Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.

Risk assessment of multistate progression of breast tumor with state-dependent genetic and environmental covariates.

Few studies have focused on the different roles risk factors play in the multistate temporal natural course of breast cancer. We proposed a three-state Markov regression model to predict the risk from free of breast cancer (FBC) to the preclinical screen-detectable phase (PCDP) and from the PCDP to the clinical phase (CP). We searched the initiators and promoters affecting onset and subsequent progression of breast tumor to build up a three-state temporal natural history model with state-dependent genetic and environmental covariates. This risk assessment model was applied to a 1 million Taiwanese women cohort. The proposed model was verified by external validation with another independent data set. We identified three kinds of initiators, including the BRCA gene, seven single nucleotides polymorphism, and breast density. ER, Ki-67, and HER-2 were found as promoters. Body mass index and age at first pregnancy both played a role. Among women carrying the BRCA gene, the 10-year predicted risk for the transition from FBC to CP was 25.83%, 20.31%, and 13.84% for the high-, intermediate-, and low-risk group, respectively. The corresponding figures were 1.55%, 1.22%, and 0.76% among noncarriers. The mean sojourn time of staying at the PCDP ranged from 0.82 years for the highest risk group to 6.21 years for the lowest group. The lack of statistical significance for external validation (x(4)2=5.30,p=0.26) revealed the adequacy of our proposed model. The three-state model with state-dependent covariates of initiators and promoters was proposed for achieving individually tailored screening and also for personalized clinical surveillance of early breast cancer.

A novel predictive score for hepatocellular carcinoma development in patients with chronic hepatitis C after sustained response to pegylated interferon and ribavirin combination therapy.

OBJECTIVES: Antiviral therapy can prevent the development of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. However, HCC still develops in patients achieving sustained virological response (SVR). We proposed to evaluate the risk factors and derive a novel risk score for HCC (score(HCC)) by summation of products of clinical weights based on the regression coefficients in the final proportional hazards model. METHODS: From March 2002 to October 2009, we enrolled 871 patients with biopsy-proven CHC, who received combined pegylated interferon and ribavirin therapy and achieved SVR. RESULTS: Cox regression analysis showed that old age [hazard ratio (HR) 3.82, 95% CI 1.74-8.37, P = 0.001], high α-fetoprotein levels (HR 3.15, 95% CI 1.60-6.19, P = 0.001), low platelet counts (HR 2.81, 95% CI 1.22-6.44, P = 0.015) and high fibrotic stage (HR 3.95, 95% CI 1.46-10.70, P = 0.007) were independent risk factors. The cut-off level of risk scores was a derived value of 10 and was able to predict the HCC risk with 89.2% sensitivity and 69.5% specificity. The AUC value for the prediction was 0.848. The score(HCC) values were further categorized into three risk groups: low risk (score(HCC) ≤10), intermediate risk (score(HCC) 11-15) and high risk (score(HCC) ≥16). The proportion of HCC development increased from 1.37% (9/657) in the low-risk group to 9.14% (16/175) in the intermediate-risk group and 30.77% (12/39) in the high-risk group (P < 0.001). CONCLUSIONS: With the novel risk scores, we can estimate the chance of HCC development more exactly and practically. This approach can be used for HCC screening in CHC patients achieving SVR.

Geographic variation in the age- and gender-specific prevalence and incidence of epilepsy: analysis of Taiwanese National Health Insurance-based data.

PURPOSE: We studied geographic variation in age- and gender-specific prevalence and incidence of epilepsy in four different areas of Taiwan. METHODS: By using large-scale, National Health Insurance (NHI)-based data from 2000-2003 in Taiwan, we identified 131,287 patients diagnosed with epilepsy (ICD code 345) receiving at least of one of 11 antiepileptic drugs (AEDs). Information on age, gender, and location were also collected. The multivariable Poisson regression analysis was used to assess the heterogeneity of the morbidity of epilepsy in different regions. External data validation was also performed to assess the accuracy of capturing epilepsy cases through our NHI data set. KEY FINDINGS: The age-adjusted prevalence and incidence of epilepsy were 5.85 (per 1,000) between 2000 and 2003 and 97 (per 100,000 person-years) during the follow-up time from 2001 to 2003 in Taiwan. The sensitivity and specificity of ICD-9 coding for epilepsy in the NHI data set were 83.91% and 99.83%, respectively, resulting in a slight overestimation. Male patients had a higher probability of having epilepsy than did females. East Taiwan had significantly higher prevalence and incidence than did other areas. The age-specific incidence pattern in east Taiwan was atypical in that it revealed clustering in young and middle-aged groups. SIGNIFICANCE: Our study demonstrated geographic variation in epidemiologic patterns of epilepsy within Taiwan. The findings are informative and provide insight into the clinical management of epilepsy based on consideration of different target groups in different areas.

Increased risk of stroke after trigeminal neuralgia--a population-based follow-up study.

BACKGROUND: There are no reports on the risk of stroke after trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether the occurrence of TN is associated with a higher risk of developing stroke. METHODS: A total of 1453 people with at least three ambulatory visits in 2001 with the principal diagnosis of TN were enrolled in the TN cohort. The non-TN cohort consisted of 5812 age- and sex-matched, randomly sampled subjects without TN. The 2-year stroke-free survival rate between the two groups was compared using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of stroke after adjustment for demographic and clinical covariates. RESULTS: In the TN cohort, 73 patients developed stroke during follow-up, while in the non-TN cohort, 157 subjects suffered a stroke. The crude hazard ratio of stroke for the subjects with TN was 1.86 (95% CI, 1.41-2.45; p<0.0001). The adjusted hazard ratio was 1.76 (95% CI, 1.33-2.33; p<0.0001) after adjusting for demographic characteristics and comorbid medical disorders. CONCLUSION: This study showed a significantly increased risk of developing stroke after TN. Further studies are needed to investigate the underlying mechanism of this association.

Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death.

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy.

STUDY OBJECTIVE: To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. DESIGN: Prospective analysis. SETTING: University-affiliated medical center in Taipei, Taiwan. PATIENTS: Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4'-hydroxyphenyl)-5-phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test--galactose single-point (GSP) measurement--were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (> or = 280 microg/ml) had a significantly higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean +/- SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 +/- 16.73 vs 68.22 +/- 44.75 and 78.95 +/- 51.67 microg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. CONCLUSION: Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.

Dynamic aspect of functional recovery after stroke using a multistate model.

OBJECTIVE: To estimate time to functional recovery and quantify the effects of significant prognostic factors affecting the dynamic change of 3-state functional outcome after stroke. DESIGN: Modeling of clinical predictions. SETTING: Referral center. PARTICIPANTS: One hundred eleven patients with first-time ischemic stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Serial Barthel Index scores at onset, 2 weeks, and 1, 2, 4, and 6 months poststroke. The severity of disability was classified into 3 functional states: poor functional state (PFS) for Barthel Index scores from 0 to 40, moderate functional state (MFS) for scores from 45 to 80, and good functional state (GFS) for scores greater than 80. A 3-state Markov regression model together with Bayesian acyclic graphic underpinning was used to estimate transition parameters and mean time to functional recovery between states and to predict the probability of functional recovery by using Gibbs sampling technique. RESULTS: The mean total recovery time was 3.1 months for patients with PFS at baseline and 1.3 months for patients with MFS at baseline. The mean recovery times to different functional states were also estimated. Age predominantly affected the probabilities of MFS to GFS transitions, younger patients had faster transition rates (rate ratio, 4.51; 95% confidence interval [CI], 2.72-7.40); but age had only borderline effects on PFS to MFS transitions. In contrast, infarct size exerted substantial effects on PFS to MFS transitions: small-size infarct correlated with a higher transition rate (rate ratio, 10.17; 95% CI, 5.25-20.13), whereas only a borderline effect on MFS to GFS transitions was found. The baseline functional state significantly affected the MFS to GFS transitions. CONCLUSIONS: By using a multistate model, overall and patient-specific mean time to functional recovery to different functional states can be estimated and the effect of clinical predictors on functional transitions can be precisely quantified to predict patient-specific probability of functional recovery.

Bayesian negative-binomial-family-based multistate Markov model for the evaluation of periodic population-based cancer screening considering incomplete information and measurement errors.

Population-based cancer screening is often asked but hardly addressed by a question: "How many rounds of screening are required before identifying a cancer of interest staying in the pre-clinical detectable phase (PCDP)?" and also a similar one related to the number of screens required for stopping screening for the low risk group. It can be answered by using longitudinal follow-up data on repeated rounds of screen, namely periodic screen, but such kind of data are rather complicated and fraught with intractable statistical properties including correlated multistate outcomes, unobserved and incomplete (censoring or truncation) information, and imperfect measurements. We therefore developed a negative-binomial-family-based discrete-time stochastic process, taking sensitivity and specificity into account, to accommodate these thorny issues. The estimation of parameters was implemented with Bayesian Markov Chain Monte Carlo method. We demonstrated how to apply this proposed negative-binomial-family-based model to the empirical data similar to the Finnish breast cancer screening program.

Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals.

BACKGROUND/AIMS: Taiwan has the highest incidence of end-stage renal disease, which requires renal replacement therapy. Chronic kidney disease (CKD) contributes to this burden. However, the current data on the epidemiologic features of CKD in Taiwan are incomplete. Therefore, we aimed to investigate the prevalence and incidence of CKD in a population-based study and then estimate the average dwelling time (ADT) in the main clinical burden of CKD (stages 3-5). METHODS: A prospective cohort study was designed with an integrated community-based multiple screening program of 106,094 individuals aged ≥20 years in Keelung, Taiwan, in 1999-2009. Prevalence was estimated as the percentage of CKD stages among individuals attending the first screening, and incidence was expressed as the ratio of total desired events in the following period to the total observational time. Finally, ADT was estimated from the ratio of prevalence to incidence. RESULTS: The participants' mean age was 47.7 ± 15.4 years. The estimated prevalence was 15.46% for total CKD and 9.06% for CKD stages 3-5. The incidence was 27.21/1,000 person-years (PY) for total CKD and 16.89/1,000-PY for CKD stages 3-5. Older patients, males, and those patients with comorbidities of diabetes mellitus (DM), hypertension, and metabolic syndrome (MetS) exhibited higher prevalence and incidence rates than their opposing counterparts. Moreover, the ADT of CKD stages 3-5 was 5.37 years (95% CI 5.17-5.57). Males and those with comorbidities of DM or MetS had shorter ADTs in CKD stages 3-5 than their opposing counterparts. Interestingly, the ADT of participants with hypertension was longer than those without. CONCLUSIONS: The prevalence and incidence of CKD in Taiwan are high. Moreover, ADT in CKD stages 3-5 varied according to sex, age, and comorbidity. Further exploration of the factors associated with the shifting of this duration will shed light on effective CKD management.

Cost-effectiveness analysis between primary and secondary preventive strategies for gastric cancer.

OBJECTIVE: The present study is done to assess the relative cost-effectiveness, optimal initial age, and interscreening interval between primary and secondary prevention strategies for gastric cancer. METHODS: Base-case estimates, including variables of natural history, efficacy of intervention, and relevant cost, were derived from two preventive programs targeting a high-risk population. Cost-effectiveness was compared between chemoprevention with (13)C urea breath testing followed by Helicobacter pylori (H. pylori) eradication and high-risk surveillance based on serum pepsinogen measurement and confirmed by endoscopy. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The incremental cost-effectiveness ratio (ICER) for once-only chemoprevention at age 30 years versus no screening was U.S. $17,044 per life-year gained. Eradication of H. pylori at later age or with a periodic scheme yielded a less favorable result. Annual high-risk screening at age of 50 years versus no screening resulted in an ICER of U.S. $29,741 per life-year gained. The ICERs of surveillance did not substantially vary with different initial ages or interscreening intervals. Chemoprevention could be dominated by high-risk surveillance when the initial age was older than 44 years. Otherwise, chemoprevention was more cost-effective than high-risk surveillance, either at ceiling ratios of U.S. $15,762 or up to U.S. $50,000. The relative cost-effectiveness was most sensitive to the infection rate of H. pylori and proportion of early gastric cancer in all detectable cases. CONCLUSIONS: Early H. pylori eradication once in lifetime seems more cost-effective than surveillance strategy. However, the choice is still subject to the risk of infection, detectability of early gastric cancer, and timing of intervention.

Estimation and prediction system for multi-state disease process: application to analysis of organized screening regime.

RATIONALE, AIMS AND OBJECTIVES: The disease progression of cancer and non-malignant chronic disease often involve a multi-state transition. However, estimation of parameters and prediction regarding the multi-state disease process are complex. This study aimed to develop an estimation and prediction system with a computer-assisted software using SAS/SCL as a platform to predict the risk of any outcome arising from the underlying multi-state process with or without the incorporation of individual characteristics. METHOD: The computer-aided system is first constructed following the theoretical framework of stochastic process. The functions provided in this software include model specification, formulation of likelihood function, parameter estimation, model validation and model prediction. An example of breast cancer screening for a high-risk group in Taiwan was used to demonstrate the usefulness of this software. RESULTS: The natural history of breast cancer of a three-state disease process has been demonstrated. Two suspected risk factors, late age at first full-term pregnancy and obesity, were considered by the form of the proportional hazard model. Formulation of intensity matrix, likelihood function, assignment of initial values, and parameter constraint and estimation were successfully demonstrated in model specification. Model validation suggested a good fit of the constructed model. The application of model prediction enables one to project the effectiveness of organized screening by different inter-screening intervals from a policy level or from an individual basis. CONCLUSIONS: A computer-aided estimation and prediction system for multi-state disease process was developed and demonstrated. This system can be applied to data with the property of multi-state transitions in association with events or disease.

Risk prediction for Down's syndrome in young pregnant women using maternal serum biomarkers: determination of cut-off risk from receiver operating characteristic curve analysis.

OBJECTIVE: The aim of this study was to establish a predictive model for Down's syndrome using maternal age as well as maternal serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and to identify an optimal cut-off risk in women under the age of 35 years to improve sensitivity. METHODS: Logistic regression models were utilized to predict fetal Down's syndrome as a function of maternal age and logarithm of levels of AFP as well as hCG using training data of 20 pregnancies with fetal Down's syndrome and 9730 unaffected pregnancies. Validation was performed using data of another nine affected pregnancies and 3496 unaffected pregnancies. Receiver operating characteristic (ROC) curves were plotted. RESULTS: Based on the newly established logistic regression equations, the optimal cut-off risk from the ROC curve analysis was at 1:499, with a 17.8% false-positive rate and a 90.0% sensitivity. A suboptimal cut-off risk was estimated at 1:332, with a 12.0% false-positive rate and an 80% sensitivity. CONCLUSION: A predictive model for Down's syndrome was developed using logistic regression. By ROC curve analysis and clinical consideration, the cut-off risk for young pregnant women could be determined.

Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome.

To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).

Progression of pre-hypertension, stage 1 and 2 hypertension (JNC 7): a population-based study in Keelung, Taiwan (Keelung Community-based Integrated Screening No. 9).

OBJECTIVE: To investigate the prevalence and progression of, and identify risk factors for, pre-hypertension, stage 1 and 2 hypertension in a population-based study. DESIGN: A prospective cohort study. SETTING: An integrated community-based multiple screening program in Keelung, Taiwan. PARTICIPANTS: A total of 67 011 individuals aged 20-79 years between 1999 and 2003 were included. Of these, 22 111 re-attended, yielding 53 689 repeated recordings of blood pressure, including movement between normal and pre-hypertension and progression from pre-hypertension to stage 1 or stage 2 hypertension. MAIN OUTCOME MEASURES: Blood pressure was defined and classified according to the JNC 7 Report as normal, pre-hypertension, stage 1, and stage 2 hypertension. RESULTS: Below 50 years of age, males had a higher progression rate, particularly from normal to pre-hypertension, than females. Annual regression rates from pre-hypertension to normal were higher in the young age group than in the old age group, particularly for females. Factors associated with the occurrence of pre-hypertension were old age, male gender, high waist circumference, abnormal blood lipids, smoking, chewing betel nuts, lack of exercise, and having parents with hypertension. Factors associated with regression from pre-hypertension to normal were body mass index, fasting glucose, high-density lipoprotein level, smoking, and parents with hypertension. Progression from pre-hypertension to stage 1 hypertension was positively related to male gender, higher waist circumference, and having parents with hypertension. CONCLUSIONS: The rates of progression and regression of hypertension vary with age and gender, anthropometric and biochemical measurements, and family history.

Effects of tooth extraction on smile esthetics and the buccal corridor: A meta-analysis.

BACKGROUND/PURPOSE: Smile esthetics is a critical factor for evaluating orthodontic treatment outcomes. The effects of tooth extraction on smile esthetics and buccal corridor remain controversial and have not been adequately investigated. Therefore, in this systematic review and meta-analysis, we evaluated the aforementioned effects. MATERIALS AND METHODS: We searched clinical studies held in PubMed, MEDLINE, Embase, and the Cochrane Library up to May 2015, with no restriction. Study selection and data extraction were conducted by two reviewers independently. A random-effects model was used for conducting a meta-analysis to assess the mean difference between the esthetic score and the buccal corridor ratio of extraction and nonextraction groups. RESULTS: Six eligible studies were included in this meta-analysis. No significant difference was observed in the esthetic score and the buccal corridor ratio between extraction and nonextraction groups. CONCLUSION: Tooth extraction does not affect smile esthetics or buccal corridor. However, additional detailed, large-scale, double-blinded, and randomized controlled trials are required for further evaluation.

Predictive survival model with time-dependent prognostic factors: development of computer-aided SAS Macro program.

AIMS AND OBJECTIVES: Computer program for the prediction of survival with respect to time-dependent proportional hazards regression model has been rarely addressed. We therefore developed a SAS Macro program for time-dependent Cox regression predictive model for empirical survival data associated with time-dependent covariates. METHOD: Time-dependent proportional hazards regression model and partial likelihood in association with time-varying predictors were explicitly delineated. Baseline hazard using Andersen's method was incorporated into proportional hazards regression model to predict the dynamic change of cumulative survival in respect of time-varying predictors. Two SAS Macro programs for time-dependent predictive survival model and model validation using receiver operative characteristics were written with SAS IML language. RESULTS: The computer program was applied to data on clinical surveillance of small hepatocellular carcinoma (HCC) treated by percutaneous ethanol injection (PEI) or transcatheter arterial embolization (TAE) with time-varying predictors such as alpha-feto protein (AFP) and other biological markers. CONCLUSION: The program is very useful for real-time prediction of cumulative survival on the basis of time-dependent covariates.

Sites of peripheral artery occlusive disease as a predictor for all-cause and cardiovascular mortality in chronic hemodialysis.

BACKGROUND: The ankle-brachial blood pressure (BP) index (ABI) not only indicates the presence of peripheral artery occlusive disease (PAOD) but predicts mortality in patients undergoing hemodialysis (HD). However, whether the site of PAOD can provide additional contribution to predicting mortality have not been investigated yet. Our primary objective was to determine the associations between the site of PAOD and all-cause and cardiovascular mortality in chronic HD (CHD) patients. METHODS: A retrospective cohort study was conducted to evaluate 444 Taiwanese CHD patients between December 2006 and June 2013. The site of PAOD together with other explanatory variables such as demographic data, body mass index, a history of cardiovascular diseases, HD vintage, biochemical data, and cardiothoracic ratio (CTR) were assessed by the Cox proportional hazards regression model. RESULTS: The frequency of PAOD was 14.6% in both legs, 4.9% in the right side only, and 5.1% in the left side only. During the study period, 127 all-cause and 93 cardiovascular deaths occurred. PAOD site was found to have significant predictive power for all-cause mortality with the order of 3.04 (95% CI: 1.56-5.90) hazard ratio on the right side, 2.48 (95% CI: 1.27-4.82) on the left side, and 4.11 (95% CI: 2.76-6.13) on both sides. The corresponding figures for cardiovascular mortality were 3.81 (95% CI: 1.87-7.76) on the right side, 2.76 (95% CI: 1.30-5.82) on the left side, and 3.95 (95% CI: 2.45-6.36) on both sides. After adjustment for other explanatory variables, only right-sided PAOD still remained to have significant predictive power for all-cause and cardiovascular mortality and bilateral PAOD kept the significant association with all-cause mortality. CONCLUSIONS: The site of PAOD revealed various predictive powers for all-cause and cardiovascular mortality in CHD patients and only right-sided PAOD remained an independent predictor for both types of mortality making allowance for relevant confounding factors.

XRCC1 Gene Polymorphism, Clinicopathological Characteristics and Stomach Cancer Survival in Thailand.

BACKGROUND: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. MATERIALS AND METHODS: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. RESULTS: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. CONCLUSIONS: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.