An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Beat-to-beat and spectral analyses of the noninvasive radial pulse and laser-Doppler signals in patients with hypertension.

This study performed beat-to-beat and spectral analyses of 20-minute skin-surface laser-Doppler-flowmetry (LDF) and radial blood-pressure-waveform (BPW) signals in order to compare the blood-flow perfusion condition and regulatory mechanisms between essential-hypertension (EHT) patients and aged-matched control subjects. Beat-to-beat LDF analyses yielded the pulse width (PW), AC-to-DC ratio (AD), and their corresponding variability indices (coefficients of variation [CVs]). The relative energy contributions (RECs) of five characteristic frequency peaks (defined as FR1-FR5) were also calculated. Spectral BPW analysis obtained the amplitude proportion (Cn) and phase angle (Pn) of each harmonic component n. PW, AD, AD_CV, and REC of FR2 were significantly smaller in the EHT group than in the control group. Regarding BPW indices, C1, C2, C4, and C5 were significantly larger and P2-P8 were significantly smaller in EHT patients than in controls. The present results indicate that BPW and LDF indices can be used to evaluate the blood-flow perfusion efficiency and microcirculatory regulatory activities in EHT. Sex differences were found, with the effects being more prominent in female patients. These findings may be partly attributable to impairment of endothelial and neural regulatory functions. The present findings might aid the development of new noninvasive methods for reducing the risk of EHT-induced damage.

Influenza vaccination reduces hemorrhagic stroke risk in patients with atrial fibrillation: A population-based cohort study.

PURPOSE: The risk of hemorrhagic stroke in patients with atrial fibrillation (AF) is low but the consequences of its occurrence are extremely severe. In this study, we investigated the association of influenza vaccination with the risk of hemorrhagic stroke to develop an efficient strategy for reducing this risk in patients with AF. METHODS: In this study, data were retrieved from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients who received a diagnosis of AF (n=14,454) before January 1, 2005 (index date) and were followed until December 31, 2012. Propensity scores were calculated using a logistic regression model to determine the effects of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) for hemorrhagic stroke in vaccinated and unvaccinated patients with AF. RESULTS: The study population comprised 6570 patients who did (2547 [38.77%]) and did not receive (4023 [61.23%]) influenza vaccination. The adjusted HRs (aHRs) for hemorrhagic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs=0.97 [0.59-1.60], 0.51 [0.30-0.87], and 0.72 [0.50-1.03], respectively). CONCLUSIONS: Influenza vaccination exerts dose-response and synergistic protective effects against hemorrhagic stroke in patients with AF who have a high risk of hemorrhagic stroke (i.e., male sex, age≥75years, Charlson comorbidity index ≥3, and hypertension) and reduces the incidence of hemorrhagic stroke.

Influenza vaccination might reduce the risk of ischemic stroke in patients with atrial fibrillation: A population-based cohort study.

PURPOSE: Atrial fibrillation (AF) is associated with the risk of ischemic stroke, regardless of the administration of appropriate antithrombotic prophylaxis. This study investigated whether influenza vaccination is associated with the risk of ischemic stroke, to determine a solution to reduce this risk in patients with AF. METHODS: We used data from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients diagnosed as having AF (n = 14 454) before January 1, 2005; these patients were followed until December 31, 2012. The index date was January 1, 2005. A propensity score was derived using a logistic regression model to estimate the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A Cox proportional hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in vaccinated and unvaccinated patients with AF. RESULTS: We included 6570 patients (2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: Influenza vaccination might exert a dose-response effect against ischemic stroke in patients with AF who have risk factors for ischemic stroke by reducing the incidence of ischemic stroke, particularly in those aged 65-74 and ≥75 y.

Statins Dose-Dependently Exert Significant Chemopreventive Effects Against Various Cancers in Chronic Obstructive Pulmonary Disease Patients: A Population-Based Cohort Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012, were recruited. Each patient was followed to assess the following protective and risk factors for all cancers: age; sex; comorbidities (diabetes, hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]); urbanization level; monthly income; and nonstatin drug use. The index date of statins use was the date of COPD confirmation. Propensity scores (PSs) were derived using a logistic regression model to estimate the effect of statins by considering the covariates predicting intervention (statins) receipt. To examine the dose-response relationship, we categorized statin use into four groups in each cohort (<28 [statin nonusers], 28-90, 91-365, and >365 cumulative defined daily dose). RESULTS: After PS adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income, we analyzed the all-cancer risk. The adjusted hazard ratios (aHRs) for the all-cancer risk were lower among statin users than among statin nonusers (aHR = 0.46, 95% confidence interval: 0.43 to 0.50). The aHRs for the all-cancer risk were lower among patients using rosuvastatin, simvastatin, atorvastatin, pravastatin, and fluvastatin than among statin nonusers (aHRs = 0.42, 0.55, 0.59, 0.66, and 0.78, respectively). Sensitivity analysis indicated that statins dose-dependently reduced the all-cancer risk. CONCLUSION: Statins dose-dependently exert a significant chemopreventive effect against various cancers in COPD patients. In particular, rosuvastatin has the strongest chemopreventive effect.

Changes in the spectral index of skin-surface laser Doppler signals of nude mice following the injection of CT26 tumor cells.

This study investigated microcirculatory-blood-flow responses in nude mice following the injection of CT26 tumor cells by analyzing the frequency content of skin blood-flow signals recorded on the skin surface. CT26 cells were injected subcutaneously (10^4/100 µl) into the right back flank of each 7-week-old mouse. Three-minute laser Doppler flowmetry (LDF) signals were measured in 60 nude mice. The data sequences were obtained at 1, 2, and 3 weeks after injecting CT26 cells. Mouse tissue samples were cut into sections and examined microscopically to determine the condition of cancer metastasis. Spectral analysis performed after 1 week revealed a significant decrease in the relative energy contribution of the endothelium-related frequency band, and significant increases in those of the myogenic and respiration-related frequency bands of the LDF signals in the metastasis group (n=12). To the best of our knowledge, this is the first study demonstrating the feasibility of evaluating metastasis in animal subjects based on changes in noninvasively measured LDF parameters. Changes in the LDF spectral indexes can be attributed to differences in the microcirculatory regulatory activities. The present measurements performed on the skin surface provide a noninvasive and real-time method for evaluating the microcirculatory responses induced by implanting CT26 tumor cells.

Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk.

BACKGROUND: Taiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin-angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients. METHODS: Of 248,797 patients who received a hypertension diagnosis in Taiwan during 2001-2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose-response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28-90, 91-365, and >365 cumulative defined daily doses (cDDDs). RESULTS: In the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50-0.65), 0.72 (0.53-0.98), and 0.47 (0.41-0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54-0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used. CONCLUSION: Statins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. RESULTS: After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use). MATERIALS AND METHODS: The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users. CONCLUSIONS: Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.

Statins dose-dependently exert a significant chemopreventive effect on colon cancer in patients with chronic obstructive pulmonary disease: A population-based cohort study.

PURPOSE: We evaluated the chemopreventive effect of statins on colon cancer in patients with chronic obstructive pulmonary disease (COPD) and identified the statin exerting the strongest chemopreventive effect. METHODS: Using the National Health Insurance Research Database, we identified patients who received a COPD diagnosis in Taiwan between January 1, 2001, and December 31, 2012, and included them in the study cohort. Each patient was followed to assess the colon cancer risk and protective factors. A propensity score was derived using a logistic regression model to estimate the effect of statins by accounting for covariates predicted during the intervention (statins). To examine the dose-response relationship, we categorized statin doses into four groups in each cohort [<28, 28-90, 91-365, and >365 cumulative defined daily dose]. RESULTS: Compared with the statin nonusers, the adjusted hazard ratio (aHR) for colon cancer decreased in the statin users (aHR = 0.52, 95% confidence interval = 0.44, 0.62). Hydrophilic statins exerted a stronger preventive effect against colon cancer. Regarding the statin type, lovastatin, pravastatin, and fluvastatin nonsignificantly reduced the colon cancer risk in the patients with COPD. Compared with the statin nonusers, the aHRs for colon cancer decreased in the individual statin users (rosuvastatin, simvastatin, and atorvastatin: aHRs = 0.28, 0.64, and 0.65, respectively). In the sensitivity analysis, statins dose-dependently reduced the colon cancer risk. CONCLUSIONS: Statins dose-dependently exert significant chemopreventive effects on colon cancer in patients with COPD, with rosuvastatin exerting the largest chemopreventive effect.

Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study.

Taiwan has the highest prevalence of chronic kidney disease (CKD) worldwide. CKD, a manifestation of vascular diseases, is associated with a high risk of dementia. Here, we estimated the association between influenza vaccination and dementia risk in patients with CKD. Data from the National Health Insurance Research Database of Taiwan were used in this study. The study cohort included all patients diagnosed with CKD (according to International Classification of Disease, Ninth Revision, Clinical Modification codes) at healthcare facilities in Taiwan (n = 32,844) from January 1, 2000, to December 31, 2007. Each patient was followed up to assess dementia risk or protective factors: demographic characteristics of age and sex; comorbidities of diabetes, hypertension, dyslipidemia, cerebrovascular diseases, parkinsonism, epilepsy, substance and alcohol use disorders, mood disorder, anxiety disorder, psychotic disorder, and sleep disorder; urbanization level; monthly income; and statin, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. A propensity score was derived using a logistic regression model for estimating the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) of dementia among vaccinated and unvaccinated CKD patients. The study population comprised 11,943 eligible patients with CKD; 5745 (48%) received influenza vaccination and the remaining 6198 (52%) did not. The adjusted HRs (aHRs) of dementia decreased in vaccinated patients compared with those in unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.68, 0.58, and 0.64; P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In the sensitivity analysis, adjustments were made to estimate the association of age and sex; diabetes, dyslipidemia, hypertension, cerebrovascular diseases, anxiety disorder; and statin, metformin, ACEI, and aspirin use with the incidence of dementia in various models. A stronger protective effect against dementia risk was demonstrated during the noninfluenza season. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor and dose-dependently reduced the risk of dementia in CKD patients. Influenza vaccination exerts dose-response and synergistic protective effects against dementia in CKD patients with dementia risk factors by reducing the incidence of dementia.

Patterns of outpatient care utilization by seniors under the National Health Insurance in Taiwan.

BACKGROUND/PURPOSE: Taiwan has one of the fastest growing aging populations in the world, which makes the effective allocation of scarce medical resources a key issue. This paper investigates patterns in the use of outpatient services by elderly individuals in Taiwan under the National Health Insurance (NHI) program. METHODS: We assembled a random sample from the NHI Research Database in Taiwan, comprising 50% of all claims made for elderly people (65 years old) in 2010 (n 1,239,836 beneficiaries) including 14 variables. RESULTS: In 2010, individuals aged 65 years or older comprised 10.74% of the population of Taiwan, and accounted for 11.39% of all physician and outpatient visits. The rate of medical care visits was 28.54 ± 21.23 (Standard deviation) times per person per annum, with a higher rate for women, those in the 80-84 age group, low-income beneficiaries, and the inhabitants of offshore islands. The three most frequent diagnoses for elderly patients were hypertension, diabetes, and acute upper respiratory infections. The mean insured medical costs per person per annum were US Dollars 1,132, with higher expenses for men, those in the 80-84 age group, and those inhabiting urban areas. CONCLUSION: This study employed nationally representative data in the detection of patterns in outpatient care utilization by elderly individuals in Taiwan. Medical care providers and policymakers should be fully aware of the complex patterns unique to older patients. The results of this study could be used as a benchmark with which to assess the impact of future medical care policy on elderly people.

Influenza vaccination reduces hospitalization for acute coronary syndrome in elderly patients with chronic obstructive pulmonary disease: a population-based cohort study.

BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of hospitalization for cardiovascular complications, especially during respiratory infections. Previous studies showed that vaccination for influenza may reduce the risk of recurrent major cardiovascular events in patients with acute coronary syndrome (ACS). The purpose of this study was to evaluate the hypothesis that influenza vaccination could reduce hospitalizations for ACS in elderly patients with COPD. METHOD: Using the Taiwan Longitudinal Health Insurance Database 1996-2008, this cohort study comprised elderly patients (≥ 55 years old) with a recorded diagnosis of COPD (n=7722) between January 1, 2000 and December 31, 2007. Each patient was followed until the end of 2007. A propensity score was derived by using a logistic regression model to reduce vaccine therapy selection bias. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the occurrence of first hospitalization for ACS in elderly COPD patients was examined by Cox proportional hazards regression analysis. In addition, we categorized the patients into four groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, and ≥ 4). RESULTS: We found that elderly patients with COPD receiving influenza vaccination had a lower risk of hospitalization for ACS (adjusted HR=0.46, 95% CI (0.39-0.55), p < 0.001). We observed similar protective effects in both sexes and all age groups (55-64, 65-74, ≥ 75) regardless of influenza seasonality. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for hospitalization because of ACS were 0.48 (0.38-0.62) and 0.20 (0.14-0.28) for patients who received 2-3 and ≥ 4 vaccinations during the follow-up period. CONCLUSION: Our data showed that there was a lower risk of ACS hospitalization in elderly patients with COPD receiving annual influenza vaccination.

Anti-angiogenic properties of ADAMTS-4 in vitro.

Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases. ADAMTS-1 and ADAMTS-8 have been reported to be anti-angiogenic. Here, we provide evidence that ADAMTS-4, like ADAMTS-1, is expressed by endothelial cells and binds to vascular endothelial groth factor (VEGF). Moreover, ADAMTS-4 inhibited human dermal microvascular endothelial cells (HuDMEC) VEGF-stimulated VEGF receptor (R) R2 phosphorylation, differentiation and migration, suggesting that ADAMTS-4 may be a novel anti-angiogenic molecule.