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1.  The Feasibility of Using CT-Guided ROI for Semiquantifying Striatal Dopamine Transporter Availability in a Hybrid SPECT/CT System 
The Scientific World Journal  2014;2014:879497.
A hybrid SPECT/CT system provides accurate coregistration of functional and morphological images. CT-guided region of interest (ROI) for semiquantifying striatal dopamine transporter (DAT) availability may be a feasible method. We therefore assessed the intra- and interobserver reproducibility of manual SPECT and CT-guided ROI methods and compared their semiquantitative data with data from MRI-guided ROIs. We enrolled twenty-eight patients who underwent Tc-99m TRODAT-1 brain SPECT/CT and brain MRI. ROIs of the striatal, caudate, putamen, and occipital cortex were manually delineated on the SPECT, CT, and MRI. ROIs from CT and MRI were transferred to the coregistered SPECT for semiquantification. The striatal, caudate, and putamen nondisplaceable binding potential (BPND) were calculated. Using CT-guided ROIs had higher intra- and interobserver concordance correlation coefficients, closer Bland-Altman biases to zero, and narrower limits of agreement than using manual SPECT ROIs. The correlation coefficients of striatal, caudate, and putamen BPND were good between manual SPECT and MRI-guided ROI methods and even better between CT-guided and MRI-guided ROI methods. Conclusively, CT-guided ROI delineation for semiquantifying striatal DAT availability in a hybrid SPECT/CT system is highly reproducible, and the semiquantitative data correlate well with data from MRI-guided ROIs.
PMCID: PMC4233671  PMID: 25531005
2.  Clinical characteristics of hyperglycemic crises in patients without a history of diabetes 
Hyperglycemic crises without a history of diabetes have not been well studied. We compared the clinical characteristics of patients with and without a history of diabetes, and evaluated the glycated hemoglobin levels.
Materials and Methods
Consecutive adult patients (aged >18 years) visiting the emergency department (ED) between January 2004 and December 2010 were enrolled if they met the criteria for a hyperglycemic crisis. Patients were separated into those without and those with a history of diabetes. The 30-day mortality was the primary end-point.
We enrolled 295 patients who made 330 visits to the ED. Patients without a history of diabetes made up 24.5% (81/330) of the hyperglycemic crises. Patients without a history of diabetes were more prone than patients with a history of diabetes to be younger and male, and to have better consciousness and renal function, more significant diabetic signs and symptoms (e.g., thirst, polydipsia, polyuria and bodyweight loss), higher blood sugar, and less opportunity of infection and mortality. Most of the patients (93.8%, 76/81) had glycated hemoglobin of ≥6.5%.
The present study delineates the clinical characteristics of patients with hyperglycemic crises, but without a history of diabetes. Most patients had glycated hemoglobin ≥6.5%, which raises the argument of using this biomarker for routine screening of diabetes.
PMCID: PMC4234228  PMID: 25422765
Hyperglycemic crisis; Mortality; New-onset
3.  A Positive Babinski Reflex Predicts Delayed Neuropsychiatric Sequelae in Chinese Patients with Carbon Monoxide Poisoning 
BioMed Research International  2014;2014:814736.
As the human population increased in China, the carbon monoxide is a serious environmental toxin in public health. However, predicting the delayed neuropsychiatric sequelae (DNS) of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of DNS in patients with COP. This study was conducted at four hospitals in China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. DNS was the primary endpoint. A positive Babinski reflex was the independent predictor for DNS: sensitivity = 53.8% (95% confidence interval [CI]: 26.1–79.6), specificity = 88.6% (95% CI: 83.7–92.1), positive predictive value (PPV) = 20.0% (95% CI: 9.1–37.5), and negative predictive value (NPV) = 97.3% (95% CI: 94.0–98.9). The area under the receiver operating characteristic curve = 0.712 (95% CI: 0.544–0.880). A positive Babinski reflex was very memorable, immediately available, and applicable in clinical practice. Even when the sensitivity and PPV of a positive Babinski reflex were unsatisfactory, it had a good specificity and NPV for excluding the risk of DNS. In patients without a positive Babinski reflex, the risk for DNS was only 2.7%. This finding may help physicians make decisions about dispositions for patients with COP.
PMCID: PMC4053277  PMID: 24959589
4.  Use of Staged Molecular Analysis to Determine Causes of Unexplained Central Nervous System Infections 
Emerging Infectious Diseases  2013;19(9):1470-1477.
No agent is implicated in most central nervous system (CNS) infections. To investigate cerebrospinal fluid samples from patients with CNS infections of unknown cause in 1 hospital in Taiwan, we used a staged molecular approach, incorporating techniques including multiplex MassTag PCR, 16S rRNA PCR, DNA microarray, and high-throughput pyrosequencing. We determined the infectious agent for 31 (24%) of 131 previously negative samples. Candidate pathogens were identified for 25 (27%) of 94 unexplained meningitis cases and 6 (16%) of 37 unexplained encephalitis cases. Epstein-Barr virus (18 infections) accounted for most of the identified agents in unexplained meningitis cases, followed by Escherichia coli (5), enterovirus (2), human herpesvirus 2 (1), and Mycobacterium tuberculosis. Herpesviruses were identified in samples from patients with unexplained encephalitis cases, including varicella-zoster virus (3 infections), human herpesvirus 1 (2), and cytomegalovirus (1). Our study confirms the power of multiplex MassTag PCR as a rapid diagnostic tool for identifying pathogens causing unexplained CNS infections.
PMCID: PMC3810931  PMID: 23965845
CNS infections; meningitis; encephalitis; MassTag PCR; 16S rRNA PCR; microarray; pyrosequencing; viruses; bacteria
5.  Geriatric Fever Score: A New Decision Rule for Geriatric Care 
PLoS ONE  2014;9(10):e110927.
Evaluating geriatric patients with fever is time-consuming and challenging. We investigated independent mortality predictors of geriatric patients with fever and developed a prediction rule for emergency care, critical care, and geriatric care physicians to classify patients into mortality risk and disposition groups.
Materials and Methods
Consecutive geriatric patients (≥65 years old) visiting the emergency department (ED) of a university-affiliated medical center between June 1 and July 21, 2010, were enrolled when they met the criteria of fever: a tympanic temperature ≥37.2°C or a baseline temperature elevated ≥1.3°C. Thirty-day mortality was the primary endpoint. Internal validation with bootstrap re-sampling was done.
Three hundred thirty geriatric patients were enrolled. We found three independent mortality predictors: Leukocytosis (WBC >12,000 cells/mm3), Severe coma (GCS ≤ 8), and Thrombocytopenia (platelets <150 103/mm3) (LST). After assigning weights to each predictor, we developed a Geriatric Fever Score that stratifies patients into two mortality-risk and disposition groups: low (4.0%) (95% CI: 2.3–6.9%): a general ward or treatment in the ED then discharge and high (30.3%) (95% CI: 17.4–47.3%): consider the intensive care unit. The area under the curve for the rule was 0.73.
We found that the Geriatric Fever Score is a simple and rapid rule for predicting 30-day mortality and classifying mortality risk and disposition in geriatric patients with fever, although external validation should be performed to confirm its usefulness in other clinical settings. It might help preserve medical resources for patients in greater need.
PMCID: PMC4207798  PMID: 25340811
6.  Long-Term Prognosis of Patients with Carbon Monoxide Poisoning: A Nationwide Cohort Study 
PLoS ONE  2014;9(8):e105503.
Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP[+]).
In this retrospective nationwide cohort study, 441 COP[+] patients and 8820 COP[−] controls (120) from 1999 to 2010 were selected from Taiwan’s National Health Insurance Research Database.
Thirty-seven (8.39%) COP[+] patients and 142 (1.61%) controls died (P<0.0001) during follow-up. Incidence rate ratios (IRR) of death were 5.24 times higher in COP[+] patients than in controls (P<0.0001). The risk of death was particularly high in the first month after COP (IRR: 308.78; 95% confidence interval [CI]: 40.79–2337.56), 1 to 6 months after (IRR: 18.92; 95% CI: 7.69–46.56), and 6–12 months after (IRR: 4.73; 95% CI: 1.02–21.90). After adjusting for age, gender, and selected comorbidities, the hazard ratio of death for COP[+] patients was still 4.097 times higher than for controls. Moreover, older age (≥30 years old), male gender, diabetes mellitus, hypertension, and low income were also independent mortality predictors.
COP significantly increases the risk for long-term mortality. Early follow-up and secondary prevention of death are needed for patients with COP.
PMCID: PMC4148326  PMID: 25167083
7.  Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients 
The Scientific World Journal  2014;2014:694326.
Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography for type 2 diabetic patients taking metformin (MET, n = 18), withdrawing from metformin (wdMET, n = 13), and not taking metformin (noMET, n = 9). Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI-) based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.
PMCID: PMC3982461  PMID: 24782665
8.  Review Analysis of the Association between the Prevalence of Activated Brown Adipose Tissue and Outdoor Temperature 
The Scientific World Journal  2012;2012:793039.
Brown adipose tissue (BAT) is important for regulating body weight. Environmental temperature influences BAT activation. Activated BAT is identifiable using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). 18F-FDG PET/CT scans done between June 2005 and May 2009 in our institution in tropical southern Taiwan and BAT studies from PubMed (2002–2011) were reviewed, and the average outdoor temperatures during the study periods were obtained. A simple linear regression was used to analyze the association between the prevalence of activated BAT (P) and the average outdoor temperature (T). The review analysis for 9 BAT studies (n = 16, 765) showed a significant negative correlation (r = −0.741, P = 0.022) between the prevalence of activated BAT and the average outdoor temperature. The equation of the regression line is P(%) = 6.99 − 0.20 × T  (°C). The prevalence of activated BAT decreased by 1% for each 5°C increase in average outdoor temperature. In a neutral ambient temperature, the prevalence of activated BAT is low and especially rare in the tropics. There is a significant linear negative correlation between the prevalence of activated BAT and the average outdoor temperature.
PMCID: PMC3349155  PMID: 22593707
9.  The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics 
Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low.
18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature.
Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043) and a higher TMA (p = 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016).
Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.
PMCID: PMC3267802  PMID: 22182284
Neoplastic status; BAT; 18F-FDG PET

Results 1-9 (9)