Wan-Chen Tsai

Acute/subacute cerebral infarction (ASCI) in HIV-negative adults with cryptococcal meningoencephalitis (CM): a MRI-based follow-up study and a clinical comparison to HIV-negative CM adults without ASCI

BackgroundAcute/subacute cerebral infarction (ASCI) in HIV-negative cryptococcal meningoencephalitis (CM) adults has rarely been examined by a series of MRI-based follow-up study. We studied a series of MRI follow-up study of CM adults and compared the clinical characters of those with ASCI and those without ASCI.MethodsThe clinical characteristics and a series of brain MRI findings of seven CM adults with ASCI were enrolled for analysis. The clinical characteristics of another 30 HIV-negative CM adults who did not have ASCI were also included for a comparative analysis.ResultsThe seven HIV-negative CM adults with ASCI were four men and three women, aged 46-78 years. Lacunar infarction was the type of ASCI, and 86% (6/7) of the ACSI were multiple infarctions distributed in both the anterior and posterior cerebrovascular territories. The seven CM patients with ASCI were significantly older and had a higher rate of DM and previous stroke than the other 30 CM adults without ASCI. They also had a higher incidence of consciousness disturbance at presentation and had a poor prognosis.ConclusionASCI was found in 18.9% (7/37) of HIV-negative CM adults. Serial MRI follow-up studies may allow a better delineation of ASCI in this specific group of infectious disease and multiple lacunar infarctions was the most common type. Older in age and presence of DM and previous stroke were the significant underlying conditions. CM patients with ASCI also had a poor therapeutic outcome.

Thermal resistance and reliability of low-cost high-power LED packages under WHTOL test

The high-power Light Emitting Diode (LED) can be potentially used for general lighting to alleviate the global warming problem. However, the LED issues, associated with high cost, high junction temperature, low luminous efficiency, and low reliability, have to be resolved before becoming realized. Featuring low-junction-temperature and low-cost design, a novel high-power COP (Chip-on-Plate) LED package is proposed and its reliability under wet high temperature operation life (WHTOL) test is evaluated. The WHTOL test is with the condition of 85degC/85%RH and 350 mA (power=1.22 W) of forward current for 1008 hrs, specified in JESD22 Method A101-B. First of all, the thermal behaviors of the COP package are investigated by experimental measurement (with LED junction temperature tester and thermal couples), a thermal resistance circuit (TRC) method and a finite element method (FEM). The junction temperature (Tj) and surface temperature of the COP package are measured by the junction temperature tester and thermal couples, respectively. Furthermore, the reliability under WHTOL test is carried out. The results show that all COP packages with phosphorus in the silicone encapsulant failed after 309 hrs at WHTOL test, but all those without phosphorus passed for 1008 hrs. The failure sites are located at aluminum wire debonding to the chip and copper pad of the substrate. For the passing packages, their junction to air thermal resistances increase with the time of WHTOL by up to 12degC/W. This is due to the decrease of the thermal conductivity of the die attach, resulting from the moisture absorption. The natural and forced convections in the chamber for WHTOL test give the same the junction-to-aluminum substrate thermal resistance, but different chip junction temperatures with a 19degC difference, which might result in different reliability data. Therefore, the standard test of WHTOL should specify flow conditions in the test chamber.

Determination of LED die strength

LED (Light Emitting Diode), converting the electron current into the light through the p-n junction of semiconductor diodes, has recently gained popularity worldwide. The high-power LEDs are found in a number of applications to high-volume consumer markets, such as illumination, signaling, screen backlights, automotives and so on. In these applications, the high-power LED packages would be subjected to mechanical, thermal, and environmental loadings during manufacturing processes and services. The strength of LED dies, cut from wafers, has to be determined for the design need in order to assure good reliability of the packages in manufacturing and service. The objective of this study is to determine high-power LED die strength with size of 1 times 1 times 0.1 mm by point-load test (PLT) and line-load test (LLT) associated with a plate-on-elastic-foundation configuration. The finite element analysis and the related stress formulation are used to correlate the failure force of the tests to die strength. It is found that the good consistency of the strength data (~1.3 GPa) with a minor scatter from both the point- and line-load tests is for the specimens failed on chip surfaces, but not for the ones (-1.2 GPa and -0.6 GPa, respectively) failed on the ground surfaces. The inconsistency of strength data from both tests for failure on ground surfaces is found due to edge chipping, observed by scanning electron microscopy. As a result, it can be confirmed that the LED die strength has been successfully determined by these feasible and reliable test methods.

Epidemiologic trend of adult bacterial meningitis in southern Taiwan (2006–2015)

The purpose of this study is to analyze recent epidemiologic trend of adult bacterial meningitis (ABM) in Taiwan. The clinical features, laboratory data and therapeutic outcomes of 157 patients with ABM from 2006-2015 were analyzed. The results were compared with those of our previous two epidemiologic studies of ABM (1st study: 202 cases, January 1986-June 1999; 2nd study: 181 cases, July 1999-December 2005). Of the 157 patients with ABM, 96 were men and 61 women, and 68.2% (107/157) of them had a postneurosurgical state as the underlying condition. Monomicrobial infections and mixed infections were found in 92.4% (145/157) and 7.6% (12/145) of the cases, respectively. Of the implicated pathogens of monomicrobial infections, staphylococcal species were the most common, accounting for 27.6% (40/145) of them and Klebsiella species were the second common accounting for 13.8% (20/145) of them. The other common Gram-negative pathogens were Pseudomonas species and Acinetobacter species, accounting for 10.3% (15/145) and 7.6% (11/145), respectively. The overall mortality rate was 25.5% (40/157), and septic shock and liver cirrhosis were significant prognostic factors. This study revealed a change in the epidemiologic trend of ABM and the study results may offer important information for clinicians managing patients with ABM.

Clinical characteristics, pathogens implicated and therapeutic outcomes of mixed infection in adult bacterial meningitis

We reviewed retrospectively the data for adult patients with bacterial meningitis over a period of 10.5 years in our hospital. The clinical characteristics and laboratory data of the 21 cases (52 strains) of mixed infection were analyzed. Two hundred and fifteen cases of single pathogen adult bacterial meningitis (ABM) were also included for comparison. Post‐neurosurgical type of ABM was presented in 86% of the mixed infection group. Brain abscess was found in three patients. Fourteen patients survived and seven cases died. The analysis showed a statistical significance for the mixed infection group having a higher rate of nosocomially‐acquired, post‐neurosurgical condition, hydrocephalus, and lower level of cerebrospinal fluid white cell count, protein and lactate than the single pathogen group. Logistic regression analysis showed the independent factor of “hydrocephalus” (p = 0.002). Presence of hydrocephalus is a significant neuroimaging feature when compared with the single pathogen group. As compared with the previous study results of mixed infection in ABM, the present study showed a change of pathogens implicated of increasing Pseudomonas spp. and Acinetobacter spp. infections, and an emergence of anaerobic pathogens. All these changes deserve special attention because of the need for an appropriate choice of empirical antibiotics and choice of culture method.

Predictors and long-term outcome of seizures in human immuno-deficiency virus (HIV)-negative cryptococcal meningitis

BackgroundSeizures are one of the most important neurologic complications of human immuno-deficiency virus (HIV)-negative cryptococcal meningitis. A better understanding of the risk associated factors can help predict those who will require treatment.MethodsThis 22-year retrospective study enrolled 180 patients. Prognostic variables independently associated with seizures or fatality were analyzed using stepwise logistic regression.ResultsTwenty-eight patients with HIV-negative cryptococcal meningitis had seizures, including 13 with early seizures and 15 with late seizures. The mean time interval from HIV-negative cryptococcal meningitis to first seizure in the early and late seizure groups were 1.5 and 51.4 days, respectively. Nine out of the 28 cases (32%) occurred within 24 hours of presentation. The overall mortality rate was 54% (15/28) and two patients progressed to epilepsy.ConclusionsPatients with seizure have worse outcomes and longer hospitalization. Most first seizures occur within one year after the diagnosis of HIV-negative cryptococcal meningitis.

Effects of antiepileptic drugs on thyroid hormone function in epilepsy patients

PURPOSE Patients with epilepsy are frequently required to take antiepileptic drugs (AEDs) for a long period of time. Many studies have shown that AEDs have a negative influence on endocrine function including the thyroid gland, however the risk factors for the development of low thyroid function in these patients are unclear. This study aimed to determine the potential risk factors of low thyroid function in patients with epilepsy. METHOD This was a cross-sectional study including 298 patients with epilepsy. Patients with previous thyroid disease were excluded. Epidemiologic data, type of epilepsy, etiology, the age of seizure onset, duration of epilepsy, intractable epilepsy, and number and dosage of AEDs were recorded. Levels of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured. RESULTS Fifty-two of the 298 (17.4%) patients had low fT4. Older age (P=0.004), female sex (P=0.014), longer duration of epilepsy (P=0.001), and intractable epilepsy (P=0.009) were significantly associated with low fT4. Regarding individual AEDs, carbamazepine (30.1%), topiramate (28.6%), and levetiracetam (24.3%) were significantly associated with the presence of low fT4. After stepwise logistic regression of all significant variables, female sex, older age, three or more AEDs, and carbamazepine were independent risk factors for low fT4. CONCLUSIONS Female patients with epilepsy and an older age, AED polytherapy, and carbamazepine treatment had a higher risk of low fT4. Thyroid function in these patients should be monitored closely.

Drug interaction between valproic acid and carbapenems in patients with epileptic seizures

Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA. Fifty‐four adult patients who were treated with VPA for epileptic seizures concomitant with carbapenems for the treatment of infections were evaluated in this study. Serum VPA levels were measured before and during combination therapy with VPA and carbapenems, and the change in serum VPA levels was calculated. The risk factors related to the decrease in serum VPA levels and clinical outcomes were evaluated. Our results show that VPA concentrations were reduced to subtherapeutic levels after the introduction of carbapenems. The reduction in VPA concentrations was found within 24 hours of the start of treatment with carbapenems. VPA levels continuously declined while the combination of treatments was used, which aggravated epileptic seizures in 48% of the patients. Renal disease and enzyme‐inducing AEDs were risk factors that contributed to the severity of reduced serum VPA levels during combined treatment with carbapenems. This study suggests that clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA.

The clinical characteristics of adult bacterial meningitis caused by non-Pseudomonas (Ps.) aeruginosa Pseudomonas species: A clinical comparison with Ps. aeruginosa meningitis

Adult bacterial meningitis (ABM) caused by non‐Pseudomonas (Ps.) aeruginosa Pseudomonas (NPAP) species infection has rarely been reported. The clinical characteristics of 52 cases of Pseudomonas ABM (11 NPAP‐ and 41 Ps. aeruginosa‐related meningitis) collected during a 30‐year study period (1986–2015) were included. Eleven cases of NPAP ABM were identified in the literature, and their clinical data were also collected. Therefore, a total of 22 NPAP ABM cases were enrolled. The clinical characteristics of the NPAP ABM and Ps. aeruginosa ABM groups were compared. Of the implicated NPAP strains, Ps. putida and Ps. stutzeri were the most common (7 cases each), followed by Ps. mendocina in 4, Ps. fluorescens in 1, Ps. fulva in 1, Ps. alcaligenes in 1, and Ps. mosselii in 1. Of the 22 cases, 50% (11/22) had an underlying postneurosurgical state. Fever (77.3%, 17/22) and altered consciousness (45.5%, 10/22) were the most common clinical presentations. Antibiotic non‐susceptibility was found in 3 strains of Ps. putida and 1 Ps. mosselii strain. Compared to the patients with Ps. aeruginosa ABM, those with NPAP ABM had a higher incidence of spontaneous infections and a better survival rate. In conclusion, although Ps. putida, Ps. stutzeri and Ps. mendocina were the major implicated strains of NPAP ABM, the clinical characteristics of this specific group of ABM demonstrated marked heterogeneity. Even though the cases with NPAP ABM had better therapeutic results than those with Ps. aeruginosa ABM, further large‐scale studies are needed to better delineate this specific group of ABM.

Risk of Microangiopathy in Patients with Epilepsy under Long-term Antiepileptic Drug Therapy

Background Long-term antiepileptic drug (AED) therapy is considered a risk factor of atherosclerosis. Furthermore, the duration of therapy contributes to acceleration of large-vessel atherosclerosis. Therefore, in this study, we tested the hypothesis that long-term AED therapy plays a crucial role in the pathogenesis of microangiopathy in patients with epilepsy. Methods We recruited 120 patients with epilepsy (age, 18–60 years) and 40 healthy controls. Optical coherence tomography (OCT) was used to measure the central macular thickness and diameters of the retinal artery and vein to evaluate atherosclerotic retinopathy; microalbumin and creatinine levels in urine were assessed to evaluate atherosclerotic nephropathy. In addition, high-sensitivity C-reactive protein (hs-CRP), lipid profiles, homocysteine, folate, uric acid, and body mass index were determined. Results The ratio of urine albumin to creatine and OCT findings showed that patients with epilepsy had higher abnormal microalbuminuria and narrowing retinal vein diameters, respectively. Multiple linear regression analysis showed that increased triglyceride and hs-CRP levels might contribute to microalbuminuria. In addition, serum creatinine, duration of AED therapy, enzyme-inducing AED therapy, and duration of enzyme-inducing AED therapy were candidate risk factors for retinal vein narrowing. Conclusion Patients with epilepsy are at a higher risk for microangiopathy presented as retinopathy and nephropathy. Long-term AED therapy, particularly with enzyme-inducing AEDs; high triglyceride levels, and inflammatory processes play an important role in the development of microangiopathy in patients with epilepsy.