Utilizing apolipoprotein E genotypes and associated comorbidities for the assessment of the risk for dementia.

Introduction: Dementia is associated with many comorbidities while being related to Apolipoprotein E (ApoE) polymorphism. However, it is unclear how these clinical illnesses and genetic factors modify the dementia risk. Methods: We enrolled 600 dementia cases and 6000 matched non-dementia controls, with identified ApoE genotype (ε4/ε4, ε4/ε3, and ε3/ε3). Eight comorbidities were selected by medical records, and counted if occurring within 3 years of enrollment. Results: The dementia group had a higher ratio of carrying ε4 allele and prevalence of comorbidities than the non-dementia group. Homozygous ε4 carriers presented the broken line of dementia risk with the peak age at 65-75 years and odds ratio (OR) up to 6.6. The risk only emerged after 65 years of age in ε3/ε4 subjects with OR around 1.6-2.4 when aged > 75 years. Cerebrovascular accident (CVA) is the commonest comorbidity (14.6%). CVA, sleep disorder, and functional gastrointestinal disorders remained as significant risk comorbidities for dementia throughout all age groups (OR = 1.7-5.0). When functional gastrointestinal disorder and ε4 allele both occurred, the dementia risk exceeded the summation of individual risks (OR = 3.7 and 1.9 individually, OR = 6.0 for the combination). Comorbidities could also be predictors of dementia. Conclusion: Combining the genetic and clinical information, we detected cognitive decline and optimize interventions early when the patients present a specific illness in a particular age and carry a specific ApoE allele. Of comorbidities, functional gastrointestinal disorder is the strongest predicting factor for dementia in ε4 allele carriers.

Left Frontotemporal Region Plays a Key Role in Letter Fluency Task-Evoked Activation and Functional Connectivity in Normal Subjects: A Functional Near-Infrared Spectroscopy Study.

Letter fluency task (LFT) is a tool that measures memory, executive function, and language function but lacks a definite cutoff value to define abnormalities. We used the optical signals of functional near-infrared spectroscopy (fNIRS) to study the differences in power and connectivity between the high-functioning and low-functioning participants while performing three successive LFTs, as well as the relationships between the brain network/power and LFT performance. We found that the most differentiating factor between these two groups was network topology rather than activation power. The high-functional group (7 men and 10 women) displayed higher left intra-hemispheric global efficiency, nodal strength, and shorter characteristic path length in the first section. They then demonstrated a higher power over the left Broca's area than the right corresponding area in the latter two sections. The low-LFT group (9 men and 11 women) displayed less left-lateralized connectivity and activation power. LFT performance was only related to the network topology rather than the power values, which was only presented in the low-functioning group in the second section. The direct correlation between power and connectivity primarily existed in the inter-hemispheric network, with the timing relationship also seeming to be present. In conclusion, the high-functioning group presented more prominent left-lateralized intra-hemispheric network connectivity and power activation, particularly in the Broca's area. The low-functioning group seemed to prefer using other networks, like the inter-hemispheric, rather than having a single focus on left intra-hemispheric connectivity. The network topology seemed to better reflect the LFT performance than did the power values.

Music, Math, and Working Memory: Magnetoencephalography Mapping of Brain Activation in Musicians.

Musical transposing is highly demanding of working memory, as it involves mentally converting notes from one musical key (i.e., pitch scale) to another key for singing or instrumental performance. Because musical transposing involves mental adjustment of notes up or down by a specific amount, it may share cognitive elements with arithmetical operations of addition and subtraction. We compared brain activity during high and low working memory load conditions of musical transposing versus math calculations in classically trained musicians. Magnetoencephalography (MEG) was sensitive to differences of task and working memory load. Frontal-occipital connections were highly active during transposing, but not during math calculations. Right motor and premotor regions were highly active in the more difficult condition of the transposing task. Multiple frontal lobe regions were highly active across tasks, including the left medial frontal area during both transposing and calculation tasks but the right medial frontal area only during calculations. In the more difficult calculation condition, right temporal regions were highly active. In coherence analyses and neural synchrony analyses, several similarities were seen across calculation tasks; however, latency analyses were sensitive to differences in task complexity across the calculation tasks due to the high temporal resolution of MEG. MEG can be used to examine musical cognition and the neural consequences of music training. Further systematic study of brain activity during high versus low memory load conditions of music and other cognitive tasks is needed to illuminate the neural bases of enhanced working memory ability in musicians as compared to non-musicians.

Strategic infarct location for post-stroke seizure.

Post-stroke seizure (PSS) can have a strong negative impact on functional recovery after stroke. Researchers have identified numerous risk factors of PSS; however, the relationship between infarction location and PSS remains unclear. We recruited patients who presented with an acute cerebral infarction between 2012 and 2017 and suffered from seizures within 1 year after stroke (PSS group). PSS group was subgrouped into early-PSS and late-PSS groups based on the interval between seizure and stroke. We also recruited an equal number of acute cerebral infarction patients without post-stroke seizures during the follow-up period (Non-PSS group). All brain MRIs from the two groups were processed, whereupon normalized infarct maps from the PSS and Non-PSS groups were compared via voxel- and volumetric-based analyses. A total of 132 subjects were enrolled in the study, including PSS (n = 66, consisting of 31 early-PSS and 35 late-PSS) and Non-PSS (n = 66) patients. No significant differences were observed between the two groups in terms of stroke lateralization or severity. Image analysis revealed that the volume of infarction was larger in the PSS group than in the Non-PSS group; however, the difference did not reach the level of significance. Unlike the Non-PSS group, the PSS group presented hot spots over the left central region, left superior parietal lobule, and right frontal operculum. We observed differences between the distribution of hot spots among patients with early-PSS and those with late-PSS. We found that some brain regions were significantly associated with the development of PSS after ischemic stroke, and these regions differed between cases of early and late PSS. It appears that the location of infarction could help clinicians assess the risk of PSS in specific post-stroke stages.

Triglyceride-Glucose Index and Intravenous Thrombolysis Outcomes for Acute Ischemic Stroke: A Multicenter Prospective-Cohort Study.

BACKGROUND: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT). METHODS: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3-6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4-8), moderate (9-15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores. RESULTS: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48-9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke. CONCLUSION: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats.

Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton's jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats' cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

Visualizing the valence states of europium ions in Eu-doped BaAl2O4 using X-ray nanoprobe mapping.

This study develops and successfully demonstrates visualization methods for the characterization of europium (Eu)-doped BaAl2O4 phosphors using X-ray nanoprobe techniques. X-ray fluorescence (XRF) mapping not only gives information on the elemental distributions but also clearly reveals the valence state distributions of the Eu2+ and Eu3+ ions. The accuracy of the estimated valence state distributions was examined by performing X-ray absorption spectroscopy (XAS) across the Eu L3-edge (6.977 keV). The X-ray excited optical luminescence (XEOL) spectra exhibit different emission lines in the selected local areas. Their corresponding emission distributions can be obtained via XEOL mapping. The emission properties can be understood through correlation analysis. The results demonstrate that the main contribution to the luminescence intensity of the Eu-doped BaAl2O4 comes from the Eu2+ activator and the emission intensity will not be influenced by the concentration of Eu2+ or Eu3+ ions. It is anticipated that X-ray nanoprobes will open new avenues with significant characterization ability for unravelling the emission mechanisms of phosphor materials.

Effectiveness of Standard-Dose vs. Low-Dose Alteplase for Acute Ischemic Stroke Within 3-4.5 h.

BACKGROUND: The efficacy and safety of intravenous alteplase administered 3-4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown. PATIENTS AND METHODS: The current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3-4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion. RESULTS: Overall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27-1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80-1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21-2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase. CONCLUSION: In the 3-4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan.

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35-3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63-4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.

Corrigendum: Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience.

[This corrects the article DOI: 10.3389/fneur.2021.628077.].

Characterization of familial hypercholesterolemia in Taiwanese ischemic stroke patients.

Familial hypercholesterolemia (FH) is a common genetic disorder characterized by a lifelong elevated low-density lipoprotein cholesterol (LDL-C) level. The relationship between FH and ischemic stroke is still controversial. We enrolled ischemic stroke patients prospectively in our neurological ward, and divided them into two groups according to LDL-C levels with a threshold of 130 mg/dl. Targeted sequencing was performed in all stroke patients for LDLR, APOB, and PCSK9 genes. The fifty-eight high-LDL subjects were older, prevalence of previous myocardial infarction/stroke history was lower, and the first stroke age was older compared with values in the sixty-three low-LDL cases. The prevalence of FH in Han-Chinese stroke patients was 5.0%, and was 10.3% in those with a higher LDL-C level. We identified six carriers, who had higher percentages of large vessel stroke subtype (66.7% vs. 15.4%) and transient ischemic attack (33.3% vs. 3.8%), previous myocardial infarction/stroke history (50.0% vs. 11.5%), statin use (50.0% vs. 11.5%), and increased carotid intima-media thickness (IMT) (0.9-1.2mm vs.0.7-9.0mm) compared with the other hypercholesterolemic patients without pathogenic variants. Ischemic stroke patients carrying FH pathogenic variants seemed to have a higher risk for large artery stroke and transient ischemic attack. The IMT exam could be useful to screen for FH in hypercholesterolemic stroke patients.

The Irradiated Brain Volume Within 12 Gy Is a Predictor for Radiation-Induced Changes After Stereotactic Radiosurgery in Patients With Unruptured Cerebral Arteriovenous Malformations.

PURPOSE: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS. RESULTS: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm3 (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS. CONCLUSIONS: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications.

Network reorganization during verbal fluency task in fronto-temporal epilepsy: A functional near-infrared spectroscopy study.

This is the first study to use functional near-infrared spectroscopy (fNIRS) to investigate how the lateralization of the epileptogenic zone affects the reconfiguration of task-related network patterns. Eleven left fronto-temporal epilepsy (L-FTE) and 11 right fronto-temporal epilepsy (R-FTE), as well as 22 age- and gender-matched controls, were enrolled. Signals from 52-channel fNIRS were recorded while the subject was undertaking verbal fluency tasks (VFTs), which included categorical (CFT) and letter (LFT) fluency tasks. Three analytic methods were used to study the network topology: network-based analysis, hub identification, and proportional threshold to select the top 20% strongest connections for both graph theory parameters and clinical correlation. Performance of CFT is accomplished primarily using the ventral pathway, and bilateral ventral pathways are augmented in fronto-temporal epilepsy patients by strengthening the inter-hemispheric connections, especially for R-FTE. LFT mainly employed the dorsal pathway, and further prioritized the left dorsal pathway in strengthening intra-hemispheric connections in fronto-temporal epilepsy, especially L-FTE. The top 20% of the strongest connections only present differences in CFT network compared with the controls. R-FTE increased inter-hemispheric network density, while L-FTE decreased inter-hemispheric average characteristic path length. Accumulative seizure burden only affects L-FTE network. Better LFT performance and longer educational years seem to promote left fronto-temporal networks, and decreased the demand from RR intra-hemispheric connectivity in L-FTE. LFT scores in R-FTE are maintained by preserved RR intra-hemispheric networks. However, CFT scores and educational years seem to have no effect on the CFT network topology in both FTE.

Clinical-CT mismatch defined NIHSS ≥ 8 and CT-ASPECTS ≥ 9 as a reliable marker of candidacy for intravenous thrombolytic therapy in acute ischemic stroke.

BACKGROUND: Clinical-diffusion mismatch between stroke severity and diffusion-weighted imaging lesion volume seems to identify stroke patients with penumbra. However, urgent magnetic resonance imaging is sometimes inaccessible or contraindicated. Thus, we hypothesized that using brain computed tomography (CT) to determine a baseline "clinical-CT mismatch" may also predict the responses to thrombolytic therapy. METHODS: Brain CT lesions were measured using the Alberta Stroke Program Early CT Score (ASPECTS). A total of 104 patients were included: 79 patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 and a CT-ASPECTS ≥ 9 who were defined as clinical-CT mismatch-positive (P group) and 25 patients with an NIHSS score ≥ 8 and a CT-ASPECTS < 9 who were defined as clinical-CT mismatch-negative (the N group). We compared their clinical outcomes, including early neurological improvement (ENI), early neurological deterioration (END), delta NIHSS score (admission NIHSS-baseline NIHSS score), symptomatic intracranial hemorrhage (sICH), mortality, and favorable outcome at 3 months. RESULTS: Patients in the P group had a greater proportion of favorable outcome at 3 months (p = 0.032) and more frequent ENI (p = 0.038) and a greater delta NIHSS score (p = 0.001), as well as a lower proportion of END (p = 0.004) than those in the N group patients. There were no significant differences in the incidence rates of sICH and mortality between the two groups. CONCLUSIONS: Clinical-CT mismatch may be able to predict which patients would benefit from intravenous thrombolysis.

Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience.

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT). Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes. Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28-18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01-25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0-1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0-2 (adjusted OR: 1.39, 95% CI, 0.97-1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77-12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT. Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.

Characterization of Hippocampal-Thalamic-Cortical Morphometric Reorganization in Temporal Lobe Epilepsy.

INTRODUCTION: Brain cortico-subcortical connectivity has been investigated in epilepsy using the functional MRI (MRI). Although structural images cannot demonstrate dynamic changes, they provide higher spatial resolution, which allows exploration of the organization of brain in greater detail. METHODS: We used high-resolution brain MRI to study the hippocampal-thalamic-cortical networks in temporal lobe epilepsy (TLE) using a volume-based morphometric method. We enrolled 22 right-TLE, 33 left-TLE, and 28 age/gender-matched controls retrospectively. FreeSurfer software was used for the thalamus segmentation. RESULTS: Among the 50 subfields, ipsilateral anterior, lateral, and parts of the intralaminar and medial nuclei, as well as the contralateral parts of lateral nuclei had significant volume loss in both TLE. The anteroventral nucleus was most vulnerable. Most thalamic subfields were susceptible to seizure burden, especially the left-TLE. SPM12 was used to conduct an analysis of the gray matter density (GMD) maps. Decreased extratemporal GMD occurred bilaterally. Both TLE demonstrated significant GMD loss over the ipsilateral inferior frontal gyrus, precentral gyrus, and medial orbital cortices. SIGNIFICANCE: Thalamic subfield atrophy was related to the ipsilateral inferior frontal GMD changes, which presented positively in left-TLE and negatively in right-TLE. These findings suggest prefrontal-thalamo-hippocampal network disruption in TLE.

Bilateral Smell Preservation is Routinely Possible following Endoscopic Endonasal Approach for Sellar/Suprasellar Lesions.

Objective The endoscopic endonasal approach (EEA) has been shown to be an effective means to access sellar lesions. However, there are limited studies centered on evaluating olfactory function after surgery. In this study, we assessed the pre- and postoperative olfactory function of patients who underwent EEA for sellar and suprasellar lesions. The impact of nasoseptal flap use on olfaction was further analyzed. Study Design A retrospective study. Setting A tertiary-care referral center in Taiwan. Participants Patients with sellar and suprasellar lesions who underwent EEA and pre- and postoperative olfaction assessment from August 2015 to March 2018 were included in the study. Main Outcome Measures The patients' olfactory function was examined pre-and postoperatively using the Sniffin' Sticks odor identification test. Data regarding demographics, olfactory scores, pathology, reconstructive technique, graft usage, and extent of resection were retrieved. Results A total of 106 patients (36 males and 70 females) were enrolled, with a mean age of 51 years. There were 76 pituitary tumors, 12 Rathke's cleft cysts, 7 craniopharyngiomas, 7 meningiomas, and 4 other lesions. The nasoseptal flap was used in 39 patients for skull base reconstruction, and these patients had no statistically significant change between pre- and postoperative olfactory scores ( p = 0.283). Moreover, a statistically significant improvement of olfactory scores was found in patients in whom the nasoseptal flap was not used. Conclusion Olfactory function may be reliably preserved after EEA, with or without nasoseptal flap harvest and use.

TREM-1 enhances Mycobacterium tuberculosis-induced inflammatory responses in macrophages.

Triggering receptor expressed on myeloid cells 1 (TREM-1) extensively interacts with toll-like receptors and amplifies pro-inflammatory responses. The effect of TREM-1 on Mycobacterium tuberculosis (MTB)-related immune responses remains to be elucidated. We isolated bone marrow-derived macrophages (BMDMs) from wild-type mice and Trem-1 KO mice and treated them with MTB whole cell lysate and EsxA (ESAT-6). Cytokine production and mRNA expression, including Trem-1, following stimulation were evaluated. Intratracheal instillation of heat-killed MTB (HKMTB) in mice was performed and the presence of TREM-1-positive macrophages was investigated by immunohistochemistry analysis. In our study, BMDMs isolated from wild-type mice produced more pro-inflammatory cytokines and demonstrated higher inflammatory gene expression levels compared with those isolated from Trem-1 KO mice when stimulated with MTB whole cell lysate. EsxA had a synergistic effect with MTB whole cell lysate on the induction of pro-inflammatory responses. The gene expression of Trem-1 was upregulated when treated with MTB-related proteins. TREM-1-positive macrophages were identified in the lung tissues from patients with active TB and from wild-type mice treated with intratracheal instillation of HKMTB. In conclusion, in mouse macrophages, TREM-1 could enhance pro-inflammatory immune responses when stimulated with MTB-related proteins. The gene expression of Trem-1 could also be induced by MTB-related stimulation.

Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?

BACKGROUND: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). OBJECTIVES: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. METHODS: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. RESULTS: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. CONCLUSIONS: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.

Better endovascular mechanical thrombectomy outcome in atrial fibrillation patients with acute ischemic stroke: A single-center experience.

BACKGROUND: Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. Atrial fibrillation (AF) is one of the major causes. However, the impact of AF on the treatment has not yet been clearly discussed. This study is to evaluate the influence of AF on the outcomes of EVT in patients with acute ischemic stroke. METHODS: Data from our Stroke Registry Database from April 2015 to July 2018 were reviewed. Technical efficacy, functional, and safety outcomes were reported and compared between patients with and without AF. A multivariate logistic regression model was performed to identify the predictors of the good functional outcome. RESULTS: We reviewed 83 eligible patients receiving EVT. Patients (51.8%) were eventually found to have AF. The substantial reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 72.1% and 55.0% in patients with and without AF, respectively, inclusive of a learning curve (p = 0.12). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 55.8% and 17.5% in patients with and without AF, respectively (p < 0.01). A multivariable logistic regression analysis showed that age <70 years, the substantial reperfusion, and the presence of AF were three significant predictors for a good functional outcome. CONCLUSION: Our study showed that patients with AF responded significantly better to EVT than those without AF did. Intracranial atherosclerotic diseases in patients without AF which were especially refractory to EVT may contribute to the difference of the functional outcomes between the two groups.