Wen-Jone Chen

Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis

BACKGROUND Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. METHODS We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18-75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00173615. FINDINGS Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0.0001) and a better 1-year survival than those who received conventional CPR (log rank p=0.007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio [HR] 0.51, 95% CI 0.35-0.74, p<0.0001), 30-day survival (HR 0.47, 95% CI 0.28-0.77, p=0.003), and 1-year survival (HR 0.53, 95% CI 0.33-0.83, p=0.006) favouring extracorporeal CPR over conventional CPR. INTERPRETATION Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin.

Vascular Endothelial Growth Factor 189 mRNA Isoform Expression Specifically Correlates With Tumor Angiogenesis, Patient Survival, and Postoperative Relapse in Non–Small-Cell Lung Cancer

PURPOSE The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer. PATIENTS AND METHODS We examined the expression of four different VEGF mRNA isoforms in 57 non-small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining. RESULTS All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence. CONCLUSION The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non-small-cell lung cancers.

Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non‐small‐cell lung cancer

We have quantified the expression of all 4 isoforms of vascular endothelial growth factor (VEGF) mRNA in non‐small‐cell lung cancer (NSCLC) using a new kinetic quantitative PCR method, real‐time quantitative (RTQ) RT‐PCR, and investigated the association between VEGF expression at the mRNA and protein levels and the clinicopathologic variables, tumor angiogenesis, patient survival and timing of relapse. Surgical tumor specimens from 72 NCSLC patients (37 squamous‐cell carcinomas, 35 adenocarcinomas) were examined. Twenty‐eight patients had stage I, 10 stage II and 34 stage IIIA or IIIB disease. Total VEGF mRNA (all 4 isoforms) was quantified by RTQ RT‐PCR, while VEGF protein expression and microvessel number in tumors were assessed immunohistochemically. VEGF mRNA was detected in all 72 tumor samples at significantly higher levels than in adjacent normal tissue. Tumoral VEGF mRNA levels correlated strongly with the VEGF protein staining score and microvessel count. Adenocarcinomas showed significantly higher VEGF mRNA expression and a higher protein staining score than squamous‐cell carcinomas. High tumoral VEGF mRNA expression was associated with advanced (IIIA or IIIB) tumor stage, lymph node metastasis, high tumoral microvessel counts, short patient survival (<24 months) and early relapse (<12 months), while a high VEGF protein staining score was associated with high tumoral microvessel counts, short patient survival and early relapse. Patients with high tumoral levels of both VEGF mRNA and protein had significantly shorter survival and earlier relapse. In multivariate analysis, the VEGF protein staining score and nodal status were the most important independent predictors of survival and recurrence. We conclude that RTQ RT‐PCR is a sensitive method for detecting and quantifying VEGF mRNA expression in NSCLC and that the expression levels of total VEGF mRNA and protein in NSCLC are strongly associated with histologic type, tumor angiogenesis, survival and timing of relapse. High VEGF expression in adenocarcinomas may contribute to their greater metastatic potential. Int. J. Cancer 89:475–483, 2000.

Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1 beta, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of < or =40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.

Ultrasonographic screening of clinically-suspected necrotizing fasciitis

OBJECTIVE To determine the accuracy of ultrasonography for the diagnosis of necrotizing fasciitis. METHODS This study was a prospective observational review of patients with clinically-suspected necrotizing fasciitis presenting to the emergency department of an urban (Taipei) medical center between October 1996 and May 1998. All patients underwent ultrasonographic examination, with the ultrasonographic diagnosis of necrotizing fasciitis based on the criterion of a diffuse thickening of the subcutaneous tissue accompanied by a layer of fluid accumulation more than 4 millimeters in depth along the deep fascial layer, when compared with the contralateral position on the corresponding normal limb. The final diagnosis of necrotizing fasciitis was determined by pathological findings for patients who underwent fasciotomy or biopsy results for patients managed nonoperatively. RESULTS Data were collected for 62 patients, of whom 17 (27.4%) were considered to suffer from necrotizing fasciitis. Ultrasonography revealed a sensitivity of 88.2%, a specificity of 93.3%, a positive predictive value of 83.3%, a negative predictive value of 95.4%, and an accuracy of 91.9% as regards the diagnosis of necrotizing fasciitis. CONCLUSIONS Ultrasonography can provide accurate information for emergency physicians for the diagnosis of necrotizing fasciitis.

Cyclosporine A regulate oxidative stress‐induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70

Previous study suggested that cyclosporine A (CsA) could partially reduce ischaemia/reperfusion‐induced injury in isolated heart, but the mechanism was still unclear. In this study, the possible mechanisms of cyclosporine A in regulating oxidative stress‐induced cardiomyocyte apoptosis were examined. Morphological (cell shrinkage, apoptotic body formation, and DNA fragmentation) and biochemical (annexin‐V staining for exposed phosphatidylserine residues) evidences showed that both hydrogen peroxide (H2O2) and hypoxia/reoxygenation could induce apoptotic change in the embryonal rat heart myoblast‐derived cells (H9c2). These effects were inhibited by pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h, but were increased with 10.0 μM CsA. While examining the mechanisms of CsA in protecting cardiomyocyte apoptosis, we found that the collapse of mitochondria membrane potential (ΔΨm) induced by oxidative stress was partially reversed by CsA (0.01–1.0 μM). Compared to the control, CSA at the concentration of 0.1 and 10.0 μM significantly increased the level of intracellular reactive oxygen species (ROS) to 117.2±12.4% and 234.4±9.3%, respectively. Co‐incubating with the antioxidant, ascorbic acid (10.0 μM), could partially reduce the protective effect of CsA (0.01–1.0 μM) and the toxic effect of 10.0 μM CsA. Pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h produced up‐regulation of heat shock protein 70 (Hsp 70), inducible nitric oxide synthase (iNOS) and also induced NO production, indicating that these factors might be associated with the cell protective effects of CsA. These results suggest that CsA could protect the oxidative stress‐induced cardiomyocyte apoptosis not only by preventing the loss of ΔΨm in mitochondria, but also through ROS generation, Hsp70, and iNOS up‐regulation.

Chin-Shan Community Cardiovascular Cohort in Taiwan–baseline data and five-year follow-up morbidity and mortality

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Relations of Epicardial Adipose Tissue Measured by Multidetector Computed Tomography to Components of the Metabolic Syndrome Are Region-Specific and Independent of Anthropometric Indexes and Intraabdominal Visceral Fat

CONTEXT Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot. Its distribution is asymmetrical and primarily concentrated in the grooves. To date, it remains unclear which measurement of EAT best reflects its metabolic risk. OBJECTIVE We aimed to examine the correlations between various multidetector computed tomographic measurements of EAT, metabolic syndrome components, and plasma levels of high-sensitivity C-reactive protein and adipokines. DESIGN, SETTING, AND PARTICIPANTS This study included 148 consecutive patients undergoing multidetector computed tomography prior to diagnostic coronary angiography. Thickness in the grooved segments, cross-sectional areas, and total volume of EAT were measured. The cross-sectional areas of sc and visceral abdominal fat depots were additionally measured in 70 randomly selected patients. RESULTS Thickness of EAT in the left atrioventricular groove was the only EAT measurement significantly correlated with all three metabolic syndrome components (blood pressure, lipid, and glucose components) and plasma levels of resistin and high-sensitivity C-reactive protein after age and gender adjustments. The association between left atrioventricular groove thickness and increasing number of metabolic syndrome components remained significant after additional adjustments for body mass index, waist circumference, and intraabdominal visceral fat area. By using the receiver operating characteristic analysis, the optimal cutoff point for left atrioventricular groove thickness to predict the presence of at least two metabolic syndrome components was 12.4 mm. CONCLUSIONS A simple measurement of EAT thickness in the left atrioventricular groove may provide a more accurate assessment of metabolic risk associated with EAT, which could not be accounted for by anthropometric indexes and intraabdominal visceral fat.

Cardiac troponin I levels are a risk factor for mortality and multiple organ failure in noncardiac critically ill patients and have an additive effect to the APACHE II score in outcome prediction.

Cardiac troponin I (cTnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). Recent studies have shown that cTnI levels can also be elevated in patients without ACS, such as in sepsis and trauma patients, and that this is associated with an adverse prognosis. We have evaluated the clinical implications and prognostic significance of serum cTnI levels in noncardiac critically ill patients in a prospective observational study in a general medical intensive care unit at a tertiary-level hospital. A total of 108 consecutive patients without ACS or other cardiac disease was enrolled. Serum cTnI levels were measured on admission using enzyme-linked immunoabsorbant assay kits. Clinical laboratory parameters and outcome were compared between patients with elevated and normal cTnI levels. The prognostic significance of cTnI levels and the Acute Physiology And Chronic Health Evaluation (APACHE) II score was also analyzed. Forty-nine patients (45%) had elevated cTnI levels and 59 (55%) had normal levels. Compared with patients with normal cTnI levels, patients with elevated levels had a higher incidence of new failure of two or more organs, had a lower left ventricular ejection fraction during admission, were more likely to be associated with bacteremia, and had a higher intensive care unit mortality; they also had a significantly shorter survival over a 180-day follow up, before and after stratification by the APACHE II score. Multiple organ failure was the leading cause of mortality in patients with elevated cTnI levels. By multivariate analysis, elevated cTnI levels, a high APACHE II score, and underlying cancer were the three most important independent predictors for a shorter survival. Combination analysis showed a shorter survival in patients with a high APACHE II score plus elevated cTnI levels than in patients with a high APACHE II score or elevated cTnI levels alone. In conclusion, elevated serum cTnI levels is a risk factor for multiple organ failure and mortality in noncardiac critically ill patients, and the cTnI levels and APACHE II score have an additive effect in outcome prediction.

The effect of hyperoxia on survival following adult cardiac arrest: A systematic review and meta-analysis of observational studies

OBJECTIVE Studies have shown the detrimental effect of hyperoxia in animals with return of spontaneous circulation (ROSC) after cardiac arrest. To maximize the value of existing clinical studies, we performed the systemic review and meta-analysis of human observational studies to examine the effect of hyperoxia on outcomes of post-ROSC patients. METHODS We searched PubMed and Embase from the inception to October 2013. We selected adult observational studies that compared different levels of partial pressure of arterial oxygen (PaO2) in post-ROSC patients with mortality or neurological status at hospital discharge as outcome. Studies comparing hypoxia with normoxia only were excluded. RESULTS Fourteen studies were identified from 2982 references. Odds ratio (OR) was used as effect estimate. OR was reconstructed if not provided in original articles. Hyperoxia was defined as a PaO2>300 mmHg. Meta-analysis indicated that hyperoxia appeared to be correlated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02-1.93; I2, 69.27%; 8 studies) but not worsened neurological outcome (OR, 1.62; 95% CI, 0.87-3.02; I2, 55.61%; 2 studies). However, the results were inconsistent in subgroup and sensitivity analyses. CONCLUSIONS Hyperoxia appears to be correlated with increased in-hospital mortality of post-ROSC patients. This result should be interpreted cautiously because of the significant heterogeneity and limited number of studies analyzed. However, because exposure to hyperoxia had no obvious benefits, clinicians should monitor PaO2 closely and titrate oxygen administration cautiously.