Ben-Chung Cheng

Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room

Background and aimThe sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED).MethodsSixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain reaction assay using primers for the human β-hemoglobin and ND2 gene. The patients’ clinical and laboratory data on admission were analyzed.ResultsThe median plasma nuclear and mitochondria DNA levels for severe septic patients on admission were significantly higher than those of the controls. The mean plasma nuclear DNA level on admission correlated with lactate concentration (γ = 0.36, p = 0.003) and plasma mitochondrial DNA on admission (γ = 0.708, p < 0.001). Significant prognostic factors for fatality included mechanical ventilation within the first 24 hours (p = 0.013), mean sequential organ failure assessment (SOFA) score on admission (p = 0.04), serum lactate (p < 0.001), and both plasma nuclear and mitochondrial DNA on admission (p < 0.001). Plasma mitochondrial DNA was an independent predictor of fatality by stepwise logistic regression such that an increase by one ng/mL in level would increase fatality rate by 0.7%.ConclusionPlasma DNA has potential use for predicting outcome in septic patients arriving at the emergency room. Plasma mitochondrial DNA level on admission is a more powerful predictor than lactate concentration or SOFA scores on admission.

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.

Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage

BackgroundHydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital.MethodsOne hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score.ResultsHydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without.ConclusionsThe presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization.

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

PURPOSE Fall-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. METHODS This prospective study enrolled 100 adult idiopathic PD patients. Stepwise logistic regressions were used to evaluate the relationships between clinical factors and fall-related fracture. RESULTS Falls 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%). DISCUSSION Higher 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

OBJECTIVES This 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). METHODS This 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. RESULTS The 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. CONCLUSIONS The 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.

Predictive Factors and Long-Term Outcome of Respiratory Failure after Guillain-Barré Syndrome

Objective:To analyze predictive factors and long-term recovery in patients with Guillain-Barré syndrome (GBS) who are in need of mechanical ventilation. Methods:In this 15-year retrospective study, 77 adult patients were identified with GBS. A comparison was made between the clinical data from patients who required mechanical ventilation and those who did not. Furthermore, the therapeutic outcomes of those 25 patients in need of mechanical ventilation during hospitalization at 1 year were determined using a modified Barthel index. A score below 12 was defined as a poor outcome, whereas a score of 12 or more was good. Results:The study revealed 32% of patients (25/77) in need of respiratory support during hospitalization. At a follow-up of 1 year among the 25 ventilated patients, 7 patients (28%) had normal or minor signs and symptoms, 6 had unassisted gait, 3 had assisted gait, 6 were wheelchair- or bed-bound, and 3 died. The cause of death was septicemia with septic shock in all 3 cases. Factors that predict respiratory failure in the study GBS patients were disability grade on admission and areflexia. Those ventilated patients who had low maximal inspiratory pressure (PImax) (<14.5 cmH2O) and maximal expiratory pressure (PEmax) (<13.5 cmH2O) values at the time of intubation and the presence of complications after mechanical ventilation inevitably had worse outcomes than those who had not. Conclusion:If low values of PImax and PEmax at intubation were detected, aggressive respiratory management, which might include tracheostomy to allow more efficient bronchial clearing, and prevention of complications caused by prolonged course of mechanical ventilation are essential to maximize the potential for survival.

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 (n = 55) and non-statin (n = 65) 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 (P < 0.001). Plasma Ox-LDL level was significantly reduced in the statin group on day 7 and day 30 compared to the non-statin group (P < 0.01). 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.

The Role of Serial Oxidative Stress Levels in Acute Traumatic Brain Injury and as Predictors of Outcome

BACKGROUND Oxidative stress is thought to participate in the pathobiology of secondary brain injury after acute traumatic brain injury (TBI). This study posits that oxidative stress levels in acute TBI are predictive of outcome. METHODS Two hundred and twenty-nine blood samples from 88 patients admitted within 24 hours after TBI were obtained on admission and on days 4 and 7. Serial plasma oxidative level and antioxidant were examined in 88 patients with acute TBI and 27 control individuals. RESULTS Compared with controls, patients with TBI had significantly increased serum glutathione (GSH) levels on presentation and significantly decreased erythrocyte superoxide dismutase levels. Outcome was assessed on discharge using the Glasgow Outcome Scale. Serum GSH and erythrocyte superoxide dismutase levels were significantly higher in the good outcome group than in the poor outcome group on day 1 (P = 0.008 and P = 0.026, respectively). In the logistic regression analysis, only motor deficits and GSH levels on presentation were independently associated with outcome. A GSH cutoff value of 1.106 μmol/L on presentation was associated with good outcome in patients with acute TBI. CONCLUSIONS Quantifying biomarkers of oxidative stress and antioxidant status of serum correlate with trauma severity and may be used to predict outcomes after TBI. Higher serum GSH levels on admission are associated with better outcome.

Serum adhesion molecules as predictors of bacteremia in adult severe sepsis patients at the emergency department.

BACKGROUND Bacteremia is a severe bacterial infection with significant mortality. Clinical parameters that reliably predict it are less elucidated. We assessed the potential of serum adhesion molecules for predicting bacteremia and compare it with current available infection biomarkers to determine a more timely predictor of adult severe sepsis patients on admission to the emergency department (ED). METHODS Sixty-seven consecutive non-traumatic, non-surgical adult patients with severe sepsis admitted to the ED were evaluated. Serum samples were collected and assessed while serum adhesion molecules were analyzed. RESULTS Thirty-one (46.2%) study patients had bacteremia. There were significant differences in both sICAM-1 and sE-selectin on admission between bacteremic and non-bacteremic patients. By stepwise logistic regression model, only sE-selectin was independently associated with bacteremia and any 1 ng/ml increase in level increased bacteremia rate by 0.8%. The cut-off value of sE-selectin level for predicting bacteremia was 117 ng/ml (84% sensitivity and 69% specificity). CONCLUSION Although serum cell adhesion markers are not specific for predicting bacteremia in septic patients, higher mean serum cell adhesion molecules levels on admission may imply both more severe infection and presence of bacteremia. Assay of serum adhesion molecules may be added as an infectious marker among the panel of bacteremic parameters in clinical practice, especially since early diagnosis and prompt antimicrobial therapy are essentially for survival.