of increase in ACR, respectively (all p < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C. CONCLUSION: Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis.

Derivation and validation of 10-year all-cause and cardiovascular disease mortality prediction model for middle-aged and elderly community-dwelling adults in Taiwan.

Prediction model mainly focused on specific diseases, such as diabetes, hypertension, cardiovascular disease, or patients with cancer, or populations of Europe and America, thereby limiting its generalization. This study aimed to develop and validate a 10-year mortality risk score by using data from a population-representative sample of adults. Data were collected from 2,221 Taichung Community Health study participants aged ≥40 years. The baseline period of the study was 2004, and all participants were followed up until death or in 2016. Cox's proportional hazards regression analyses were used to develop the prediction model. A total of 262 deaths were ascertained during the 10-year follow-up. The all-cause mortality prediction model calculated the significant risk factors, namely, age, sex, marital status, physical activity, tobacco use, estimated glomerular filtration rate, and albumin-to-creatinine ratio, among the baseline risk factors. The expanded cardiovascular disease (CVD) mortality prediction model consisted of six variables: age, sex, body mass index, heart disease plus heart disease medication use, stroke plus medication use, and ankle-brachial index. The areas under receiver operating curves of the 3-, 5- and 10-year predictive models varied between 0.97, 0.96, and 0.88 for all-cause mortality, and between 0.97, 0.98, and 0.84 for expanded CVD mortality. These mortality prediction models are valid and can be used as tools to identify the increased risk for mortality.

Diabetes mellitus associated with an increased risk of percutaneous coronary intervention long-term adverse outcomes in Taiwan: A nationwide population-based cohort study.

AIMS: This study compared the incidence rates of patients with diabetes mellitus (DM) and patients without DM with percutaneous coronary intervention (PCI) in a national population-based cohort to determine if the patients with DM have an increased risk of adverse outcomes. METHODS: We performed a retrospective cohort study among 92,624 patients with and without DM, who underwent PCI for the first time in 2000-2008. The patients were identified from National Health Insurance Program Database through propensity score matching. Endpoints were the occurrence of PCI adverse outcomes, including myocardial infarction (MI), need for target vessel revascularization by either bypass surgery or repeat PCI, all-cause mortality or 2011/12/31. Incidence rate was calculated and hazard ratios of PCI adverse events were estimated using Cox's proportional hazard regression model. RESULTS: During the mean six-year follow up, the rates of MI (incidence rate 20.96 vs. 15.59 per 1000 person-years), bypass surgery (incidence rate 8.15 vs. 5.15 per 1000 person-years), all-cause mortality (incidence rate 6.20 vs. 4.72 per 1000 person-years), and the composite measure of MI, repeat PCI, bypass surgery, all-cause mortality (incidence rate 37.31 vs. 28.14 per 1000 person-years) were higher in patients with DM. The corresponding hazard ratios (HRs) and their 95% confidence intervals (CIs) were 1.34 (95% CI: 1.29, 1.39), 1.46 (1.38, 1.56), 1.34 (1.25, 1.44), and 1.31 (1.27, 1.35). However, the repeat PCI rate (incidence rate 2.65 vs. 2.70 per 1000 person-years); with an adjusted HR of 0.97 (0.88, 1.07) was not statistically different. CONCLUSIONS: This nationwide retrospective cohort study determined a positive correlation between PCI adverse events and DM. As the prevalence of DM and PCI continues to increase, novel treatments and intensified surveillance coronary angiography for high risk patients are needed.

Important gene-gene interaction of TNF-α and VDR on osteoporosis in community-dwelling elders.

Gene effects on osteoporosis have been studied separately and may have been masked by gene-gene and gene-environment interactions. We evaluated gene-gene and gene-physical activity interactions of the variants of tumor necrosis factor-α (TNF-α) and vitamin D receptor (VDR) genes on osteoporosis. A total of 472 elders were included. Seven variants (TNF-α: rs1799964, rs1800629, rs3093662; VDR: rs7975232, rs1544410, rs2239185, rs3782905) were genotyped. Bone mineral densities of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Predictive models' ability to discriminate osteoporosis status was evaluated by areas under the receiver operating characteristics (AUROC) curve. After multivariable adjustment, significant interactions of TNF-α rs1800629 and VDR rs3782905 were observed on overall and lumbar spine osteoporosis. In elderly women, we found that those carrying the CG/CC genotype of VDR rs3782905 were significantly associated with increased odds of overall osteoporosis compared with those carrying the GG genotype of VDR rs3782905 among those carrying TNF-α rs1800629 GG genotype. The adjusted odds ratios (ORs) for VDR rs3782905 CG/CC genotype in elderly women carrying TNF-α rs1800629 AG/AA and GG genotypes were 0.1 (0.01, 0.98) and 3.54 (1.51, 8.30), respectively. We observed significant differences in AUROCs between the model with traditional covariates plus variants and their interaction term and the model with traditional covariates only (AUROCs: 0.77 and 0.81; p = 0.028). Although the sample size of this study may have been relatively small, our results suggest that the interaction of the CG/CC genotype of VDR rs3782905 with TNF-α rs1800629 GG genotype was associated with increased odds of overall and lumbar spine osteoporosis in elderly women.

Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD.

Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utilizing PM-treated human pulmonary fibroblasts (HPF) models, we analyzed gene expression microarray data and Ingenuity Pathway Analysis (IPA) to identify that the transcription factor sterol regulatory element-binding protein 1 (SREBP1) was the main downstream regulator of Sirtuin1 (SIRT1). Quantitative PCR and western blot results showed that SIRT1 inhibited SREBP1 and further downregulated Pirin (PIR) and Nod-like receptor protein 3 (NLRP3) inflammasome after PM exposure. Inhibitors of SIRT1, SREBP1, and PIR could reverse PM-induced inflammation. An in silico analysis revealed that PIR correlated with smoke exposure and early COPD. Immunohistochemical analysis of tissue microarrays from PM-fed mouse models was used to determine the association of PIR with PM. These data demonstrate that the SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may be associated with PM-induced adverse health issues. SIRT1 functions as a protector from PM exposure, whereas PIR acts as a predictor of PM-induced pulmonary disease. The SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may present several potential therapeutic targets for PM-related adverse health events.

Changes of gut microbiota between different weight reduction programs.

BACKGROUND: Gut microbiota may induce obesity, diabetes, and metabolic syndrome. Different weight reduction programs may induce different changes in gut microbiota. OBJECTIVES: To assess the changes in gut microbiota between obese adults who participated in 2 different weight reduction programs, the dietary counseling (DC) group and sleeve gastrectomy (SG) group, for 3 months. SETTING: A University Hospital. METHODS: Ten obese participants from each group were matched according to sex, age, and body mass index. Gut microbiota compositions were determined by metagenomics using next-generation sequencing before and after treatment. Anthropometric indices, metabolic factors, and gut microbiota were compared between and within groups. RESULTS: After 3 months of treatment, compared with subjects in DC group, subjects in SG group experienced a greater reduction in body weight, body mass index, body fat, waist and hip circumference, diastolic blood pressure, hemoglobin, insulin, insulin resistance, glutamate pyruvate transaminase, blood urine nitrogen, and glycated hemoglobin (HbA1C). A total of 8, 17, and 46 species experienced significant abundance changes in DC, in SG, and between the 2 groups, respectively. Diversity of the gut flora increased in SG and between the 2 groups after treatment. The weight change over the course of the weight loss program was further adjusted and only 4 species, including Peptoniphilus lacrimalis 315 B, Selenomonas 4 sp., Prevotella 2 sp., and Pseudobutyrivibrio sp., were found to be significantly different between the 2 weight loss programs. These 4 species may be the different gut microbiota change between internal and surgical weight reduction programs. CONCLUSIONS: There are significant differences not only in anthropometric indices and metabolic factors but also in gut microbiota change between the 2 programs.

Risk score system for the prediction of hepatocellular carcinoma in patients with type 2 diabetes: Taiwan Diabetes Study.

This study aims to develop a risk score system for hepatocellular carcinoma (HCC) in patients with type 2 diabetes using the Taiwan National Diabetes Care Management Program database. This retrospective cohort study included 31,723 Chinese patients who had type 2 diabetes, aged 30-84 years. Participants were randomly grouped into derivation and validation sets in 2:1 ratio. Cox proportional hazard regression models were used to identify the risk factors of HCC in the derivation set. Discrimination ability of the model was assessed by means of a receiver operating characteristic curve and performance was expressed as the c statistic, assessed internally on validation data sets. The average follow-up was 8.33 years with 748 HCC incident cases in the derivation set. The final HCC risk score system included age (-2 to 8 points), gender (0-2 points), smoking (0-2 points), variation in hemoglobin A1c (0-1 point), serum glutamic-pyruvic transaminase (0-6 points), liver cirrhosis (9 points), hepatitis B (4 points), hepatitis C (3 points), antidiabetes medications (0-3 points), and antihyperlipidemia medications and total/high-density lipoprotein cholesterol ratio (-4 to 2 points). The HCC risk score was the sum of these individual scores (range -6 to 40). The area under the receiver operating characteristic curve for 3-, 5-, and 10-year HCC risks was 0.81, 0.80, and 0.77 for the derivation set, respectively. This HCC risk score system has good prediction accuracy and discriminatory ability, and serves a simple tool for HCC risk prediction.

Mid-upper arm circumference, calf circumference and mortality in Chinese long-term care facility residents: a prospective cohort study.

OBJECTIVE: To investigate the association between mid-upper arm circumference (MUAC), calf circumference (CC) and all-cause mortality in a Chinese population. DESIGN: Prospective cohort study. SETTING: Eight long-term care facilities in central Taiwan. PARTICIPANTS: A total of 329 residents age 60 years and older (median 79.0 years, range 60-101; 139 men, 190 women) were enrolled. METHODS: Anthropometrics and metabolic parameters were measured at the time of enrolment to the study. Mean MUAC and CC were 24.2±3.4 cm and 27.5±4.3 cm, respectively. Mortality data were obtained from the Department of Health in Taiwan. MAIN OUTCOME MEASURE: To identify the association between all-cause mortality and MUAC or CC. RESULTS: There were 255 deaths during the 7-year follow-up period. After adjusting for age, sex, cigarette smoking, betel nut chewing, alcohol use, Karnofsky Performance Status Scale score, serum albumin level, hypertension and diabetes mellitus, subjects in the highest tertile of MUAC (27.8±2.2 cm) and CC (32.1±2.6 cm) had a significantly lower mortality rate than did subjects in the lowest tertile (MUAC 20.6±1.7 cm; CC 22.8±1.9 cm). The adjusted HR for all-cause mortality in the highest versus lowest MUAC tertile was 0.64 (95% CI 0.45 to 0.90). The adjusted HR for all-cause mortality in the highest versus lowest CC tertile was 0.51 (95% CI 0.35 to 0.74). CONCLUSIONS: MUAC and CC are negative predictors for all-cause mortality in older Chinese adults living in long-term care facilities. Participants with higher MUAC and CC had lower all-cause mortality.

Establishment and validation of a prediction model for ischemic stroke risks in patients with type 2 diabetes.

AIMS: A risk scoring system for predicting ischemic stroke incidence may identify type 2 diabetes patients at high risk for ischemic stroke who can benefit from preventive intervention programs. Such a risk scoring system can serve as a benchmark to test novel putative risk factors. METHODS: The study adopted a retrospective cohort, including 28,124 Chinese patients with type 2 diabetes aged 30-84 years during 2001-2004. Participants were randomly assigned to the derivation and validation sets at a 2:1 ratio. Cox's proportional hazard regression model was used to identify risk factors of ischemic stroke incidence in the derivation set. And then the steps proposed by the Framingham Heart Study for establishing an ischemic stroke prediction model with a scoring system was used. RESULTS: Among 9374 patients in the validation set, 1076 subjects (11.48%) developed ischemic stroke with a mean follow up period of 8.0 years. We identified the following risk factors: age, gender, smoking habit, duration of type 2 diabetes, blood pressure, HbA1c level, total cholesterol to high-density lipoprotein ratio, creatinine, fasting plasma glucose variation (FPG-CV), arterial embolism and thrombosis, diabetes retinopathy, hypoglycemia, anti-diabetes medication use, and cardiovascular medication. The area under receiver operating characteristic curve of the 3-year, 5-year, and 8-year ischemic stroke incidence risks were 0.72, 0.71, and 0.68 for the validation set, respectively. CONCLUSIONS: This proposed ischemic stroke incidence risk prediction model is the first model established for Chinese patients with type 2 diabetes recruited from nationwide clinical settings.

Prevailing Ethical Dilemmas Encountered by Physicians in Terminal Cancer Care Changed After the Enactment of the Natural Death Act: 15 Years' Follow-up Survey.

CONTEXT: Advance directive laws have influences on ethical dilemmas encountered by physicians caring for terminal cancer patients. OBJECTIVES: To identify the prevailing ethical dilemmas among terminal care physicians 15 years after the Natural Death Act was enacted in Taiwan. METHODS: This study is a cross-sectional survey from April 2014 to February 2015 using the clustering sampling method and a well-structured questionnaire. Targeted participants included physicians at oncology and related wards or palliative care units where terminal cancer care may be provided in Taiwan. RESULTS: Among the 500 physicians surveyed, 383 responded (response rate 76.6%) and 346 valid questionnaires were included in the final analysis (effective response rate 69.2%). The most frequently identified ethical dilemma was "place of care," followed by "use of antimicrobial agents" and "artificial nutrition and hydration." The dilemma of "truth telling," which ranked first in the 2005-2006 survey, now ranked at the fourth place. Stepwise logistic regression analysis revealed that female gender and knowledge of palliative care were negatively correlated with the extent of dilemmas regarding issues of "life and death." CONCLUSION: The prevailing ethical dilemmas have changed in Taiwan 15 years after the enactment of the Natural Death Act, supporting that some previous strategies had worked. Our results suggest that education on the core values of palliative care, improvement of community-based hospice care program, and creating treatment guidelines with prognostication may resolve the current dilemmas. This type of survey should be adapted by individual countries to guide policy decisions on end-of-life care.