Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.

Influenza vaccination and risk of atrial fibrillation in patients with gout: A nationwide population-based cohort study.

Objective: Although influenza vaccination reduces the risk of atrial fibrillation (AF), its protective effect in patients with gout remains unclear. The present study aimed to evaluate the protective effect of influenza vaccination in patients with gout. Methods: A total of 26,243 patients with gout, aged 55 and older, were enrolled from the National Health Insurance Research Database (NHIRD) between 1 January 2001, and 31 December 2012. The patients were divided into vaccinated (n = 13,201) and unvaccinated groups (n = 13,042). After adjusting comorbidities, medications, sociodemographic characteristics, the risk of AF during follow-up period was analyzed. Results: In influenza, non-influenza seasons and all seasons, the risk of AF was significantly lower in vaccinated than in unvaccinated patients (Adjust hazard ratio [aHR]: 0.59, 95% confidence interval [CI]: 0.50-0.68; aHR: 0.50, 95% CI: 0.42-0.63; aHR: 0.55, 95% CI: 0.49-0.62, respectively). In addition, the risk of AF significantly decreased with increased influenza vaccination (aHR: 0.85, 95% CI: 0.69-1.04; aHR: 0.72, 95% CI: 0.60-0.87; aHR: 0.40, 95% CI: 0.33-0.49, after first, 2-3 times, and ≥4 times of vaccination, respectively). Furthermore, sensitivity analysis indicated that the risk of AF significantly decreased after influenza vaccination for patients with different sexes, medication histories, and comorbidities. Conclusions: Influenza vaccination is associated with a lower risk of AF in patients with gout. This potentially protective effect seems to depend on the dose administered.

Machine Learning Analyses Revealed Distinct Arterial Pulse Variability According to Side Effects of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2).

Various adverse events and complications have been attributed to COVID-19 (coronavirus disease 2019) vaccinations, which can affect the cardiovascular system, with conditions such as myocarditis, thrombosis, and ischemia. The aim of this study was to combine noninvasive pulse measurements and frequency domain analysis to determine if the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) vaccination and its accompanying cardiovascular side effects will induce changes in arterial pulse transmission and waveform. Radial blood pressure waveform and photoplethysmography signals were measured noninvasively for 1 min in 112 subjects who visited Shuang-Ho Hospital for a BNT162b2 vaccination. Based on side effects, each subject was assigned to Group N (no side effects), Group CV (cardiac or vascular side effects), Group C (cardiac side effects only), or Group V (vascular side effects only). Two classification methods were used: (1) machine-learning (ML) analysis using 40 harmonic pulse indices (amplitude proportions, phase angles, and their variability indices) as features, and (2) a pulse-variability score analysis developed in the present study. Significant effects on the pulse harmonic indices were noted in Group V following vaccination. ML and pulse-variability score analyses provided acceptable AUCs (0.67 and 0.80, respectively) and hence can aid discriminations among subjects with cardiovascular side effects. When excluding ambiguous data points, the AUC of the score analysis further improved to 0.94 (with an adopted proportion of around 64.1%) for vascular side effects. The present findings may help to facilitate a time-saving and easy-to-use method for detecting changes in the vascular properties associated with the cardiovascular side effects following BNT162b2 vaccination.

Effect of Influenza Vaccination on the Reduction of the Incidence of Chronic Kidney Disease and Dialysis in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus (T2DM) have a higher risk of chronic kidney disease (CKD) due to vascular complications and chronic inflammation. T2DM contributes to a higher risk of mortality and morbidity related to influenza. In Taiwan, influenza vaccination is recommended for patients with T2DM. A previous meta-analysis reported the efficacy of influenza vaccination in reducing hospitalization and mortality in patients with diabetes; however, the renal protective effect of the vaccine remains unclear. This study evaluated whether influenza vaccination could reduce the incidence of CKD and dialysis in patients with T2DM. The study cohort included all patients aged ≥55 years who were diagnosed as having T2DM between 1 January 2000 and 31 December 2012, by using data from Taiwan's National Health Insurance Research Database. Each patient was followed up with to assess factors associated with CKD. A time-dependent Cox proportional hazard regression model after adjustment for potential confounders was used to calculate the hazard ratio (HR) of CKD in the vaccinated and unvaccinated patients. The study population comprised 48,017 eligible patients with DM; 23,839 (49.7%) received influenza vaccination and the remaining 24,178 (50.3%) did not. The adjusted HRs (aHRs) for CKD/dialysis decreased in the vaccinated patients compared with the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs: 0.47/0.47, 0.48/0.49, and 0.48/0.48, respectively, all p < 0.0001). We observed similar protective effects against CKD during the influenza and noninfluenza seasons. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor. Furthermore, aHRs for CKD/dialysis were 0.71 (0.65−0.77)/0.77 (0.68−0.87), 0.57 (0.52−0.61)/0.69 (0.56−0.70), and 0.30 (0.28−0.33)/0.28 (0.24−0.31) in the patients who received 1, 2−3, and ≥4 vaccinations during the follow-up period, respectively. This population-based cohort study demonstrated that influenza vaccination exerts a dose-dependent and synergistic protective effect against CKD in the patients with T2DM with associated risk factors.

Association between Stroke Risk and Influenza Vaccination in Patients with Gout: A Nationwide Population-Based Study.

The risk of stroke in patients with gout is high. The effect of vaccines in lowering the stroke risk in patients with gout remains unclear. We retrospectively analyzed 23,949 patients with gout (age ≥ 55 years) from the National Health Insurance Research Database over a 12-year period. The patients were divided into vaccinated (n = 11,649) and unvaccinated groups (n = 12,300). Overall, the vaccinated group had significantly lower risks of all stroke, hemorrhagic stroke, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR], 0.59 and 95% confidence interval [CI], 0.55-0.63; aHR, 0.60 and 95% CI, 0.49-0.73; and aHR, 0.60 and 95% CI, 0.55-0.65, respectively). The association appeared to be dose-dependent for both hemorrhagic and ischemic stroke (hemorrhagic stroke: aHR, 0.81 and 95% CI, 0.61-1.08; aHR, 0.80 and 95% CI, 0.62-1.02; and aHR, 0.37 and 95% CI, 0.28-0.48; ischemic stroke: aHR, 0.83 and 95% CI, 0.74-0.94; aHR, 0.73 and 95% CI, 0.65-0.81; and aHR, 0.42 and 95% CI, 0.38-0.47 for patients vaccinated 1, 2 or 3, and ≥4 times, respectively, during the follow-up period). Patients with a history of atrial fibrillation did not have a lower risk of hemorrhagic stroke even after receiving four vaccinations (aHR, 0.59; 95% CI, 0.25-1.38). Influenza vaccination was associated with a lower risk of all stroke in people with gout, and the association appeared to be dose-dependent.

Influenza Vaccination and Risk of Stroke in Women With Chronic Obstructive Pulmonary Disease: A Nationwide, Population-Based, Propensity-Matched Cohort Study.

Backgrounds: The risk of stroke is higher among patients with chronic obstructive pulmonary disease (COPD) than among the healthy population. Moreover, women generally have worse long-term stroke outcomes than men. Methods: The data of 6681 women with COPD (aged ≥ 65 years) registered in Taiwan's National Health Insurance Research Database were retrospectively analyzed from January 1, 2001 to December 31, 2011. After 1:1 propensity score matching, the patients were divided into vaccinated and unvaccinated groups. Results: In total, 5102 women were enrolled. The vaccinated group had a significantly lower risk of total, hemorrhagic, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR]: 0.60, 95% confidence interval [CI]: 0.54-0.67; aHR: 0.59, 95% CI: 0.43-0.83; and aHR: 0.59, 95% CI: 0.52-0.68, respectively). A lower risk of stroke was observed among the women aged 65-74 and ≥75 years, and the association was dose-dependent in all types of stroke (aHR: 1.08, 95% CI: 0.92-1.26; aHR: 0.70, 95% CI: 0.60-0.82; and aHR: 0.32, 95% CI: 0.26-0.38 for those vaccinated 1, 2 to 3, and ≥4 times, respectively, during the follow-up period). Women with a CHA2DS2-VASc score (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2-3 and ≥4 had a significantly lower risk of ischemic stroke while receiving more vaccinations. A smaller significant lower risk of hemorrhagic stroke after more than 4 times of vaccination was noted in the women with a CHA2DS2-VASc score of ≥4. Both interrupted and non-interrupted vaccination was associated with lower risk of stroke occurrence. Conclusion: Influenza vaccination is associated with a lower risk of total, hemorrhagic, and ischemic stroke among women with COPD, and the association is dose-dependent. However, the findings may be limited by unmeasurable confounders. Further investigations on this subject are warranted.

Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study.

Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan's National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38−0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66−1.25), 0.49 (0.34−0.71), and 0.25 (0.17−0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.

Association between sleep disorder and atrial fibrillation: A nationwide population-based cohort study.

OBJECTIVES: Sleep disorder (SD), especially sleep apnea, and its effect on atrial fibrillation (AF) are gathering attention. However, other SDs may also play an essential role in AF. The aim of the study is to investigate the effects of other SDs on the risk of atrial fibrillation development. METHODS: This study investigated the risk of AF in people diagnosed with SD compared with that in age and sex-matched unaffected individuals. This longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) of individuals diagnosed with SD from January 1, 2001, to December 31, 2012. RESULTS: The sample consisted of 193,288 people with the SD, which include of 4406 people with sleep apnea, 73,704 people with insomnia, 107,395 people with sleep disturbance, 7,783 people with other SD, and 193,288 matched controls. A Cox proportional hazard regression was used to compute the risk of AF in people with SD and subgroup of SD, relative to that in people without SD. The AF incidences were 1.21-fold higher (95% CI 1.15-1.27) in the SD cohort, 1.19-fold higher (95% CI 0.91-1.56) in the sleep apnea cohort, 1.26-fold higher (95% CI 1.19-1.34) in the insomnia cohort, 1.15-fold higher (95% CI 1.08-1.22) in the sleep disturbance cohort, and 1.30-fold higher (95% CI 1.11-1.53) in other SDs, than in the control cohort, after age, sex, and comorbidities were adjusted. CONCLUSIONS: This nationwide population-based cohort study indicates a strong relationship between SD and incident AF, and insomnia has a higher impact on AF compared with other SD.

HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.

BACKGROUND: The treatment of non-small-cell lung cancer (NSCLC) involves platinum-based chemotherapy. It is typically accompanied by chemoresistance resulting from antioxidant properties conferred by cancer stem cells (CSCs). Human epidermal growth factor receptor 2 (HER2) enhances CSCs and antioxidant properties in cancers, including NSCLC. METHODS: Here, we elucidated the role of histamine N-methyltransferase (HNMT), a histamine metabolism enzyme significantly upregulated in NSCLC and coexpressed with HER2. HNMT expression in lung cancer tissues was determined using quantitative reverse transcription PCR (RT-qPCR). A publicly available dataset was used to determine HNMT's potential as an NSCLC target molecule. Immunohistochemistry and coimmunoprecipitation were used to determine HNMT-HER2 correlations and interactions, respectively. HNMT shRNA and overexpression plasmids were used to explore HNMT functions in vitro and in vivo. We also examined miRNAs that may target HNMT and investigated HNMT/HER2's role on NSCLC cells' antioxidant properties. Finally, how HNMT loss affects NSCLC cells' sensitivity to cisplatin was investigated. RESULTS: HNMT was significantly upregulated in human NSCLC tissues, conferred a worse prognosis, and was coexpressed with HER2. HNMT depletion and overexpression respectively decreased and increased cell proliferation, colony formation, tumorsphere formation, and CSCs marker expression. Coimmunoprecipitation analysis indicated that HNMT directly interacts with HER2. TARGETSCAN analysis revealed that HNMT is a miR-223 and miR-3065-5p target. TBHp treatment increased HER2 expression, whereas shHNMT disrupted the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ hemeoxygenase-1 (HO-1)/HER2 axis and increased reactive oxygen species accumulation in NSCLC cells. Finally, shHNMT sensitized H441 cells to cisplatin treatment in vitro and in vivo. CONCLUSIONS: Therefore, HNMT upregulation in NSCLC cells may upregulate HER2 expression, increasing tumorigenicity and chemoresistance through CSCs maintenance and antioxidant properties. This newly discovered regulatory axis may aid in retarding NSCLC progression and chemoresistance.

Consumption of Non-Nutritive Sweetener, Acesulfame Potassium Exacerbates Atherosclerosis through Dysregulation of Lipid Metabolism in ApoE-/- Mice.

Obesity is associated with the risk of cardiovascular disease, and non-nutritive sweetener, such as acesulfame potassium (AceK) has been used to combat obesity. However, the effects of AceK on cardiovascular disease are still unclear. In this study, high cholesterol diet (HCD)-fed ApoE-/- mice had dysregulated plasma lipid profile, and developed atherosclerosis, determined by atherosclerotic plaque in the aorta. Supplement of AceK in HCD worsened the dyslipidemia and increased atherosclerotic plaque, as compared with HCD-fed ApoE-/- mice. Since treatment of AceK in RAW264.7 macrophages showed no significant effects on inflammatory cytokine expressions, we then investigated the impacts of AceK on lipid metabolism. We found that AceK consumption enhanced hepatic lipogenesis and decreased ß-oxidation in ApoE-/- mice. In addition, AceK directly increased lipogenesis and decreased ß-oxidation in HepG2 cells. Taken together, a concurrent consumption of AceK exacerbated HCD-induced dyslipidemia and atherosclerotic lesion in ApoE-/- mice, and AceK might increase the risk of atherosclerosis under HCD.

Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study.

Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with chronic obstructive pulmonary disease (COPD). However, the effects of the vaccine on decreasing the risk of ventricular arrhythmia (VA) development in such patients remain unclear. Methods: We retrospectively analyzed the data of 18,658 patients with COPD (≥55 years old) from the National Health Insurance Research Database from January 1, 2001, to December 31, 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated and unvaccinated groups. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of influenza vaccination exposure. Results: The risk of VA occurrence was significantly lower in the vaccinated group during influenza season and all seasons [adjusted hazard ratio (aHR): 0.62, 95% CI: 0.41-0.95; aHR: 0.69, 95% CI: 0.44-1.08; and aHR: 0.65, 95% CI: 0.48-0.89, in the influenza season, non-influenza season, and all seasons, respectively]. Among patients with CHA2DS2-VASc scores (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2-3, receiving one time and two to three times of influenza vaccination were associated with lower risk of VA occurrence in all seasons (aHR: 0.28, 95% CI: 0.10-0.80; aHR: 0.27, 95% CI: 0.10-0.68, respectively). Among patients without stroke, peripheral vascular disease, and diabetes, a lower risk of VA occurrence after receiving one and two to three times vaccination was observed in all seasons. Among patients with a history of asthma and patients without a history of heart failure, ischemic heart disease, angina hypertension, or renal failure, a significantly lower risk of VA occurrence was observed after the first time of vaccination in all seasons. Conclusions: Influenza vaccination may be associated with lower risks of VA among patients with COPD aged 55-74. Further investigation is still needed to resolve this clinical question.

Role of Annual Influenza Vaccination against Lung Cancer in Type 2 Diabetic Patients from a Population-Based Cohort Study.

Type 2 diabetes mellitus (DM) patients are at a higher risk for developing lung cancer due to immune dysfunction and chronic inflammation. They also have increased morbidity and mortality related to influenza, and it is recommended that they receive an annual influenza vaccination. In this study, we evaluate whether influenza vaccination could reduce the incidence of lung cancer in DM patients. This cohort study included DM patients (≥55 years old) between 1 January 2002 and 31 December 2012 by using the Taiwan Health Insurance Database. Cox proportional hazard regression method was used to compare the relation between the influenza vaccination and lung cancer incidence after adjusting for potential confounders. Sub-group analyses were done according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, ≥4) and evaluated the dose-dependent effects on lung cancer events. Among 22,252 eligible DM patients, 7860 (35.32%) received an influenza vaccination and 67.68% (14392) did not receive an influenza vaccination. Lung cancer incidence was significantly lower in the vaccinated group versus the unvaccinated group (adjusted HR 0.77; 95% CI 0.62-0.95, p < 0.05). Significant protective effects were observed among male sex (adjusted HR 0.72; 95% CI 0.55-0.94, p < 0.05) and 55-64 year (adjusted HR 0.61; 95% CI 0.40-0.94, p < 0.05) and ≥75 year (adjusted HR 0.63; 95% CI 0.42-0.92, p < 0.05) age groups, respectively. A dose-dependent protective effect was noted with a significant protective effect in those that received ≥4 vaccinations (adjusted HR 0.42; 95% CI 0.29-0.61, p < 0.001). In sub-group analysis, elder patients with ≥65 years of age were significantly protected from ≥4 vaccinations (adjusted HR 0.37; 95% CI 0.23-0.62, p < 0.001 in 65-74 years and adjusted HR 0.31; 95% CI 0.15-0.66, p = 0.002 in ≥75 years group, respectively). Male sex with ≥4 vaccinations had a significantly lower risk of lung cancer (adjusted HR 0.35; 95% CI 0.21-0.57, p < 0.001). Patients with comorbid conditions that received ≥4 vaccinations were also protected, and was especially significant among those with CCI ≥ 3 (adjusted HR 0.38; 95% CI 0.18-0.80, p = 0.009) as compared to 1 and 2-3 vaccination groups, including those with hypertension (adjusted HR 0.35; 95% CI 0.22-0.57, p < 0.001). This population-based cohort study demonstrated that annual influenza vaccination significantly reduced the lung cancer risk in DM patients and specifically demonstrates that a higher number of vaccinations is related with a more protective effect. Whether this is due to vaccine booster effects on anti-tumor immune regulation among DM patients still needs to be explored.

Association between chronic obstructive pulmonary disease and ventricular arrhythmia: a nationwide population-based cohort study.

The ventricular arrhythmia (VA)-chronic obstructive pulmonary disease (COPD) association and related risk factors remain unclear. Using 2001-2012 data from National Health Insurance Research Database, we retrospectively reviewed 71,838 patients diagnosed as having COPD and 71,838 age- and sex-matched controls. After adjustments for comorbidities, medication, urbanization level, and monthly income, patients with COPD had higher incidence rates of VA than did the controls (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 1.45 [1.25-1.68]). More hospitalization or emergency visits because of acute COPD exacerbation (aHRs [95% CIs] for first, second, and third visits: 1.28 [1.08-1.50], 1.75 [1.32-2.32], and 1.88 [1.46-2.41], respectively) and asthma-COPD overlap (aHR [95% CI]: 1.49 [1.25-1.79]) were associated with high VA risk in patients with COPD. In the multivariate analysis, heart failure (aHR [95% CI]: 2.37 [1.79-3.14]), diabetes (aHR [95% CI]:1.64 [1.29-2.08]), age ≥75 (aHR [95% CI]: 2.48 [1.68-3.67]), male (aHR [95% CI]: 1.69[1.34-2.12]), and class III antiarrhythmic drug use (aHR [95% CI]: 2.49 [1.88-3.28]) are the most significant risk factors of new onset of VA in patients with COPD.

A systematic review and meta-analysis of the comparison of performance among step-tip, split-tip, and symmetrical-tip hemodialysis catheters.

OBJECTIVE: Patients with end-stage renal disease need vascular access to ensure sufficient blood flow during hemodialysis (HD). Patients who are poor candidates for arteriovenous access creation require long-term catheter placement. Problems such as dialysate recirculation, thrombosis, catheter-related infections, and malfunction can occur with HD catheters. Different tip designs (step, split, and symmetrical) have been developed to ameliorate the catheter-related problems. The aim of the study was to compare the efficacy and safety of split-tip, step-tip, and symmetrical-tip HD catheters. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before November 2017. Studies comparing the clinical and rheologic outcomes of step-, split-, or symmetrical-tip catheters in patients undergoing HD were included in this meta-analysis. We conducted meta-analyses using random-effects models. The primary outcomes were catheter survival time and incidence of functioning catheters. The secondary outcomes were delivered blood flow rate, blood recirculation rate, and incidence of catheter-related complications. RESULTS: Seven randomized controlled trials and one retrospective study with a total of 988 patients were included. No significant differences were observed in the delivered blood flow rate (weighted mean difference, -5.37 mL/min; 95% confidence interval [CI], -23.75 to 13.02), incidence of catheter-related infections (risk ratio [RR], 1.18; 95% CI, 0.63-2.22), or incidence of catheter-related thrombosis (RR, 1.29; 95% CI, 0.64-2.59) between step-tip catheters and advanced (both split-tip and symmetrical-tip) catheters. Moreover, a meta-analysis of the incidence of functioning catheters at 1 month, 6 months, and 12 months revealed that the outcome of step-tip catheter use was better than that of split-tip catheter use, but with a significant difference only at 6 months (RR, 1.22; 95% CI, 1.02-1.46). CONCLUSIONS: None of the catheter types exhibited unique features that can enhance their suitability for application. Hence, catheters can be selected by also considering different factors, including costs, ease of procedures, expertise of the clinician, and education and preference of the patient.

CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a Mycophenolate-based Immunosuppressive Regimen.

BACKGROUND: CXC motif chemokine receptor 4 (CXCR4) blockade is pursued as an alternative to mesenchymal stem cell treatment in transplantation based on our previous report that burixafor, through CXCR4 antagonism, mobilizes immunomodulatory mesenchymal stem cells. Here, we explored the efficacy of combining mycophenolate mofetil (MMF)-based immunosuppressants with repetitive burixafor administration. METHODS: Swine heterotopic cardiac allograft recipients received MMF and corticosteroids (control, n = 10) combined with burixafor as a 2-dose (burixafor2D, n = 7) or 2-dose plus booster injections (burixafor2D + B, n = 5) regimen. The efficacy endpoints were graft survival, freedom from first acute rejection, and the severity of intimal hyperplasia. Each specimen was sacrificed either at its first graft arrest or after 150 days. RESULTS: After 150 days, all specimens in the control group had died, but 28.5% of the burixafor2D group survived, and 60% of the burixafor2D + B group survived (P = 0.0088). Although the control group demonstrated acute rejection at a median of 33.5 days, the burixafor2D + B group survived without acute rejection for a median of 136 days (P = 0.0209). Burixafor administration significantly attenuated the incidence rate of acute rejection (P = 0.002) and the severity of intimal hyperplasia (P = 0.0097) at end point relative to the controls. These findings were associated with reduced cell infiltrates in the allografts, and modulation of C-reactive protein profiles in the circulation. CONCLUSIONS: The augmentation of conventional MMF plus corticosteroids with a CXCR4 antagonist is potentially effective in improving outcomes after heart transplantation in minipigs. Future studies are warranted into optimizing the therapeutic regimens for humans.

Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects. METHODS: In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay. RESULTS: Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively. CONCLUSIONS: In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.

Fasting but not changes of plasma metabolome during oral glucose tolerance tests improves the diagnosis of severe coronary arterial stenosis.

BACKGROUND: Noninvasive stress tests for the diagnosis of significant coronary arterial stenosis requiring intervention are not perfect. We investigated whether plasma metabolome during the oral glucose tolerance test (OGTT) can improve the diagnosis. METHODS: A total of 117 subjects with positive stress test results who received coronary angiography were recruited. After excluding subjects with a history of myocardial infarction and subjects who did not receive OGTT, the 18 subjects without significant stenosis were selected as controls. Another 18 age- and sex-matched subjects with significant stenosis were selected as cases. Plasma metabolome from samples obtained in fasting, 30 and 120 min after OGTT was measured using liquid chromatography combined with time-of-flight mass spectrometry. RESULTS: We found five metabolites which can identify patients with significant stenosis independent to clinical risk factors, including diabetes, hypertension, hypercholesterolaemia, smoking and history of percutaneous coronary intervention (all P < 0·05). The area under the receiver operating characteristic (AUROC) curve of these metabolites was 0·799-0·818 at fasting and 30 min after OGTT. The addition of metabolites to clinical factors increases the AUROC (0·616, 95%CI 0·429-0·803 for model with clinical factors only; 0·824, 95%CI 0·689-0·959 for model with four metabolites and clinical factors). The changes of plasma metabolite levels during OGTT did not significantly improve the diagnostic performance. CONCLUSIONS: Fasting plasma metabolome, but not change of plasma metabolome during OGTT, can improve the diagnosis of significant stenosis in patients with positive noninvasive stress test results.

Mechanisms of early and delayed stroke after systematic off-pump coronary artery bypass.

BACKGROUND/PURPOSE: Stroke is one of the most devastating complications after cardiac surgery. Off-pump coronary artery bypass (OPCAB) has been reported to offer a lower risk of stroke. However, limited information was available on timing and mechanisms of stroke after OPCAB. We sought to assess the incidence, timing, and mechanisms of stroke after OPCAB. METHODS: A retrospective review of 1010 patients undergoing systematic OPCAB between 2001 and 2012. Stroke was defined as any focal or global neurologic deficits lasting for more than 24 hours. Stroke was classified as early stroke when it occurred less than 24 hours postoperatively, and delayed stroke when it occurred more than 24 hours postoperatively. Stroke mechanisms were classified as embolic or hypoperfusion. RESULTS: In a total of 10 patients (1.0%) 11 episodes of stroke developed after OPCAB. Early stroke occurred in five (0.5%) patients and delayed stroke occurred in six (0.6%) patients. Of five early strokes, the mechanisms were embolic in two (40%) and hypoperfusion in three (60%). Of six delayed strokes, the mechanisms were embolic in five (83%) and unknown in one. Of six delayed strokes, all the patients had diabetes mellitus and acute cardiac events prior to surgery, and five patients had postoperative atrial fibrillation. CONCLUSION: The incidence of stroke after systematic OPCAB was low. Early and delayed strokes were equally distributed. Stroke mechanisms were predominantly embolic. Early and delayed stroke differed in their mechanisms. Early and delayed stroke should be considered as two separate entities and different preventive strategies should be applied in future intervention.