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BACKGROUND: Left ventricular (LV) thrombus formation is a common but potentially serious complication, typically occurring after myocardial infarction. Due to perceived high thromboembolic risk and lack of safety data, stress cardiac magnetic resonance (CMR) imaging especially with dobutamine is usually avoided despite its high diagnostic yield. This study aimed to investigate the characteristics, safety and outcome of patients with LV thrombus undergoing dobutamine or vasodilator stress CMR. METHODS: Patients undergoing stress CMR with concomitant LV thrombus were retrospectively included. Risk factors, comorbidities, and previous embolic events were recorded. Periprocedural safety was assessed for up to 48 h following the examination. Major adverse cardiac events (MACE) 12 months before the diagnosis were compared to 12 months after the exam and between patients and a matched control group. Additionally, patients were followed up for all-cause mortality. RESULTS: 95 patients (78 male, 65 ± 10.7 years) were included. Among them, 43 patients underwent dobutamine (36 high-dose, 7 low-dose) and 52 vasodilator stress CMR. Periprocedural safety was excellent with no adverse events. During a period of 24 months, 27 MACE (14.7%) occurred in patients and controls with no statistical difference between groups. During a median follow-up of 33.7 months (IQR 37.6 months), 6 deaths (6.3%) occurred. Type of stress agent, thrombus mobility, or protrusion were not correlated to embolic events or death. CONCLUSION: The addition of a stress test to a CMR exam is safe and does increase the generally high cardioembolic event rate in LV thrombus patients. Therefore, it is useful to support reperfusion decision-making.
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Dobutamina , Trombose , Humanos , Masculino , Dobutamina/efeitos adversos , Adenosina , Imagem Cinética por Ressonância Magnética , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Vasodilatadores/efeitos adversos , Trombose/diagnóstico , Trombose/etiologia , Trombose/patologiaRESUMO
As the number of coronary computed tomography angiography (CTA) examinations is expected to increase, technologies to optimize the imaging workflow are of great interest. The aim of this study was to investigate the potential of artificial intelligence (AI) to improve clinical workflow and diagnostic accuracy in high-volume cardiac imaging centers. A total of 120 patients (79 men; 62.4 (55.0-72.7) years; 26.7 (24.9-30.3) kg/m2) undergoing coronary CTA were randomly assigned to a standard or an AI-based (human AI) coronary analysis group. Severity of coronary artery disease was graded according to CAD-RADS. Initial reports were reviewed and changes were classified. Both groups were similar with regard to age, sex, body mass index, heart rate, Agatston score, and CAD-RADS. The time for coronary CTA assessment (142.5 (106.5-215.0) s vs. 195.0 (146.0-265.5) s; p < 0.002) and the total reporting time (274.0 (208.0-377.0) s vs. 350 (264.0-445.5) s; p < 0.02) were lower in the human AI than in the standard group. The number of cases with no, minor, or CAD-RADS relevant changes did not differ significantly between groups (52, 7, 1 vs. 50, 8, 2; p = 0.80). AI-based analysis significantly improves clinical workflow, even in a specialized high-volume setting, by reducing CTA analysis and overall reporting time without compromising diagnostic accuracy.
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Introduction: Advanced chronic kidney disease (CKD) is an independent risk factor for coronary artery disease (CAD). Due to its unique uremia-derived pathophysiology of atherosclerosis and the limitations of using potentially harmful contrast agents, the best non-invasive approach to assess CAD in these patients remains unclear. We sought to investigate the accuracy, safety, and prognosis of patients with severe CKD undergoing dobutamine stress cardiac magnetic resonance imaging (CMR). Materials and methods: In this retrospective, single-center study, patients on dialysis or with a glomerular filtration rate of <15â ml/min/1.73â m2 who underwent dobutamine stress CMR were included. A rest and stress wall motion analysis was performed using dobutamine/atropine as stressor. The target heart rate was 85% of the maximum heart rate. Periprocedural adverse events and 1-year follow-up data were obtained. Results: A total of 176 patients (127 men, 49 women) with a mean age of 60.9 ± 14.7 years were included, of which 156 patients were on permanent dialysis. Short-term symptoms such as angina or shortness of breath during stress CMR were frequent (22.1%), but major complications were rare (one patient with myocardial infarction, 0.6%). The 1-year event rate was high (16.4%) with a significant independent correlation to reduced ejection fraction at rest (p = 0.037) and failure to achieve the target heart rate (p = 0.029). The overall accuracy for predicting significant CAD was good (sensitivity of 71.4%, specificity of 98.4%) and excellent if the target heart rate was achieved (83.3%, 97.9%). A negative stress CMR was highly predictive for the absence of major adverse cardiac event or any coronary revascularization during the 1-year follow-up (negative predictive value of 95.0%). Discussion: Dobutamine stress CMR is a safe and accurate diagnostic imaging technique in patients at advanced stages of chronic kidney disease. A reduced ejection fraction and the inability to reach the target heart rate are independent predictors of a poor outcome.
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Purpose: The combined testing for coronary artery and pulmonary diseases is of clinical interest as risk factors are shared. In this study, a novel ECG-gated tin-filtered ultra-low dose chest CT protocol (GCCT) for integrated heart and lung acquisition and the applicability of artificial intelligence (AI)-based coronary artery calcium scoring were assessed. Methods: In a clinical registry of 10481 patients undergoing heart and lung CT, GCCT was applied in 44 patients on a dual-source CT. Coronary calcium scans (CCS) with 120 kVp, 100 kVp, and tin-filtered 100 kVp (Sn100) of controls, matched with regard to age, sex, and body-mass index, were retrieved from the registry (ntotal=176, 66.5 (59.4-74.0) years, 52 men). Automatic tube current modulation was used in all scans. In 20 patients undergoing GCCT and Sn100 CCS, Agatston scores were measured both semi-automatically by experts and by AI, and classified into six groups (0, <10, <100, <400, <1000, ≥1000). Results: Effective dose decreased significantly from 120 kVp CCS (0.50 (0.41-0.61) mSv) to 100 kVp CCS (0.34 (0.26-0.37) mSv) to Sn100 CCS (0.14 (0.11-0.17) mSv). GCCT showed higher values (0.28 (0.21-0.32) mSv) than Sn100 CCS but lower than 120 kVp and 100 kVp CCS (all p < 0.05) despite greater scan length. Agatston scores correlated strongly between GCCT and Sn100 CCS in semi-automatic and AI-based measurements (both ρ = 0.98, p < 0.001) resulting in high agreement in Agatston score classification (κ = 0.97, 95% CI 0.92-1.00; κ = 0.89, 95% CI 0.79-0.99). Regarding chest findings, further diagnostic steps were recommended in 28 patients. Conclusions: GCCT allows for reliable coronary artery disease and lung cancer screening with ultra-low radiation exposure. GCCT-derived Agatston score shows excellent agreement with standard CCS, resulting in equivalent risk stratification.
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BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.
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(1) Background: Surgery for spinal metastases has gained a decisive role in modern oncological treatment. Recently, carbon-fiber-reinforced (CFR) polyethyl-ether-ether-ketone (PEEK) pedicle screw systems were introduced, reducing artifacts on imaging and showing less perturbation effects on photon radiation. Preliminary clinical experience with CFR-PEEK implants for spinal metastases exists. The aim of this monocentric study is to report on the safety and efficacy of CFR-PEEK pedicle screw systems for spinal neoplasms in a large cohort of consecutive patients. (2) Methods: We retrospectively analyzed prospectively the collected data of consecutive patients being operated on from 1 August 2015 to 31 October 2021 using a CFR-PEEK pedicle screw system for posterior stabilization because of spinal metastases or primary bone tumors of the spine. (3) Results: We included 321 patients of a mean age of 65 ± 13 years. On average, 5 ± 2 levels were instrumented. Anterior reconstruction was performed in 121 (37.7%) patients. Intraoperative complications were documented in 30 (9.3%) patients. Revision surgery for postoperative complications was necessary in 55 (17.1%) patients. Implant-related complications, such as intraoperative screw breakage (3.4%) and screw loosening (2.2%), were rare. (4) Conclusions: CFR-PEEK is a safe and efficient alternative to titanium for oncological spinal instrumentation, with low complication and revision rates in routine use and with the advantage of its radiolucency.
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OBJECTIVES: Since the safety of coronary CT angiography (CTA) is of great importance, especially with regard to widening indications and increasing morbidity, the aim of this study was to assess influencing factors. METHODS: Patients undergoing coronary CTA in a third-generation dual-source CT in a radiological centre were included in a clinical registry. Up to 20 mg metoprolol was administered intravenously to attain a heart rate ≤65/min. Glyceryl trinitrate (GTN) was administered in doses of 0.8 mg and 0.4 mg. Blood pressure was measured before the administration and after the CTA. RESULTS: Out of 5500 consecutive patients (3194 men, 62.3 (54.9-70.0) years), adverse events occurred in 68 patients (1.2%) with mild anaphylactoid reactions (0.4%), vasovagal symptoms (0.3%) and extravasation (0.3%) being most frequent. Anti-allergic drugs were given in 17 patients, atropine in 3 patients and volume in 1 patient. Drug administration resulted in a significant mean arterial pressure decline (96.0 (88.3-106.0) vs 108.7 (99.7-117.3) mmHg; p<0.001). Patients who suffered systolic blood pressure drops >20 mmHg or >40 mmHg were older (66.5 (58.6-73.3) vs 60.5 (53.6-68.3) years; 70.2 (63.3-76.5) vs 62.1 (54.7-69.6) years), more often male (65.1% vs 54.4%; 68.9% vs 57.3%) and had higher Agatston score equivalents (83.0 (2.0-432.0) vs 15.0 (0.0-172.0); 163.0 (16.3-830.8) vs 25.0 (0.0-220.0); all p<0.001). GTN dose reduction lowered the fraction of patients suffering from blood pressure drops >20 mmHg or >40 mmHg from 34.5% to 27.4% and from 6.1% to 3.5% (both p<0.001), respectively. The proportion of coronary segments with impaired image quality did not differ significantly. CONCLUSIONS: Coronary CTA with intravenous beta-blocker administration is a safe procedure in an outpatient setting as adverse events are rare and mostly mild. Reduced GTN doses can further improve safety by lowering the rate of significant blood pressure drops, which occurred especially in elderly men with increased plaque burden. TRIAL REGISTRATION NUMBER: NCT03815123.
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Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Idoso , Angiografia por Tomografia Computadorizada/efeitos adversos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Masculino , Nitroglicerina/efeitos adversos , Pacientes Ambulatoriais , Sistema de Registros , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/métodosRESUMO
We investigate the effect of social capital on health outcomes during the Covid-19 pandemic in independent analyses for Austria, Germany, Great Britain, Italy, the Netherlands, Sweden and Switzerland. Exploiting detailed geographical variation within countries, we show that a one-standard-deviation increase in social capital leads to between 14% and 34% fewer Covid-19 cases per capita accumulated from mid-March until end of June 2020, as well as between 6% and 35% fewer excess deaths per capita. Our results highlight the positive health returns of strengthening social capital.
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COVID-19 , Capital Social , Europa (Continente)/epidemiologia , Humanos , Pandemias , SARS-CoV-2RESUMO
Background: Coronary artery disease (CAD) shows a chronic but heterogeneous clinical course. Coronary CT angiography (CTA) allows for the visualization of the entire coronary tree and the detection of early stages of CAD. The aim of this study was to assess short-time changes in non-calcified and mixed plaques and their clinical impact using coronary CTA in a real-world setting. Methods: Between 11/2014 and 07/2019, 6,701 patients had a coronary CTA with a third-generation dual-source CT, of whom 77 patients (57 males, 63.8 ± 10.8 years) with a chronic CAD received clinically indicated follow-up CTA. Non-calcified and mixed plaques were analyzed in 1,211 coronary segments. Patients were divided into groups: stable, progressive, or regressive plaques. Results: Within the follow-up period of 22.3 ± 10.4 months, 44 patients (58%) showed stable plaques, 27 (36%) showed progression, 5 (7%) showed regression. One patient was excluded due to an undetermined CAD course showing both, progressive and regressive plaques. Age did not differ significantly between groups. Patients with plaque regression were predominantly female (80 vs. 20%), whereas patients showing progression were mainly male (85 vs. 15%; p < 0.01 for both). Regression was only observed in patients with mild CAD or one-vessel disease. The follow-up CTA led to changes in patient management in the majority of subjects (n = 50; 66%). Conclusions: Changes in coronary artery plaques can be observed within a short period resulting in an adjustment of the clinical management in the majority of CAD patients. Follow-up coronary CTA renders the non-invasive assessment of plaque development possible and allows for an individualized diagnostics and therapy optimization.
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Following publication of the original article [1], the author reported that an incorrect figure has been published as Figure 2. The correct Figure 2 is shown below.
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BACKGROUND: Sub-nuclear structures or locations are associated with various nuclear processes. Proteins localized in these substructures are important to understand the interior nuclear mechanisms. Despite advances in high-throughput methods, experimental protein annotations remain limited. Predictions of cellular compartments have become very accurate, largely at the expense of leaving out substructures inside the nucleus making a fine-grained analysis impossible. RESULTS: Here, we present a new method (LocNuclei) that predicts nuclear substructures from sequence alone. LocNuclei used a string-based Profile Kernel with Support Vector Machines (SVMs). It distinguishes sub-nuclear localization in 13 distinct substructures and distinguishes between nuclear proteins confined to the nucleus and those that are also native to other compartments (traveler proteins). High performance was achieved by implicitly leveraging a large biological knowledge-base in creating predictions by homology-based inference through BLAST. Using this approach, the performance reached AUC = 0.70-0.74 and Q13 = 59-65%. Travelling proteins (nucleus and other) were identified at Q2 = 70-74%. A Gene Ontology (GO) analysis of the enrichment of biological processes revealed that the predicted sub-nuclear compartments matched the expected functionality. Analysis of protein-protein interactions (PPI) show that formation of compartments and functionality of proteins in these compartments highly rely on interactions between proteins. This suggested that the LocNuclei predictions carry important information about function. The source code and data sets are available through GitHub: https://github.com/Rostlab/LocNuclei . CONCLUSIONS: LocNuclei predicts subnuclear compartments and traveler proteins accurately. These predictions carry important information about functionality and PPIs.
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Núcleo Celular/química , Biologia Computacional/métodos , Proteínas Nucleares , Análise de Sequência de Proteína/métodos , Proteínas Nucleares/química , Proteínas Nucleares/classificação , Proteínas Nucleares/fisiologia , Proteínas/química , Proteínas/classificação , Proteínas/fisiologia , Máquina de Vetores de SuporteRESUMO
Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.
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Proteínas de Ligação a DNA/genética , Neutropenia/congênito , Osteoporose/etiologia , Fatores de Transcrição/genética , Animais , Peso Corporal , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Diferenciação Celular , Síndrome Congênita de Insuficiência da Medula Óssea , Citocinas/genética , Citocinas/metabolismo , Proteínas de Ligação a DNA/deficiência , Extremidades/patologia , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutropenia/etiologia , Neutropenia/genética , Neutropenia/patologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese , Osteoporose/genética , Osteoporose/patologia , Osteoprotegerina/sangue , Pasteurellaceae/patogenicidade , Ligante RANK/sangue , Fatores de Transcrição/deficiência , Trichomonas/patogenicidadeRESUMO
Mast cells, important sensor and effector cells of the immune system, may influence bone metabolism as their number is increased in osteoporotic patients. They are also present during bone fracture healing with currently unknown functions. Using a novel c-Kit-independent mouse model of mast cell deficiency, we demonstrated that mast cells did not affect physiological bone turnover. However, they triggered local and systemic inflammation after fracture by inducing release of inflammatory mediators and the recruitment of innate immune cells. In later healing stages, mast cells accumulated and regulated osteoclast activity to remodel the bony fracture callus. Furthermore, they were essential to induce osteoclast formation after ovariectomy. Additional in vitro studies revealed that they promote osteoclastogenesis via granular mediators, mainly histamine. In conclusion, mast cells are redundant in physiologic bone turnover but exert crucial functions after challenging the system, implicating mast cells as a potential target for treating inflammatory bone disorders. © 2017 American Society for Bone and Mineral Research.
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Fraturas Ósseas/patologia , Inflamação/patologia , Mastócitos/patologia , Osteoclastos/patologia , Animais , Reabsorção Óssea/patologia , Calo Ósseo/patologia , Quimiocinas/metabolismo , Feminino , Consolidação da Fratura , Histamina/metabolismo , Masculino , Camundongos , Osteogênese , Ovariectomia , Periósteo/patologia , FenótipoRESUMO
BACKGROUND: The usage of coronary CT angiography (CTA) is appropriate in patients with acute or chronic chest pain; however the diagnostic accuracy may be challenged with increased Agatston score (AS), increased heart rate, arrhythmia and severe obesity. Thus, we aim to determine the potential of the recently introduced third-generation dual-source CT (DSCT) for CTA in a 'real-life' clinical setting. METHODS: Two hundred and sixty-eight consecutive patients (age: 67 ± 10 years; BMI: 27 ± 5 kg/m²; 61% male) undergoing clinically indicated CTA with DSCT were included in the retrospective single-center analysis. A contrast-enhanced volume dataset was acquired in sequential (SSM) (n = 151) or helical scan mode (HSM) (n = 117). Coronary segments were classified in diagnostic or non-diagnostic image quality. A subset underwent invasive angiography to determine the diagnostic accuracy of CTA. RESULTS: SSM (96.8 ± 6%) and HSM (97.5 ± 8%) provided no significant differences in the overall diagnostic image quality. However, AS had significant influence on diagnostic image quality exclusively in SSM (B = 0.003; p = 0.0001), but not in HSM. Diagnostic image quality significantly decreased in SSM in patients with AS ≥2,000 (p = 0.03). SSM (sensitivity: 93.9%; specificity: 96.7%; PPV: 88.6%; NPV: 98.3%) and HSM (sensitivity: 97.4%; specificity: 94.3%; PPV: 86.0%; NPV: 99.0%) provided comparable diagnostic accuracy (p = n.s.). SSM yielded significantly lower radiation doses as compared to HSM (2.1 ± 2.0 vs. 5.1 ± 3.3 mSv; p = 0.0001) in age and BMI-matched cohorts. CONCLUSION: SSM in third-generation DSCT enables significant dose savings and provides robust diagnostic image quality in patients with AS ≤2000 independent of heart rate, heart rhythm or obesity.
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Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Doses de Radiação , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
To assess the value of cardiac magnetic resonance imaging (CMR) in evaluating cardiac tumours in a tertiary cardiology centre. Between 2004 and 2014, 125 patients (pts.) from a total of 17000 who received a CMR examination in our institution were referred with the suspicion of cardiac tumours. A dedicated protocol was used that included standard cine SSFP acquisitions as well as tissue characterization using T1 and T2 black-blood (T1 BB and T2 BB respectively) with and without fat suppression, perfusion of the structure and late gadolinium enhancement. Patients' files were retrospectively analysed and data related to clinical status, results from other examinations (echocardiography), therapeutic approach and histology results, when performed, were collected. In 65 pts., a diagnosis of cardiac tumour was reached. 45 Pts had a biopsy. The CMR examination was concordant with the histology results in 35 (76%) pts. superior to that showed by echocardiography, 26 (58%) pts., p = 0.03. Forty-two (65%) pts. had a benign tumour and 23 (35%) a malignant process. Myxoma was the most frequent benign tumour, 27 (65%) and cardiac metastases were the most frequent form of malignancies, 21 (91%), with B cell non-Hodgkin lymphoma being the most frequent one, 4 (19%). Benign tumours were mostly located in the left atrium, 27 (64%) versus 6 (26%), p = 0.007, whereas malignant tumours had a predilection for the right atrium und left ventricle [11 (48%) vs. 3 (7%), p = 0.001 and 8 (35%) vs. 3 (7%), p = 0.03]. All benign cardiac tumours were single and did not show signs of infiltration. Conversely, malignant cardiac tumours were larger (43 ± 35 vs. 24 ± 16, p = 0.007) with a significant proportion (65%) showing myocardial infiltration. Pts with malignant cardiac tumours had a higher proportion of LGE (82 vs. 60%, p = 0.05) and exhibited more frequently an isointense signal in T1 BB images (78 vs. 61%, p = 0.04). Both groups showed similar proportion of perfusion and signal intensity in the T2 BB acquisitions (p = NS). CMR is a valuable tool in evaluating cardiac tumours, proving superior to echocardiography in establishing the type of cardiac tumour.
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Serviço Hospitalar de Cardiologia , Neoplasias Cardíacas/diagnóstico por imagem , Hospitais com Alto Volume de Atendimentos , Imagem Cinética por Ressonância Magnética , Mixoma/diagnóstico por imagem , Centros de Atenção Terciária , Adulto , Idoso , Protocolos Clínicos , Meios de Contraste/administração & dosagem , Ecocardiografia , Feminino , Gadolínio DTPA/administração & dosagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/secundário , Neoplasias Cardíacas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/patologia , Mixoma/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Carga TumoralRESUMO
Consistent with clinical observations demonstrating that hypervitaminosis A is associated with increased skeletal fracture risk, we have previously found that dietary retinol deprivation partially corrects the bone mineralization defects in a mouse model of X-linked hypophosphatemic rickets. That retinol-dependent signaling pathways impact the skeleton is further supported by various findings demonstrating a negative influence of retinoic acid (RA) on bone-forming osteoblasts. We hypothesized that RA would directly regulate the expression of specific target genes in osteoblasts, and we aimed to identify these by genome-wide expression analyses. Here we show that high dietary retinol intake in mice causes low bone mass associated with increased osteoclastogenesis and decreased osteoblastogenesis, but intact bone matrix mineralization. We additionally found that short-term treatment of primary osteoblasts with RA causes a rapid induction of specific genes involved in either retinol-dependent signaling (i.e. Rara, Crabp2) or skeletal remodeling (i.e. Twist2, Tnfsf11). In contrast, neither expression of established osteoblast differentiation markers nor the proliferation rate was immediately affected by RA administration. Collectively, our data suggest that the negative effects of vitamin A on skeletal integrity are explainable by an immediate influence of RA signaling on specific genes in osteoblasts that in turn influence bone remodeling.
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Regulação da Expressão Gênica/efeitos dos fármacos , Osteoblastos/metabolismo , Tretinoína/farmacologia , Animais , Células Cultivadas , Feminino , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Coloração e RotulagemRESUMO
BACKGROUND: Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR. METHODS: 40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula. RESULTS: LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches. LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI (67 ± 8 s vs. 180 ± 14 s, p < 0.0001). Additionally, LAS-epi/mid performed significantly better than MAPSE (Delta AUC = 0.09; p < 0.005) and the ejection fraction (Delta AUC = 0.11; p = 0.0002). Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was -17.1 ± 2.3 %. Mean values for men were significantly lower compared to women (-16.5 ± 2.2 vs. -17.9 ± 2.1 %; p < 0.0001), while LAS decreased with age. CONCLUSIONS: LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain.
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Cardiomiopatias/diagnóstico , Interpretação de Imagem Assistida por Computador/normas , Imagem Cinética por Ressonância Magnética/normas , Contração Miocárdica , Função Ventricular Esquerda , Adulto , Fatores Etários , Área Sob a Curva , Fenômenos Biomecânicos , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores Sexuais , Estresse Mecânico , Fatores de TempoRESUMO
AIM: To investigate if magnetic resonance (MR)-guided biopsy can improve the performance and safety of such procedures. METHODS: A novel MR-compatible bioptome was evaluated in a series of in-vitro experiments in a 1.5T magnetic resonance imaging (MRI) system. The bioptome was inserted into explanted porcine and bovine hearts under real-time MR-guidance employing a steady state free precession sequence. The artifact produced by the metal element at the tip and the signal voids caused by the bioptome were visually tracked for navigation and allowed its constant and precise localization. RESULTS: Cardiac structural elements and the target regions for the biopsy were clearly visible. Our method allowed a significantly better spatial visualization of the bioptoms tip compared to conventional X-ray guidance. The specific device design of the bioptome avoided inducible currents and therefore subsequent heating. The novel MR-compatible bioptome provided a superior cardiovascular magnetic resonance (imaging) soft-tissue visualization for MR-guided myocardial biopsies. Not at least the use of MRI guidance for endomyocardial biopsies completely avoided radiation exposure for both patients and interventionalists. CONCLUSION: MRI-guided endomyocardial biopsies provide a better than conventional X-ray guided navigation and could therefore improve the specificity and reproducibility of cardiac biopsies in future studies.
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OBJECTIVES: T1 mapping by cardiac magnetic resonance imaging (CMR) is able to determine the extracellular volume fraction. Wild-type transthyretin amyloidosis (WT-ATTR) is characterized by extracellular amyloid deposition in the heart. Recent reports indicated a reduction of left ventricular (LV) myocardial mass in WT-ATTR after consumption of epigallocatechin-3-gallate, the main catechin in green tea. It remained unclear, whether reduction of LV myocardial mass reflects decrease of amyloid load or progressive atrophy of cardiomyocytes. METHODS: This study included 7 male patients with CMR repetitively performed before and 12 months after daily consumption of green tea extract (600 mg epigallocatechin-3-gallate). Short axis slices as well as 2-, 3-, and 4-chamber views were acquired using SSFP sequences. T1 mapping was created out of 11 mid-ventricular short axis views with increasing inversion times using a single breath-hold modified look-locker inversion recovery sequence before and 15 min after Gadolinium contrast administration. RESULTS: After 12 months, a significant decrease of LV myocardial mass [198 (160; 212) vs. 180 (142; 204) g; p < 0.05] was observed. Moreover, a significant decrease of native [T1 1110 (1072; 1150) ms vs. 1080 (970; 1101), p < 0.05 or p = 0.03] was noticed. The calculated extracellular volume decreased in 5 patients (62.5%) by 7% and increased in 2 patients (37.5%) by 9.5%, in trend resulting in a (not significant) decrease of median ECV by 2.4%. Left ventricular ejection fraction (LVEF) [57 (48; 65) vs. 55 (47; 64) %; p = 0.3] remained unchanged. CONCLUSIONS: This study provided further evidence of LV myocardial mass reduction in patients with WT-ATTR daily consuming green tea extract. Additionally, this study gave first insights into the histomorphological correlate of LV mass reduction using T1 mapping. LV mass reduction appeared to be rather due to a decrease of amyloid load than atrophy of cardiomyocytes.
Assuntos
Amiloidose/tratamento farmacológico , Camellia sinensis , Cardiomiopatias/tratamento farmacológico , Catequina/análogos & derivados , Matriz Extracelular/metabolismo , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Extratos Vegetais/química , Remodelação Ventricular/efeitos dos fármacos , Administração Oral , Idoso , Amiloide/metabolismo , Amiloidose/metabolismo , Amiloidose/patologia , Camellia sinensis/química , Cápsulas , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Catequina/administração & dosagem , Catequina/isolamento & purificação , Meios de Contraste , Fibrose , Gadolínio DTPA , Alemanha , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Miocárdio/metabolismo , Extratos Vegetais/isolamento & purificação , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To investigate whether myocardial deformation imaging, assessed by feature tracking cardiac magnetic resonance (FTI-CMR), would allow objective quantification of myocardial strain and estimation of functional recovery in patients with first time ST-elevation myocardial infarction (STEMI). METHODS: Cardiac magnetic resonance (CMR) imaging was performed in 74 consecutive patients 2-4 days after successfully reperfused STEMI, using a 1.5T CMR scanner (Philips Achieva). Peak systolic circumferential and longitudinal strains were measured using the FTI applied to SSFP cine sequences and were compared to infarct size, determined by late gadolinium enhancement (LGE). Follow-up CMR at 6 months was performed in order to assess residual ejection fraction, which deemed as the reference standard for the estimation of functional recovery. RESULTS: During the follow-up period 53 of 74 (72%) patients exhibited preserved residual ejection fraction ≥50%. A cut-off value of -19.3% for global circumferential strain identified patients with preserved ejection fraction ≥50% at follow-up with sensitivity of 76% and specificity of 85% (AUC=0.86, 95% CI=0.75-0.93, p<0.001), which was superior to that provided by longitudinal strain (ΔAUC=0.13, SE=0.05, z-statistic=2.5, p=0.01), and non-inferior to that provided by LGE (ΔAUC=0.07, p=NS). Multivariate analysis showed that global circumferential strain and LGE exhibited independent value for the prediction of preserved LV-function, surpassing that provided by age, diabetes and baseline ejection fraction (HR=1.4, 95% CI=1.0-1.9 and HR=1.4, 95% CI=1.1-1.7, respectively, p<0.05 for both). CONCLUSIONS: Estimation of circumferential strain by FTI provides objective assessment of infarct size without the need for contrast agent administration and estimation of functional recovery with non-inferior accuracy compared to that provided by LGE.