RESUMO
BACKGROUND: Whether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied. METHODS: A total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index ([Formula: see text] index). RESULTS: Given the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yielded [Formula: see text] index of 0.7236-0.8222 and 0.7279-0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the best [Formula: see text] index of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level. CONCLUSIONS: Deep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.
Assuntos
Isquemia Encefálica , Aprendizado Profundo , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , PrognósticoRESUMO
Background and Purpose: This study aimed to investigate the value of d-dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d-dimer levels. Methods: A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d-dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. Results: The risk of recurrent stroke increased significantly with the increasing d-dimer quartile (log-rank P=0.001). Patients in the higher d-dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P=0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P<0.001, respectively; Ptrend<0.001). Binary analyses showed a significant association between a high d-dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P=0.005). In subgroup analyses, a high d-dimer level was associated with a significantly higher risk of recurrent stroke in men than in women (P=0.039). Conclusions: Our findings suggest that d-dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.
Assuntos
AVC Embólico/sangue , AVC Embólico/diagnóstico por imagem , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Estudos RetrospectivosRESUMO
OBJECTIVE: AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. METHODS: Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. RESULTS: In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). CONCLUSION: Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.
Assuntos
Inflamação/metabolismo , Osteogênese/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Espondilite Anquilosante/metabolismo , Células-Tronco/efeitos dos fármacos , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Ileíte/metabolismo , Ileíte/patologia , Inflamação/diagnóstico por imagem , Inflamação/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoblastos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Fator de Transcrição STAT3/efeitos dos fármacos , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/patologia , Tiofenos/farmacologia , Microtomografia por Raio-X , Adulto Jovem , beta-Glucanas/farmacologiaRESUMO
High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein-an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.
Assuntos
Fármacos Neuroprotetores/farmacologia , Salicilatos/farmacologia , Zumbido/induzido quimicamente , Zumbido/tratamento farmacológico , Ácido Valproico/farmacologia , Animais , Linhagem Celular Tumoral , Ácido Glutâmico/metabolismo , Humanos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Zumbido/metabolismoRESUMO
BACKGROUND AND PURPOSE: We investigated the impact of the presence, burden, and location of cerebral microbleeds (CMBs) on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in patients with acute ischemic stroke and atrial fibrillation treated with oral anticoagulants (OACs). We also examined whether the clinical effect of CMBs differs according to the type of OACs. METHODS: A total of 1742 patients with acute ischemic stroke and atrial fibrillation treated with OACs were enrolled in this cohort study. The primary composite outcome was the occurrence of MACCE (a composite of stroke, acute myocardial infarction, or vascular death) over a 2-year period according to CMB status. RESULTS: CMB presence was significantly associated with the risk of future MACCE (hazard ratio, 1.89 [95% CI, 1.23-2.88]; P=0.003) after adjustment for confounders in patients with acute ischemic stroke and atrial fibrillation taking OACs. Patients with exactly 1 CMB had a similar rate of MACCE compared with those without CMBs (P=0.461). However, patients with multiple CMBs (≥2), particularly high burden CMBs (≥5), had a significantly higher proportion of MACCE. Both CMB-positive groups with lobar and deep CMB had more frequent MACCE than the CMB-negative group, and the rate of MACCE was not different according to CMB location. In patients treated with warfarin, CMB was significantly associated with a risk of MACCE (P=0.002), but not in patients treated with direct OACs (P=0.517). CONCLUSIONS: The study results indicate that the risk of future MACCE increased with increasing CMB burden in patients with AIS and atrial fibrillation taking OACs, while the anatomic location of CMBs did not influence the risk of future MACCE. This risk seemed to be more apparent in patients taking warfarin.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , AVC Embólico/tratamento farmacológico , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Infarto do Miocárdio/epidemiologia , Doenças Vasculares/mortalidade , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Hemorragia Cerebral/diagnóstico por imagem , AVC Embólico/epidemiologia , AVC Embólico/etiologia , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.
Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Tireoglobulina , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND: The aim of this study was to investigate changes in myocardial uptake evaluated by oncologic 18F-fluorodeoxyglucose (FDG) PET/CT scans and to determine the relationship between myocardial FDG uptake and cancer therapy-induced cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. METHODS: We reviewed 121 consecutive patients who underwent oncologic FDG PET/CT and echocardiography at baseline and post-therapy with anthracyclines or trastuzumab for breast cancer. Grade in LV wall, uptake pattern in LV wall, and the presence of RV wall uptake were assessed by visual analysis, and the mean SUV in the LV and RV walls and the change of SUV (ΔSUV) between baseline and post-therapy PET/CT were measured by quantitative analysis. Multiple logistic regression analyses were performed to evaluate the association between PET parameters and cardiotoxicity. RESULTS: Fifteen patients (12%) showed cardiotoxicity after therapy. The cardiotoxic group tended to show more diffuse LV uptake, higher SUV, and ΔSUV of RV wall than the non-cardiotoxic group following therapy with anthracyclines or trastuzumab. Logistic regression analysis showed that the presence of RV wall uptake, SUV of RV wall (> 1.8), and ΔSUV of RV wall (> 0.4) were significantly associated with cardiotoxicity after controlling for age, radiotherapy, and treatment. CONCLUSIONS: The presence of RV wall uptake and the increase of SUV of RV wall on post-therapy PET/CT were associated with cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. Oncologic FDG PET/CT scans can provide information regarding cancer therapy-induced cardiotoxicity as well as tumor response.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Fluordesoxiglucose F18 , Ventrículos do Coração/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Disfunção Ventricular Direita/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Sensibilidade e Especificidade , Trastuzumab/administração & dosagemRESUMO
Correct guiding of the catheter is a critical issue in almost all balloon catheter applications, including arterial stenosis expansion, coronary arterial diseases, and gastrointestinal tracking. To achieve safe and precise guiding of the balloon catheter, a novel imaging method with high-resolution, sufficient depth of penetration, and real-time display is required. Here, we present a new balloon catheter guiding method using fast photoacoustic microscopy (PAM) technique for precise balloon catheter tracking and visualization as a feasibility study. We implemented ex vivo and in vivo experiments with three different medium conditions of balloon catheter: no air, air, and water. Acquired cross-sectional, maximum amplitude projection (MAP), and volumetric 3D PAM images demonstrated its capability as a new imaging guiding tool for balloon catheter tracking and visualization.
Assuntos
Catéteres , Microscopia , Técnicas Fotoacústicas , Estudos Transversais , Estudos de Viabilidade , HumanosRESUMO
Background and Purpose- We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods- A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results- The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P=0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions- These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.
RESUMO
Background and Purpose- We analyzed the association between cerebral microbleeds (CMBs) and clinical outcome in acute ischemic stroke patients and especially in a subgroup of patients with successful recanalization. Methods- A total of 1532 acute ischemic stroke patients treated with intravenous thrombolysis or mechanical thrombectomy were enrolled in this prospective cohort study. The primary outcome was measured using the modified Rankin Scale at 3 months, according to the CMB status based on magnetic resonance imaging at admission. Favorable outcome was defined as functional independence with modified Rankin Scale scores of 0 to 2. Secondary outcomes included the occurrence of symptomatic intracranial hemorrhage. Results- There was no statistically significant association between the presence of CMB and favorable outcome at 3 months when considering all patients (44.3% versus 37.6%; P=0.121). In patients with recanalization, the number of patients with favorable outcomes was significantly higher in the CMB-negative than in the CMB-positive group (57.0% versus 36.0%; P<0.001). In the final multivariate analysis, the presence of CMB, and in particular high CMB burden (≥5), and lobar location, were significantly associated with less favorable 3-month outcomes (odds ratio=0.57; 95% CI, 0.33-0.97; P=0.038) and symptomatic intracranial hemorrhage (odds ratio=3.21; 95% CI, 1.37-7.49; P=0.007) in patients with recanalization. In the analysis of subgroups, a statistically significant interaction was found between CMB presence and recanalization in predicting functional outcomes at 3 months. Conclusions- These results indicate that the presence of CMBs, and especially high burden and lobar location, are independent predictors of poor 3-month clinical outcomes and may increase symptomatic intracranial hemorrhage risk in acute ischemic stroke patients with recanalization. Our findings suggest that CMBs lead to more unfavorable effects in patients with recanalization after large vessel occlusion than in those without recanalization.
RESUMO
Background and Purpose- The purpose of this study was to investigate the association between adiposity using adipose tissue imaging and stroke outcomes in acute ischemic stroke patients treated with intravenous thrombolysis. Methods- A total of 127 patients with acute ischemic stroke treated with intravenous thrombolysis who underwent abdominal computed tomography on admission were enrolled in this prospective cohort study. Patients were grouped according to their visceral adipose tissue (VAT) proportion tertile. The primary outcome was measured using the modified Rankin Scale 3 months after symptom onset. Favorable and excellent outcomes were defined as modified Rankin Scale scores of 0 to 2 and 0 to 1, respectively. Results- As VAT proportion tertile increased, the number of patients exhibiting a favorable or excellent outcome decreased. In the final multivariable analysis after adjustments for confounders, patients in the highest VAT proportion tertile showed a decreased probability of a favorable and excellent outcome compared with those in the lowest tertile (odds ratio=0.18; 95% CI, 0.05-0.60; P=0.005 and odds ratio=0.13; 95% CI, 0.02-0.64; P=0.012, respectively). Obese patients (body mass index ≥25) also showed an excellent outcome compared with nonobese patients (odds ratio=4.88; 95% CI, 1.47-7.85; P=0.011). Among obese patients, those with an excellent outcome presented a significantly lower VAT proportion than those without (38.2% versus 46.1%, P=0.006). Conclusions- Results of this study indicate that low visceral abdominal fat proportion is associated with a favorable and excellent outcome in acute ischemic stroke patients treated with intravenous thrombolysis. Better clinical outcomes in obese patients were also associated with a lower proportion of VAT.
Assuntos
Adiposidade , Isquemia Encefálica , Gordura Intra-Abdominal/diagnóstico por imagem , Obesidade , Sistema de Registros , Acidente Vascular Cerebral , Terapia Trombolítica , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Obesidade/mortalidade , Obesidade/terapia , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapiaRESUMO
PURPOSE: The purpose of this study is to evaluate whether fluorodeoxyglucose (FDG) uptake of the large arteries can predict coronary artery calcium (CAC) progression in asymptomatic individuals. METHODS: Ninety-six asymptomatic individuals who underwent FDG positron emission tomography (PET) and CAC scoring on the same day for health screening and follow-up CAC scoring ≥1 year after baseline studies (mean 4.3 years) were included. Vascular FDG uptake was measured and corrected for blood pool activity to obtain peak and average target-to-blood pool ratios (TBRpeak and TBRavg, respectively) for the carotid arteries, and ascending and abdominal aorta. CAC scores at baseline and follow-up of each individual were measured and absolute CAC change (ΔCAC), annual CAC change (ΔCAC/year), and annual CAC change rate (ΔCAC%/year) were calculated. CAC progression was defined as ΔCAC >0 for individuals with negative baseline CAC; ΔCAC/year ≥10 for those with baseline CAC of 0Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem
, Doença da Artéria Coronariana/metabolismo
, Fluordesoxiglucose F18/farmacocinética
, Tomografia por Emissão de Pósitrons/métodos
, Calcificação Vascular/diagnóstico por imagem
, Calcificação Vascular/metabolismo
, Algoritmos
, Doenças Assintomáticas
, Simulação por Computador
, Doença da Artéria Coronariana/etiologia
, Progressão da Doença
, Feminino
, Humanos
, Interpretação de Imagem Assistida por Computador/métodos
, Masculino
, Pessoa de Meia-Idade
, Modelos Cardiovasculares
, Prognóstico
, Compostos Radiofarmacêuticos/farmacocinética
, Reprodutibilidade dos Testes
, Sensibilidade e Especificidade
, Calcificação Vascular/complicações
RESUMO
PURPOSE: The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. METHODS: One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. RESULTS: MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3° vs. 35.3 ± 18.9°; p <0.001), stress PBW (147.6 ± 54.6° vs. 96.8 ± 59.2°; p = 0.001) and resting PBW (126.8 ± 37.5° vs. 96.6 ± 48.9°; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5° and stress PBW ≥126.0° were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. CONCLUSIONS: LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging tool in patients with acute MI and multivessel disease.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Imagem do Acúmulo Cardíaco de Comporta/estatística & dados numéricos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Causalidade , Comorbidade , Intervalo Livre de Doença , Feminino , Imagem do Acúmulo Cardíaco de Comporta/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Volume Sistólico , Taxa de SobrevidaRESUMO
BACKGROUND AND PURPOSE: Most patients with cerebral infarction die of brain edema because of the breakdown of the blood-brain barrier (BBB) in ischemic tissue. Caveolins (a group of proteins) are key modulators of vascular permeability; however, a direct role of caveolin-1 (Cav-1) in the regulation of BBB permeability during ischemic injury has yet to be identified. METHODS: Cav-1 expression was measured by immunoblotting after photothrombotic ischemia. A direct functional role of Cav-1 in cerebral edema and BBB permeability during cerebral ischemia was investigated by genetic manipulation (gene disruption and re-expression) of Cav-1 protein expression in mice. RESULTS: There was a significant correlation between the extent of BBB disruption and the Cav-1 expression. In Cav-1-deficient (Cav-1(-/-)) mice, the extent of BBB disruption after cerebral ischemia was increased compared with wild-type (Cav-1(+/+)) mice, whereas the increase in cerebral edema volume was ameliorated by lentiviral-mediated re-expression of Cav-1. Furthermore, Cav-1(-/-) mice had significantly higher degradation of tight junction proteins and proteolytic activity of matrix metalloproteinase than Cav-1(+/+) mice. Conversely, re-expression of Cav-1 in Cav-1(-/-) mice restored tight junction protein expression and reduced matrix metalloproteinase proteolytic activity. CONCLUSIONS: These results indicate that Cav-1 is a critical determinant of BBB permeability. Strategies for regulating Cav-1 represent a novel therapeutic approach to controlling BBB disruption and subsequent neurological deterioration during cerebral ischemia.
Assuntos
Barreira Hematoencefálica/metabolismo , Edema Encefálico/metabolismo , Isquemia Encefálica/metabolismo , Caveolina 1/metabolismo , Animais , Caveolina 1/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Camundongos , Camundongos KnockoutRESUMO
PURPOSE: 18F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of 18F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischaemic stroke in cancer patients. METHODS: From among cancer patients presenting with various neurological symptoms and hemiparesis, 134 were selected as eligible for this retrospective analysis. A new infarct lesion on brain MRI within 1 year of FDG PET/CT defined future ischaemic stroke. The target-to-background ratio (TBR) of each arterial segment was used to define arterial inflammation on PET imaging. Abdominal obesity was defined in terms of the area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT) on a single CT slice at the umbilical level. RESULTS: Ischaemic stroke confirmed by MRI occurred in 30 patients. Patients with stroke had higher TBRs in the carotid arteries and abdominal aorta (P < 0.001) and a higher VAT proportion (P = 0.021) and TAT proportion (P = 0.041) than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and the presence of a metabolically active tumour were significantly associated with future ischaemic stroke. Combining PET and CT variables improved the power for predicting future ischaemic stroke. CONCLUSION: Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET and the VAT proportion on CT could be independent predictors of future ischaemic stroke in patients with cancer and could identify those patients who would benefit from medical treatment.
Assuntos
Fluordesoxiglucose F18 , Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Idoso , Causalidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Infarto Miocárdico de Parede Anterior/tratamento farmacológico , Compostos de Bifenilo/uso terapêutico , Cardiotônicos/uso terapêutico , Pirimidinas/uso terapêutico , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/fisiologia , 3-Iodobenzilguanidina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Infarto Miocárdico de Parede Anterior/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Fluordesoxiglucose F18 , Perindopril/uso terapêutico , Tomografia por Emissão de Pósitrons , Distribuição Aleatória , Suínos , Tomografia Computadorizada de Emissão de Fóton Único , Valsartana/uso terapêuticoRESUMO
The contribution that F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG) PET/CT makes to the diagnosis of malignancy in patients with hemophagocytic lymphohistiocytosis (HLH) is still uncertain. The aim of this study was to evaluate the diagnostic performance of F-18 FDG PET/CT for the detection of underlying malignancy, to investigate the correlation between PET and laboratory parameters, and to identify prognosis-related factors in patients with secondary HLH. We enrolled 14 patients who were diagnosed with HLH and referred for F-18 FDG PET/CT to exclude malignancy. The diagnostic performance of F-18 FDG PET/CT for malignancy detection was assessed. The correlations between PET and laboratory parameters were determined. The prognostic significance of the following factors was evaluated: PET and laboratory parameters, age in years, presence of underlying malignancy, and fever and splenomegaly. Six of the 14 patients had malignancies (four with lymphoma, one with multiple myeloma, and one with colonic malignancy). Sensitivity, specificity, and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 83, 62.5, and 71.4 %, respectively. F-18 FDG uptake in the bone marrow and spleen was positively correlated with neutrophil count and C-reactive protein. All of the PET parameters, but none of the clinical or laboratory parameters, were significantly associated with patient outcome, as determined by univariate analysis. Given the small sample size, F-18 FDG PET/CT was useful for detecting underlying malignancy, and PET parameters correlated with laboratory parameters that reflected inflammatory status. F-18 FDG PET/CT might provide prognostic information for the management of patients with secondary HLH.