Nai-Wen Tsai

The value of serial plasma nuclear and mitochondrial DNA levels in patients with acute ischemic stroke

BACKGROUND Elevated circulating cell-free DNA in plasma is reported in several critical diseases. This study hypothesized that since plasma nuclear and mitochondrial DNA substantially increase after acute ischemic stroke and decrease thereafter, their levels can predict treatment outcomes. METHODS Plasma nuclear and mitochondrial DNA levels were serially examined in 50 acute ischemic stroke patients and in 50 at risk control subjects during the study period. RESULTS Levels of plasma nuclear and mitochondrial DNA in patients with acute ischemic stroke were significantly higher than those in the controls (p<0.05). Elevated circulating nuclear DNA in plasma persisted until one month after the acute stroke. Levels of plasma nuclear DNA positively correlated to the clinical severity of stroke as reflected by the National Institutes of Health Stroke Scale. CONCLUSION Levels of plasma nuclear and mitochondrial DNA reflect the severity of cerebral damage after acute cerebral infarction. Assay of plasma DNA levels can be considered a neuro-pathologic marker of patients with acute ischemic stroke.

Post-neurosurgical nosocomial bacterial meningitis in adults: microbiology, clinical features, and outcomes

The clinical data of 62 adult patients who suffered post-neurosurgical nosocomial bacterial meningitis, retrospectively collected over a 16-year period, were studied. Cases were divided into two groups based on the date of presentation, the first period being 1986-1993 and the second 1994-2001. Fever and progressive consciousness disturbance were the most consistent clinical features - signs that may also be attributed to other postoperative neurosurgical problems. The common pathogens included Staphylococcus aureus, coagulase negative Staphylococcus, Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. An increase in polymicrobial infections and multi-antibiotic resistance during the second period was identified. In the first half of the study, mortality was 22%, and in the second half 36%. Adult post-neurosurgical nosocomial bacterial meningitis has become an important clinical problem. The choice of appropriate empirical antibiotics is challenging and must be guided by an awareness of the relative frequency of various pathogens and the increasing incidence of resistant strains. Although high mortality rates may, in part, be related to the primary brain pathology, early diagnosis and the timely use of antibiotics based on antimicrobial susceptibility testing are essential for survival.

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.

Factors predictive of fatality in massive middle cerebral artery territory infarction and clinical experience of decompressive hemicraniectomy.

To determine the factors predictive of fatality in massive middle cerebral artery (MCA) territory infarction and outcome of decompressive hemicraniectomy, 62 patients who were retrospectively verified with first event massive MCA infarctions were enrolled in this study. Amongst them, 21 received decompressive hemicraniectomy during hospitalization. Clinical data between early and late hemicraniectomy groups were also compared. Significant deterioration occurred in 40 cases, 21 of whom received decompressive hemicraniectomy. The other 19 received conservative treatment. The mortality rate of these 40 cases between decompressive hemicraniectomy and conservative treatment was 29% (six of 21) and 42% (eight of 19), respectively. Factors that predicted fatalities in our massive MCA infarction patients with or without decompressive hemicraniectomy were total scores of baseline GCS at the time of admission, associated with coronary artery diseases, and significant deterioration during hospitalization. This study confirms the lifesaving procedure of hemicraniectomy that prevents death in patients deteriorating because of cerebral edema after infarction, although it may produce severe disability with an unacceptably poor quality of life in survival. Despite high mortality and morbidity, decompressive hemicraniectomy to prevent cerebral herniation when significant deterioration is demonstrated are essential for maximizing the potential for survival.

White matter damage and systemic inflammation in obstructive sleep apnea.

STUDY OBJECTIVES To evaluate white matter integrity in patients with obstructive sleep apnea (OSA) using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. DESIGN Cross-sectional study. SETTING One tertiary medical center research institute. PATIENTS OR PARTICIPANTS Twenty patients with severe OSA (apnea-hypopnea index [AHI] > 30, 18 men and 2 women) and 14 healthy volunteers (AHI < 5, 11 men and 3 women). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients with severe OSA and healthy volunteers underwent polysomnography to determine the severity of sleep apnea, and DTI scanning to determine fiber integrity. Early or late phase changes in leukocyte apoptosis and its subsets were determined by flow cytometry. DTI-related indices (including fractional anisotropy [FA], axial diffusivity [AD], radial diffusivity [RD], and mean diffusivity [MD]) were derived from DTI. The FA maps were compared using voxel-based statistics to determine differences between the severe OSA and control groups. The differences in DTI indices, clinical severity, and leukocyte apoptosis were correlated after adjusting for age, sex, body mass index, and systolic blood pressure. Exploratory group-wise comparison between the two groups revealed that patients with OSA exhibited low FA accomplished by high RD in several brain locations, without any differences in AD and MD. The FA values were negatively correlated with clinical disease severity and leukocyte early apoptosis. CONCLUSIONS Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in OSA.

Spinal epidural abscess in adults caused by Staphylococcus aureus: Clinical characteristics and prognostic factors

OBJECTIVE Spinal epidural abscess (SEA) is a devastating infectious disease, which may result in neurologic sequelae. Staphylococcus (S.) aureus is a common pathogen of SEA. Here, we analyzed the clinical characteristics and laboratory data of adult patients with S. aureus SEA and compared the clinical characteristics of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections. METHODS Between 2003 and 2008, we collected data regarding 29 adult cases of S. aureus SEA and analyzed the clinical presentations, magnetic resonance (MR) imaging features, therapeutic outcome, and prognostic factors. Antibiotic susceptibility test results of 11 implicated MRSA strains were also further analyzed. RESULTS We identified 17 MSSA strains and 12 MRSA strains. Lumbar and lumbosacral spine segments were the most commonly involved segments. All 29 patients had back pain. Other findings included sensory abnormalities (25), motor weakness (21), fever (16), bladder dysfunction (16), and altered consciousness (3). Disease onset at admission was acute in 6 cases and chronic in 23. The stages of disease severity were early stage in 9 and late stage in 20. After therapy, 21 patients had a good prognosis and 8 had a poor prognosis. Significant prognostic factors included older age (>70years), presence of diabetes mellitus, adrenal insufficiency, and MRSA infection. The prognosis alone was clinically different between patients with MSSA and MRSA infections. CONCLUSIONS Patients with localized back pain, particularly those with a fever and compromised immune system, should undergo MR imaging to ensure an early diagnosis and management.

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.

Prediction, clinical characteristics and prognosis of intracerebral hemorrhage in hepatocellular carcinoma patients with intracerebral metastasis

The clinical characteristics of intracerebral hemorrhage (ICH) in hepatocellular carcinoma (HCC) patients with intracerebral metastasis (IcM) have not been reported on extensively. We compared the clinical characteristics between patients with ICH (w-ICH, 18 patients) and without ICH (wo-ICH, 24 patients) in HCC patients with IcM. Using multivariate logistic regression, only habitual alcohol consumption is a significant predictor of ICH in HCC patients with IcM (adjusted odds ratio [OR]=4.7, 95% CI=1.26-17.71, p=0.022). Patients with ICH also had lower Glasgow Coma Scale scores at the time of admission (p=0.032) and lower incidence of infratentorial metastasis (p=0.014). Using correlation analysis, only blood platelet count on admission was positively correlated with survival duration after the diagnosis of IcM in the wo-ICH group (p=0.000) but not in the w-ICH group.