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1.
Neuroscience ; 472: 103-115, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364954

RESUMO

The global fractional anisotropy (gFA) is a structural marker of white matter myelination and integrity. Previous studies already evidenced that aging-related reduced integrity of specific white matter tracts is associated with decreased functional connectivity in several hubs. However, the correlations between gFA and functional brain connectivity remain unknown. In this cross-sectional study, we analyzed structural and functional MR datasets of 79 healthy participants from the Leipzig Study for Mind-Body-Emotion Interactions. DTI model-based method was used to quantify gFA values. We tested associations between gFA, age, and gender. The fractional amplitude of low-frequency fluctuations (fALFF) and ROI-to-ROI connectivity were analyzed in a regression model for evaluating the effects of gFA on brain activity and networking, respectively. A negative correlation was found between gFA and age (ρ = -0.343; p = 0.002). No statistically significant correlation as found between gFA and gender (p = 0.229). Higher values of gFA were associated with increased brain regional activity, including areas of the default mode network. There was a higher degree of correlation between some regions, particularly those that conform to the limbic system. Our study demonstrates that gFA influences regional neural activity and brain networking on resting, particularly the limbic system.


Assuntos
Encéfalo , Substância Branca , Anisotropia , Encéfalo/diagnóstico por imagem , Estudos Transversais , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem
2.
J Neurointerv Surg ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452989

RESUMO

BACKGROUND: Balloon guide catheter (BGC) in stent retriever based thrombectomy (BGC+SR) for patients with large vessel occlusion strokes (LVOS) improves outcomes. It is conceivable that the addition of a large bore distal access catheter (DAC) to BGC+SR leads to higher efficacy. We aimed to investigate whether the combined BGC+DAC+SR approach improves angiographic and clinical outcomes compared with BGC+SR alone for thrombectomy in anterior circulation LVOS. METHODS: Consecutive patients with anterior circulation LVOS from June 2019 to November 2020 were recruited from the ROSSETTI registry. Demographic, clinical, angiographic, and outcome data were compared between patients treated with BGC+SR alone versus BGC+DAC+SR. The primary outcome was first pass effect (FPE) rate, defined as near complete/complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after single device pass. RESULTS: We included 401 patients (BGC+SR alone, 273 (66.6%) patients). Patients treated with BGC+SR alone were older (median age 79 (IQR 68-85) vs 73.5 (65-82) years; p=0.033) and had shorter procedural times (puncture to revascularization 24 (14-46) vs 37 (24.5-63.5) min, p<0.001) than the BGC+DAC+SR group. Both approaches had a similar FPE rate (52% in BGC+SR alone vs 46.9% in BGC+DAC+SR, p=0.337). Although the BGC+SR alone group showed higher rates for final successful reperfusion (mTICI ≥2b (86.8% vs 74.2%, p=0.002) and excellent reperfusion, mTICI ≥2 c (76.2% vs 55.5%, p<0.001)), there were no significant differences in 24 hour National Institutes of Health Stroke Scale score or rates of good functional outcome (modified Rankin Scale score of 0-2) at 3 months across these techniques. CONCLUSIONS: Our data showed that addition of distal intracranial aspiration catheters to BGC+SR based thrombectomy in patients with acute anterior circulation LVO did not provide higher rates of FPE or improved clinical outcomes.

3.
J Xray Sci Technol ; 29(5): 823-834, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334443

RESUMO

BACKGROUND AND OBJECTIVE: Estimates of parameters used to select patients for endovascular thrombectomy (EVT) for acute ischemic stroke differ among software packages for automated computed tomography (CT) perfusion analysis. To determine impact of these differences in decision making, we analyzed intra-observer and inter-observer agreement in recommendations about whether to perform EVT based on perfusion maps from 4 packages. METHODS: Perfusion CT datasets from 63 consecutive patients with suspected acute ischemic stroke were retrospectively postprocessed with 4 packages of Minerva, RAPID, Olea, and IntelliSpace Portal (ISP). We used Pearson correlation coefficients and Bland-Altman analysis to compare volumes of infarct core, penumbra, and mismatch calculated by Minerva and RAPID. We used kappa analysis to assess agreement among decisions of 3 radiologists about whether to recommend EVT based on maps generated by 4 packages. RESULTS: We found significant differences between using Minerva and RAPID to estimate penumbra (67.39±41.37mL vs. 78.35±45.38 mL, p < 0.001) and mismatch (48.41±32.03 vs. 61.27±32.73mL, p < 0.001), but not of infarct core (p = 0.230). Pearson correlation coefficients were 0.94 (95%CI:0.90-0.96) for infarct core, 0.87 (95%CI:0.79-0.91) for penumbra, and 0.72 (95%CI:0.57-0.83) for mismatch volumes (p < 0.001). Limits of agreements were (-21.22-25.02) for infarct core volumes, (-54.79-32.88) for penumbra volumes, and (-60.16-34.45) for mismatch volumes. Final agreement for EVT decision-making was substantial between Minerva vs. RAPID (k = 0.722), Minerva vs. Olea (k = 0.761), and RAPID vs. Olea (k = 0.782), but moderate for ISP vs. the other three. CONCLUSIONS: Despite quantitative differences in estimates of infarct core, penumbra, and mismatch using 4 software packages, their impact on radiologists' decisions about EVT is relatively small.

4.
Clin Neuroradiol ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34286344

RESUMO

BACKGROUND: Large-bore aspiration catheters enabling greater flow rates and suction force for mechanical thrombectomy might improve outcomes in patients with stroke secondary to large-vessel occlusion. Complete or near-complete reperfusion after a single thrombectomy pass (first-pass effect) is associated with improved clinical outcomes. We assessed the efficacy and safety of novel MIVI Q™ aspiration catheters in combination with stent-retriever devices. METHODS: We retrospectively analyzed demographics, procedure characteristics, and clinical data from consecutive patients with acute anterior large-vessel occlusion treated with a combined approach using MIVI Q™ aspiration catheters and stent retrievers. Reperfusion was defined according to the modified thrombolysis in cerebral infarction (mTICI) score. Clinical outcomes were measured by the National Institute of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores. RESULTS: We included 52 patients (median age, 75 y IQR: 64-83); 31 (59.6%) women; 14 (26.9%) with terminal internal carotid artery occlusions, 26 (50%) middle cerebral artery (MCA) segment M1 occlusions, and 12 (23.1%) MCA segment M2 occlusions; median NIHSS score at admission was 19 (IQR: 13-22). After the first pass, 25 (48%) patients had mTICI ≥ 2c. At the end of the procedure, 47 (90.4%) had mTICI ≥ 2b and 35 (67.3%) had mTICI ≥ 2c. No serious device-related adverse events were observed. Symptomatic intracranial hemorrhage developed in 1 patient. Mean NIHSS score was 13 at 24 h and 5 at discharge. At 90 days, 24 (46.2%) patients were functionally independent (mRS 0-2). CONCLUSION: This preliminary study found good efficacy and safety for MIVI Q™ aspiration catheters used in combination with stent-retriever devices.

5.
Sci Rep ; 11(1): 13490, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188114

RESUMO

Stroke has a deleterious impact on quality of life. However, it is less well known if stroke lesions in different brain regions are associated with reduced quality of life (QoL). We therefore investigated this association by multivariate lesion-symptom mapping. We analyzed magnetic resonance imaging and clinical data from the WAKE-UP trial. European Quality of Life 5 Dimensions (EQ-5D) 3 level questionnaires were completed 90 days after stroke. Lesion symptom mapping was performed using a multivariate machine learning algorithm (support vector regression) based on stroke lesions 22-36 h after stroke. Brain regions with significant associations were explored in reference to white matter tracts. Of 503 randomized patients, 329 were included in the analysis (mean age 65.4 years, SD 11.5; median NIHSS = 6, IQR 4-9; median EQ-5D score 90 days after stroke 1, IQR 0-4, median lesion volume 3.3 ml, IQR 1.1-16.9 ml). After controlling for lesion volume, significant associations between lesions and EQ-5D score were detected for the right putamen, and internal capsules of both hemispheres. Multivariate lesion inference analysis revealed an association between injuries of the cortico-spinal tracts with worse self-reported quality of life 90 days after stroke in comparably small stroke lesions, extending previous reports of the association of striato-capsular lesions with worse functional outcome. Our findings are of value to identify patients at risk of impaired QoL after stroke.

6.
Nat Commun ; 12(1): 2590, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972513

RESUMO

Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI95% [-8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI95% [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Progressão da Doença , Fibrinolíticos/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo
7.
Microbiome ; 9(1): 104, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962692

RESUMO

BACKGROUND: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. RESULTS: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient's mice. In line with the results in humans, transplantation from 'high ferritin donors' resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient's mice. CONCLUSIONS: Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. Video abstract.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Microbioma Gastrointestinal/genética , Ferro , Camundongos , Obesidade
8.
J Neurointerv Surg ; 13(9): 773-778, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33632881

RESUMO

BACKGROUND: First-pass effect (FPE) has been established as a key metric for technical success and strongly correlates with better clinical outcomes. Most data supporting improved outcomes with the use of a balloon guide catheter (BGC) predate the advent of last-generation large-bore intracranial aspiration catheters. We aim to evaluate the impact of BGC in FPE and clinical outcomes in a large cohort of patients treated with contemporary technology. METHODS: Patients were recruited from the prospectively ongoing ROSSETTI registry. This registry includes all consecutive patients with anterior circulation large-vessel occlusion (LVO) from 10 comprehensive stroke centers in Spain. Demographic, clinical, angiographic, and clinical outcome data were compared between BGC and non-BGC groups. FPE was defined as the achievement of mTICI2c-3 after a single device pass. RESULTS: 426 patients were included out of which 271 (63.62%) used BCG. BGC-treated patients had higher FPE rate (45.8% vs 27.7%; P<0.001), higher final mTICI ≥2 c recanalization rate (76.8% vs 50.3%, respectively; P<0.001), shorter procedural time [median (IQR), 30 (19-58) vs 43 (33-71) min; P<0.001], higher NIHSS difference from admission to 24 hours [median (IQR), 8 (2-12) vs 3 (0-10); P=0.001], and lower mortality rate (17.6% vs 29.8%, P=0.026) compared with non-BGC patients. BGC use was an independent predictor of FPE (OR 2.197, 95% CI 1.436 to 3.361; P<0.001), and excellent clinical outcome at 3 months (OR 0.34, 95% CI 0.17 to 0.68; P=0.002). CONCLUSIONS: Our results support the benefit of BGC use on angiographic and clinical outcomes in anterior circulation LVO ischemic stroke remain significant even when considering recent improvements in intracranial aspiration technology.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Cateteres , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Tecnologia , Trombectomia , Resultado do Tratamento
9.
Gut ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514598

RESUMO

BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice. CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

10.
Free Radic Biol Med ; 162: 38-52, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271279

RESUMO

Available evidences point to methionine metabolism as a key target to study the molecular adaptive mechanisms underlying differences in longevity. The plasma methionine metabolic profile was determined using a LC-MS/MS platform to systematically define specific phenotypic patterns associated with genotypes of human extreme longevity (centenarians). Our findings demonstrate the presence of a specific plasma profile associated with human longevity characterized by an enhanced transsulfuration pathway and tricarboxylic acid (TCA) cycle intermediates, as well as a reduced content of specific amino acids. Furthermore, our work reveals that centenarians maintain a strongly correlated methionine metabolism, suggesting an improved network integrity, homeostasis and more tightly regulated metabolism. We have discovered a particular methionine signature related to the condition of extreme longevity, allowing the identification of potential mechanisms and biomarkers of healthy aging.


Assuntos
Metionina , Espectrometria de Massas em Tandem , Idoso de 80 Anos ou mais , Cromatografia Líquida , Humanos , Longevidade/genética , Metaboloma , Metionina/metabolismo
11.
Clin Cancer Res ; 27(2): 645-655, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33106291

RESUMO

PURPOSE: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials. EXPERIMENTAL DESIGN: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes. RESULTS: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes. CONCLUSIONS: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

12.
Cereb Cortex ; 31(5): 2466-2481, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33350451

RESUMO

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

13.
Stroke ; 52(1): 203-212, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33317416

RESUMO

BACKGROUND AND PURPOSE: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. METHODS: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. RESULTS: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]). CONCLUSIONS: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.


Assuntos
Fibrinolíticos/uso terapêutico , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/tratamento farmacológico , Angiografia por Tomografia Computadorizada , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Reperfusão , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Cell Metab ; 32(4): 548-560.e7, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33027674

RESUMO

The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.

15.
Clin Cancer Res ; 26(24): 6600-6609, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32998960

RESUMO

PURPOSE: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities. RESULTS: We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS cluster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies, SHC1 and TCIRG1, selected on the basis of RNA differential transcriptomic expression. The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4+ T cells, and activated dendritic cells, indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination. CONCLUSIONS: There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.

16.
Stroke ; 51(11): 3232-3240, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33070714

RESUMO

BACKGROUND AND PURPOSE: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. METHODS: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. RESULTS: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5-12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase (P=0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23-4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88-3.25]). CONCLUSIONS: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.


Assuntos
Fibrinolíticos/uso terapêutico , Infarto da Artéria Cerebral Anterior/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Posterior/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Angiografia Cerebral , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Humanos , Infarto da Artéria Cerebral Anterior/diagnóstico por imagem , Infarto da Artéria Cerebral Anterior/fisiopatologia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Posterior/diagnóstico por imagem , Infarto da Artéria Cerebral Posterior/fisiopatologia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Neurology ; 95(24): e3364-e3372, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32989100

RESUMO

OBJECTIVE: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature. METHODS: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation. RESULTS: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours. CONCLUSIONS: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.


Assuntos
Progressão da Doença , Procedimentos Endovasculares , Fibrinolíticos/administração & dosagem , AVC Isquêmico/terapia , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Índice de Gravidade de Doença , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/terapia , Doenças Arteriais Cerebrais/terapia , Procedimentos Endovasculares/estatística & dados numéricos , Feminino , Seguimentos , Humanos , AVC Isquêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Trombectomia/estatística & dados numéricos
18.
Obesity (Silver Spring) ; 28(9): 1663-1670, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32776483

RESUMO

OBJECTIVE: The impact of weight loss induced by bariatric surgery (BS) and nonsurgical approaches on cardiovascular risk factors (CVRFs) has not been fully elucidated. We assessed the effects of BS and a nonsurgical approach on carotid intima-media thickness (CIMT) and CVRFs in participants with class 3 obesity. METHODS: A total of 87 participants with obesity (59 women; 46 [37-52] years old; BMI, 43 [40-47]) and 75 controls were recruited; 21 (25%) participants with obesity underwent BS. BMI, blood pressure, cholesterol, triglycerides, fasting plasma glucose, C-reactive protein, CIMT, and Framingham Risk Score were measured at baseline and at 3-year follow-up. Independent factors for reduction in CIMT were analyzed. The literature on the effects of BS and CIMT was reviewed. RESULTS: After BS, BMI decreased from 45.45 to 27.28 (P < 0.001), and mean CIMT decreased from 0.64 mm (0.56-0.75 mm) to 0.54 mm (0.46-0.65) mm (P < 0.012), equivalent to 0.005 mm/kg of weight lost. At 3-year follow-up, participants who had undergone BS had similar CIMT and CVRFs to the control group. No changes in CVRFs were seen related to the nonsurgical approach. BMI reduction after BS had the strongest independent association with decreased CIMT. CONCLUSIONS: Weight loss after BS decreases CIMT and CVRFs in middle-aged participants with class 3 obesity, resulting in CIMT similar to that observed in lean participants.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea/efeitos adversos , Fatores de Risco de Doenças Cardíacas , Obesidade/complicações , Adulto , Doenças Cardiovasculares/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
19.
Abdom Radiol (NY) ; 45(12): 4150-4159, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32705314

RESUMO

OBJECTIVES: To evaluate the potential clinical and technical utility to manage in practice the use of a robotic MRI in-bore-targeted prostate biopsies in the current work-up of prostate cancer diagnosis. METHODS: Thirty patients with a single cancer suspicious lesion interpreted on MRI using PI-RADSv2.1 category ≥ 3 underwent in-bore robotic transrectal MRI remote-controlled-guided biopsy. It was analyzed the technical success, clinical details, biopsy findings in correlation with the MRI examination, complications and cancer detection rate (CDR). RESULTS: The overall CDR for any cancer was 73% (22/30). It was 86% (19/22) for significant tumors (Gleason score of more than 6 or maximum cancer core length greater than 3 mm for Gleason 6) and 77% (17/22) for tumors with Gleason > 6. CDR for biopsy-naïve patients was 89% (16/18) and 50% (6/12) for patients with prior negative transrectal ultrasound-guided biopsies. The CDR for PI-RADS > 3 was 92% (22/24). All the lesions (n = 30) were reachable with the robotic MRI device. A self-limited rectal hemorrhagic complication was reported. CONCLUSION: This initial data show that a robotic MRI-guided biopsy could be useful, efficient and feasible procedure in the new paradigm to diagnose significant prostate cancer in selected patients.


Assuntos
Imagem por Ressonância Magnética Intervencionista , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Estudos de Viabilidade , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Neoplasias da Próstata/diagnóstico por imagem
20.
Mech Ageing Dev ; 189: 111257, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32437737

RESUMO

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged ≥50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.


Assuntos
Envelhecimento , Espessura Intima-Media Carotídea , Imageamento por Ressonância Magnética , Imagem Corporal Total , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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