Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute.

Objectives: Accelerator-based stereotactic radiosurgery (SRS) is a noninvasive and effective treatment modality widely used for benign brain tumors. This study aims to report 20-year treatment outcomes in our institute. Materials and Methods: From May 2001 to December 2020, 127 patients treated with LINAC-based single-fraction SRS for their benign brain lesions were included. A neurosurgeon and two radiation oncologists retrospectively reviewed all data. Computed tomography (CT) simulation was performed after head-frame fixation under local anesthesia. All planning CT images were co-registered and fused with gadolinium-enhanced magnetic resonance imaging taken within 3 months for lesions targeting and critical organs delineation. The marginal dose was prescribed at 60%-90% isodose lines, respectively, to cover ≥95% planning target volume. Outcome evaluations included clinical tumor control rate (TCR), defined as the need for salvage therapy, and radiological response, defined as no enlargement of >2 cm in the maximal diameter. Overall survival (OS) and adverse reaction (defined according to CTCAE 5.0) were also analyzed. Results: The present study included 76 female and 51 male patients for analysis. The median age was 59 years (range, 20-88 years). Their diagnoses were vestibular schwannoma (VS, n = 54), nonvestibular cranial nerve schwannoma (n = 6), meningioma (n = 50), and pituitary adenoma (n = 17). Totally 136 lesions were treated in a single fraction, predominantly skull base tumors, accounting for 69.1%. Median and mean follow-up duration was 49 and 61 months (range, 1-214 months), Overall TCR was 92.9%. The 5-year disease-specific TCR for VS, nonvestibular schwannoma, meningioma, and pituitary adenoma were 97.4%, 91.7%, 93.8%, and 83.3%. Salvage therapy was indicated for eight patients at 4-110 months after SRS. Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 evaluable patients was 94.6% (shrinkage, 28.8%; stable, 65.8%). OS was 96.1% without treatment-related mortality. One patient with post-SRS cranial nerve injury (0.8%, involving the trigeminal nerve, grade 2 toxicities). No grade 3-4 acute or late toxicity was found. Conclusion: Our results suggested that LINAC-based SRS effectively controls tumor growth and tumor-related neurological symptoms for patients with benign brain tumors. SRS is less aggressive, associated with low neurological morbidity and no mortality. Continuous follow-up is indicated to conclude longer outcomes.

End-of-Life Decisions of Intracranial Hemorrhage Patients Successfully Weaned From Prolonged Mechanical Ventilation.

Factors related to the end-of-life decisions of patients with intracranial hemorrhage who were successfully weaned from prolonged mechanical ventilation remain unclear. This study aimed to evaluate factors that influence the end-of-life decisions of these patients. METHODS: This retrospective study examined patients with intracranial hemorrhage successfully weaned from prolonged mechanical ventilation between January 2012 and December 2017. The following data was collected and analyzed: age, gender, comorbidities, Glasgow Coma Scale scores, receipt or non-receipt of intracranial hemorrhage surgery, discharge status, and end-of-life decisions. RESULTS: In total, 91 patients with intracranial hemorrhage were successfully weaned from prolonged mechanical ventilation. The families of 62 (68.1%) patients signed the do-not-resuscitate order. A Glasgow Coma Scale score of ≥10 at discharge from the respiratory care center and zero comorbidities were the influencing factors between patients whose do-not-resuscitate orders were signed and those whose orders were not signed. Patients with intracranial hemorrhage successfully weaned from prolonged mechanical ventilation had chronic kidney disease comorbidity and Glasgow Coma Scale score of <7 on admission to respiratory care center with a general ward mortality rate of 83.3%. CONCLUSIONS: The families of intracranial hemorrhage patients with multiple comorbidities and higher neurologic impairment after successful weaning from the ventilator believed that palliative therapy would provide a greater benefit. Patients with intracranial hemorrhage successfully weaned from prolonged mechanical ventilation with chronic kidney disease comorbidity and Glasgow Coma Scale score of <7 on admission to respiratory care center are candidates for the consideration of hospice care with ventilator withdrawal.

Caffeine Inhibits Growth of Temozolomide-Treated Glioma via Increasing Autophagy and Apoptosis but Not via Modulating Hypoxia, Angiogenesis, or Endoplasmic Reticulum Stress in Rats.

Thirty rats with glioma were divided into control group, temozolomide (TMZ) group (TMZ 30 mg/kg once daily for 5 day), and TMZ plus Caffeine group (TMZ 30 mg/kg once daily for 5 day and caffeine 100 mg/kg once daily for 2 weeks). The relative tumor fold and expression of hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), neuropilin-1 (NRP-1), CCAAT/enhancer-binding protein homologous protein (CHOP), LC-3A/B, apoptosis-inducing factor-1 (AIF-1), and cleaved caspase three were compared. The relative tumor fold of TMZ plus Caffeine group was lower significantly than that of TMZ group at day 14. HIF-1α, VEGF, NRP-1, and CHOP expressions were not significantly different in the three groups. The LC-3A/B expression of TMZ plus Caffeine group was higher significantly than that of the control group and TMZ group. The AIF expressions of TMZ group and TMZ plus Caffeine group were higher significantly than that of the control group. The caspase-3 expression of TMZ plus Caffeine group was higher significantly than that of the control group and TMZ group. In conclusions, the inhibitory effect of caffeine on TMZ-treated glioma might be associated with increasing expressions of autophagy- and apoptosis-related genes.

Blockage of Autophagy Increases Timosaponin AIII-Induced Apoptosis of Glioma Cells In Vitro and In Vivo.

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma.

Overexpression of Lipocalin-2 Inhibits Proliferation and Invasiveness of Human Glioblastoma Multiforme Cells by Activating ERK Targeting Cathepsin D Expression.

Lipocalin-2 (LCN2) exhibits pro- and anti-carcinogenic effects in several cancers, but its role in the progression of glioblastoma multiforme (GBM) remains unclear. This study aims to elucidate the effect of LCN2 in human GBM cell, and the mechanism underlying its effects on GBM malignant progression. We observed that LCN2 expression was significantly lower in GBM than in normal tissues and was associated with poorer GBM patient survival. LCN2-overexpressing GBM cells showed significantly reduced proliferation and migration/invasion abilities. Human protease antibody array analysis showed that the expression of cathepsin D (CTSD) protein and mRNA was lower in LCN2-overexpressing GBM cells than in controls. Higher CTSD expression was observed in GBM tumors than in normal tissues, and higher CTSD expression was associated with poorer overall and disease-free survival. LCN2-overexpressing GBM cells exhibited increased ERK phosphorylation. Treatment of these cells with a MEK inhibitor (U0126) restored CTSD expression, cell migration, and cell invasiveness. In conclusion, LCN2 might be serving as a prognostic marker and promising anti-proliferative and anti-metastatic target for treating GBM.

The Long-Term Survival of Intracranial Hemorrhage Patients Successfully Weaned from Prolonged Mechanical Ventilation.

BACKGROUND: Ninety-one intracranial hemorrhage prolonged mechanical ventilation patients were successfully weaned from the ventilator. No article had discussed the factors related to 1-year survival in successfully weaned prolonged mechanical ventilation patients with intracranial hemorrhage. This study aimed to evaluate the factors influencing the one-year survival of successfully weaned intracranial hemorrhage prolonged mechanical ventilation patients. The identification of patients with a poor long-term prognosis could guide long-term care decisions after discharge in such patients. PATIENTS AND METHODS: We performed this retrospective study on the respiratory care center of Dalin Tzu Chi hospital and enrolled all successfully weaned intracranial hemorrhage prolonged mechanical ventilation patients between 1 January 2012 and 31 December 2017. We analyzed data including age, gender, comorbidities, intracranial hemorrhage type, spontaneous or traumatic intracranial hemorrhage, location of intracerebral hemorrhage, presence or not of an intraventricular hemorrhage, Glasgow Coma Scale, receipt or not of intracranial hemorrhage surgery, receipt or not of tracheostomy, long-term survival, and end-of-life decisions. RESULTS: We had long-term follow-up data on 69 of these successfully weaned intracranial hemorrhage prolonged mechanical ventilation patients. The 1-year survival rate of successfully weaned patients was 43.5%. The factors unrelated to the 1-year survival rate were comorbidities, intracranial hemorrhage type, spontaneous or traumatic intracranial hemorrhage, location of the intracerebral hemorrhage, presence or not of an intraventricular hemorrhage, intracranial hemorrhage surgery, and tracheostomy. Four factors were independently associated with the 1-year survival rate of these patients: Glasgow Coma Scale score at discharge from the respiratory care center, age ≥ 65 years, signed do-not-resuscitate and do-not-intubate orders, and the absence of comorbidity. CONCLUSION: This study emphasizes an important key factor in terms of the survival of successfully weaned intracranial hemorrhage prolonged mechanical ventilation patients. The patient's Glasgow Coma Scale score at discharge from the respiratory care center is an important predictor of outcomes. These results can help physician better plan the clinical course for intracranial hemorrhage prolonged mechanical ventilation patients.

FDG PET/CT of Benign Psammomatous Meningioma Effacing the Medulla.

ABSTRACT: A 62-year-old woman had progressively developing throbbing right neck pain for 1 year. The pain radiated to the right suboccipital area, sometimes accompanied by breathlessness. To rule out cancer, patient received FDG PET/CT, which showed an intraspinal cord intense FDG-avid calcified mass at the level of the first cervical spine, mimicking malignancy. MRI showed it effacing the medulla; surgery is probably a challenge. She received laminectomy with tumor removal; pathology showed psammomatous meningioma, World Health Organization grade I. This case suggests that benign spinal cord psammomatous meningioma with calcification may show high FDG uptake, mimicking malignancy.

Effects of Cinnamaldehyde on the Viability and Expression of Chemokine Receptor Genes in Temozolomide-treated Glioma Cells.

BACKGROUND/AIM: The effects of cinnamaldehyde on glioma are still unclear. We aimed to investigate the effects of cinnamaldehyde on the viability and expression of chemokine receptors CXCR4 and CXCR7 in temozolomide (TMZ)-treated glioma cells. MATERIALS AND METHODS: Cell viability and CXCR4 and CXCR7 expression were measured by western blotting at 72 h after treatment with various concentrations of cinnamaldehyde and TMZ. RESULTS: Cell viability was significantly lower after treatment with 300 µM TMZ, 50 µM cinnamaldehyde, 75 µM cinnamaldehyde, or combined treatment with 300 µM TMZ plus 50 µM or 75 µM cinnamaldehyde than after no treatment (i.e., without TMZ or cinnamaldehyde); and significantly lower after combined treatment with 300 µM TMZ plus 75 µM cinnamaldehyde but not 50 µM cinnamaldehyde, than treatment with 300 µM TMZ alone. Western blotting showed that either single treatments or combined treatments had lower CXCR4 expression (compared to the no-treatment control). Compared to 300 µM TMZ alone, both combined treatment of 300 µM TMZ plus 50 µM cinnamaldehyde or 75 µM cinnamaldehyde had significantly lowered CXCR4 expression. However, CXCR7 expression was not significantly different in all groups. CONCLUSION: Cinnamaldehyde, acting with TMZ, reduces glioma cell viability possibly via decreasing CXCR4 expression.

Association of periodic limb movements during sleep and Parkinson disease: A retrospective clinical study.

Both of periodic limb movements during sleep (PLMS) and Parkinson disease (PD) were related with dopaminergic system dysfunction. We aimed to investigate the detailed association of PLMS severity and PD.Clinical and overnight polysomnographic data of 2230 adults older than 40 from a community hospital between November 2011 and June 2017 in Taiwan were collected retrospectively. The association of PLMS severity and PD was analyzed by Fisher exact test, univariate, and multivariate logistic regression.The mean age was 55.6 years old (standard deviation = 9.8, range = 40-91) for all subjects. There were 2205 subjects without PD and 25 subjects with PD in this study. The distribution of PLMS severity was not significantly different between subjects without PD and with PD (Fischer exact test, P = .215). Also, PLMS was not significantly associated with PD using univariate and multivariate logistic regression.The PLMS severity was not associated with PD.

Risks of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache.

Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio [aHR], 2.73; 95% confidence interval [95% CI], 2.62-2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91-3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74-2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77-2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache.

Effects of Far-infrared Ray on Temozolomide-treated Glioma in Rats.

BACKGROUND/AIM: Malignant glioma is a rapidly progressive primary brain cancer. The aim of the study was to investigate the effect of far-infrared ray (FIR) on temozolomide (TMZ)-treated glioma in rats. MATERIALS AND METHODS: Male, 8-week old, Fischer 344 inbred rats with glioma were randomly divided into three study groups (20 rats in each group). The control group received saline only once daily for 5 days. The TMZ group received TMZ (30 mg/kg) once daily for 5 days. The TMZ plus FIR group received TMZ (30 mg/kg) once daily for 5 days and infrared-c irradiation of 40 min twice daily for 4 weeks. The relative tumor fold and the expression of hypoxia-induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were compared using one-way ANOVA at the end of study. RESULTS: The relative tumor fold of the TMZ+FIR group was significantly higher compared to the control group, and was borderline higher compared to the TMZ group at Day 7. The relative tumor fold of TMZ+FIR group was significantly higher compared to the control group and the TMZ group at Days 14, 21 and 28. HIF-1α expression of TMZ+FIR group was borderline higher compared to the control group at Day 28. The VEGF expression of TMZ+FIR group was significantly higher compared to the control group and the TMZ group at Day 28. CONCLUSION: FIR might increase the growth of glioma under TMZ treatment in rats possibly via increasing VEGF expression, but not HIF-1α expression.

Tinnitus Is Associated with a Higher Risk of Benign Brain Tumors: A Nationwide, Population-Based Secondary Cohort Study of Young and Middle-Aged Adults.

BACKGROUND: It remains unclear whether tinnitus is associated with a higher risk of benign or malignant brain tumors in humans. Therefore, the aim of this secondary study was to investigate the risk of brain tumors in adult with tinnitus using data from a nationwide health claims research database. METHODS: Patients aged 20-50 years who were newly diagnosed with tinnitus were identified from the Taiwan's National Health Insurance Research Database and they served as the study cohort. A comparison cohort was formed by using patients without tinnitus from the same database with frequency matching (4: 1) by 10-year age interval and gender to the patients in the tinnitus cohort. Cox proportional hazards models were used to calculate the adjusted hazard ratios (AHR) for benign and malignant brain tumors in patients with tinnitus, adjusting for age, gender, and comorbidities. RESULTS: There were 15,819 patients in the tinnitus cohort and 63,276 in the comparison cohort. A significantly higher proportion of patients with tinnitus had benign brain tumor (p = 0.003) and all 11 comorbid conditions (p < 0.001) compared to those without tinnitus. Cox proportional hazards regression analysis performed on the basis of age, gender, and the 11 comorbidities revealed that tinnitus was independently associated with a higher risk for benign brain tumor (AHR 1.65, 95% CI 1.24-2.20, p = 0.001) and but not with malignant brain tumors (AHR 1.66, 95% CI 0.93-2.94, p = 0.085). CONCLUSIONS: Findings from this secondary cohort analysis indicated that tinnitus is associated with a higher risk of benign brain tumors.

The association between tinnitus and the risk of ischemic cerebrovascular disease in young and middle-aged patients: A secondary case-control analysis of a nationwide, population-based health claims database.

BACKGROUND: Tinnitus and ischemic cerebrovascular disease (ICVD) may share common pathophysiologic mechanisms. Nevertheless, no studies have investigated whether tinnitus is associated with a higher risk of ICVD. The aim of this study was to evaluate the risk of ICVD among young and middle-aged patients with tinnitus. METHODS: Using the Taiwan's National Health Insurance Research Database, we identified 3,474 patients 20-45 years old with incident ICVD diagnosed between January 1, 2000 and December 31, 2010 and 17,370 controls, frequency matched on age interval, sex, and year of the index date. Risk of ICVD associated with tinnitus was assessed using multiple logistic regression analyses. RESULTS: Tinnitus was significantly associated with a higher risk of incident ICVD among young and middle-aged patients (adjusted odds ratio [OR] 1.66, 95% confidence interval [CI] 1.34-2.04), adjusting for sex, age, and comorbidities. In addition, sex-stratified analysis showed that the associations were significant in both male (adjusted OR 1.55, 95% CI 1.16-2.07) and female patients (adjusted OR 1.77, 95% CI 1.30-2.41). Furthermore, tinnitus was significantly associated with a higher risk of ICVD in the 20.0-29.9 years (adjusted OR 4.11, 95% CI 1.98-8.52) and 30.0-39.9 years (adjusted OR 2.19, 95% CI 1.57-3.05) age groups, but not in the 40.0-45.0 years age group. CONCLUSIONS: Tinnitus could be a novel risk factor or clinical indicator for young ischemic stroke, and further investigations are warranted.

Risk of Peripheral Artery Occlusive Disease in Patients with Vertigo, Tinnitus, or Sudden Deafness: A Secondary Case-Control Analysis of a Nationwide, Population-Based Health Claims Database.

BACKGROUND: Cochleovestibular symptoms, such as vertigo, tinnitus, and sudden deafness, are common manifestations of microvascular diseases. However, it is unclear whether these symptoms occurred preceding the diagnosis of peripheral artery occlusive disease (PAOD). Therefore, the aim of this case-control study was to investigate the risk of PAOD among patients with vertigo, tinnitus, and sudden deafness using a nationwide, population-based health claim database in Taiwan. METHODS: We identified 5,340 adult patients with PAOD diagnosed between January 1, 2006 and December 31, 2010 and 16,020 controls, frequency matched on age interval, sex, and year of index date, from the Taiwan National Health Insurance Research Database. Risks of PAOD in patients with vertigo, tinnitus, or sudden deafness were separately evaluated with multivariate logistic regression analyses. RESULTS: Of the 5,340 patients with PAOD, 12.7%, 6.7%, and 0.3% were diagnosed with vertigo, tinnitus, and sudden deafness, respectively. In the controls, 10.6%, 6.1%, and 0.3% were diagnosed with vertigo (P < 0.001), tinnitus (P = 0.161), and sudden deafness (P = 0.774), respectively. Results from the multivariate logistic regression analyses showed that the risk of PAOD was significantly increased in patients with vertigo (adjusted odds ratio = 1.12, P = 0.027) but not in those with tinnitus or sudden deafness. CONCLUSIONS: A modest increase in the risk of PAOD was observed among Taiwanese patients with vertigo, after adjustment for comorbidities.

Effects of caffeine on cell viability and activity of histone deacetylase 1 and histone acetyltransferase in glioma cells.

OBJECTIVE: The prognosis of patients with glioblastoma remains poor even after various treatments such as surgery, radiotherapy, and chemotherapy. Thus, development of new drugs is urgently needed. The mechanisms underlying the cytotoxicity of caffeine in glioma cells are not clearly understood. This study aimed to assess the activities of histone deacetylase 1 (HDAC1) and histone acetyltransferase (p300) in RT2 glioma cells treated with caffeine. MATERIALS AND METHODS: Cell viability and activity of HDAC1 and p300 in RT2 glioma cells were assayed after treatment with caffeine for 48 hours. RESULTS: Cell viability decreased significantly after treatment with 0.5mM, 1mM, and 2mM caffeine. HDAC1 protein activity decreased significantly with various concentrations of caffeine, whereas the activity of p300 increased significantly. In addition, the viability of RT2 cells remained high, but HDAC1 activity decreased, and p300 activity increased markedly with 0.5mM caffeine treatment. We used microRNA and small interfering RNA (siRNA) to regulate HDAC1 and p300 to further understand the impact on glioblastomas. siRNA downregulated p300 and thus increased the viability of RT2 cells, therefore, caffeine combined with siRNA abolished the efficacy of caffeine, which confirmed that caffeine upregulated p300 and reduced cell viability. We also found increased HDAC1 activity when RT2 cells were treated with a combination of caffeine and miR-449a and thus increased the viability of RT2 cells. CONCLUSION: Our data suggest that a new strategy, caffeine, could increase glioma cell death by decreasing HDAC1 activity and/or by increasing p300 activity. The changes in HDAC1 and p300 activities appeared to occur earlier than loss of RT2 cells.

Multiplex polymerase chain reaction assay developed to diagnose adult bacterial meningitis in Taiwan.

Acute bacterial meningitis causes high morbidity and mortality; the associated clinical symptoms often are insensitive or non-specific; and the pathogenic bacteria are geographically diverse. Clinical diagnosis requires a rapid and accurate methodology. This study aimed to develop a new multiplex polymerase chain reaction (mPCR) assay to detect simultaneously six major bacteria that cause adult bacterial meningitis in Taiwan: Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. Species-specific primers for the six bacteria were developed using reference strains. The specificities of the mPCRs for these bacteria were validated, and the sensitivities were evaluated via serial dilutions. The mPCR assay specifically detected all of the six pathogens, particularly with sensitivities of 12 colony forming units (CFU)/mL, 90 CFU/mL, and 390 CFU/mL for E. coli, S. pneumoniae, and K. pneumoniae, respectively. This mPCR assay is a rapid and specific tool to detect the six major bacterial pathogens that cause acute adult meningitis in Taiwan, particularly sensitive for detecting E. coli, S. pneumoniae, and K. pneumoniae. The assay may facilitate early diagnosis and guidance for antimicrobial therapy for adult patients with this deadly disease in Taiwan.

Expression of Antioxidant Genes in the Mouse Cochlea and Brain in Salicylate-Induced Tinnitus and Effect of Treatment with Spirulina platensis Water Extract.

Salicylate increased manganese-superoxide dismutase (Mn-SOD) gene expression, but decreased catalase (CAT) gene expression in the cochlea and various brain regions of mice with tinnitus. Spirulinaplatensis water extract reduced salicylate-induced overexpression of the Mn-SOD gene, but increased salicylate-induced downregulation of the CAT gene. With the exception of significantly increased SOD activity in the brainstem and inferior colliculus of the Spirulina group, SOD and CAT enzyme activities did not differ among the three groups. The tinnitus group had higher malondialdehyde (MDA) levels than the control group in the temporal and the frontal lobes. S.platensis water extract reduced salicylate-induced elevations of MDA levels in many brain areas. We proposed that altered expression of antioxidant genes may reflect states of oxidative stress associated with tinnitus.

Obstructive sleep apnea and risk of Parkinson's disease: a population-based cohort study.

Sleep disorders could be associated with neurodegenerative diseases. This study aimed to determine the risk of Parkinson's disease in patients with obstructive sleep apnea. The incident cases of newly diagnosed obstructive sleep apnea were identified between 2000 and 2009 from the medical claims database of National Health Institute of Taiwan. The risk of Parkinson's disease onset at least 1 year after the diagnosis of obstructive sleep apnea was measured during and up to 11 years of period, compared to that of age- and gender-matched controls estimated in the same period. A total of 5864 patients with newly diagnosed obstructive sleep apnea and 23,269 subjects without obstructive sleep apnea were identified for data analysis. The study reported that the incidence of Parkinson's disease in the obstructive sleep apnea cohort was approximately two times higher than that in the control cohort (2.57 versus 1.32 per 1000 person-years), with an adjusted hazard ratio of 1.84. Furthermore, the risk of Parkinson's disease was particularly greater for the obstructive sleep apnea with insomnia subgroup (adjusted hazard ratio = 1.97, 95% confidence interval = 1.44-2.69) than for the control cohort. The sex-age-specific analysis further discovered that the most elevated risk of Parkinson's disease onset was noted in female obstructive sleep apnea patients aged 50-69 years (adjusted hazard ratio = 2.82). This population-based study indicated that patients with obstructive sleep apnea, especially those who suffered from insomnia, are at an increased risk of Parkinson's disease onset.

Preoperative risk score predicting 90-day mortality after liver resection in a population-based study.

The impact of important preexisting comorbidities, such as liver and renal disease, on the outcome of liver resection remains unclear. Identification of patients at risk of mortality will aid in improving preoperative preparations. The purpose of this study is to develop and validate a population-based score based on available preoperative and predictable parameters predicting 90-day mortality after liver resection using data from a hepatitis endemic country.We identified 13,159 patients who underwent liver resection between 2002 and 2006 in the Taiwan National Health Insurance Research Database. In a randomly selected half of the total patients, multivariate logistic regression analysis was used to develop a prediction score for estimating the risk of 90-day mortality by patient demographics, preoperative liver disease and comorbidities, indication for surgery, and procedure type. The score was validated with the remaining half of the patients.Overall 90-day mortality was 3.9%. Predictive characteristics included in the model were age, preexisting cirrhosis-related complications, ischemic heart disease, heart failure, cerebrovascular disease, renal disease, malignancy, and procedure type. Four risk groups were stratified by mortality scores of 1.1%, 2.2%, 7.7%, and 15%. Preexisting renal disease and cirrhosis-related complications were the strongest predictors. The score discriminated well in both the derivation and validation sets with c-statistics of 0.75 and 0.75, respectively.This population-based score could identify patients at risk of 90-day mortality before liver resection. Preexisting renal disease and cirrhosis-related complications had the strongest influence on mortality. This score enables preoperative risk stratification, decision-making, quality assessment, and counseling for individual patients.

Sleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study.

INTRODUCTION: Obstructive sleep apnea (OSA) was associated with increased incidence of all cancers. We aimed to determine the risk for primary central nervous system (CNS) cancers in patients with sleep apnea syndrome. METHODS: A total of 23,055 incident cases of newly diagnosed sleep apnea syndrome (sleep apnea group) were identified between 2000 and 2003 in the medical claims database of Taiwan's National Health Institute (NHI) program and were matched by age and gender to patients without OSA (comparison group) in the same period. The occurrence of primary malignant CNS cancers was measured 2 years after the index date over a 10-year period. RESULTS: The incidence density of primary CNS cancers (per 10,000 individual-years) was 2.14 and 1.28, respectively, for the OSA and comparison groups. The overall risk for developing primary CNS cancers was significantly higher in the OSA group (adjusted hazard ratio [HR], 1.54; P=0.046) after adjusting for age, gender, and obesity, among other variables. Subgroup analysis revealed a significantly higher risk for primary brain cancers but not primary spinal cord cancers in the OSA subgroup (adjusted HR, 1.71; P=0.027). The analysis also revealed a significantly higher risk for primary CNS cancers in the insomnia with OSA subgroup (adjusted HR, 2.20; P=0.001) and in the OSA without surgical treatment subgroup (adjusted HR, 1.831; P=0.003). CONCLUSIONS: OSA, especially with insomnia, may increase the risk for primary CNS cancer development, though surgical treatment may reduce this risk in participants with OSA.