Showing papers by "Taipei Veterans General Hospital published in 2010"
TL;DR: Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins.
813 citations
TL;DR: The direct regulation of BMI1 by the EMT regulator, Twist1 is shown, suggesting that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes.
Abstract: The epithelial-mesenchymal transition (EMT), one of the main mechanisms underlying development of cancer metastasis, induces stem-like properties in epithelial cells. Bmi1 is a polycomb-group protein that maintains self-renewal, and is frequently overexpressed in human cancers. Here, we show the direct regulation of BMI1 by the EMT regulator, Twist1. Furthermore, Twist1 and Bmi1 were mutually essential to promote EMT and tumour-initiating capability. Twist1 and Bmi1 act cooperatively to repress expression of both E-cadherin and p16INK4a. In patients with head and neck cancers, increased levels of both Twist1 and Bmi1 correlated with downregulation of E-cadherin and p16INK4a, and was associated with the worst prognosis. These results suggest that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes.
614 citations
TL;DR: Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians.
367 citations
TL;DR: Pb, a transit time–independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness.
Abstract: The value of increased arterial wave reflection, usually assessed by the transit time-dependent augmentation index and augmented pressure (Pa), in the prediction of cardiovascular events may have been underestimated. We investigated whether the transit time-independent measures of reflected wave magnitude predict cardiovascular outcomes independent of arterial stiffness indexed by carotid-femoral pulse wave velocity. A total of 1272 participants (47% women; mean age: 52+/-13 years; range: 30 to 79 years) from a community-based survey were studied. Carotid pressure waveforms derived by tonometry were decomposed into their forward wave amplitudes, backward wave amplitudes (Pb), and a reflection index (=[Pb/(forward wave amplitude+Pb)]), in addition to augmentation index, Pa, and reflected wave transit time. During a median follow-up of 15 years, 225 deaths occurred (17.6%), including 64 cardiovascular origins (5%). In univariate Cox proportional hazard regression analysis, pulse wave velocity, Pa, and Pb predicted all-cause and cardiovascular mortality in both men and women, whereas augmentation index, reflected wave transit time, and reflection index were predictive only in men. In multivariate analysis accounting for age, height, and heart rate, Pb predicted cardiovascular mortality in both men and women, whereas Pa was predictive only in men. Per 1-SD increment (6 mm Hg), Pb predicted 15-year cardiovascular mortality independent of brachial but not central pressure, pulse wave velocity, augmentation index, Pa, and conventional cardiovascular risk factors with hazard ratios of approximately 1.60 (all P<0.05). In conclusion, Pb, a transit time-independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness.
343 citations
01 Sep 2010
TL;DR: Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.
Abstract: Objective To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery. Material and Methods Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group. Results In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival. Conclusion Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.
273 citations
TL;DR: This review summarizes currently available data regarding the protective role of hydrogen, provides an outline of recent advances in research on the use of hydrogen as a therapeutic medical gas in diverse models of disease and discusses the feasibility of hydrogenAs a therapeutic strategy.
Abstract: Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and anti-apoptotic protective effects on cells and organs. Therapeutic hydrogen has been applied by different delivery methods including straightforward inhalation, drinking hydrogen dissolved in water and injection with hydrogen-saturated saline. This review summarizes currently available data regarding the protective role of hydrogen, provides an outline of recent advances in research on the use of hydrogen as a therapeutic medical gas in diverse models of disease and discusses the feasibility of hydrogen as a therapeutic strategy. It is not an overstatement to say that hydrogen's impact on therapeutic and preventive medicine could be enormous in the future.
271 citations
TL;DR: The authors' results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC.
Abstract: Summary Background Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Methods Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB–IV); an Eastern Cooperative Oncology Group performance status of 0–2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7·5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. Findings At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade ≥3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported. Interpretation Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC. Funding F Hoffmann-La Roche Ltd.
250 citations
TL;DR: The data suggested that SirT1 could be a crucial factor involved in the endothelium cells of atherosclerotic CAGB patients and aging rats and RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells.
Abstract: Aim: Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential mediator of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including transcription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)-induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress.Methods: SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardiac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activation on oxidative stress-induced aging, senescence-associated β-galactosidase (SA-β-gal) expression in RV-treated human umbilical vein endothelial cells (HUVECs) with or without H2O2 treatment was evaluated.Results: SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-dependently increased in RV-treated HUVECs. The SA-β gal assay showed that RV inhibited the senescent phenotype of H2O2-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-β gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H2O2-treated HUVECs by siRNA-SirT1.Conclusion: Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.
223 citations
TL;DR: VBM findings indicated that patients whose MDD remitted were cognitively and morphologically different from non-remitters, and Voxel-based structural deficits in the left DLPFC may characterize a subgroup of people with recurrent MDD who respond poorly to antidepressants.
210 citations
TL;DR: In adenomyosis, the serum E2 level was negatively correlated with E‐cadherin expression in the epithelial components of the eutopic endometrium andadenomyotic lesions, suggesting the involvement of oestrogen‐induced EMT in endometrial cells.
Abstract: Adenomyosis is an oestrogen-dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen-induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17β-oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up-regulated and E-cadherin expression was down-regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E-cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast-like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up-regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen-induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen-dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen-induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for adenomyosis patients.
196 citations
TL;DR: Future research on ischemic stroke should consider age as a factor that influences stroke prevention and treatment, and should focus on the management of acute stroke in the elderly to reduce the incidence and improve outcomes in this vulnerable group.
Abstract: Stroke mostly occurs in elderly people and patient outcomes after stroke are highly influenced by age. A better understanding of the causes of stroke in the elderly might have important practical implications not only for clinical management, but also for preventive strategies and future health-care policies. In this Review, we explore the evidence from both human and animal studies relating to the effect of old age-in terms of susceptibility, patient outcomes and response to treatment-on ischemic stroke. Several aging-related changes in the brain have been identified that are associated with an increase in vulnerability to ischemic stroke in the elderly. Furthermore, risk factor profiles for stroke and mechanisms of ischemic injury differ between young and elderly patients. Elderly patients with ischemic stroke often receive less-effective treatment and have poorer outcomes than younger individuals who develop this condition. Neuroprotective agents for ischemic stroke have been sought for decades but none has proved effective in humans. One contributing factor for this translational failure is that most preclinical studies have used young animals. Future research on ischemic stroke should consider age as a factor that influences stroke prevention and treatment, and should focus on the management of acute stroke in the elderly to reduce the incidence and improve outcomes in this vulnerable group.
TL;DR: The pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease are discussed and the therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.
TL;DR: The results demonstrate that the development of suicidal behaviors in major depression is related to widespread but discrete volume reduction in several cortical and subcortical structures, fitting with the hypothesis that decreased cerebral volume in certain regions renders biological susceptibility to attempt suicide during depressive states.
Abstract: Late-onset major depression is thought to have a biological (vascular) basis, which could be a result of brain structure change. Vascular lesions can affect both the gray matter (GM) and white matter (WM), while most previous studies addressed WM abnormality. This study explored the disease- and symptom (history of suicide attempt) -related GM morphometry in elderly male patients with late-onset depression. A total of 70 patients with depression admitted to our geriatric psychiatric ward were investigated, and 26 age-matched males were recruited as controls. We used T1-weighted magnetic resonance imaging (MRI) to obtain cerebral structural information and adopted voxel-based morphometry (VBM) to investigate brain volume change related to disease (depression vs control) and symptom (depression with history of suicide attempt vs depression without history of suicide attempt). Late-onset depression was associated with smaller volumes in several regions of GM (insula and the posterior cingulate region) and WM (subcallosal cingulate cortex, floor of lateral ventricles, parahippocampal region, insula, and the cerebellum). Compared with nonsuicidal counterpart, suicidal depression was associated with decreased GM and WM volume in the frontal, parietal, and temporal regions, and the insula, lentiform nucleus, midbrain, and the cerebellum. Marked regional volume reduction was noticed at dorsal medial prefrontal cortex. Our results demonstrate that the development of suicidal behaviors in major depression is related to widespread but discrete volume reduction in several cortical and subcortical structures, fitting with the hypothesis that decreased cerebral volume in certain regions renders biological susceptibility to attempt suicide during depressive states.
TL;DR: This is so far the first study to validate the Elixhauser method and compare it to other methods in the Asia region, and is the first to report its differences in data periods between short- and long-term outcomes.
Abstract: It is important to find a comorbidity measure with better performance for use with administrative data. The new method proposed by Elixhauser et al. has never been validated and compared to the widely used Charlson method in the Asia region. The objective of this study was to compare the performance of three comorbidity measures using information from different data periods in predicting short- and long-term mortality among patients with acute myocardial infarction (AMI) and chronic obstructive pulmonary disease (COPD). We conducted a retrospective cohort study using National Health Insurance claims data (2001-2002) in Taiwan. We constructed the Elixhauser, the Charlson/Deyo, and the Charlson/Romano methods based on the International Classification of Disease, 9th Revision, Clinical Modification codes in the claims data. Two data periods, including the index hospitalization as well as the index and prior 1-year hospitalizations, were used in the analysis. The performances were compared using the c-statistics derived from multiple logistic regression models that included age, gender, race, and whether the patient received surgery or not. The outcomes of interest were in-hospital and 1-year mortality. The performance was in the same rank order among both populations regardless of the outcome and data period: Elixhauser > Charlson/Romano > Charlson/Deyo. In predicting in-hospital mortality, the Elixhauser models using information from the index hospitalization performed best, even better than the Charlson/Deyo or Charlson/Romano models using information from the index and prior hospitalizations. Nevertheless, in predicting 1-year mortality, the Elixhauser models using information from the index and 1-year prior hospitalizations performed better than using information from the index hospitalization only. This is so far the first study to validate the Elixhauser method and compare it to other methods in the Asia region, and is the first to report its differences in data periods between short- and long-term outcomes. The comorbidity measurement developed by Elixhauser et al. has relatively good predictive validity, and researchers should consider its use in claims-based studies.
TL;DR: The results showed that PAG is functionally connected to ACC (rostral and pregenual ACC) and also rostral ventromedial medulla (RVM), forming a core ACC-PAG-RVM network for pain modulation even no pain stimulus is applied.
TL;DR: Patients with IIM are at increased risk for cancer and should receive age-appropriate and gender-appropriate malignancy evaluations, with additional assessment for nasopharyngeal, lung and hematologic malignancies following diagnosis, and with continued vigilance for development of cancers in follow-up.
Abstract: Introduction
The association of idiopathic inflammatory myositis (IIM) and malignancies has been reported, but rarely in Asian countries. Our aim was to investigate the risk of cancer among IIM patients without a prior history of malignancies, in Taiwan.
TL;DR: TTV may be a feasible tumoral prognostic predictor for HCC and provides the best prognostic ability among 12 TTV-based and currently used staging systems, according to a single-hospital study that included patients with early to advanced cancer stages.
TL;DR: The tip−apex distance (TAD) was shown to be the most important predictive factor for cutout, followed by screw position, fracture pattern, reduction and patient age, which means it is important to ensure good fracture reduction and to place the lag screw in either the middle/middle or inferior/middle position with appropriate TAD.
Abstract: The aim of this study was designed to assess the risk factors of lag-screw cutout in the treatment of intertrochanteric fracture with a dynamic hip screw (DHS). From 2003 to 2007, 1,150 patients who had acute unilateral intertrochanteric fractures of the femur were enrolled to the study. All fractures were managed by closed reduction and internal fixation with 135° DHS devices. Patient demographics, fracture patterns, reduction and fixation and perioperative course parameters were all recorded. The follow-up period was 38 months on average (range 16–60 months). Finally, 937 patients were available for evaluation of final results in which we focused on lag-screw cutout. Excluding complications not related to screw position, 64 patients (6.8%) with screw cutout were encountered, and the remaining 873 patients had uneventful union, with the average union time of 17.5 weeks (range15–24 weeks). Upon analysis with logistic regression, the tip−apex distance (TAD) was shown to be the most important predictive factor for cutout, followed by screw position, fracture pattern, reduction and patient age. In order to decrease the risk of lag-screw cutout, it is important to ensure good fracture reduction and to place the lag screw in either the middle/middle or inferior/middle position with appropriate TAD.
TL;DR: Analytical results verified the psychometric properties of the SAQ-C at Taiwanese hospitals and found that healthcare workers with positive attitudes to each SAQ dimension were more likely to perceive good collaboration with coworkers, and their hospitals were morelikely to encourage safety reporting and to prioritize safety training programs.
Abstract: Safety activities have been initiated at many hospitals in Taiwan, but little is known about the safety culture at these hospitals. The aims of this study were to verify a safety culture survey instrument in Chinese and to assess hospital safety culture in Taiwan. The Taiwan Patient Safety Culture Survey was conducted in 2008, using the adapted Safety Attitude Questionnaire in Chinese (SAQ-C). Hospitals and their healthcare workers participated in the survey on a voluntary basis. The psychometric properties of the five SAQ-C dimensions were examined, including teamwork climate, safety climate, job satisfaction, perception of management, and working conditions. Additional safety measures were asked to assess healthcare workers' attitudes toward their collaboration with nurses, physicians, and pharmacists, respectively, and perceptions of hospitals' encouragement of safety reporting, safety training, and delivery delays due to communication breakdowns in clinical areas. The associations between the respondents' attitudes to each SAQ-C dimension and safety measures were analyzed by generalized estimating equations, adjusting for the clustering effects at hospital levels. A total of 45,242 valid questionnaires were returned from 200 hospitals with a mean response rate of 69.4%. The Cronbach's alpha was 0.792 for teamwork climate, 0.816 for safety climate, 0.912 for job satisfaction, 0.874 for perception of management, and 0.785 for working conditions. Confirmatory factor analyses demonstrated a good model fit for each dimension and the entire construct. The percentage of hospital healthcare workers holding positive attitude was 48.9% for teamwork climate, 45.2% for perception of management, 42.1% for job satisfaction, 37.2% for safety climate, and 31.8% for working conditions. There were wide variations in the range of SAQ-C scores in each dimension among hospitals. Compared to those without positive attitudes, healthcare workers with positive attitudes to each SAQ dimension were more likely to perceive good collaboration with coworkers, and their hospitals were more likely to encourage safety reporting and to prioritize safety training programs (Wald chi-square test, p < 0.001 for all). Analytical results verified the psychometric properties of the SAQ-C at Taiwanese hospitals. The safety culture at most hospitals has not fully developed and there is considerable room for improvement.
TL;DR: In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.
Abstract: Previously, we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. In this study, we report that cancerous inhibitor of protein phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediates the apoptotic effect of bortezomib in HCC. Silencing PP2A by small interference RNA (siRNA) abolishes bortezomib-induced down-regulation of phospho-Akt and apoptosis. Bortezomib increases PP2A activity in sensitive HCC cells, including Sk-Hep1, Hep3B and Huh-7, but not in resistant PLC5 cells. Bortezomib down-regulates CIP2A in a dose- and time-dependent manner in all sensitive HCC cells, whereas no alterations in CIP2A were found in resistant PLC5 cells. Knockdown of CIP2A by siRNA restored bortezomib's effects on apoptosis and PP2A activity in PLC5 cells. Moreover, over-expression of CIP2A up-regulated phospho-Akt and protected Sk-Hep1 cells from bortezomib-induced apoptosis. It is significant that, ectopic expression of CIP2A decreased Akt-related PP2A activity, whereas silencing CIP2A increased this activity, indicating that CIP2A negatively regulates Akt-related PP2A activity in HCC cells, furthermore, our in vivo data showed that bortezomib down-regulates CIP2A and up-regulates PP2A activity in Huh-7 tumors, but not in PLC5 tumors. In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.
TL;DR: It is demonstrated that abnormal GM volume changes are present in PDM patients even in the absence of pain, highlighting that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.
Abstract: Primary dysmenorrhea (PDM) is the most prevalent gynecological disorder for women in the reproductive age. PDM patients suffer from lower abdominal pain that starts with the onset of the menstrual flow. Prolonged nociceptive input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero-nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization. Previously, we hypothesized that disinhibition of orbitofrontal networks could be responsible for increased pain and negative affect in PDM. Here, we further tested this hypothesis. We used an optimized voxel-based morphometry (VBM) approach to compare total and regional gray matter (GM) increases and decreases in 32 PDM patients with 32 healthy age and menstrual cycle matched (peri-ovulatory phase) controls. Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affected regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top-down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain. Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.
TL;DR: ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.
Abstract: A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients
TL;DR: Lower eGFR at dialysis initiation is associated with lower mortality, andPropensity score analysis showed a higher eG FR to be associated with increased mortality risks, and further study is needed.
Abstract: Background. Glomerular filtration rate (GFR) and comorbidity at dialysis initiation in relation to mortality in end-stage renal disease is still controversial. We studied factors potentially related to the mortality in incident haemodialysis (HD) patients. Methods. A national database included 23 551 incident HD patients from July 2001 to December 2004. Kaplan–Meier and Cox regression analyses were performed to assess the association between GFR estimated by the four-variable Modified Diet in Renal Disease equation and all-cause mortality. Analyses were performed from Day 91 after the start of dialysis. Patients were classified into five groups (quintiles) based on estimated glomerular filtration rate (eGFR) at the start of dialysis. Results. The median eGFR at dialysis initiation was low (4.7 mL/min/1.73 m 2 ), as was the mortality in the first year of dialysis [13.2/100 patient-year, 95% confidence interval (95% CI)=12.8–13.7]. There was an inverse association between lower eGFR and higher survival rate. The Cox regression model revealed an increase in mortality risk in Q5 (hazard ratio [HR]=2.44, 95% CI=2.11–2.81), Q4 (HR= 1.66, 95% CI=1.43–1.93), Q3 (HR=1.21, 95% CI=1.04– 1.41) and Q2 (HR=1.18, 95% CI=1.01–1.37) compared with the reference group of Q1 after adjusting for year of application, primary diseases (chronic glomerulonephritis, diabetic nephropathy, hypertension, chronic tubulointerstitial nephritis and others), demographics (age, sex), presence of co-morbidity (diabetes mellitus, hypertension, congestive heart failure, ischaemic heart diseases, cerebrovascular diseases, malignancies, liver cirrhosis, tuberculosis, other diseases and free of reported of comorbidities) and haematocrit. Propensity score analysis also showed a higher eGFR to be associated with increased mortality risks. Adjustment for all covariates explained a high percentage of excess risk of mortality in the groups with low eGFR, but less risk in the groups with higher eGFR. Conclusions. Lower eGFR at dialysis initiation is associated with lower mortality. Conditions at dialysis initiation explained excess 1-year mortality risk differently in patients who began dialysis at different levels of eGFR. Other factors likely contribute to the mortality of patients initiating dialysis at higher eGFR levels, and further study is needed.
TL;DR: The incidences and outcomes of metabolic inborn error diseases found in the nationwide MS/MS newborn screening program in Taiwan are reported.
Abstract: In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.
TL;DR: In this paper, a retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999-2004 was conducted to evaluate annual prevalence and incidence of Type 2 diabetes and examine possible trends among adults in Taiwan.
Abstract: Diabet. Med. 27, 636–643 (2010)
Abstract
Aim To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan.
Methods A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999–2004. Adult patients aged ≥ 20 years old with prevalent and incident Type 2 diabetes were identified using ICD-9-CM diagnostic codes. Age-specific and age-direct-standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression.
Results During the study years, the age-standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and ≥ 80 years. The age-standardized incidence rates of Type 2 diabetes per 1000 person-years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20–1.42) for men and 1.04 (1.01–1.08) for women. The incidence trends for people aged ≥ 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001).
Conclusions This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999–2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20–40 years were most susceptible to higher incidence of Type 2 diabetes.
TL;DR: K. pneumoniae continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008 and was associated with a more fulminant course and a worse prognosis than bactEREmic CAP due to Streptococcus pneumoniae.
Abstract: Klebsiella pneumoniae is the major cause of community-acquired pyogenic infections in Taiwan. This retrospective study evaluated the clinical and microbiological characteristics of bacteremic community-acquired pneumonia due to K. pneumoniae in Taiwanese adults. The clinical characteristics of bacteremic community-acquired pneumonia (CAP) in adults due to K. pneumoniae were compared to those of adults with bacteremic CAP due to Streptococcus pneumoniae at a tertiary medical center in Taiwan from 2001-2008. Risk factors for mortality of bacteremic CAP due to K. pneumoniae were analyzed. All clinical isolates of K. pneumoniae were examined for capsular serotypes, hypermucoviscosity phenotype, aerobactin and rmpA gene.
K. pneumoniae was the dominant cause of bacteremic CAP and was associated with a more fulminant course and a worse prognosis than bacteremic CAP due to Streptococcus pneumoniae. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality. Serotype K1 and K2 comprised around half of all isolates. There were no significant differences in the clinical characteristics of patients with bacteremic CAP due to K1/K2 and non-K1/K2 isolates. Hypermucoviscosity phenotype as well as the aerobactin and rmpA genes were highly prevalent in the K. pneumoniae isolates.
K. pneumoniae continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality from K. pneumoniae bacteremic CAP. Serotypes K1/K2 comprised around half of all isolates, but did not predispose patients to a poor clinical outcome. Physicians should be aware of the poor prognosis of any patient with bacteremic K. pneumoniae CAP and monitor these patients more closely.
TL;DR: The bevacizumab–capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC.
Abstract: Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma
TL;DR: The data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.
TL;DR: The pathogenesis of PTC, and the clinical implications of BRAFV600E mutation in the diagnosis, prognosis and potential targeted therapeutic strategies for thyroid cancers are reviewed.
Abstract: Papillary thyroid cancer (PTC) is the most common endocrine malignancy, accounting for 85–90% of all thyroid cancers. Genetic alternations involving the mitogen-activated protein kinase (MAPK) pathway are frequently demonstrated in PTC, such as RET/PTC, RAS, and B-type Raf kinase (BRAF) mutations. Over 90% of BRAF mutations are T1799A, resulting in a BRAF V600E mutation. BRAF V600E is present in ∼50% of PTC and also found in aggressive histologic variants and PTC-derived anaplastic thyroid cancer, but is rare in follicular variants, and not found in follicular thyroid cancer. The tumorigenic role of BRAF V600E in the development of PTC was documented in thyroid-targeted BRAF V600E transgenic mice, and rat thyroid cells overexpressed with BRAF V600E suggested that BRAF V600E is an initiator of tumorigenesis and is required for tumor progression in PTC. Most clinical studies have demonstrated an association of BRAF V600E mutation with aggressive clinicopathologic characteristics and high tumor recurrence, although the results are controversial. The association is also observed in patients with papillary thyroid microcarcinomas and low-risk PTC. As a highly specific and unique mutation in PTC, testing for BRAF V600E in fine-needle aspiration specimens has been shown to refine the diagnostic accuracy of PTC in indeterminate cytology. Preoperative BRAF V600E analysis in low-risk patients may provide important value for prognostication, and these patients might benefit from receiving more intensive management and frequent follow-up. BRAF-targeted therapies have been developed to treat various human cancers including advanced thyroid cancers. Preclinical results are encouraging, but the anticancer effects of clinical trials are disappointing. Studies of multi-kinase inhibitors and/or combination with other regimens are underway in the treatment of advanced thyroid cancers. In this article, we review the pathogenesis of PTC, and the clinical implications of BRAF V600E mutation in the diagnosis, prognosis and potential targeted therapeutic strategies for thyroid cancers.
TL;DR: A raised WBC is associated with higher risk of type 2 diabetes, and the presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.
Abstract: Objective: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated. Research Design and Methods: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 noncases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored. Results: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p=1.5*10 218 ). Substantial heterogeneity was present (I 2 =83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p=1.5*10 24 ), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p=0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p=0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p=7.7*10 213 ), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p=7.7*10 25 ). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference. Conclusions: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.