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 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.

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.

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.

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.

Malignant ventricular arrhythmias after off-pump coronary artery bypass.

BACKGROUND/PURPOSE: Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are rare complications after coronary surgery. Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative complications. No studies to date have specifically addressed VT/VF after OPCAB. We sought to assess the incidence, risk factors, and outcome of VT/VF after OPCAB. METHODS: The study included a retrospective review of 1010 patients undergoing OPCAB between 2000 and 2012. Data were compared between the VT/VF patients and control patients who were the first cases of OPCAB in each month during the study period and did not have VT/VF. RESULTS: Twenty-three patients (2.3%) developed VT/VF after OPCAB. The hospital mortality rate was 17.4%. In univariate analysis, the risk factors for VT/VF were old age, rapid heart rate, prolonged corrected QT interval, severe congestive heart failure, poor left ventricular ejection fraction, large left ventricular end-diastolic diameter, chronic kidney disease, preoperative dialysis, low blood hemoglobin level, preoperative intubation, recent myocardial infarction, high European System for Cardiac Operative Risk Evaluation, urgent/emergent operation, use of intra-aortic balloon pump, conversion to on-pump beating heart, postoperative dialysis, and no use of beta-blockers after operation. Multivariate analysis identified preoperative corrected QT interval > 426 milliseconds [odds ratio (OR) = 4.501; 95% confidence interval (CI) = 1.153-17.570] and estimated glomerular filtration rate < 30 mL/minute/1.73 m(2) (OR = 4.876; 95% CI = 1.112-21.374) as independent risk factors. CONCLUSION: Postoperative VT/VF was rare after OPCAB but was associated with high mortality. Prolonged corrected QT interval and chronic kidney disease were independent risk factors. Recognition of these risk factors, proper prevention, and early intervention may improve survival.

Cardiac surgery in patients with liver cirrhosis: risk factors for predicting mortality.

AIM: To evaluate the results of cardiac surgery in cirrhotic patients and to find the predictors of early and late mortality. METHODS: We included 55 consecutive cirrhotic patients undergoing cardiac surgery between 1993 and 2012. Child-Turcotte-Pugh (Child) classification and Model for End-Stage Liver Disease (MELD) score were used to assess the severity of liver cirrhosis. The online EuroSCORE II calculator was used to calculate the logistic EuroSCORE in each patient. Stepwise logistic regression analysis was used to identify the risk factors for mortality at different times after surgery. Multivariate Cox proportional hazard models were applied to estimate the hazard ratios (HR) of predictors for mortality. The Kaplan-Meier method was used to generate survival curves, and the survival rates between groups were compared using the log-rank test. RESULTS: There were 30 patients in Child class A, 20 in Child B, and five in Child C. The hospital mortality rate was 16.4%. The actuarial survival rates were 70%, 64%, 56%, and 44% at 1, 2, 3, and 5 years after surgery, respectively. There were no significant differences in major postoperative complications, and early and late mortality between patients with mild and advanced cirrhosis. Multivariate logistic regression showed preoperative serum bilirubin, the EuroSCORE and coronary artery bypass grafting (CABG) were associated with early and late mortality; however, Child class and MELD score were not. Cox regression analysis identified male gender (HR = 0.319; P = 0.009), preoperative serum bilirubin (HR = 1.244; P = 0.044), the EuroSCORE (HR = 1.415; P = 0.001), and CABG (HR = 3.344; P = 0.01) as independent risk factors for overall mortality. CONCLUSION: Advanced liver cirrhosis should not preclude patients from cardiac surgery. Preoperative serum bilirubin, the EuroSCORE, and CABG are major predictors of early and late mortality.

Blood stream infection in patients undergoing systematic off-pump coronary artery bypass: incidence, risk factors, outcome, and associated pathogens.

BACKGROUND: Blood stream infection (BSI) is a major cause of mortality and morbidity for patients undergoing cardiac surgery. However, information is lacking about patients undergoing off-pump coronary artery bypass (OPCAB). The purpose of this study was to assess the incidence, risk factors, outcome and associated pathogens of BSI after OPCAB. METHODS: One thousand ten consecutive patients undergoing OPCAB between 2001 and 2012 were included in a retrospective case-control study. A propensity-matched control was used for risk factor analysis. RESULTS: Of the 1,010 patients, 26 patients (2.6%) had 32 episodes of BSI after surgery, which occurred at a median of 14 d after surgery. Gram-negative bacilli and gram-positive cocci were distributed equally. Methicillin-resistant Staphylococcus aureus was the pathogen identified most frequently, and the most common source of infection was a surgical site. The hospital mortality rate was 54%. By univariable analysis, diabetes mellitus, pre-operative renal impairment, pre-operative low hemoglobin, pre-operative endotracheal intubation, dialysis before or after surgery, cardiogenic shock, left ventricular ejection fraction of less than 40%, non-elective surgery, low number of distal anastomoses, atrial fibrillation after surgery, and re-operation for bleeding were significant risk factors. By multivariable analysis, the independent risk factors were left ventricular ejection fraction of less than 40%, low number of distal anastomoses, atrial fibrillation after surgery, and dialysis after surgery. CONCLUSIONS: Blood stream infections remained a common complication after OPCAB, and the mortality was high. Gram-negative bacilli and gram-positive cocci were distributed equally. Methicillin-resistant S. aureus was the pathogen identified most frequently. Preventive tactics should target likely pathogens and high-risk patients undergoing OPCAB.

Care bundle to prevent methicillin-resistant Staphylococcus aureus sternal wound infection after off-pump coronary artery bypass.

Methicillin-resistant Staphylococcus aureus (MRSA) sternal wound infection (SWI) after cardiac surgery is endemic in our hospital. An infection control care bundle with preoperative chlorhexidine showering and povidone iodine paint before bathing was introduced in 2006. From 2001 to 2012, 23 (2.3%) of 1,010 patients undergoing off-pump coronary artery bypass had SWIs. SWI significantly decreased after 2006 (1.4% vs 3.4%, respectively; P = .03). Care bundle was more protective against MRSA infection (2.3% vs 0.5%, respectively; P = .021). SWI remained a common complication after off-pump coronary artery bypass. MRSA infection was most common, and the mortality was high. Care bundle can effectively decrease the incidence of SWI, especially infection caused by MRSA.

Primary Infected Aortic Aneurysm: Clinical Presentation, Pathogen, and Outcome.

PURPOSE: Infected aneurysm of the aorta and adjacent arteries is rarely occurring and can be fatal without surgical intervention. Within the medical community, the most efficacious treatment strategy to address infected aortic aneurysm remains controversial. In this study, we have reviewed our treatment experience with 109 patients. METHODS: We included in our study all consecutive patients treated for primary infected aortic aneurysm at our facility between 1995 and 2011. Aneurysm-related mortality was defined as the presence of in-hospital and late mortality related to infection or postoperative complications. RESULTS: The median patient age was 72 years (range, 35-88), and 87 (80%) were male. Pathogen was isolated in 101 patients, and the most common microorganism identified was non-typhoid Salmonella in 61 (60%), followed by Staphylococcus aureus in 16 (16%) and Streptococci species in 7 (7%). Eighty-five (78%) patients underwent surgical treatment. Surgery included open repair with in-situ graft replacement in 77 (71%) and endovascular repair in 8 (7%). The aneurysm-related mortality rate was 67% in medically treated and 21% in surgically treated patients, with a median follow-up duration of 31.5 months (range 1-189). Additionally, risk factors for aneurysm-related mortality included old age, chronic lung disease, psoas muscle abscess, short duration of preoperative antibiotics, no operation, and probably endovascular repair. CONCLUSIONS: Non-typhoid Salmonella was the most common pathogen found in our study group patients with infected aortic aneurysm. It appears that prolonged preoperative antibiotic treatment followed by open in-situ graft replacement remains the preferred and most effective treatment strategy. KEY WORDS: Infected aortic aneurysm; Outcome; Pathogen; Surgery.

Surgical proficiency and quality indicators in off-pump coronary artery bypass.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative mortality and morbidity. Surgeon experience influences outcome. The required levels of surgical proficiency and maturation of technical skills are uncertain. We sought to assess the surgical proficiency in OPCAB and to identify the required levels of technical maturation. METHODS: We included 1,055 consecutive patients undergoing OPCAB. Patients were divided by 100s into 11 groups by timing of operation. Surgical proficiency was evaluated by 2 quality indicators: revascularization index and conversion rate in nonemergency cases. RESULTS: Mode of intervention was elective in 768 patients, urgent in 185 patients, and emergent in 102 patients (9.7%). The in-hospital mortality rate was 5.1% and ranged from 3% (group 3) to 9% (group 11). The percentage of triple-vessel disease and the mean number of diseased vessels increased over time. The mean number of distal anastomoses increased over time, from 2.64 ± 0.82 in group 1 to 4.13 ± 0.98 in group 11. It reached a plateau of 4.0 at group 7 (cases 600-700). The revascularization index also increased over time, from 1.01 ± 0.20 in group 1 to 1.41 ± 0.28 in group 11. It reached a plateau of 1.4 at group 7 (cases 600-700). The conversion rate in nonemergent cases decreased rapidly as the volume of OPCAB increased, and it reached a baseline of 5% at group 3 (cases 200-300). CONCLUSIONS: Surgical proficiency at performing OPCAB could be evaluated with 2 quality indicators: revascularization index of 1.4 or more and conversion rate in nonemergent cases of 5% or less. The required case number for technical maturation was 200 to 300 for conversion and 600 to 700 for complete revascularization.

Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis.

Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow-derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10(+) and IFN-γ(+) cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10(+)IFN-γ(+)CD4(+) regulatory T type 1 (T(R)1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10(+)IFN-γ(+)CD4(+) cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble T(R)1-like cells. Both cyclooxygenase-derived PGE(2) and IDO help to induce T(R)1-like cells by MSCs. MSCs constitutively secrete PGE(2), which is augmented in allogeneic reactions. However, T(R)1-like cells were deficient in PGE(2) and 4-fold less potent than were MSCs in suppressing MLR. PGE(2) mimetic supplements can enhance the immunosuppressive potency of T(R)1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced T(R)1-like cells combined with PGE(2), but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: T(R)1-like cells + PGE(2): 11 ± 10%; PGE(2) alone: 93 ± 8.7%; T(R)1-like cells alone: 88 ± 2.4% versus untreated 94 ± 0.9%, p < 0.001). These findings indicate that PGE(2) helps MSC-induced IL-10(+)IFN-γ(+)CD4(+) T(R)1-like cells inhibit TA. PGE(2) combined with MSC-induced T(R)1-like cells represents a new approach for achieving immune tolerance.

Autologous mesenchymal stem cells prevent transplant arteriosclerosis by enhancing local expression of interleukin-10, interferon-γ, and indoleamine 2,3-dioxygenase.

Transplant arteriosclerosis (TA) remains the major limitation of long-term graft survival in heart transplantation despite the advances in immunosuppressants. Mesenchymal stem cells (MSCs) have been demonstrated to suppress allogeneic immune responses by numerous in vitro studies. However, the immunomodulatory effects of MSCs in vivo are controversial and the underlying molecular mechanisms are not conclusive. In this study, we investigated the therapeutic potential of autologous bone marrow-derived MSCs on TA in a porcine model of femoral artery transplantation. MSCs or saline were injected into the soft tissue surrounding the arterial grafts immediately postanastomosis. Four weeks after transplantation, neointimal formation increased significantly in untreated allografts compared with the MSC-treated grafts as assessed by intravascular ultrasound (maximum luminal area stenosis: 40 ± 12% vs. 18 ± 6%, p < 0.001). Grafts harvested at 4 weeks showed dense perivascular lymphocyte infiltration accompanied by significant intimal hyperplasia in the untreated but not in the MSC-treated allografts. Serial angiographic examination showed that all of the untreated allografts became occluded at the 8th week whereas the majority of the MSC-treated grafts remained patent at the 12th week posttransplantation (n = 12 each group, p < 0.001). Quantitative PCR analysis revealed that Foxp3 expression was comparable between the untreated and the MSC-treated groups. However, expression of interleukin-10 (IL-10), interferon-γ (IFN-γ), and indoleamine 2,3-dioxygenase (IDO) was increased significantly in the MSC-treated allografts compared with that in the allograft controls (p = 0.021 for IL-10, p = 0.003 for IFN-γ, and p = 0.008 for IDO). In conclusion, local delivery of autologous MSCs alleviates TA by inducing allograft tolerance via enhanced expression of IL-10, IFN-γ, and IDO but not Foxp3-positive cells in the vessel wall. These results suggest that MSCs induce immune tolerance by activating the type 1 regulatory T-like cells.

Serum vascular adhesion protein-1 predicts 10-year cardiovascular and cancer mortality in individuals with type 2 diabetes.

OBJECTIVE: Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan. RESULTS: The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17-4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A(1c), diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17-28.97) for cardiovascular mortality, 6.32 (95% CI 1.25-32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57-65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly. CONCLUSIONS: Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

Food pattern and quality of life in metabolic syndrome patients who underwent coronary artery bypass grafting in Taiwan.

Metabolic syndrome is associated with poor operative outcomes of coronary artery bypass grafting surgery (CABG). A healthy food pattern for metabolic syndrome patients is necessary not only in the initial stage to prevent cardiovascular disease but for those who experience cardiovascular problems and undergo heart surgery. Empirical studies that explore food pattern and quality of life metabolic syndrome patients who undergo CABG are lacking. Therefore, the objectives of this study are to explore the food pattern and quality of life of metabolic syndrome patients who undergo CABG and to examine the relationship between these two variables. A descriptive, correlational and cross section design was conducted. Through convenience sampling, 104 patients were recruited. Data were collected through three instruments: a demographic questionnaire; the Chinese Food Frequency Questionnaire-Short Form (Short C-FFQ), used to assess food pattern; and the Taiwanese version of the Medical Outcomes Study Short Form 36-Health Survey (SF-36), used to assess quality of life. Descriptive analysis, one-way analysis of variance (ANOVA) and Pearson correlation were used to analyze the data. The results indicated that patients who ate fruit more frequently tended to have a better quality of life, while the intake of fried food was more frequently associated with a poor quality of life. The use of these data gives the health care provider a better understanding of food pattern and their impact on quality of life in this population. Such an understanding can be used to develop targeted interventions to promote health in this and in other populations.