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Background: This study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methods: Adult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results: 1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P

Background/purpose: Distinct hepatitis relapse has been observed after discontinuing entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients. End-of-therapy (EOT) serum cytokines were compared and used for outcome prediction. Methods: A total of 80 non-cirrhotic CHB patients in a tertiary medical center in Taiwan who discontinued ETV (n = 51) or TDF (n = 29) therapy after fulfilling the APASL guidelines were prospectively enrolled. Serum cytokines were measured at EOT and 3rd month afterwards. Multivariable analysis was performed to predict virological relapse (VR, HBV DNA >2000 IU/mL), clinical relapse (CR, VR and alanine aminotransferase > 2-fold upper limit of normal) and hepatitis B surface antigen (HBsAg) seroclearance. Results: Compared with TDF group, ETV stoppers had greater interleukin 5 (IL-5), IL-12 p70, IL-13, IL-17 A and tumor necrosis factor alpha (TNF-alpha) (all P

Abstract Background Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. Methods We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. Results Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. Conclusions Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.

Introduction: Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. Methods: Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. Results: Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 105 IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (Pinteraction = 0.005) and adiponectin-liver death associations (Pinteraction = 0.0157), with higher risk among genotype C. Conclusion: Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

In response to the adverse effects of climate change-induced frequent extreme disasters on agricultural production and supply stability, this study develops a comprehensive agricultural disaster prevention system based on current adaptation strategies for mitigating agricultural meteorological disasters. The primary goal is to enhance disaster preparedness and recovery through three core platforms: a fine-scale weather forecast service system, a crop disaster early warning system, and an agricultural information service platform for disasters. The results show that every major agricultural production township in Taiwan now has dedicated agricultural weather stations and access to refined weather forecasts. Additionally, a disaster prevention calendar for 76 important crops is established, integrating cultivation management practices and critical disaster thresholds for different growth periods. Utilizing this calendar, the crop disaster early warning system can provide timely disaster-related information and pre-disaster prevention assistance to farmers through various information dissemination tools. As a disaster approaches, the agricultural information service platform for disasters provides updates on current crop growth conditions. This service not only pinpoints areas at higher risk of disasters and vulnerable crop types but also offers mitigation suggestions to prevent potential damage. Administrative efficiency is then improved with a response mechanism incorporating drones and image analysis for early disaster detection and rapid response. In summary, the collaborative efforts outlined in this study demonstrate a proactive approach to agricultural disaster prevention. By leveraging technological advancements and interdisciplinary cooperation, the aim is to safeguard agricultural livelihoods and ensure food security in the face of climate-induced challenges.

Abstract RUNX1 mutations are frequently detected in various myeloid neoplasms and implicate unfavourable clinical outcomes in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). On the other hand, high expression of RUNX1 is also correlated with poor prognosis in AML patients. However, the clinical relevancy of RUNX1 expression in MDS patients remains elusive. This study aimed to investigate the prognostic and biologic impacts of RUNX1 expression in MDS patients. We recruited 341 MDS patients who had sufficient bone marrow samples for next‐generation sequencing. Higher RUNX1 expression occurred more frequently in the patients with Revised International Prognostic Scoring System (IPSS‐R) higher‐risk MDS than the lower‐risk group. It was closely associated with poor‐risk cytogenetics and mutations in ASXL1, NPM1, RUNX1, SRSF2, STAG2, TET2 and TP53. Furthermore, patients with higher RUNX1 expression had significantly shorter leukaemia‐free survival (LFS) and overall survival (OS) than those with lower expression. Subgroups analysis revealed that higher‐RUNX1 group consistently had shorter LFS and OS than the lower‐RUNX1 group, no matter RUNX1 was mutated or not. The same findings were observed in IPSS‐R subgroups. In multivariable analysis, higher RUNX1 expression appeared as an independent adverse risk factor for survival. The prognostic significance of RUNX1 expression was validated in two external public cohorts, GSE 114922 and GSE15061. In summary, we present the characteristics and prognosis of MDS patients with various RUNX1 expressions and propose that RUNX1 expression complement RUNX1 mutation in MDS prognostication, wherein patients with wild RUNX1 but high expression may need more proactive treatment.

Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform. Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture-sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC. Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones, and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort. Discussion/Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.

Abstract Since bone and fat mass are derived from mesenchyme in early development, adipokines secreted by adipose tissue may have an effect on bone metabolism. The relationship between adiponectin and bone mineral density (BMD) has been inconsistent in previous reports, with results being dependent on age, gender, menopausal status and bone sites. We investigated the relationship between serum adiponectin levels and the BMD of proximal femur and vertebrae bones in a 96-week longitudinal study of post-menopausal women with repeated measures of both. Linear regression models were used to determine the relation between adiponectin and BMD at each time point cross-sectionally, and a generalized estimating equation (GEE) model was used to investigate the longitudinal trends. Among 431 subjects, 376 (87%) provided baseline adiponectin measurements and 373 provided more than two measurements for longitudinal analysis. The means of serum adiponectin and BMD decreased with time. In linear regression models, adiponectin at baseline, the 48th week and the 96th week appeared to be inversely associated with BMD of proximal femur bone, but not lumbar spine after adjusting for age and various confounders. However, they all turn insignificant with further adjustment of body mass index. The inverse association between adiponectin and BMD of proximal femur is substantiated by all generalized equation models. Before adding the BMI in the model, the increase of 1 mg/dL of adiponectin can accelerate the decrease of proximal femur BMD by 0.001 (SE = 0.0004, p = 0.008). With BMI in the model, the drop rate was 0.0008 (SE = 0.0004, p = 0.026) and remained similar with further adjustment of two bone turnover markers. In this longitudinal analysis with both adiponectin and BMD measured at three time points, we demonstrate that with the increase of adiponectin level, the decline of proximal femur BMD in postmenopausal women accelerated during a period of 96 weeks.

Background: The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. Methods: Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated. Results: Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73–4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35–4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards. Conclusion: In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.

Abstract Both weather fluctuation and farming system influence the epidemiology of crop diseases. However, short-term experiments are difficult to mechanistically extrapolate into long-term ecological responses. Using a mechanistic model with Bayesian inference, long-term data spanning 10 years were used to construct relationships among weather fluctuation (temperature, relative humidity, wind, and rainfall), farming system (conventional and low-external-input farming), and crop disease in experimental rice fields in Taiwan. Conventional and low-external-input farming had similar influences on the disease incidence of rice blast. Temperature had a positive influence on the disease incidence only under high relative humidity. Rainfall positively affected the disease incidence until an optimum level of rainfall. Low-external-input farming, with a lower application of fertilizers and other sustainable nutrient management, achieved similar effects on the disease incidence to those achieved by conventional farming. This suggests that weather fluctuation may override the effect of the farming systems on fungal disease incidence in rice fields.

Abstract Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state.

Abstract Background We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. Methods Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence ( 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01–2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26–3.08), early recurrence (HR = 6.62, 95% CI:3.79–11.6) and late recurrence (HR = 3.75, 95% CI:1.99–7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. Conclusion Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

The prevalence of hepatitis C virus (HCV) infection in Taiwan was approximately 4% a decade ago, much higher than the worldwide average. This study aimed to assess the HCV burden among 4 million voluntary blood donors after 2 decades of prevention and treatment policies. We retrieved screening results for anti‐HCV and HCV RNA from the Database for Evaluating Voluntary Taiwanese Eligible Donors. First‐time blood donors who donated blood after 1999 and repeat donors who donated blood more than once between 2013 and 2017 were included to estimate HCV prevalence and incidence, respectively. The Cox proportional hazards model was used to estimate hazard ratios. Geographic variation in HCV prevalence and incidence in 364 townships was also analyzed. The prevalence study included 3,656,598 first‐time donors. The overall crude prevalence of anti‐HCV decreased from 15.5 to 4.5 per 1,000 donors between 1999 and 2017. Younger birth cohorts had a significantly lower prevalence of anti‐HCV. The majority of townships (64.3%) in Taiwan showed a significantly decreased prevalence. The incidence study included 1,393,014 repeat donors followed for 3,436,607 person‐years. Ninety‐eight donors seroconverted to HCV RNA positivity, resulting in an HCV incidence of 2.9 per 100,000 person‐years. Donors living in townships where HCV RNA prevalence was greater than 2 per 1,000 had at least 2.5‐fold greater risk of new HCV infection. Conclusion: HCV prevalence in Taiwanese first‐time blood donors decreased by 71% in the last 2 decades. However, townships with higher HCV prevalence also showed higher HCV incidence and require more active intervention.

Background: The prevalence rate of obstructive sleep apnea (OSA) in the community Down syndrome (DS) children is not clear. Moreover, the impact of OSA and sleep structure on the cognitive function is inconclusive. The present study aimed to investigate 1) the prevalence rate of OSA in the community DS children and 2) the impact of OSA and sleep structure on cognitive performance. Methods: Thirty DS children aged 6–18 years were recruited and evaluated with the performance of the language domain and sensorimotor domain, combining neuropsychological tests and parent-rated behavior. The outcomes were the age-adjusted scores, of which the lower the score was, the better was the patient's ability. The association of score with OSA and sleep structures was determined by linear regression. To diminish the age-related difference, all analyses were conducted separately for all subjects and 6–12-year-old subjects. Results: The median age was 11.3 years and median Full-Scale Intelligence Quotient (FSIQ) was 44. The prevalence of OSA (apnea–hypopnea index ≥ 1/h) was 80% and 62.5% in all subjects and 6–12-year-old subjects, respectively. For 6–12-year-old subjects, after adjustment for age and FSIQ, both %REM and OSA were associated with lower score of the subtest of language domain, WPPSI-R Vocabulary, while %REM was also associated with lower score of VABS-II Communication – Expressive. In contrary, % slow wave sleep was not associated with any subtest. Conclusion: This study identified that OSA may be highly prevalent in community DS children. Among 6–12-year-old DS children, OSA and % REM were associated with their language function. Keywords: Down syndrome, Neuropsychological tests, Polysomnography, Sleep apnea, Slow wave sleep

Prenatal genetic counseling of fetuses diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1–BP2 region is difficult due to limited information and controversial opinion on prognosis. In total, we collected the data of 36 pregnant women who underwent prenatal microarray analysis from 2010 to 2017 and were assessed at National Taiwan University Hospital. Comparison of the maternal characteristics, prenatal ultrasound findings, and postnatal outcomes among the different cases involving the 15q11.2 BP1–BP2 region were presented. Out of the 36 fetuses diagnosed with CNVs involving the BP1–BP2 region, five were diagnosed with microduplications and 31 with microdeletions. Among the participants, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its low pathogenicity. In our study, the prenatal abnormal ultrasound findings were recorded in 12 participants and were associated with 15q11.2 deletions. No obvious developmental delay or neurological disorders were detected in early childhood.

Background/purpose: A synthesis design and multistate analysis is required for assessing the clinical efficacy of antiviral therapy on dynamics of multistate disease progression and in reducing the mortality and enhancing the recovery of patients with COVID-19. A case study on remdesivir was illustrated for the clinical application of such a novel design and analysis. Methods: A Bayesian synthesis design was applied to integrating the empirical evidence on the one-arm compassion study and the two-arm ACTT-1 trial for COVID-19 patients treated with remdesivir. A multistate model was developed to model the dynamics of hospitalized COVID-19 patients from three transient states of low, medium-, and high-risk until the two outcomes of recovery and death. The outcome measures for clinical efficacy comprised high-risk state, death, and discharge. Results: The efficacy of remdesivir in reducing the risk of death and enhancing the odds of recovery were estimated as 31% (95% CI, 18–44%) and 10% (95% CI, 1–18%), respectively. Remdesivir therapy for patients with low-risk state showed the efficacy in reducing subsequent progression to high-risk state and death by 26% (relative rate (RR), 0.74; 95% CI, 0.55–0.93) and 62% (RR, 0.38; 95% CI, 0.29–0.48), respectively. Less but still statistically significant efficacy in mortality reduction was noted for the medium- and high-risk patients. Remdesivir treated patients had a significantly shorter period of hospitalization (9.9 days) compared with standard care group (12.9 days). Conclusion: The clinical efficacy of remdesvir therapy in reducing mortality and accelerating discharge has been proved by the Bayesian synthesis design and multistate analysis.

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

Background and aimsCost-effective serology tests may increase the predictive accuracy of colonoscopy for colorectal cancer screening. Reportedly, gamma-glutamyl transferase (GGT) is associated with oxidative stress and carcinogenesis and has been found to be elevated in the serum of cancer patients and colorectal adenoma tissue. We aimed to investigate the association between serum GGT levels and colorectal adenoma.MethodsThis single-center, health examination-based cohort enrolled 2475 subjects from 2006 to 2015. Baseline characteristics, laboratory data, bidirectional gastrointestinal endoscopy, and transabdominal ultrasonography were used to evaluate the severity of fatty liver.ResultsWe found an elevated median GGT level in subjects with tubular adenoma compared with those without (23 IU/L and 20 IU/L, pConclusionsThe results suggested a positive correlation of GGT with colon adenoma incidence and a predictive value with a cutoff point of >20 IU/L, which is within the normal range. The effect may be most prominent for those without steatohepatitis.

Background: Anti-tuberculous (TB) medications are common causes of drug-induced liver injury (DILI). Limited data are available on systemic inflammatory mediators as biomarkers for predicting DILI before treatment. We aimed to select predictive markers among potential candidates and to formulate a predictive model of DILI for TB patients. Methods: Adult active TB patients from a prospective cohort were enrolled, and all participants received standard anti-tuberculous treatment. Development of DILI, defined as ≥5× ULN for alanine transaminase or ≥2.6× ULN of total bilirubin with causality assessment (RUCAM, Roussel Uclaf causality assessment method), was regularly monitored. Pre-treatment plasma was assayed for 15 candidates, and a set of risk prediction scores was established using Cox regression and receiver-operating characteristic analyses. Results: A total of 19 (7.9%) in 240 patients developed DILI (including six carriers of hepatitis B virus) following anti-TB treatment. Interleukin (IL)-22 binding protein (BP), interferon gamma-induced protein 1 (IP-10), soluble CD163 (sCD163), IL-6, and CD206 were significant univariable factors associated with DILI development, and the former three were backward selected as multivariable factors, with adjusted hazards of 0.20 (0.07–0.58), 3.71 (1.35–10.21), and 3.28 (1.07–10.06), respectively. A score set composed of IL-22BP, IP-10, and sCD163 had an improved area under the curve of 0.744 (p < 0.001). Conclusions: Pre-treatment IL-22BP was a protective biomarker against DILI development under anti-TB treatment, and a score set by additional risk factors of IP-10 and sCD163 employed an adequate DILI prediction.

Objective: To evaluate the concurrent interaction of laparoscopic and robotic-assisted surgery in the initial learning period of endometrial cancer staging. Materials and methods: A retrospective cohort study was performed for the first 44 consecutive patients with endometrial cancer underwent laparoscopic (LSS) or robotic-assisted staging surgery (RSS) from February 2012 to October 2015 by a single surgeon in a tertiary care referral hospital. Demographics, diagnosis, perioperative variables, and complications were recorded. Quality of surgery was determined by the number of lymph nodes dissected and learning curve was estimated by operative time with respect to chronologic order of operation. Results: Twenty-four patients received LSS and 20 patients received RSS. RSS required longer operative time, but obtained more total number of lymph nodes compared with LSS (286.9 vs. 201.9 min (p

Abstract Background To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. Methods We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. Results In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850–17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330–16,450), high blood pressure (11,190 deaths, 95% UI: 8,190–14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370–9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970–9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040–9,190), and 7,400 deaths (95% UI: 6,670–8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220–13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610–6,980) and 3,170 deaths (95% UI: 1,860–4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190–2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. Conclusions High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level.

Abstract Background Ribonuclease-L (RNase-L) was known to be a ubiquitous enzyme involved in several cellular functions, especially innate immunity. It was recently shown to participate in adipogenesis in rodents. Here, we developed a method to measure serum levels of RNase-L and analyzed the relationship between RNase-L and metabolic syndrome (MetS). Methods A total of 396 subjects were recruited from a health check-up program. An in-house RNase-L immunoassay was developed. The serum RNase-L levels of these subjects were measured, and the association of MetS-related factors with RNase-L levels was assessed. Results The mean serum level of RNase-L of the subjects with MetS were lower than those without (16.5 ± 6.4 vs. 18.4 ± 8.0 μg/ml, P = 0.018). The subjects with central obesity, elevated blood pressure, or impaired fasting glucose also had lower serum RNase-L levels in comparison to those without. In multivariate linear regression analysis, diastolic blood pressure (β = −0.129, P = 0.024) and high-density lipoprotein cholesterol (HDL-C) (β = 0.127, P = 0.036) were related to serum RNase-L. For every 5 μg/ml increase in serum RNase-L levels, it is associated with a reduced risk of MetS (OR 0.83, 95% CI 0.71–0.98, P = 0.028), central obesity (OR 0.82, 95% CI 0.71–0.94, P = 0.005), or low HDL-C (OR 0.86, 95% CI 0.74–1.00, P = 0.042). Moreover, age is inversely related to serum RNase-L levels in various analyses. Conclusions The serum RNase-L levels were inversely associated with MetS, unfavorable metabolic profiles, and age.

Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls. Methods: A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes. In addition, the association of IL28B rs8099917 genotype with baseline data, including HCV RNA level, HCV genotype, histological activity grade, fibrosis stage, and body mass index, were evaluated and further stratified by covariant factors. Results: Compared with healthy controls, CHC patients had a lower prevalence rate of favorable IL28B rs8099917 TT genotype (81.0% vs. 89.3%, p = 0.025). In addition, the prevalence rates of favorable TT genotype in patients with HCV genotypes 1 and 2 were 76.0% and 86.0%, respectively (p = 0.007). Using ordered logistic regression analysis, higher fibrosis stages were found to be associated with a lower prevalence of TT genotype (p = 0.033), but not histological activity grades (p = 0.748). The association with fibrosis stages was more pronounced in female patients (p = 0.024). Conclusion: In Taiwan, CHC patients have a lower frequency of favorable IL28B TT genotype than healthy controls. Among patients with CHC, the frequency of TT genotype is higher in HCV genotype 2 patients than in HCV genotype 1 patients. In addition, CHC patients with TT genotype, particularly females, have a lower likelihood of advanced fibrosis.

In experimental stroke studies, a neuroanatomy-based functional examination of behaviors is critical to predict the pathological extent of infarcts because brain-imaging studies are not always available. However, there is a lack of systematic studies to examine the efficiency of a behavioral test for this purpose. Our work aimed to design a new score for this goal in stroke rats, by simplifying the Garcia score (with subscore 1–6) and adding circling as subscore 7. MRI and 2,3,5-triphenyltetrazolium chloride staining were used to determine the pathological extent after transient middle cerebral artery occlusion. The modified summations of subscores were designed according to the predictability of each subscore for locations and sizes of infarcts in one group of stroke rats, and were validated in another group. The original Garcia score was able to predict the pathological extent of edema-adjusted infarct size ≥30%, and the summation of subscore 4, 6, and 7 (4: climbing, 6: vibrissae sensation, 7: circling) also could predict it well. The original Garcia score failed to predict infarct at the primary motor cortex, while the summation of subscore 4, 6, and 7 potentially could predict not only the primary motor cortex, but also the forelimb, hindlimb, and barrel field regions of the primary sensory cortex. Accordingly, this neuroanatomy-correlated functional assessment system composed of subscore 4, 6, and 7 was proposed, with less examination time and better inter-rater reliability than the original Garcia score. In summary, this new scoring system, summation (4,6,7) score, examined motor and sensory functions based on neuroanatomical involvement, having the potential to predict the pathological extent and specific relevant brain areas of infarcts, respectively.

BACKGROUND:Studies showed that the endotoxemia-related biomarker, lipopolysaccharide-binding protein (LBP), is associated with obesity and fatty liver. The level of LBP is reduced after surgical weight loss. This study aimed to verify the change of serum LBP levels after one-year medical weight management in subjects with obesity. METHODS AND FINDINGS:A total of 62 subjects with obesity, 39 subjects with overweight, and 21 subjects with normal body mass index were enrolled for a one-year weight management program. Basic information, body composition analysis, clinical data, serum LBP level, and abdominal ultrasonography findings were collected. At baseline, the serum LBP levels of the obese and overweight subjects were significantly higher than that of the normal group (30.9±7.4 and 29.6±6.3 versus 23.1±5.6 μg/mL, respectively, p

[This corrects the article DOI: 10.1371/journal.pone.0187032.].

BACKGROUND:The present study aimed to test if the temporal sequence between sleep apnea (SA) diagnosis and incident myocardial infarction (MI) was associated with the long-term mortality and cardiovascular event in a community-based cohort. METHODS:We retrieved data from 9,453 incident MI patients between Jan. 1st 2000 and Dec. 31st 2012 from the Taiwan National Health Insurance Research Database. The study subjects included 207 MI patients with SA (SA-MI), further stratified into 110 with pre-existing SA before MI (SA-bMI) and 96 diagnosed with SA after MI (SA-pMI). The median follow-up period was 4.2 years. Propensity-score-matched controls were selected from 9,246 non-SA MI patients (non-SA-MI). The association of SA and outcomes including all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) were analyzed by a Cox proportional hazards model. RESULTS:The result showed that SA was not associated with mortality regardless of the timing of SA diagnosis. SA-pMI was associated with increased risk of MACCEs (Hazard ratio [HR]: 1.412, 95% confidence interval [CI]: 1.037~1.923, p = 0.029) including re-MI or revascularization and ischemic heart disease hospitalization. Such an association was most significant for SA diagnosed within one year after MI (HR: 2.029, 95% CI: 1.265~3.254, p = 0.003), which was not seen in patients treated with continuous positive airway pressure (CPAP). CONCLUSION:The temporal sequence and the time interval between SA diagnosis and incident MI was associated with the cardiovascular events after MI, especially within one year after MI. Early assessment for the presence of SA after incident MI and early CPAP intervention may reduce the risk of further adverse cardiovascular events.

Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. Methods: The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1st year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. Results: In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. Conclusion: The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors.

Background: Uterine leiomyosarcomas (LMSs) are rare and aggressive but difficult to predict before surgery. Minimally invasive surgery using morcellation might cause tumor spreading during manipulating of tumor tissue. We aim to study the influence of morcellation on the prognosis of patients with early uterine LMS. Methods: We retrospectively reviewed the medical records of all patients with stage 1 LMS treated between April 1993 and April 2014. Demographics and outcomes were compared between patients who underwent total hysterectomy without morcellation and those who underwent surgery with abdominal, vaginal, and laparoscopic morcellation. Results: In total, 43 consecutive patients were identified, including 29 without morcellation and 14 with morcellation. Tumor size was significantly smaller (7.3 cm vs. 11.6 cm, p = 0.006) in patients with morcellation. Six (42.9%) patients with morcellation received reoperation at 18.5 days after the initial surgery. Patients with morcellation did not show higher recurrence rate, including the recurrence rate at the pelvic cavity, compared with patients without morcellation. Compared with patients without morcellation, Kaplan–Meier curves did not show significant difference in the disease-free survival (DFS) and overall survival (OS) in patients with morcellation. In univariate and multivariate analyses, tumor size was significantly associated with poor DFS and OS. Morcellation was not associated with survivals. Conclusion: In patients with stage 1 LMS, survival is associated with tumor size. Morcellation does not seem to be associated with a worse prognosis in early stage LMS.

Objective: To evaluate the influence of morcellation during surgery on clinical outcome in unexpected early uterine leiomyosarcomas (LMSs) using a tumor-size-matched comparison study. Materials and methods: We retrospectively reviewed the clinicopathological characteristics, prognostic factors, and treatment outcomes of patients with Stage 1 uterine LMS from April 1993 to April 2014 in a university-based tertiary hospital. Patients who received morcellation via abdomen, vagina, or laparoscopy were compared with tumor-size-matched patients who underwent total hysterectomy without morcellation. Results: In total, 34 consecutive patients were identified, including 14 patients with morcellation and 20 patients without morcellation. There were no significant difference between the two groups of patients in age, parity, mitotic count, lymph node dissection, and adjuvant therapy. Six (42.9%) patients with morcellation were reoperated at 18.5 days after the initial surgery. Tumor recurrence rates at local and distant sites showed no difference between the two groups of patients. Patients with morcellation had a marginally lower disease-free survival (DFS) and overall survival (OS) rates compared with patients without morcellation. In univariate analysis, morcellation was marginally significantly associated with lower DFS [hazard ratio (HR), 2.62; 95% confidence interval, 0.89–7.71; p = 0.08] and OS (HR, 2.70; 95% confidence interval, 0.89–8.20; p = 0.08). In multivariate analysis, morcellation was associated with lower OS in marginal significance (HR, 2.94; 95% confidence interval, 0.83–10.39; p = 0.09). Conclusion: Tumor morcellation did not increase the abdominal–pelvic recurrence rate, but may be associated with lower DFS and OS in Stage 1 LMS.

Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon.We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy.LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects.

This study aimed to determine the effect of combining positive airway pressure (PAP) therapy and mandibular advancement device (MAD) in patients with severe obstructive sleep apnea (OSA) who were pressure intolerant for PAP and were unresponsive to MAD.This retrospective study reviewed the medical records of severe OSA patients with apnea-hypopnea index (AHI) ≥ 30/hr who were diagnosed between October 1, 2008 and June 30, 2014. Patients were initially treated with 2 weeks of PAP, and those who were intolerant to high-pressure PAP (≥15 cm H2O) were switched to 12 weeks of MAD, which is a monobloc designed at 75% of maximum protrusion. Patients who had high residual AHI (≥15/hr) on MAD underwent 12 weeks of combination therapy (CT) with MAD and CPAP and were enrolled in the present study. Enrolled subjects who completed the 12-week CT were followed-up until June 30, 2016.A total of 14 male patients were included. All three treatments effectively reduced AHI, oxygen desaturation index (ODI), and total sleep time with SpO2

Objectives: To assess the learning curve and safety of laparoendoscopic single-site (LESS) surgery of gynecological surgeries. Materials and methods: Sixty-three women who underwent LESS surgery by a single experienced laparoscopic surgeon from February 2011 to August 2011 were included. Commercialized single-incision laparoscopic surgery homemade ports were used, along with conventional straight instruments. The learning curve has been defined as the additional surgical time with respect to surgical order of LESS surgery, which has been estimated using a smooth function in a linear model with generalized least squares, with some adjustments made due to influencing factors of the operations. Results: All women completed LESS surgeries without the need for ancillary ports, except for two laparotomy conversions due to incidental ovarian malignancy. Three women, one with a gastrointestinal stromal tumor, one with laparoscopic myomectomy, and one who had been receiving simultaneous hysteroscopic myomectomy, were excluded. Of the 58 women included, 39 underwent adnexal surgeries and 19 underwent hysterectomies. Complications occurred with one woman who required a blood transfusion during the procedure. Surgical time was longer in bilateral cystectomy compared with unilateral cystectomy and unilateral/bilateral salpingo-oophorectomy (110.6 ± 51.1 minutes vs. 73.0 ± 26.3 minutes and 66.3 ± 26.9 minutes; p

Metabolic syndrome and left ventricular hypertrophy (LVH) carry high cardiovascular risks. We performed a cross-sectional study to evaluate the effect of different amounts of physical activity (PA) on the prevalence of metabolic syndrome and LVH in our study population. Methods: This study was a cross-sectional survey of 1494 apparently healthy subjects: 776 men with a mean age of 57.6 + 12.3 years, and 718 women with a mean age of 56.4+ 11.0 years. The metabolic syndrome was defined according to modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. LVH was diagnosed by electrocardiography voltage criteria. The amount of PA was determined with a questionnaire and stratified into low, moderate or high levels. Results: The prevalence of metabolic syndrome and its components was as follows: metabolic syndrome, 15.5%; obesity, 29.7%; high triglyceride level, 21.7%; low high-density lipoprotein-cholesterol level, 35.9%; high blood pressure, 56.9%; and impaired fasting glucose, 13.1%. A high amount of PA (> 14km per week walking distance) was significantly associated with lower prevalence of metabolic syndrome [odds ratio (OR) = 0.53, p = 0.001], lower prevalence of obesity (OR = 0.56, p = 0.001), triglyceridemia (OR = 0.58, p = 0.007) and LVH (OR=0.37, p = 0.006). Conclusion: This study suggests that high amounts of PA are inversely correlated with the prevalence of metabolic syndrome and LVH in men and women.

Adipose tissue is now accepted by the scientific and medical community to be a genuine endocrine organ, in addition to its classical role as an energy store. Adiponectin is one of the many adipocytokines that are secreted almost exclusively by adipose tissue. Alteration in blood adiponectin concentrations has been linked to many human diseases in numerous cross-sectional and prospective studies. In this review, we describe briefly the biological effects of adiponectin as revealed by basic scientific investigations. We also summarize the principles of blood adiponectin assays. Overall, lower blood adiponectin concentration is found in subjects with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. These medical conditions are components of the metabolic syndrome and major risk factors for accelerated atherosclerosis. Plasma adiponectin levels are also expected to be lower in subjects with cardiovascular diseases, such as coronary artery disease, ischemic stroke and peripheral artery disease. Congestive heart failure (CHF) and cardiac arrhythmia are common end points in cardiovascular diseases. Surprisingly, higher blood adiponectin levels are frequently reported to predict mortality associated with CHF. Few human data regarding adiponectin and cardiac arrhythmia are available. Higher blood adiponectin level has been documented only in atrial fibrillation. We also summarize data on the role of the high molecular weight (HMW) iso-forms of adiponectin and the effects of clinical treatment on the levels of total or HMW adiponectin. Whether adiponectin is a risk marker or a risk factor for the diseases reviewed in this article, and in many other human diseases, and their detailed pathogenic links awaits further investigation.

Elevation of C-reactive protein (CRP) level is associated with increased risk of cardiovascular events. The 1059 G > C polymorphism in exon 2 of the CRP gene has been shown to affect plasma concentration of CRP. We want to elucidate the effect of this polymorphism on the development of coronary artery disease (CAD) among the Chinese population in Taiwan. Methods: We scrutinized 536 patients undergoing coronary angiography (365 patients with CAD and 171 controls with patent coronaries) and evaluated the association of CRP gene 1059 G > C polymorphism with CAD. Genotyping of the polymorphism was performed by polymerase chain reaction and MaeIII restriction enzyme digestion. Results: The CC genotype was associated with lower plasma CRP concentration (GG, 6.5 ± 5.8; GC, 3.3 ± 4.4; CC, 2.3 ± 3.1 mg/L; p = 0.02). Subjects with CAD or myocardial infarction (MI) had significantly higher plasma CRP concentration than that in controls (CAD vs. controls, 8.9 ± 18.9 vs. 3.3 ± 7.2 mg/L; p < 0.001), while patients with MI showed higher CRP when compared to those with chronic stable angina (13.5 ± 22.9 vs. 5.2 ± 14.1 mg/L; p < 0.001). However, this polymorphism was not associated with CAD in our population. Conclusion: Our data suggest that human CRP gene 1059 G > C polymorphism is associated with plasma CRP concentration among Chinese in Taiwan receiving coronary angiography.

BACKGROUND: To identify the ranges of hemoglobin A(1c) (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) levels which are associated with the lowest all-cause mortality. METHODS: A retrospective cohort of 12,643 type 2 diabetic patients (aged ≥18 years) were generated from 2002 to 2010, in Far-Eastern Memorial Hospital, New Taipei city, Taiwan. Patients were identified to include any outpatient diabetes diagnosis (ICD-9: 250), and drug prescriptions that included any oral hypoglycemic agents or insulin prescribed during the 6 months following their first outpatient visit for diabetes. HbA1c, SBP, and LDL-C levels were assessed by the mean value of all available data, from index date to death or censor date. Deaths were ascertained by matching patient records with the Taiwan National Register of Deaths. RESULTS: Our results showed general U-shaped associations, where the lowest hazard ratios occurred at HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL. The risk of mortality gradually increases if the patient's mean HbA1c, SBP, or LDL-C during the follow-up period was higher or lower than these ranges. In comparison to the whole population, the adjusted hazard ratio (95% CI) for patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL were 0.69 (0.62-0.77), 0.80 (0.72-0.90), and 0.68 (0.61-0.75), respectively. CONCLUSIONS: In our type 2 diabetic cohort, the patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, or LDL-C 100-130 mg/dL had the lowest all-cause mortality. Additional research is needed to confirm these associations and to further investigate their detailed mechanisms.

Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects.A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay.DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, p

BACKGROUND: Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. METHODS: Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels. FINDINGS: There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28-5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI ≥ 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. CONCLUSION: We provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk.

BACKGROUND & AIMS: Quantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection. METHODS: This is a retrospective cohort study conducted in a university hospital. Treatment-naïve HBeAg-negative carriers followed for more than 3 years were recruited. Their hepatitis activities were categorized by longitudinal HBV-DNA levels into high viral-load (HVL: HBV-DNA >/ =2000 IU/mL persistently), low viral-load (LVL: HBV-DNA 1000, 100-999,

INTRODUCTION: The association of vegetarian status with the risk of metabolic syndrome (MetS) is not clear. In Asia, Buddhists often have vegetarian behavior for religious rather than for health reasons. We hypothesize that the vegetarian in Buddhism is associated with better metabolic profiles, lower risk for the MetS and insulin resistance (IR). METHODS: We enrolled 391 female vegetarians (~80% lacto-ovo-vegetarians) and 315 non-vegetarians from health-checkup clinics at a Buddhist hospital in Taiwan. RESULTS: The vegetarian status was associated with lower body mass index, smaller waist circumference, lower total cholesterol, lower low density lipoprotein-cholesterol (LDL-C), and lower HDL-C in multivariate linear regression analyses. Despite having lower HDL-C level, the vegetarians had significantly lower total cholesterol/HDL-C and LDL-C/HDL-C ratios. After adjusting the other covariates, the risks for the MetS were lower for ovo-lacto-vegetarians of 1-11 years and >11 years respectively by 54% (odds ratio [OR] =0.46, 95%C.I.:0.26-0.79) and 57% (OR=0.43, 95%C.I.:0.23-0.76) compared to non-vegetarians by the IDF criteria. Likewise, they were lower respectively by 45% (OR=0.55, 95%C.I.:0.32-0.92) and 42% (OR=0.58, 95%C.I.:0.33-0.997), for the MetS by the modified NCEP criteria. In the subgroup of non-diabetic subjects, the vegetarians also had lower risk for IR by HOMA compared to the non-vegetarians (OR=0.71, 95%C.I.:0.48-1.06). CONCLUSION: The vegetarian behavior, mainly lacto-ovo-vegetarian, related to Buddhism, although not meant for its health effects, is associated with reduced risk for the MetS and IR and may potentially provide metabolic and cardiovascular protective effects in women.