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1.
Insights Imaging ; 15(1): 75, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499900

RESUMO

PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

2.
Eur Radiol ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189980

RESUMO

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

3.
J Magn Reson Imaging ; 59(3): 1034-1042, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37272790

RESUMO

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.


Assuntos
Hepatoblastoma , Neoplasias Hepáticas , Masculino , Criança , Humanos , Pré-Escolar , Lactente , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/patologia , Hepatoblastoma/cirurgia , Terapia Neoadjuvante , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Veias Hepáticas , Sensibilidade e Especificidade , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias
4.
J Med Virol ; 95(11): e29208, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37947293

RESUMO

The main proteases (Mpro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of Mpro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-Mpro effect (IC50 = 37.82 µg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify Mpro . We subsequently verified the anti-Mpro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 Mpro in dose- and time- dependent manners, with the IC50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of Mpro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants.


Assuntos
COVID-19 , Plantas Medicinais , Humanos , SARS-CoV-2 , Ensaios de Triagem em Larga Escala , Quercetina/farmacologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Extratos Vegetais/farmacologia , Antivirais/farmacologia , Antivirais/química , Ácido Gálico/farmacologia , Simulação de Acoplamento Molecular
5.
Eur Radiol ; 33(12): 8477-8487, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37389610

RESUMO

OBJECTIVE: The current study aimed to explore a deep convolutional neural network (DCNN) model that integrates multidimensional CMR data to accurately identify LV paradoxical pulsation after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. METHODS: A total of 401 participants (311 patients and 90 age-matched volunteers) were recruited for this prospective study. The two-dimensional UNet segmentation model of the LV and classification model for identifying paradoxical pulsation were established using the DCNN model. Features of 2- and 3-chamber images were extracted with 2-dimensional (2D) and 3D ResNets with masks generated by a segmentation model. Next, the accuracy of the segmentation model was evaluated using the Dice score and classification model by receiver operating characteristic (ROC) curve and confusion matrix. The areas under the ROC curve (AUCs) of the physicians in training and DCNN models were compared using the DeLong method. RESULTS: The DCNN model showed that the AUCs for the detection of paradoxical pulsation were 0.97, 0.91, and 0.83 in the training, internal, and external testing cohorts, respectively (p < 0.001). The 2.5-dimensional model established using the end-systolic and end-diastolic images combined with 2-chamber and 3-chamber images was more efficient than the 3D model. The discrimination performance of the DCNN model was better than that of physicians in training (p < 0.05). CONCLUSIONS: Compared to the model trained by 2-chamber or 3-chamber images alone or 3D multiview, our 2.5D multiview model can combine the information of 2-chamber and 3-chamber more efficiently and obtain the highest diagnostic sensitivity. CLINICAL RELEVANCE STATEMENT: A deep convolutional neural network model that integrates 2-chamber and 3-chamber CMR images can identify LV paradoxical pulsation which correlates with LV thrombosis, heart failure, ventricular tachycardia after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. KEY POINTS: • The epicardial segmentation model was established using the 2D UNet based on end-diastole 2- and 3-chamber cine images. • The DCNN model proposed in this study had better performance for discriminating LV paradoxical pulsation accurately and objectively using CMR cine images after anterior AMI compared to the diagnosis of physicians in training. • The 2.5-dimensional multiview model combined the information of 2- and 3-chamber efficiently and obtained the highest diagnostic sensitivity.


Assuntos
Aprendizado Profundo , Infarto do Miocárdio , Humanos , Estudos Prospectivos , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Infarto do Miocárdio/diagnóstico por imagem
6.
Insights Imaging ; 14(1): 50, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941401

RESUMO

OBJECTIVES: This study aimed to investigate the influence of microvascular impairment on myocardial characteristic alterations in remote myocardium at multiple time points, and its prognostic significance after acute ST-segment elevation myocardial infarction (STEMI). METHODS: Patients were enrolled prospectively and performed CMR at baseline, 30 days, and 6 months. The primary endpoint was major adverse cardiac events (MACE): death, myocardial reinfarction, malignant arrhythmia, and hospitalization for heart failure. Cox proportional hazards regression modeling was analyzed to estimate the correlation between T1 mapping of remote myocardium and MACE in patients with and without microvascular obstruction (MVO). RESULTS: A total of 135 patients (mean age 60.72 years; 12.70% female, median follow-up 510 days) were included, of whom 86 (63.70%) had MVO and 26 (19.26%) with MACE occurred in patients. Native T1 values of remote myocardium changed dynamically. At 1 week and 30 days, T1 values of remote myocardium in the group with MVO were higher than those without MVO (p = 0.030 and p = 0.001, respectively). In multivariable cox regression analysis of 135 patients, native1w T1 (HR 1.03, 95%CI 1.01-1.04, p = 0.002), native30D T1 (HR 1.05, 95%CI 1.03-1.07, p < 0.001) and LGE (HR 1.10, 95%CI 1.05-1.15, p < 0.001) were joint independent predictors of MACE. In multivariable cox regression analysis of 86 patients with MVO, native30D T1 (HR 1.05, 95%CI 1.04-1.07, p < 0.001) and LGE (HR 1.10, 95%CI 1.05-1.15, p < 0.001) were joint independent predictors of MACE. CONCLUSIONS: The evolution of native T1 in remote myocardium was associated with the extent of microvascular impairment after reperfusion injury. In patients with MVO, native30D T1 and LGE were joint independent predictors of MACE.

7.
Eur Radiol ; 33(1): 283-293, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35925386

RESUMO

OBJECTIVE: This study aimed to investigate the correlation between increased extracellular matrix estimated by cardiac magnetic resonance (CMR) and left ventricular aneurysm after acute myocardial infarction. METHODS: A total of 175 patients from 3 centers with an isolated left anterior descending culprit vessel underwent CMR examinations within 1 week and at a 6-month follow-up. Of these, 92 were identified to have left ventricular aneurysms (LVAs): 74 with functional aneurysm and 18 with anatomical aneurysm. The predictive significance of acute extracellular volume (ECV), left gadolinium enhancement (LGE), and other characteristics were analyzed using binary logistic regression analysis. RESULTS: Patients with LVA were more likely to present with left ventricular adverse remodeling (LVAR) than those without (p = 0.009). With optimal cutoff values of 30.90% for LGE and 33% for ECV to discriminate LVA from non-LVA, the area under the curve (AUC) by receiver operator characteristic curve (ROC) analysis was 0.92 (95% CI: 0.87-0.96; p < 0.001) and 0.93 (95% CI: 0.88-0.96; p < 0.001), respectively. ECV was significantly better than LGE at discriminating between functional and anatomical LVA (p < 0.001). Both acute LGE and ECV were predictors of LVA, with an odds ratio of 1.35 (95% CI: 1.21-1.52, p < 0.001) and 1.23 (95% CI: 1.13-1.33, p < 0.001), respectively, by multivariable logistic regression analysis. CONCLUSIONS: Acute LGE and ECV of the myocardium provided predictive significance for LVA. The discriminative significance of ECV for functional versus anatomical LVA was better than the discriminative significance of LGE. KEY POINTS: • Patients with LVA were more likely to present with LVAR. • Acute LGE and ECV of the myocardium provided the strongest predictive significance for LVA. • The discriminative significance of ECV for functional versus anatomical LVA was better than that of LGE.


Assuntos
Meios de Contraste , Infarto do Miocárdio , Humanos , Meios de Contraste/farmacologia , Gadolínio , Miocárdio/patologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Remodelação Ventricular , Valor Preditivo dos Testes , Espectroscopia de Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda
8.
Cardiovasc Diagn Ther ; 13(6): 1030-1042, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38162100

RESUMO

Background: Trabecular complexity can be quantified by fractal analysis based on cine images of cardiovascular magnetic resonance (CMR), yielding fractal dimension (FD) index. We aimed to investigate the prognostic value of biventricular FD in patients with hypertrophic cardiomyopathy (HCM). Methods: This retrospective study included 284 (192 men, median age 53 years) patients with HCM who underwent CMR, with median follow-up of 24 months. Biventricular trabeculae complexity was quantified as FD using short-axis cine images. The primary end point included sudden cardiac death (SCD) events. The secondary end point included both SCD events and rehospitalization due to heart failure. Cox regressions were performed. Prediction models were established by adding ventricular FDs to ESC predictors and late gadolinium enhancement (LGE) percentage and the C indices were calculated. Results: Cox regressions revealed that left ventricular (LV) maximal apical FD (HR range 1.114-1.133; all P<0.05) and right ventricular (RV) global FD (HR range 1.135-1.150; all P<0.05) were significant prognostic factors of both end points after adjustment for the European Society of Cardiology (ESC) predictors (age, maximum LV wall thickness, LV atrial size, peak left ventricular outflow tract (LVOT) gradient, family history of SCD, unexplained syncope, non-sustained ventricular tachycardia), and LGE percentage. The prediction model with the addition of biventricular FDs (C-index: 0.864-0.877) had the best performance. Conclusions: LV maximal apical FD and RV global FD were independent predictors of SCD events and rehospitalization due to heart failure in patients with HCM. The addition of biventricular FDs to the conventional prediction model contributed incremental prognosis value in HCM.

9.
Int J Cardiovasc Imaging ; 38(11): 2373-2384, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36434326

RESUMO

Left ventricular thrombus (LVT) after acute ST-segment elevation myocardial infarction (STEMI) are generally associated with poorer outcomes for patients at long-term follow-up. We hypothesis that tissue characteristics and strain parameters by cardiac magnetic resonance (CMR) imaging may indicate the interactions of LVT with ventricular myocardium remodeling at both acute stage and chronic stages in STEMI patients. This retrospective study included 111 consecutive STEMI patients (38 with LVT and 73 without LVT). All patients underwent CMR during acute stage (within 7 days) and chronic stage (after at least 2 months) periods after percutaneous coronary intervention (PCI). Left ventricular native T1, extracellular volume (ECV), radial, circumferential, and longitudinal strain were analyzed in both phases. Major adverse cardiac events (MACE, including cardiovascular death, myocardial reinfarction, and hospitalization for heart failure), thromboembolic and bleeding events, were the clinical endpoints of the study. During the acute stage, left ventricular ejection fraction (LVEF) (OR 0.77, P value = 0.01) and longitudinal strain (OR 1.90, P value < 0.001) were correlated with LVT formation. Strain parameters were reduced, while the native T1 and ECV values of both the infarcted area and remote myocardium were elevated in LVT patients. During the chronic stage, LVT resolved in 29 of 38 patients (76%). LVT remaining patients had lower LVEF, a larger LV, and higher ECV in the acute stage than those of the LVT-resolved patients. In the long-term follow up of 678 days, LVT (HR 2.45, P value = 0.02), aneurysm (HR 1.81, P value = 0.04), and native T1 (HR 2.44, P value = 0.01) were identified as three independent predictors of MACE, the incidence of thromboembolic events and bleeding events by a multivariable stepwise Cox proportional hazards regression. STEMI patients developing LVT had worse LV function, myocardial infarction extent, strain, and higher T1 and ECV values than STEMI patients without LVT. The LVT-remaining patients in the chronic stage had poorer functional and mapping parameters beginning in the first week. During the acute stage, LVEF and global longitudinal strain were independent correlated with LVT formation. During the long-term follow up, LVT, aneurysm and elevated myocardial T1 were associated with adverse outcomes in acute STEMI patients.


Assuntos
Infarto Miocárdico de Parede Anterior , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Intervenção Coronária Percutânea/efeitos adversos , Volume Sistólico , Estudos Retrospectivos , Função Ventricular Esquerda , Valor Preditivo dos Testes , Infarto Miocárdico de Parede Anterior/complicações , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Infarto Miocárdico de Parede Anterior/terapia , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/terapia , Infarto do Miocárdio/complicações , Arritmias Cardíacas/complicações , Imageamento por Ressonância Magnética/efeitos adversos
12.
J Magn Reson Imaging ; 56(3): 779-789, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35049073

RESUMO

BACKGROUND: Myocardial T1 and extracellular volume (ECV) fraction values have important roles in the prognostication of heart failure with preserved ejection fraction (HFpEF). However, the traditional mean quantification of intensity levels is not sufficient. PURPOSE: To evaluate a T1 map-based radiomic nomogram as a long-term prognosticator for HFpEF in systemic lupus erythematosus (SLE) patients. STUDY TYPE: Prospective. POPULATION: A total of 115 SLE patients and 50 age- and gender-matched controls. FIELD STRENGTH/SEQUENCE: A 3.0 T scanner; cine imaging, precontrast and post-contrast T1 mapping and T2 mapping sequences. ASSESSMENT: A radiomic nomogram was developed based on precontrast T1 mapping. Three independent readers assessed and compared the ECV value and the value of the radiomic nomogram for predicting HFpEF in SLE patients. STATISTICAL TEST: Cox proportional hazard models, Youden index for determining cut-off values for high HFpEF risk vs. low HFpEF risk classification, Kaplan-Meier analysis, intraclass correlation (ICC), and Uno C statistic test. RESULTS: During a median follow-up of 27 (interquartile range, 19-37) months, 31 SLE patients developed HFpEF. Patients with elevated ECV (≥31%) and a higher output (≥42.7) from the radiomic feature "S_33_sum average" of the precontrast T1 map had a significantly higher risk of developing HFpEF than those who had lower ECV (<31%) and an output <42.7. Patients with a higher "S_33_sum average" value on precontrast T1 map had a significantly increased risk for HFpEF (hazard ratio, 1.363, 95% CI, 1.130-1.645), after adjusting for covariates including ECV and LVEF. Finally, "S_33_sum average" from precontrast T1 mapping had modest but significantly incremental prognostic value over the mean ECV value (Uno C statistic comparing models, 0.860 vs. 0.835). DATA CONCLUSION: The precontrast T1 map-based radiomic nomogram, as a measure of diffuse myocardial fibrosis was associated with HFpEF and provided modest prognostic value for predicting HFpEF in SLE patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.


Assuntos
Insuficiência Cardíaca , Lúpus Eritematoso Sistêmico , Fibrose , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Imageamento por Ressonância Magnética/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Nomogramas , Valor Preditivo dos Testes , Estudos Prospectivos , Volume Sistólico , Função Ventricular Esquerda
13.
Acta Pharmacol Sin ; 43(4): 781-787, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34294887

RESUMO

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.


Assuntos
Antivirais , COVID-19 , Antivirais/química , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2
14.
Int J Cardiovasc Imaging ; 37(12): 3549-3560, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34279752

RESUMO

OBJECTIVES: We sought to distinguish area at risk from salvage myocardial zone and to predict left ventricle functional recovery in the convalescent stage by Texture Analysis (TA) of T2-Mapping. METHODS: One hundred and six patients diagnosed with AMI and treated with percutaneous coronary intervention (PCI) underwent acute cardiac magnetic resonance imaging (CMR) and 45 of whom had a subsequent CMR scan following recovery. Cine imaging, T2-Mapping, T2-weighted STIR imaging, and LGE imaging were performed. In the texture analysis, regions of interest (infarcted, salvageable, and remote) were drawn by two blinded, independent readers. RESULTS: Seven independent texture features on T2-Mapping were selected: Perc.50%, S(2,2)InvDfMom, S(2.-2)AngScMom, S(4,0)Entropy, 45dgrLngREmph, 45dgr_Fraction and 135dr_GLevNonU. Among them, the average value of 135dr_GLevNonU in the infarct zone, AAR zone, and the remote zone was: 61.96±26.03, 31.811±18.933 and 99.839±26.231, respectively. Additionally, 135dr_GLevNonU provided the highest area under the curve (AUC) from the receiver operating characteristic curve (ROC curve) for distinguishing AAR from the infarct zone in each subgroup (all patients, patients with MVO and)were 0.845 ± 0.052 0.855 ± 0.083 and 0.845 ± 0.066, respectively, and were more promise than T2-Mapping mean (p<0.001). The AUC for differentiating AAR from the remote zone is 0.942±0.041. Texture features are not associated with convalescent decreased strain, ejection fraction (EF) or left ventricle remodeling (LVR) in analysis (p>0.05). CONCLUSION: TA of T2-mapping can distinguish AAR from both the infarct zone and the remote myocardial zone without LGE imaging in reperfused AMI. However, these features are not able to predict patients' functional recovery in the convalescent stage.


Assuntos
Intervenção Coronária Percutânea , Meios de Contraste , Humanos , Imagem Cinética por Ressonância Magnética , Miocárdio , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes
15.
Abdom Radiol (NY) ; 46(9): 4226-4237, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33914139

RESUMO

Pancreatic ductal adenocarcinomas (PDACs) occasionally have atypical and uncommon imaging presentations that can present a diagnostic dilemma and result in false interpretation. This article aimed to illustrate these CT and MR imaging findings, including isoattenuating PDAC, coexisting acute pancreatitis, PDAC with a cystic feature, groove PDAC, diffuse PDAC, hypointensity on diffusion-weighted imaging (DWI), multifocal PDAC, intratumoral calcification, and extrapancreatic invasion with a barely discernable mass. A subset of PDACs with atypical features are occasionally encountered during routine clinical practice. Knowledge of and attention to these atypical and uncommon variable imaging features may allow radiologists to avoid misinterpretation and a delayed diagnosis.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite , Doença Aguda , Carcinoma Ductal Pancreático/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
16.
Eur Heart J Cardiovasc Imaging ; 22(8): 844-851, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33686389

RESUMO

AIMS: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms. METHODS AND RESULTS: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001). CONCLUSION: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent.


Assuntos
COVID-19 , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Estudos Prospectivos , SARS-CoV-2
19.
J Magn Reson Imaging ; 53(2): 516-526, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32841481

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) is a disease with high morbidity and mortality worldwide and the evaluation of myocardial injury and perfusion status following myocardial ischemia and reperfusion is of clinical value. PURPOSE: To assess the diagnostic utility of simplified perfusion fraction (SPF) in differentiating salvage and infarcted myocardium and its predictive value for left ventricular remodeling in patients with reperfusion ST-segment elevation myocardial infarction (STEMI). STUDY TYPE: Prospective. POPULATION: Forty-one reperfused STEMI patients and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T MRI. The MR examination included cine, T2 -short tau inversion recovery (T2 -STIR), first pass perfusiong (FPP),phase sensitive inversion recovery (PSIR), and diffusion-weighted imaging (DWI). ASSESSMENT: SPF values among different myocardium regions (infarcted, salvaged, remote, and MVO) and stages of reperfused STEMI patients as well as normal controls were measured. The diagnostic utility of SPF values in differentiating salvaged and infarcted myocardium was assessed. STATISTICAL ANALYSIS: Independent t-test and the Mann-Whitney U-test. Logistic regression. RESULTS: SPF values in healthy controls were not significantly different than SPF values in the remote myocardium of patients (40.09 ± 1.47% vs. 40.28 ± 1.93%, P = 0.698). In reperfusion STEMI patients, SPF values were lower in infarcted myocardium compared to remote and salvaged myocardium (32.15 ± 2.36% vs. 40.28 ± 1.93%, P < 0.001; 32.15 ± 2.36% vs. 36.68 ± 2.71%, P < 0.001). SPF values of infarcted myocardium showed a rebound increase from acute to convalescent stages (32.15 ± 2.36% vs. 34.69 ± 3.69%, P < 0.001). When differentiating infarcted and salvaged myocardium, SPF values demonstrated an area under the curve (AUC) of 0.89 (sensitivity 85.4%, specificity 80.5%, cutoff 34.42%). Lower SPF values were associated with lower odds ratio (OR = 0.304) of left ventricular remodeling after adjusting for potential confounders with a confidence interval (CI) of 0.129-0.717, P = 0.007. DATA CONCLUSION: SPF might be able to differentiate salvaged and infarcted myocardium and is a strong predictor of left ventricular remodeling in reperfused STEMI patients. Level of Evidence 2 Technical Efficacy Stage 2.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Função Ventricular Esquerda
20.
Eur Radiol ; 31(1): 504-514, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32785772

RESUMO

OBJECTIVES: Our study sought to explore the prognostic value of radiomic TA (texture analysis) on quantitative ECV (extracellular volume) fraction mapping to differentiate between reversible and irreversible myocardial damage and to predict left ventricular adverse remodeling in patients with reperfused STEMI (ST-elevation myocardial infarction). METHODS: This observational prospective cohort study identified 70 patients (62 ± 9 years, 62 men [85.70%]) with STEMI for TA who consecutively performed native and contrast T1 mapping. Texture features were extracted from each stack of ECV mapping based on ROI (region of interest) analysis. RESULTS: After texture feature selection and dimension reduction, five selected texture features were found to be statistically significant for differentiating the extent of myocardial injury. ROC (receiver operating characteristic) curve analysis for the differentiation of unsalvageable infarction and salvageable myocardium demonstrated a significantly higher AUC (area under the curve) (0.91 [95% CI, 0.86-0.96], p < 0.0001) for horizontal fraction than other texture features (p < 0.05). LVAR (left ventricular adverse remodeling) was predicted by those selected features. The differences in qualitative and quantitative baseline parameters and horizontal fractions were significant between the patients with and without LVAR. LGE (late gadolinium enhancement) and horizontal fraction features of infarcted myocardium in acute STEMI were the only two parameters selected in forming the optimal overall multivariable model for LVAR at 6 months. CONCLUSIONS: Radiomic analysis of ECV could discriminate reversible from irreversible myocardial injury after STEMI. LGE as well as radiomics TA (texture analysis) of ECV may provide an alternative to predict LVAR and functional recovery. KEY POINTS: • ECV quantification was able to differentiate between infarcted myocardium and non-infarcted myocardium. • Radiomics analysis of ECV could discriminate reversible from irreversible myocardial injury. • Radiomics TA analysis shows a promising similarity with LGE findings which could aid the prognosis of myocardial infarction patients.


Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST , Meios de Contraste , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Miocárdio , Valor Preditivo dos Testes , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular
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