Chih-Min Su

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.

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 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.

Life-threatening cardiotoxicity due to chronic oral phenytoin overdose

Severe cardiac adverse effects are often related to intravenous phenytoin overdose. However, there is no reported cardiotoxicity resulting from oral overdose of phenytoin. We report a patient with post-traumatic epilepsy who received oral phenytoin for five months and developed life-threatening junctional bradycardia, with his serum phenytoin level reaching up to 91 microg/mL. The patient was successfully treated with temporary transvenous pacemaker implantation for his severe bradycardia and hypotension. To our knowledge, our patient had the most serious cardiovascular toxicity ever reported with chronic oral phenytoin overdose. From emergency department (ED) physicians perspective, when a patient with dysrhythmias and cardiovascular collapse is presented to the ED, severe phenytoin overdose should be considered in patients on oral phenytoin with hyperbilirubinemia, hypoalbuminemia, and severe electrolyte imbalance.

The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis

Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy. Methods. Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations. Results. The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (P = 0.009). Conclusion. Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients.

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.

Impact of inflammation and oxidative stress on carotid intima‐media thickness in obstructive sleep apnea patients without metabolic syndrome

Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases, and carotid intima‐media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. This study tested the hypothesis that inflammation and oxidative stress determined carotid IMT in patients with OSA. The carotid IMT, mean systolic and diastolic pressure (night and morning) were significantly higher and the level of thiols and high‐density lipoprotein were significantly lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea index was correlated positively with E‐selectin (r = 0.222, P = 0.014), total cholesterol (r = 0.185, P = 0.042), low‐density lipoprotein (r = 0.264, P = 0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high‐density lipoprotein level (r = −0.203, P = 0.025) in the 121 patients with OSA. In OSA subjects, multiple linear regression analysis revealed that age, systolic blood pressure and intercellular cell adhesion molecule‐1 level associated independently with carotid IMT. Besides both age and systolic blood pressure, our study demonstrated that intercellular cell adhesion molecule‐1 level was associated significantly with carotid IMT in those patients who had OSA but without metabolic syndrome.

The experiences of non-operative treatment in patients with bacterial brain abscess.

Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.