Yi-Fang Chiang

The Roles of Biomarkers of Oxidative Stress and Antioxidant in Alzheimer’s Disease: A Systematic Review

Purpose. Oxidative stress plays an important role in the pathogenesis of Alzheimers disease (AD). This paper aims to examine whether biomarkers of oxidative stress and antioxidants could be useful biomarkers in AD, which might form the bases of future clinical studies. Methods. PubMed, SCOPUS, and Web of Science were systematically queried to obtain studies with available data regarding markers of oxidative stress and antioxidants from subjects with AD. Results and Conclusion. Although most studies show elevated serum markers of lipid peroxidation in AD, there is no sufficient evidence to justify the routine use of biomarkers as predictors of severity or outcome in AD.

Factors associated with fall-related fractures in Parkinson's disease

PURPOSEnFall-related fracture is one of the most disabling features of idiopathic Parkinsons disease (PD). A better understanding of the associated factors is needed to predict PD patients who will require treatment.nnnMETHODSnThis prospective study enrolled 100 adult idiopathic PD patients. Stepwise logistic regressions were used to evaluate the relationships between clinical factors and fall-related fracture.nnnRESULTSnFalls occurred in 56 PD patients, including 32 with fall-related fractures. The rate of falls in the study period was 2.2 ± 1.4 per 18 months. The percentage of osteoporosis was 34% (19/56) and 11% in PD patients with and without falls, respectively. Risk factors associated with fall-related fracture were sex, underlying knee osteoarthritis, mean Unified Parkinsons Disease Rating Scale score, mean Morse fall scale, mean Hoehn and Yahr stage, and exercise habit. By stepwise logistic regression, sex and mean Morse fall scale were independently associated with fall-related fracture. Females had an odds ratio of 3.8 compared to males and the cut-off value of the Morse fall scale for predicting fall-related fracture was 72.5 (sensitivity 72% and specificity 70%).nnnDISCUSSIONnHigher mean Morse fall scales (>72.5) and female sex are associated with higher risk of fall-related fractures. Preventing falls in the high-risk PD group is an important safety issue and highly relevant for their quality of life.

The association between circulating endothelial progenitor cells and outcome in different subtypes of acute ischemic stroke

OBJECTIVESnThis study evaluated the relationship between serial changes in circulating endothelial progenitor cells (EPCs) and outcomes in patients with different subtypes of acute ischemic stroke (AIS).nnnMETHODSnThis prospective cohort study evaluated 65 patients with AIS, including 45 with small-vessel and 20 with large-vessel diseases. The circulating level of EPCs (CD133(+)/CD34(+) and KDR(+)/CD34(+) cells) was determined at different time points (within 48h and on Days 7 and 30 post-stroke). For comparison, the EPC levels of 65 age- and sex-matched controls were also evaluated.nnnRESULTSnThe levels of CD133(+)/CD34(+) and KDR(+)/CD34(+) EPCs were significantly lower in the AIS group than in the control group (p<0.05). There were fewer CD133(+)/CD34(+) EPCs in the large-vessel disease group than in the small-vessel disease group on Day 1 post-stroke (p<0.05). After adjusting for covariance using stepwise logistic regression, only stroke subtype (OR: 30.2, 95% CI: 5.3-171.4; p<0.001) and KDR(+)/CD34(+) on admission (OR: 0.188, 95% CI: 0.04-0.86; p=0.031) were independently associated with 6-month outcome.nnnCONCLUSIONSnThe number of circulating EPCs is significantly lower in patients with large-vessel disease than in those with small-vessel disease. Fewer number of EPCs on admission is an independent risk factor for poor 6-month outcome in patients with AIS.

Association between Oxidative Stress and Outcome in Different Subtypes of Acute Ischemic Stroke

Objectives. This study investigated serum thiobarbituric acid-reactive substances (TBARS) and free thiol levels in different subtypes of acute ischemic stroke (AIS) and evaluated their association with clinical outcomes. Methods. This prospective study evaluated 100 AIS patients, including 75 with small-vessel and 25 with large-vessel diseases. Serum oxidative stress (TBARS) and antioxidant (thiol) were determined within 48 hours and days 7 and 30 after stroke. For comparison, 80 age- and sex-matched participants were evaluated as controls. Results. Serum TBARS was significantly higher and free thiol was lower in stroke patients than in the controls on days 1 and 7 after AIS. The level of free thiol was significantly lower in the large-vessel disease than in the small-vessel disease on day 7 after stroke. Using the stepwise logistic regression model for potential variables, only stroke subtype, NIHSS score, and serum TBARS level were independently associated with three-month outcome. Higher TBARS and lower thiol levels in the acute phase of stroke were associated with poor outcome. Conclusions. Patients with large-vessel disease have higher oxidative stress but lower antioxidant defense compared to those with small-vessel disease after AIS. Serum TBARS level at the acute phase of stroke is a potential predictor for three-month outcome.

The association of statin therapy and high-sensitivity C-reactive protein level for predicting clinical outcome in acute non-cardioembolic ischemic stroke.

BACKGROUNDnStatins reportedly have anti-inflammatory effects aside from their cholesterol-lowering effect. We investigated the effects of statins on serum hs-CRP level and clinical outcome of acute ischemic stroke (IS) patients.nnnMETHODSnThis prospective cohort study consequently evaluated patients with acute IS in a single medical center. Serum hs-CRP levels were measured at different time points (within 48 h and 30 days post-stroke). The patients clinical and laboratory data on admission were analyzed.nnnRESULTSnTotal 100 patients with acute IS were divided in the statin group (n=50) and the non-statin group (n=50). Serum hs-CRP level was similar in the 2 groups within 48 h after acute IS, but was significantly lower in the statin group on Day 30 compared to the non-statin group (p<0.05). The statin group also had favorable 3-month outcome compared to the non-statin group (p<0.05). After adjustments for covariance using stepwise logistic regression, only NIHSS on admission (OR=1.38, 95% CI=1.06-1.80; p=0.02) and hs-CRP in the acute phase (OR=1.74, 95% CI=1.30-2.33; p=0.001) were significantly and independently predictive of 3-month outcome.nnnCONCLUSIONnStatin therapy reduces serum hs-CRP level and may be associated with favorable 3-month outcome in patients after acute IS.

Statin therapy reduces oxidized low density lipoprotein level, a risk factor for stroke outcome

IntroductionStatins are reported to have anti-inflammatory and anti-oxidative effects aside from cholesterol-lowering effects. This study aimed to evaluate the effects of statin therapy on oxidized LDL (Ox-LDL) and the clinical outcome of patients with acute ischemic stroke (AIS).MethodsThis prospective study enrolled 120 patients with AIS divided in the statin (nu2009=u200955) and non-statin (nu2009=u200965) groups. Eighty sex- and age- matched participants were recruited as risk controls. Ox-LDL was measured using a monoclonal antibody-based enzyme-linked immune-sorbent assay at different time points after AIS. The clinical outcomes were analyzed between the statin and non-statin groups.ResultsPlasma Ox-LDL was significantly higher in stroke patients than in the controls (Pu2009<u20090.001). Plasma Ox-LDL level was significantly reduced in the statin group on day 7 and day 30 compared to the non-statin group (Pu2009<u20090.01). The plasma Ox-LDL positively correlated with serum total cholesterol, LDL-cholesterol, and hemoglobin A1c (HbA1c). Among the potential risk factors, only National Institutes of Health stroke scale (NIHSS) score and Ox-LDL level on admission were independently associated with 3-month outcome.ConclusionsOur study demonstrates that statin therapy reduces plasma Ox-LDL level after AIS. Plasma Ox-LDL may be a more powerful predictor than serum LDL, high-sensitivity C-reactive protein or white blood cell counts for stroke outcome. Therefore, assay of plasma Ox-LDL should be added as a predictor among the panel of conventional biomarkers in stroke outcome.

Statin pre-treatment is associated with lower platelet activity and favorable outcome in patients with acute non-cardio-embolic ischemic stroke

IntroductionStatins reportedly have anti-inflammatory and anti-thrombotic effects aside from cholesterol-lowering. This study aimed to evaluate the effect of pre-existing statin use on platelet activation markers and clinical outcome in acute ischemic stroke patients.MethodsThis prospective study evaluated 172 patients with acute ischemic stroke divided in two groups: patients with pre-existing statin (n = 43) and without pre-existing statin (66 cases with statins initiated post-stroke and 63 without statin treatment). Platelet activation markers (CD62P and CD63) were measured by flow cytometry at different time points after stroke and analyzed with clinical outcome.ResultsThe CD62P and CD63 expressions on platelets were significantly lower in the patients with pre-existing statin use compared to the patients without pre-existing statin use on Day 1 post-stroke (p < 0.05). The CD62P expression was significantly lower in the patients with pre-existing statin use on 90 days after the acute stroke (p < 0.05). Patients with pre-existing statin use had lower incidences of early neurologic deterioration (END) than those without treatment (p < 0.05). Among several baseline clinical variables, admission NIHSS score, history of coronary artery disease, and pre-existing statin use were independent predictions of good clinical outcome at three months.ConclusionsPre-existing statin use is associated with decreased platelet activity as well as improved clinical outcome and reduced END in patients with acute ischemic stroke.

Serum adhesion molecules as outcome predictors in adult severe sepsis patients requiring mechanical ventilation in the emergency department

BACKGROUND AND AIMnSerum adhesion molecules play a pivotal role in the pathogenesis of sepsis syndrome. This study aimed to evaluate the prognostic value of serum adhesion molecules in patients with severe sepsis and mechanical ventilation (MV) at the emergency department.nnnMETHODSnEighty-seven consecutive patients with severe sepsis, including 35 with MV, were evaluated. Serum samples were collected for analysis of serum adhesion molecules. The patients clinical and laboratory data on admission were also recorded.nnnRESULTSnThe maximum 24-h APACHE II and 24-h SOFA scores were significantly higher in the severe sepsis patients requiring MV than in patients without MV (p=0.02 and p<0.001). Mortality rate was significantly higher in severe sepsis patients requiring MV than in patients without MV (40% [14/35] vs. 9.6% [5/52], p=0.001). Both VCAM-1 level (p=0.03) and lactate concentration (p=0.04) on admission had significant differences between survivors and non-survivors in patients requiring MV. In the logistic regression model, only VCAM-1 level (p=0.049) was independently predictive of mortality. By correlation analysis, lactate concentration significantly correlated with the mean VCAM-1 level on admission (γ=0.484, p=0.004). The area under the ROC curve for VCAM-1 level was 0.747 (p=0.02, 95% CI: 0.576-0.918). The cut-off value of VCAM-1 level for predicting hospital mortality in severe sepsis patients receiving MV was 1870ng/mL, with 77% sensitivity and 71% specificity; then the likelihood ratio equals 2.7.nnnCONCLUSIONSnIn this study, VCAM-1 level is a more powerful outcome predictor of hospital mortality in severe sepsis patients requiring MV than lactate concentration and other conventional parameters on admission. This suggests that increased plasma VCAM-1 concentration may be useful in identifying who are at risk of hospital mortality among severely septic patients requiring MV.

The prognostic value of leukocyte apoptosis in patients with severe sepsis at the emergency department

BACKGROUND AND AIMnCell apoptosis in critically ill patients plays a pivotal role in the pathogenesis of sepsis. This study aimed to determine the prognostic value of leukocyte apoptosis in patients with severe sepsis.nnnMETHODSnLeukocyte apoptosis was determined by flow cytometry. The values of annexin V, APO2.7, and 7-amino-actinomycin D (7AAD) for each subtype of leukocyte were analyzed in 87 patients with severe sepsis and 27 controls.nnnRESULTSnThe percentages of apoptosis (APO2.7 [%]) in the leukocyte subsets were significantly higher in the patients with severe sepsis than in the controls. The percentages of APO2.7 in leukocyte apoptosis, APO2.7 in lymphocytes apoptosis, and annexin V+7AAD in monocytes apoptosis were significantly higher in non-survivors than in survivors. Levels of APO2.7 in lymphocytes apoptosis, annexin V+7AAD in monocytes apoptosis, and serum lactate were all independently predictive of mortality.nnnCONCLUSIONnLeukocyte apoptosis is significantly higher in patients with severe sepsis. The percentages of late lymphocyte and monocyte apoptosis may be predictive of outcome in such patients. Aside from serum lactate, APO2.7 level in lymphocyte apoptosis is also a useful predictor of outcome on admission to the emergency department.

Elevated Serum Vascular Cell Adhesion Molecule-1 Is Associated with Septic Encephalopathy in Adult Community-Onset Severe Sepsis Patients

Background and Aim. Septic encephalopathy (SE) is a common complication of severe sepsis. Increased concentrations of circulating soluble adhesion molecules are reported in septic patients. This study aimed to determine whether serum adhesion molecules are associated with SE. Methods. Seventy nontraumatic, nonsurgical adult patients with severe sepsis admitted through ER were evaluated. Serum adhesion molecules were assessed for their relationship with SE, and compared with other clinical predictors and biomarkers. Results. Twenty-three (32.8%) patients had SE. SE group had higher in-hospital mortality (40% versus 11%, P = 0.009) and their sVCAM-1, sICAM-1, and lactate levels on admission were also higher than non-SE group. By stepwise logistic regression model, sVCAM-1, age, and maximum 24-hours SOFA score were independently associated with septic encephalopathy. The AUC analysis of ROC curve of different biomarkers showed that sVCAM-1 is better to predict SE. The sVCAM-1 levels in the SE group were significantly higher than those of the non-SE group at three time periods (Days 1, 4, and 7). Conclusions. Septic encephalopathy implies higher mortality in nontraumatic, nonsurgical patients with severe sepsis. VCAM-1 level on presentation is a more powerful predictor of SE in these patients than lactate concentration and other adhesion molecules on admission.