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1.
Eur Heart J ; 45(4): 287-305, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37992083

RESUMO

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Benzofenonas , Isoxazóis , Doenças Vasculares , Humanos , Fator de Transcrição AP-1 , Aminopropionitrilo , Estudos Transversais , Dissecção Aórtica/genética , Doenças da Aorta/patologia , Doenças Vasculares/patologia , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Fatores de Necrose Tumoral
2.
Neurobiol Dis ; 191: 106409, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218457

RESUMO

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks.


Assuntos
Eletroencefalografia , Epilepsias Parciais , Humanos , Sono , Eletrocorticografia , Vigília
3.
Clin Exp Immunol ; 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39432677

RESUMO

Coronary artery involvement (CAI) is a special but not rare manifestation of Takayasu arteritis (TAK). Granzyme B (GzmB) is a multifunctional protease associated with the immune system and coronary artery disease. However, its role in patients with TAK and CAI remains unclear. This study investigates the role of GzmB+ cell subsets in TAK. The study included 105 TAK patients and 58 healthy controls. The percentages of different GzmB+ cells in blood samples were analyzed by flow cytometry. We found that age, age at onset, BMI, disease duration month, hypertension, and hyperlipidemia were significantly different between TAK patients with and without CAI (P=0.000, P=0.038, P=0.003, P=0.031, P=0.039, P=0.000). The proportions of CD3+CD8+cells (P=0.001) and CD3+CD4+cells (P=0.000) in GzmB+ cells were significantly increased, while the proportion of CD3-CD56+cells (P=0.001) in GzmB+ cells was decreased in TAK patients. The proportions of three types of GzmB+ subsets in lymphocytes (CD3+CD4+GzmB+, CD3+CD8+GzmB+, CD3+CD56+ GzmB+) were higher in TAK patients with CAI compared to those without CAI (P=0.021, P=0.007, P=0.007). The increased proportion of CD3+CD8+GzmB+cells/lymphocytes was an independent risk factor for coronary involvement in TAK (OR=4.990 [1.766-14.098], P=0.002). Additionally, patients with a high CD3+CD8+GzmB+cells/lymphocytes ratio had a higher MACE rate than those with a low ratio in TAK (P=0.019). Our results indicate that CD8 cell-derived Gzm B may be a predictor for CAI and MACE in TAK patients. Targeting CD3+CD8+GzmB+ lymphocytes or using GzmB inhibitors could be a potential therapeutic approach for the treatment of CAI in TAK.

4.
New Phytol ; 244(4): 1552-1569, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39327824

RESUMO

Plant secondary metabolism represents an important and ancient form of defense against pathogens. Phytopathogens secrete effectors to suppress plant defenses and promote infection. However, it is largely unknown, how fungal effectors directly manipulate plant secondary metabolism. Here, we characterized a fungal defense-suppressing effector CfEC28 from Colletotrichum fructicola. Gene deletion assays showed that ∆CfEC28-mutants differentiated appressoria normally on plant surface but were almost nonpathogenic due to increased number of plant papilla accumulation at attempted penetration sites. CfEC28 interacted with a family of chloroplast-localized 3-deoxy-d-arabinose-heptulonic acid-7-phosphate synthases (DAHPSs) in apple. CfEC28 inhibited the enzymatic activity of an apple DAHPS (MdDAHPS1) and suppressed DAHPS-mediated secondary metabolite accumulation through blocking the manganese ion binding region of DAHPS. Dramatically, transgene analysis revealed that overexpression of MdDAHPS1 provided apple with a complete resistance to C. fructicola. We showed that a novel effector CfEC28 can be delivered into plant chloroplasts and contributes to the full virulence of C. fructicola by targeting the DAHPS to disrupt the pathway linking the metabolism of primary carbohydrates with the biosynthesis of aromatic defense compounds. Our study provides important insights for understanding plant-microbe interactions and a valuable gene for improving plant disease resistance.


Assuntos
Cloroplastos , Colletotrichum , Proteínas Fúngicas , Malus , Imunidade Vegetal , Cloroplastos/metabolismo , Colletotrichum/patogenicidade , Colletotrichum/fisiologia , Malus/microbiologia , Malus/imunologia , Malus/genética , Malus/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Virulência , Metabolismo Secundário
5.
Arterioscler Thromb Vasc Biol ; 43(6): e172-e189, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37128913

RESUMO

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear. METHODS: Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet-induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed. RESULTS: We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a ß-aminopropionitrile diet, Marfan mice with fibrillin-1 haploinsufficiency (Fbn1C1041G/+), and ApoE-/- mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in ß-aminopropionitrile-treated mice, Fbn1C1041G/+ mice, and Ang II-infused ApoE-/- mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that FcγR (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated FcγR-mediated ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or FcγR deficiency. CONCLUSIONS: This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid-lowering drug may represent a promising therapeutic approach for TAAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Água Potável , Hiperuricemia , Camundongos , Animais , Ácido Úrico , Aminopropionitrilo/efeitos adversos , Alopurinol/efeitos adversos , Água Potável/efeitos adversos , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Receptores de IgG , Transdução de Sinais , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/prevenção & controle , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/genética , Dissecção Aórtica/prevenção & controle , RNA , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
6.
J Integr Neurosci ; 23(7): 130, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39082289

RESUMO

The blood-brain barrier (BBB) is a selectively semi-permeable layer, crucial in shielding the brain from external pathogens and toxic substances while maintaining ionic homeostasis and sufficient nutrient supply. However, it poses a significant challenge for drugs to penetrate the BBB in order to effectively target brain tumors. Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive technique that employs thermal energy to cauterize intracranial lesions with the potential to temporarily disrupt the BBB. This further opens a possible therapeutic window to enhance patient outcomes. Here, we review the impact of MRg-LITT on BBB and blood tumor barrier (BTB) and the duration of the BBB disruption. Studies have shown that MRg-LITT is effective due to its minimally invasive nature, precise tumor targeting, and low complication rates. Although the disruption duration varies across studies, the average peak disruption is within the initial two weeks post-ablation period and subsequently exhibits a gradual decline. However, further research involving larger groups with extended follow-up periods is required to determine disruption duration more accurately. In addition, evaluating toxicity and glymphatic system disruption is crucial to circumvent potential risks associated with this procedure.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Terapia a Laser , Humanos , Terapia a Laser/métodos , Animais , Imageamento por Ressonância Magnética
7.
Eur Heart J ; 44(14): 1248-1261, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-36638776

RESUMO

AIMS: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive. METHODS AND RESULTS: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a ß-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001. CONCLUSION: The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Camundongos , Animais , Aminopropionitrilo/efeitos adversos , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Transdução de Sinais , Aneurisma da Aorta Torácica/prevenção & controle
8.
Hum Brain Mapp ; 44(11): 4200-4210, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37227015

RESUMO

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset. Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± SD of targets between intra- and inter-subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.


Assuntos
Conectoma , Estimulação Encefálica Profunda , Transtorno Depressivo Resistente a Tratamento , Substância Branca , Humanos , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Estimulação Encefálica Profunda/métodos , Depressão , Substância Branca/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/terapia
9.
Epilepsia ; 64(4): 973-985, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36695000

RESUMO

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Humanos , Eletroencefalografia , Epilepsia/patologia , Epilepsias Parciais/diagnóstico , Convulsões/patologia , Sono/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico
10.
Epilepsy Behav ; 145: 109344, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37459719

RESUMO

BACKGROUND AND PURPOSE: In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery. METHOD: To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines. RESULTS: Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018-3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619-4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety. CONCLUSIONS: Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the well-being of individuals with epilepsy.


Assuntos
COVID-19 , Epilepsias Parciais , Adolescente , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Pandemias , Prevalência , Convulsões , Vacinação/efeitos adversos
11.
Epilepsy Behav ; 143: 109212, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37172446

RESUMO

Responsive neurostimulation (RNS) has shown promising but limited efficacy in the treatment of drug-resistant epilepsy. The clinical utility of RNS is hindered by the incomplete understanding of the mechanism behind its therapeutic effects. Thus, assessing the acute effects of responsive stimulation (AERS) based on intracranial EEG recordings in the temporal lobe epilepsy rat model may provide a better understanding of the potential therapeutic mechanisms underlying the antiepileptic effect of RNS. Furthermore, clarifying the correlation between AERS and seizure severity may help guide the optimization of RNS parameter settings. In this study, RNS with high (130 Hz) and low frequencies (5 Hz) was applied to the subiculum (SUB) and CA1. To quantify the changes induced by RNS, we calculated the AERS during synchronization by Granger causality and analyzed the band power ratio in the classic power band after different stimulations were delivered in the interictal and seizure onset periods, respectively. This demonstrates that only targets combined with an appropriate stimulation frequency could be efficient for seizure control. High-frequency stimulation of CA1 significantly shortened the ongoing seizure duration, which may be causally related to increased synchronization after stimulation. Both high-frequency stimulation of the CA1 and low-frequency stimulation delivered to the SUB reduced seizure frequency, and the reduced seizure risk may correlate with the change in power ratio near the theta band. It indicated that different stimulations may control seizures in diverse manners, perhaps with disparate mechanisms. More focus should be placed on understanding the correlation between seizure severity and synchronization and rhythm around theta bands to simplify the process of parameter optimization.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Animais , Ratos , Convulsões/terapia , Epilepsia Resistente a Medicamentos/terapia , Epilepsia do Lobo Temporal/terapia , Eletrocorticografia
12.
Perfusion ; 38(7): 1478-1491, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35941723

RESUMO

OBJECTIVE: To analyze the effect of sex on the short-time prognosis in two different age subgroups (≤55 years old and >55 years old). METHODS: From January 2009 to 2019, 1522 patients with DeBakey I acute aortic dissection (AAD) underwent frozen elephant trunk and total arch replacement at a Tertiary Center in China were divided into female group (n = 324) and male group (n = 1198). The demographic characteristics, clinical presentation, management, short-term outcomes were described in the different sex groups. The risk factors of 30-days mortality for females and males were identified by univariate and multivariable logistic regression analysis. Then, random Forest regression was used to analyze the association between age and 30-days mortality in the different sexes groups. The cut-off age for 30-days mortality in females was then identified as 55 years. The patients were divided into two subgroups: young patients (≤55 years old) and elderly patients (>55 years old). Clinical prognosis between different sex groups was further compared in the age subgroups. RESULTS: Approximately four-fifths of the patients were males. Males with DeBakey I AAD were younger than females (47 vs 52 years; p < 0.01). The proportion of males gradually declined with age. The cut-off age for 30-days mortality in females and males was identified as 55 years old and 63 years old, respectively. In young patients (≤55 years old), the 30-days mortality rate for females was lower than males (hazard ratio [HR, 2.02, p < 0.05). Following adjustment using the multivariable Cox regression analysis, females were identified as an independent protective factor for 30-days mortality (HR, 2.24, p = 0.03). CONCLUSIONS: Our study showed that females present with DeBakey I AAD less frequently than males and they tend to present with DeBakey AAD later in life. In young patients, females had better early outcomes despite similar time for symptom onset to diagnosis and surgical technique than males.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Adulto , Lactente , Prótese Vascular , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Resultado do Tratamento , Aorta Torácica/cirurgia
13.
Heart Lung Circ ; 32(8): e47-e50, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37308365

RESUMO

The open anastomosis technique has become more popular since it was first used in hemiarch replacement; however, hypothermic circulatory arrest is unavoidable. This institution performed a novel surgical technique called the arch-clamping technique. It has been used in the treatment of patients with ascending aortic aneurysm extending to the proximal aortic arch and avoids the use of hypothermic circulatory arrest. Thirty patients had a hemiarch replacement with the arch-clamping technique from 2021 to 2022; all of them were discharged uneventfully.


Assuntos
Aneurisma da Aorta Torácica , Aneurisma Aórtico , Implante de Prótese Vascular , Parada Cardíaca , Humanos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Constrição , Aneurisma Aórtico/cirurgia , Parada Cardíaca Induzida/métodos , Parada Cardíaca/etiologia , Resultado do Tratamento , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/etiologia , Implante de Prótese Vascular/métodos
14.
Rev Cardiovasc Med ; 23(6): 206, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39077165

RESUMO

Background and Aims: Epicardial adipose tissue, exosomes, and miRNAs have important activities in atherosclerosis. The purpose of this study was to establish miRNA expression profiles of epicardial adipose tissue-derived exosomes in patients with coronary atherosclerosis. Methods: Biopsies of epicardial adipose tissue were obtained from patients with and without coronary artery disease (CAD, n = 12 and NCAD, n = 12) during elective open-heart surgeries. Tissue was incubated with DMEM-F12 for 24 hours. Exosomes were isolated, then nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting were performed to confirm the existence of exosomes. Total RNA in exosomes was subjected to high-throughput sequencing to identify differentially expressed miRNAs. MicroRNA target gene prediction was performed, and target genes were analyzed by Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and mirPath to identify function. Reverse transcription quantitative PCR was performed to confirm the differentially expressed miRNAs. Results: Fifty-three unique miRNAs were identified (adjusted p < 0.05, fold of change > 2), among which 32 miRNAs were upregulated and 21 miRNAs were downregulated in coronary artery disease patients. Reverse transcription quantitative PCR validated the results for seven miRNAs including miR-141-3p, miR-183-5p, miR-200a-5p, miR-205-5p, miR-429, miR-382-5p and miR-485-3p, with the last two downregulated. GO and KEGG analysis by mirPath indicated that these differentially expressed miRNAs were enriched in cell survival, apoptosis, proliferation, and differentiation. Conclusions: Coronary artery disease patients showed differential epicardial adipose tissue exosomal miRNA expression compared with patients without coronary artery disease. The results provide clues for further studies of mechanisms of atherosclerosis.

15.
Eur J Nucl Med Mol Imaging ; 49(5): 1560-1573, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34746970

RESUMO

BACKGROUND: PET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age-specific PET template. This study aims to develop a pediatric age-specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. METHODS: We recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6-10 years (n = 17) and 11-18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template). RESULTS: Spatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%). CONCLUSION: The PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT. TRIAL REGISTRATION: NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162.


Assuntos
Epilepsia , Fluordesoxiglucose F18 , Adulto , Fatores Etários , Criança , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos
16.
Neurol Sci ; 43(2): 1427-1430, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34812967

RESUMO

OBJECTIVE: Research on individuals with brain-computer interface (BCI) presents not only technological challenges but ethical challenges (e.g., psychological aspects) as well. We assessed the mental health of a senile patient with tetraplegia after an invasive implantation of BCI and a long-term daily training, in order to provide new experience about the ethical impact of BCI on users and inform future clinical applications of such devices. METHODS: This case was a 71-year-old man with tetraplegia for 2 years. Prior to the implant surgery of BCI, and 1 month, 2 months, 3 months, and 9 months after training, a series of tests for cognition, emotion, social support, sleep, and quality of life were performed to evaluate the patient's mental health. RESULTS: Compared with baseline before surgery, the patients' cognition, emotion, social support, sleep, and quality of life improved after the surgery and the long-term daily training. At 3 months post-training, the patient's cognitive score measured by Mini-mental State Examination reached the cutoff point for cognitive impairment in the elderly. Subjective well-being and quality of life showed a slight decline at 9 months post-training compared with that 3 months post-training but remained above the baseline. CONCLUSION: This study shows the psychological benefits in a senile patient after an invasive BCI implantation and a long-term daily training. BCI ethics is still in its early stages, and further research is needed to understand emerging psychological states of this specific population.


Assuntos
Interfaces Cérebro-Computador , Idoso , Humanos , Masculino , Quadriplegia , Qualidade de Vida , Sono
17.
Neurol Sci ; 43(5): 3333-3341, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34816317

RESUMO

BACKGROUND: Low-grade epilepsy-associated neuroepithelial tumor (LEAT) is highly responsive to surgery in general. The appropriate surgical strategy remains controversial in temporal LEAT. The aim of this study is to analyze the surgical seizure outcome of temporal LEAT, focusing on the aspects of surgical strategy. METHODS: Sixty-one patients from a single epilepsy center with temporal LEAT underwent surgery. The surgical strategy was according to the multidisciplinary presurgical evaluation. Electrocorticogram (ECoG)-assisted resection was utilized. Surgical extent including lesionectomy and extended resection was described in detail. Seizure outcome was classified as satisfactory (Engel class I) and unsatisfactory (Engel classes II-IV). RESULTS: After a median follow-up of 36.0 (30.0) months, 83.6% of patients achieved satisfactory outcome, including 72.1% with Engel class Ia. There was 39.3% (24/61) of patients with antiepileptic drug (AED) withdrawal. Use of ECoG (χ2 = 0.000, P > 0.1), preresection spike (χ2 = 0.000, P = 0.763), or spike residue (P = 0.545) was not correlated with the seizure outcome. For lateral temporal LEAT, outcome from lesionectomy was comparable to extended resection (χ2 = 0.499, P > 0.1). For mesial temporal LEAT, 94.7% (18/19) of patients who underwent additional hippocampectomy were satisfactory, whereas only 25% (1/4) of patients who underwent lesionectomy were satisfactory (P = 0.009). CONCLUSION: Surgical treatment was highly effective for temporal LEAT. ECoG may not influence the seizure outcome. For lateral temporal LEAT, lesionectomy with or without cortectomy was sufficient in most patients. For mesial temporal LEAT, extended resection was recommended.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Neoplasias Neuroepiteliomatosas , Eletroencefalografia , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/patologia , Humanos , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/cirurgia , Estudos Retrospectivos , Convulsões/patologia , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Resultado do Tratamento
18.
Ann Vasc Surg ; 83: 231-239, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34933107

RESUMO

BACKGROUND: Stanford type A acute aortic dissection (TAAAD) is often accompanied by preoperative disorders of coagulation. The study aimed to evaluate the relationship between computed tomography angiography imaging features and preoperative coagulopathy in TAAAD patients. METHODS: This was a single-center retrospective review of adult patients undergoing TAAAD surgery from January 2015 to January 2019 in the Beijing Anzhen Hospital (Beijing, China). Images were obtained using preoperative enhanced computed tomography in 174 patients with TAAAD. Preoperative coagulopathy was defined as the disseminated intravascular coagulation score greater than 5. The patients were divided into coagulopathy and non-coagulopathy groups. Circumferential arc lengths of the false lumen (Fx) and true lumen (Tx) were measured at four planes (ascending aorta, thoracic-descending aorta, descending aorta and abdominal aorta). We define the value of Fx/(Tx+Fx) × 100% as tear index (TI) and take the four planes' averages to weighed the false lumen's size. By analyzing the two groups of clinical data and computed tomography angiography imaging data, potentially related factors were detected by univariate analysis and multivariate binary logistic regression analysis. RESULTS: The incidence of preoperative coagulopathy for TAAAD patients was 12.07%. In adjusted multivariate binary logistic regression analysis, white blood cell count (odds ratio [OR]: 1.204, 95% confidence interval [CI]: 1.035-1.400, P = 0.016); longitude length of aortic dissection (OR: 1.076, 95% CI: 1.016-1.139, P = 0.012); and Tear index (OR = 1.177, 95% CI: 1.075-1.289, P < 0.001) were significant factors related to the occurrence of preoperative coagulopathy for TAAAD. CONCLUSIONS: The incidence of preoperative coagulopathy in TAAAD patients was 12.07%. The longitude length of AD, TI and white blood cell count were significant factors related to preoperative coagulopathy in patients with TAAAD. The significance of imaging and anatomic changes related to coagulopathy are worth further study in TAAAD patients.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Adulto , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
19.
Thorac Cardiovasc Surg ; 70(4): 289-296, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33465798

RESUMO

BACKGROUND: The aim of this study is to test if the newly proposed 45 mm size criterion for ascending aortic replacement (AAR) in bicuspid aortic valve (BAV) patients undergoing aortic valve replacement (AVR) is predictive of improved early outcomes. METHODS: Data of 306 BAV patients with an aortic diameter of ≥45 mm undergoing AVR alone or with AAR were retrospectively analyzed. Patients were divided into groups of AVR + AAR (n = 220) and AVR only (n = 86) based on if surgery was performed according to the 45 mm criterion. End point was early adverse events, including 30-day and in-hospital mortality, cardiac events, acute renal failure, stroke, and reoperation for bleeding. Cox regression was used to assess if conformance to 45 mm criterion could predict fewer early adverse events. RESULTS: AVR + AAR group had significantly higher postoperative left ventricular ejection fraction (LVEF) (0.59 ± 0.09 vs. 0.55 ± 0.11, p = 0.006) and longer cardiopulmonary bypass (CPB) time (128 vs. 111 minutes, p = 0.002). Early adverse events occurred in 45 patients (14.7%), which was more prevalent in the AVR-only group (22.1% vs. 11.8%, p = 0.020). Conformance to the 45 mm criterion predicted lower rate of early adverse events (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.28-0.98, p = 0.042). After adjustment for gender, age, AAo diameter, sinuses of Valsalva diameter, preoperative LVEF, Sievers subtypes, BAV valvulopathy, and CPB and cross-clamp times, conformance to the 45 mm size criterion still predicted lower incidence of early adverse events (HR: 0.37, 95% CI: 0.15-0.90, p = 0.028). CONCLUSIONS: This study shows that conformance to 45 mm size cutoff for preemptive AAR during aortic valve replacement in patients with BAV was not associated with increased risk for adverse events and may improve early surgical outcomes.


Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Implante de Prótese de Valva Cardíaca , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
20.
J Cardiothorac Vasc Anesth ; 36(3): 870-879, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34507886

RESUMO

OBJECTIVE: The purpose of this cohort study was to investigate the relationship between non-thyroidal illness syndrome (NTIS) and severe multiorgan dysfunction, measured by Sequential Organ Failure Assessment score ≥11, after surgical repair of type A aortic dissection (TAAD). SETTING: An observational study. PARTICIPANTS: The present study included 310 patients with TAAD surgically repaired between January 2019 and December 2020 in Beijing Anzhen Hospital. INTERVENTIONS: Patients after surgical repair after TAAD. MEASUREMENTS AND MAIN RESULTS: Among a total of 310 patients with TAAD undergoing surgical repair included in this study, 132 (42.6%) experienced surgery-associated NTIS. Severe multiorgan dysfunction was experienced more often in patients with NTIS (27.3% v 11.2%, p < 0.0001). Multivariate analysis demonstrated NTIS was associated closely with an increased risk of severe multiorgan dysfunction (odds ratio [OR] = 2.54, 95% CI = 1.39-4.64 p = 0.002), which predicted an in-hospital death rate of 95%. Non-thyroidal illness syndrome also was related with in-hospital major adverse cardiovascular and cerebral events (OR = 2.12, 95% CI = 1.30-3.46 p = 0.003), acute kidney injury (OR = 3.17, 95% CI = 1.17-8.47 p = 0.023), and postoperative pulmonary complications (OR = 2.32, 95% CI = 1.34-4.03 p = 0.003). However, hepatic inadequacy was comparable in the NTIS and control groups. CONCLUSIONS: Non-thyroidal illness syndrome was associated closely with multiorgan dysfunction after surgical repair of TAAD, which may be correlated further with an increased incidence of in-hospital mortality and complications.


Assuntos
Dissecção Aórtica , Síndromes do Eutireóideo Doente , Dissecção Aórtica/complicações , Dissecção Aórtica/cirurgia , Estudos de Coortes , Síndromes do Eutireóideo Doente/diagnóstico , Síndromes do Eutireóideo Doente/epidemiologia , Síndromes do Eutireóideo Doente/etiologia , Mortalidade Hospitalar , Humanos , Incidência
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