Ultrasensitive Upconversion Nanoparticle Immunoassay for Human Serum Cardiac Troponin I Detection Achieved with Resonant Waveguide Grating.

Selective detection of biomarkers at low concentrations in blood is crucial for the clinical diagnosis of many diseases but remains challenging. In this work, we aimed to develop an ultrasensitive immunoassay that can detect biomarkers in serum with an attomolar limit of detection (LOD). We proposed a sandwich-type heterogeneous immunosensor in a 3 × 3 well array format by integrating a resonant waveguide grating (RWG) substrate with upconversion nanoparticles (UCNPs). UCNPs were used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG substrate, and the RWG substrate was used to enhance the upconversion luminescence (UCL) of UCNPs through excitation resonance. The LOD of the immunosensor was greatly reduced due to the increased UCL of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface by coating the RWG substrate surface with a carboxymethyl dextran layer. The immunosensor exhibited an extremely low LOD [0.24 fg/mL (9.1 aM)] and wide detection range (1 fg/mL to 100 pg/mL) in the detection of cardiac troponin I (cTnI). The cTnI concentrations in human serum samples collected at different times during cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) chemotherapy in a breast cancer patient were measured by an immunosensor, and the results showed that the CEF chemotherapy did cause cardiotoxicity in the patient. Having a higher number of wells in such an array-based biosensor, the sensor can be developed as a high-throughput diagnostic tool for clinically important biomarkers.

The differential impact of Type D personality on the prognosis of patients with stable coronary artery disease.

OBJECTIVE: This study investigated the association between Type D personality and prognoses in stable coronary artery disease (CAD) patients by mode of endpoints, age, and methodological debates to explain substantial heterogeneity among Type D studies. DESIGN: The prospective study was designed to recruit 590 stable CAD patients in Taiwan. Main outcome measures: Demographic and clinical characteristics, and the 14-item Type D scale-Taiwanese version were recorded at discharge. RESULTS: Hierarchical logistic regression analyses showed, regardless of the methodological debates, Type D personality was significantly associated with MACEs though not non-cardiac outcomes in stable CAD patients after adjusting for possible confounders. Furthermore, Type D personality was especially associated with MACEs in stable CAD patients with younger age (<65 y), rather than older age (≥65 y). Subgroup analysis also showed the adverse effect of Type D personality on MACEs was larger among males, those living in the rural region, those with PTCA or stent, those with heart failure, hypertension, diabetes, and those who were smokers. CONCLUSIONS: Regardless of whether the methodological debate is dichotomous or continuous, Type D personality was significantly associated with MACEs in stable CAD patients, some of whom had younger age, were males, smokers, or had comorbidities.

No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan's national health insurance claims data.

Background: Clarithromycin is widely used to treat various bacterial infections and has been reported to have potential cardiovascular risk. However, it is uncertain whether this association was dose dependent and confounded by indication bias in patients with stable coronary heart disease (CHD). Methods: This cohort study retrospectively analyzed a national health insurance claims data from Taiwan's 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9,631 eligible clarithromycin users and 9,631 non-users in 2004-2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes were also addressed. Results: Clarithromycin use, compared with non-use, was associated with higher risk for all-cause [adjusted hazard ratios (aHR), 1.43; 95% confidence interval, 1.29-1.58], cardiovascular (1.35; 1.09-1.67), and non-cardiovascular (1.45; 1.29-1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04-1.51) in clarithromycin users than non-users. However, there was no relationship of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01-1.45), especially heart events (1.39; 1.10-1.45), all-cause (1.57; 1.38-1.80), cardiovascular (1.58; 1.20-2.08), and non-cardiovascular (1.57; 1.35-1.83) mortality during the first 3 years. Thereafter, clarithromycin effect on all outcomes almost dissipated. Conclusion: Clarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD, which was not dose dependent and confounded by indications. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease.

BACKGROUND: Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). METHODS: This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. RESULTS: Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. CONCLUSION: Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

The impact of sources of perceived social support on readmissions in patients with heart failure.

BACKGROUND: Lower levels of perceived social support have been known as an independent predictor of hospital readmissions in patients with heart failure (HF). However, the impact of sources of perceived social support on readmissions remain unexplored. PURPOSE: The main purpose of this study was to investigate and compare the relative importance of social support from significant other, family, and friends on all-cause readmission and cardiac readmission in patients with HF. METHODS: The prospective cohort study was used to recruit a total of 299 patients with HF in Taiwan between May 2012 and December 2014. Demographic and clinical characteristics, Multidimensional Perceived Social Support Scale (MPSSS), and 18-month follow-up readmissions were recorded during the hospital stay. Univariate and multivariate logistic regressions were constructed to determine the impact of levels and sources of perceived social support with all-cause readmission and cardiac readmission. RESULTS: A total of 158 patients (52.8%) and 118 patients (39.5%), respectively, had all-cause readmission and cardiac readmissions within 18 months. Multivariate logistic regression yielded inverse associations between levels of perceived social support and readmissions by 18-months. Importantly, social support from significant other was significantly associated with a lower risk of readmissions, both of all-cause readmission and cardiac readmission, in patients with HF, even after controlling for possible covariates, social support from family and friends. CONCLUSIONS: Social support from significant other, rather than from family and friends, was relatively and inversely associated with 18-month all-cause readmission and cardiac readmission in patients with HF, which is consistent with the hierarchical compensatory model.

Negative Affectivity Is Associated with a Higher Systolic and Diastolic Blood Pressure in Normotensive Middle-Aged and Older Adults: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: Type D personality, characterized by two stable traits (social inhibition and negative affectivity), is associated with adverse cardiovascular events. A possible mediating factor for this association could be hypertension. Previous research has shown that individuals with Type D personality were associated with an increased risk of hypertension. However, the association of negative affectivity and social inhibition on blood pressure in normotensive individuals has not yet been reported. Therefore, the aim of this study was to investigate whether negative affectivity and social inhibition were associated with systolic and diastolic blood pressure in normotensive middle-aged and older Taiwanese adults. MATERIALS AND METHODS: A cross-sectional study design was used. Individuals attending general health examination at a regional hospital in southern Taiwan who were 40 to 75 years old were recruited. Patients with self-reported hypertension or currently receiving antihypertensive medication were excluded. Negative affectivity and social inhibition were assessed with the 14-item Type D Scale-Taiwanese version. Multiple linear regression analyses were conducted to determine the association of Z-score transformed negative affectivity and social inhibition on blood pressure. RESULTS: A total of 92 patients with a mean age of 51.5 years were included in the study, and 15 (16.3%) were defined as having a Type D personality. The Z-score transformed negative affectivity score (p = 0.035, effect size = 0.18) and Z-score transformed social inhibition score (p = 0.054, effect size = 0.17) were significantly associated with a higher systolic blood pressure. In addition, the Z-score transformed negative affectivity score (p = 0.036, effect size = 0.28) and Z-score transformed social inhibition score (p = 0.154, effect size = 0.24) were significantly associated with a higher diastolic blood pressure. CONCLUSIONS: Negative affectivity of the Type D personality was significantly associated with higher systolic and diastolic blood pressure, with a medium effect size, in apparently healthy middle-aged and older adults. Assessment of negative affectivity may be clinically useful in identifying individuals at risk of hypertension.

Immune checkpoint inhibitors: a new era for esophageal cancer.

Introduction: The poor prognosis for patients with esophageal cancer (EC) requires evolving current treatment regimens. Immune checkpoint inhibitors show clinical efficacy and a great safety profile in multiple tumors. And the monoclonal antibodies that target programmed death receptor-1/programmed death receptor ligand-1 or the cytotoxic T lymphocyte antigen-4 pathway has shown potential curable effect of EC. Areas covered: This review article covers the prognostic significance of immune checkpoint expression, the accumulating current clinical studies of checkpoint inhibitors in esophageal cancer patients, and future directions. Expert opinion: Many clinical studies have reported favorable survival results with manageable toxicity of anti-programmed death receptor-1/programmed death receptor ligand-1 and anti-cytotoxic T lymphocyte antigen-4 treatment. More results are expected from future clinical studies. It is believed that combining chemoradiotherapy and immune checkpoint inhibitors can induce safe and efficient anti-tumor immune responses and can be a promising therapeutic strategy.

Prognostic Value of Anxiety Between Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction.

Background Evidence suggests differences in clinical characteristics, causes, and prognoses between heart failure with reduced ejection fraction ( HF r EF ) and heart failure with preserved ejection fraction (HFpEF). Most studies have failed to support the prognostic relevance of anxiety in HF r EF or unclassified HF with mean left ventricular ejection fraction <40%. Meanwhile, the association between anxiety and prognoses in HF p EF remains unexamined. This study compared the prognostic value of anxiety between HF r EF and HF p EF . Methods and Results A total of 158 patients with HF r EF (left ventricular ejection fraction=28.51±7.53%) and 108 patients with HFpEF (left ventricular ejection fraction=64.53±9.67%) were recruited between May 2012 and December 2014. Demographic and clinical characteristics, Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory- II scale, and 18-month follow-up outcomes were recorded during the hospital stay. There were significant differences in age, sex, comorbidities, laboratory biomarkers, discharge medications, and unhealthy behaviors, which supported the contention that HF r EF and HF p EF represent 2 distinct phenotypes, although there were no significant differences in anxiety and 18-month outcomes. Multiple logistic regression yielded no significant associations between anxiety and 18-month outcomes in HF r EF . By contrast, trait anxiety could predict 18-month all-cause mortality (odds ratio, 1.429; 95% CI, 1.020-2.000; P=0.038), all-cause readmission or death (odds ratio, 1.147; 95% CI , 1.036-1.271; P=0.008), and cardiac readmission or death (odds ratio, 1.133; 95% CI , 1.031-1.245; P=0.010) in HF p EF after adjusting for possible confounders. Conclusions Trait anxiety was independently associated with 18-month all-cause mortality, all-cause readmission or death, and cardiac readmission or death in HF p EF , but not in HF r EF .

Negative affectivity and social inhibition are associated with increased cardiac readmission in patients with heart failure: A preliminary observation study.

BACKGROUND: Type D personality was hypothesized to influence clinical and patient-centered outcomes patients with heart failure. The aim of this study was to investigate the association between negative affectivity and social inhibition components of Type D personality and cardiac readmission in patients with heart failure. METHODS: A prospective observational study design was used. A total of 222 patients with heart failure were recruited from the department of cardiology in two regional hospitals in Taiwan. The 14-item Type D Scale-Taiwanese version was used to assess negative affectivity and social inhibition of the patients. Logistic regression analyses were conducted to determine the association of both Z-score transformed and dichotomized negative affectivity and social inhibition with 6-month and 18-month cardiac readmissions. RESULTS: A total of 55 patients (24.8%) and 89 patients (40.1%) had cardiac readmissions within 6 months and 18 months, respectively. Multiple logistic regression analyses of Z-score transformed negative affectivity and social inhibition were significantly associated with (1) 6-month cardiac readmission with odds ratios of 1.62 (P = 0.003) and 1.48 (P = 0.014), respectively and (2) 18-month cardiac readmission with odds ratios of 1.45 (P = 0.013) and 1.38 (P = 0.031), respectively. Similar findings were obtained when negative affectivity and social inhibition were analyzed as dichotomized scores. CONCLUSIONS: Negative affectivity and social inhibition components of the Type D personality were significantly associated with a higher risk of cardiac readmission in both 6 months and 18 months after the initial hospitalization in patients with heart failure.

A pilot-study to assess the feasibility and acceptability of an Internet-based cognitive-behavior group therapy using video conference for patients with coronary artery heart disease.

BACKGROUND: Many patients with coronary artery heart disease are unable to access traditional psychosocial rehabilitation conducted face to face due to excessive travel distance. Therefore, this study developed and assessed the feasibility and acceptability of an 8-week Internet-based cognitive-behavior group therapy program, described the patterns of use and measured change in risk factors. METHODS: This study adopted an online video conference system, JointNet, to maintain group interaction functions similar to face to face groups online, and also built an self-learning platform to deliver psychoeducation content and cognitive-behavior therapy related materials and homework. Forty-three out-patients were recruited in the pilot study, who then chose to participate in either the Internet-based cognitive-behavior group therapy or face to face group based on their preference. Fourteen patients were assigned to the waiting-list control. RESULTS: Seventeen participants (17/43 = 39.5%) chose the Internet-based cognitive-behavior group therapy program. Among them, thirteen participants (13/17 = 76.5%) finished the program and were more male (92.3% vs. 50%), employed (53.8% vs. 35.3%), and had longer education duration (13.9 vs. 12.5 years) than the counterparts of the face to face group. Furthermore, they were highly motivated with average number of log-ins (66.5 time), website surfing time (950.94 min), reading frequency (78.15 time) and reading time (355.90 min) for the self-learning platform during eight weeks; and also highly satisfied (97%) with visiting the self-learning platform and video conferences. The treatment effectiveness of Internet-based cognitive-behavior group therapy was comparable with face to face one in reducing anxiety, hostility, respiration rate, and in improving vasodilation but not depression compared with the waiting-list control. CONCLUSION: These results indicated that the Internet-based group therapy program using video conference is feasible and acceptable for the psychosocial rehabilitation of patients with coronary artery heart disease, and provides an alternative for patients who are unable to obtain conventional psychosocial rehabilitation conducted face to face.

Blood Pressure Reactivity and Recovery to Anger Recall in Hypertensive Patients with Type D Personality.

BACKGROUND: Type D, otherwise known as distressed personality type, has been associated with an increased risk of cardiovascular morbidity and mortality. Blood pressure reactivity and recovery to stress could be a possible underlying pathway linking type D personality and cardiovascular events. METHODS: A total of 41 patients with hypertension were recruited from a regional hospital in southern Taiwan. Demographic and clinical characteristics were obtained from all participants. Type D personality was assessed using the 14-item Type D Scale-Taiwanese version. Systolic blood pressure, diastolic blood pressure, and heart rate were measured at the end of baseline, anger recall, verbal, and recovery phases of an anger recall task. Analysis of covariance was used to examine differences in blood pressure and heart rate at the anger recall, verbal, and recovery phase between patients with or without type D personality. RESULTS: After adjusting for baseline measurements, sex, and age, systolic blood pressure (p = 0.002) and diastolic blood pressure (p = 0.011) at the recovery phase were significantly higher in the patients with type D personality. No significant differences in blood pressure or heart rate were observed in the anger recall or verbal phase between the two groups of patients. CONCLUSIONS: The findings of this study support the notion that prolonged blood pressure recovery rather than high reactivity could be an underlying pathway linking type D personality and the risk of future cardiovascular events among patients with hypertension.

Atrial deformation correlated with functional capacity in mitral stenosis patients.

BACKGROUND: Left atrial (LA) dysfunction, expressed as impaired LA deformation using two-dimensional (2D) strain imaging, has been observed in association with rheumatic mitral stenosis (MS). However, the clinical role of speckle tracking echocardiography (STE)-derived LA strain has rarely been studied in MS. AIM: This study aimed to identify the determinants of New York Heart Association (NYHA) functional class in patients with mitral stenosis and to investigate the relationship between left atrial deformation as measured by two-dimensional STE-derived LA strain and heart failure symptoms. METHODS: Sixty-nine consecutive patients (20 males and 49 females; mean age: 61 ± 14 years) with rheumatic MS were evaluated using comprehensive 2D and color Doppler echocardiography including STE-derived LA strain (LAS) and peak positive filling strain rate (LASRr) during the LA reservoir phase. Those results were then correlated with NYHA functional class. RESULTS: There were 15 (22%) patients in functional class I, 42 (61%) in functional class II, and 12 (17%) in functional class III. There were no significant differences in mitral valve area, pressure gradient, pulmonary artery pressure, LA emptying fraction, or left ventricular ejection fraction between functional classes. Upon multivariate analysis (controlling for diuretics usage), LAS (ß = -0.233, P = .045) and LASRr (ß = -0.277, P = .014) were independent factors in determining NYHA functional class. CONCLUSIONS: In stable patients with MS, NYHA functional class independently correlated with LAS and LASRr. Left atrial (LA) deformation correlated with heart failure symptoms in patients with MS.

FRAX® Fracture Risks Are Associated with Coronary Artery Calcification Score.

PURPOSE: To examine the association between fracture risk assessment tool (FRAX) scores and coronary artery calcification (CAC) score in adults. METHODS: The medical records of 81 adults who underwent both coronary computed tomography and bone mineral density (BMD) studies in a package during their health exams were reviewed at a regional hospital in Southern Taiwan. Data collected included health history, anthropomorphic characteristics, clinical laboratory results, and BMD. Fracture risk was determined using FRAX. Univariate and multivariate linear regression analysis were used to assess the association between CAC score and 10-year probability of hip fracture (HF) and major osteoporotic fracture (MOF) determined by FRAX. RESULTS: The mean age of the patients was 55.8 years, and 63.0% were male. Univariate linear regression analysis showed that increases in MOF and HF risks, as measured by FRAX, were significantly and positively associated with CAC score. Multiple linear regression analysis adjusting for potential confounders showed that CAC score remained significantly associated with four FRAX indicators, including right MOF (r = 0.45, P < 0.001), left MOF (r = 0.31, P = 0.021), right HF (r = 0.38, P = 0.001), and left HF (r = 0.23, P = 0.049). CONCLUSIONS: Increased risks of MOF and HF as determined by FRAX were significantly and independently associated with CAC score.

TBS Predict Coronary Artery Calcification in Adults.

PURPOSE: This study analyzes the association between the bony microarchitecture score (trabecular bone score, TBS) and coronary artery calcification (CAC) in adults undergoing health exams. MATERIALS AND METHODS: We retrospectively collected subjects (N = 81) who underwent coronary computed tomography and bone mineral density studies simultaneously. CAC was categorized to three levels (Group 0, G0, no CAC, score = 0, N = 45; Group 1, G1, moderate CAC, score = 1-100, N = 17; Group 2, G2, high CAC, score ≧ 101, N = 19). Multinomial logistic regression was used to study the association between TBS and CAC levels. RESULTS: CAC is present in 44.4% of the population. Mean TBS ± SD was 1.399 ± 0.090. Per 1 SD increase in TBS, the unadjusted odds ratio (2.393) of moderate CAC compared with no CAC was significantly increased (95% CI, 1.219-4.696, p = 0.011). However, there has been no association of TBS with high CAC (OR: 1.026, 95% CI: 0.586-1.797, p = 0.928). These relationships also existed when individually adjusted for age, sex, and multiple other covariates. CONCLUSIONS: Higher TBS was related to moderate CAC, but not high CAC; a possible explanation may be that bone microarchitecture remodeling becomes more active when early coronary artery calcification occurs. However, further researches are needed to clarify this pathophysiology.