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BACKGROUND: Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA (cfDNA) in blood, as an indication of lung cell death. METHODS: We sorted human lung alveolar and bronchial epithelial cells from surgical specimens, and obtained their methylomes using whole-genome bisulfite sequencing. We developed a PCR sequencing assay determining the methylation status of 17 loci with lung-specific methylation patterns, and used it to assess lung-derived cfDNA in the plasma of healthy volunteers and patients with lung disease. RESULTS: Loci that are uniquely unmethylated in alveolar or bronchial epithelial cells are enriched for enhancers controlling lung-specific genes. Methylation markers extracted from these methylomes revealed that normal lung cell turnover probably releases cfDNA into the air spaces, rather than to blood. People with advanced lung cancer show a massive elevation of lung cfDNA concentration in blood. Among individuals undergoing bronchoscopy, lung-derived cfDNA is observed in the plasma of those later diagnosed with lung cancer, and to a lesser extent in those diagnosed with other lung diseases. Lung cfDNA is also elevated in patients with acute exacerbation of COPD compared with patients with stable disease, and is associated with future exacerbation and mortality in these patients. CONCLUSIONS: Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.
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Ácidos Nucleicos Livres , Neoplasias Pulmonares , Humanos , Metilação de DNA , Ácidos Nucleicos Livres/genética , Biópsia Líquida , Biomarcadores , Epitélio , Pulmão , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVES: Endomyocardial biopsy (EMB) is a diagnostic tool for evaluating various cardiac conditions, such as myocarditis and myocardial infiltrative diseases. It is also the gold standard screening technique for detecting allograft rejection after heart transplantation. Despite advances in noninvasive imaging modalities for myocardial tissue characterization, EMB is still necessary for making a definitive diagnosis and determining treatment for certain conditions. Herein, we report our recent experience using EMB and its diagnostic yield. METHODS AND RESULTS: We retrospectively reviewed EMBs performed at our institution from March 2018 through March 2023. Clinical data, including patient characteristics, indication and diagnostic yield of EMB, and procedure-related complications, were collected. Histopathological findings of the biopsies were recorded and classified based on the degree to which they matched the clinical diagnosis and cardiac magnetic resonance imaging (CMR) findings. A total of 212 EMBs obtained in 178 consecutive patients were retrospectively analyzed, with 42 biopsies performed for allograft rejection surveillance (10 patients) and the remaining performed for presumptive diagnosis of acute myocarditis or unexplained cardiomyopathy. Among the non-heart transplant cases, 54.7% of EMBs provided a clear diagnosis. The most common diagnosis was myocarditis (69%), followed by cardiac amyloidosis (CA) (26%). EMB was also helpful in detecting several rare cardiac conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), Fabry disease, and cardiac sarcoidosis. In a cohort of 101 patients who underwent both CMR and EMB, the results were concordant in 66% of cases. However, in 24.7% of patients, EMB was able to identify pathological conditions where CMR results were inconclusive, highlighting its complementary role in determining an accurate diagnosis. No complications were reported in any of the 212 EMBs performed. CONCLUSIONS: With advances in cardiac imaging modalities, EMB is not routinely indicated for the diagnosis of cardiomyopathy. However, EMB is still an important tool for diagnosing specific cardiac diseases and could be crucial for confirming the diagnosis. EMB is generally safe if performed at experienced centers.
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BACKGROUND: Nucleic acid amplification tests (NAAT) are considered the gold standard for COVID-19 diagnosis. These tests require professional manpower and equipment, long processing and swab sampling which is unpleasant to the patients. Several volatile organic compounds (VOCs) have been identified in the breath of COVID-19 patients. Detection of these VOCs using a breath test could help rapidly identify COVID-19 patients. OBJECTIVE: Assess the accuracy of 'Breath of Health' (BOH) COVID-19 Fourier-transform infra-red (FTIR) Spectroscopy-based breath test. METHODS: Breath samples from patients with or without symptoms suggestive for COVID-19 who had NAAT results were collected using Tedlar bags and were blindly analysed using BOH FTIR spectroscopy. BOH Measures several VOCs simultaneously and differentiating positive and negative results. BOH results were compared to NAAT results as gold standard. RESULTS: Breath samples from 531 patients were analysed. The sensitivity of BOH breath test was found to be 79.5% and specificity was 87.2%. Positive predictive value (PPV) was 74.7% and negative predictive value (NPV) 90.0%. Calculated accuracy rate was 84.8% and area under the curve 0.834. Subgroup analysis revealed that the NPV of patients without respiratory symptoms was superior over the NPV of symptomatic patients (94.7% vs 80.7%, P-value < 0.0001) and PPV of patients with respiratory symptoms outranks the PPV of individuals without symptoms (85.3% vs 69.2%, P-value 0.0196). CONCLUSION: We found BOH COVID-19 breath test to be a patient-friendly, rapid, non-invasive diagnostic test with high accuracy rate and NPV that could efficiently rule out COVID-19 especially among individuals with low pre-test probability.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Teste para COVID-19 , Testes Respiratórios/métodos , Análise Espectral , Sensibilidade e EspecificidadeRESUMO
Infective endocarditis caused by gram-negative enteral bacteria is very rare. Herein, we report the first case of infective endocarditis complicated by a paravalvular mycotic pseudoaneurysm of the left ventricle caused by Escherichia coli post transcatheter aortic valve replacement, highlighting the diagnostic workup, multimodality imaging, and treatment options.
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Non-bacterial thrombotic endocarditis is an uncommon entity that tends to be related to malignancy or rheumatological disorders. The diagnosis is complex and requires a high index of suspicion. It commonly causes recurrent emboli; however, coronary embolism remains an infrequently reported entity. Herein we report a unique case of sequential pulmonary embolism, ST-elevation myocardial infarction (MI), and stroke associated with multi-valvular non-bacterial thrombotic endocarditis. The cornerstone of management is treating the underlying cause and anticoagulation therapy. Surgical treatment should be considered in patients with acute heart failure secondary to valvular dysfunction and recurrent thromboembolism despite proper anticoagulation. We have performed an extensive literature search and found nine cases of established antemortem diagnosis of myocardial infarction secondary to non-bacterial thrombotic endocarditis, and we reviewed them according to cause, treatment, and outcome.
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Cardiac lipomas, especially ones originating from the left ventricle, are extremely rare. They may be asymptomatic or may present with various non-specific symptoms. Herein, we report a case of a giant lipoma of the left ventricle, with frequent ventricular premature beats on electrocardiogram. An echocardiogram demonstrated a large hyperechoic mass occupying a significant portion of the left ventricle. We further describe the diagnostic workup utilizing multimodality cardiac imaging and treatment options. Cardiac MRI demonstrated fat suppression, and cardiac CT showed a homogenous low-attenuation mass suggesting lipomatous matter. The mass was subsequently surgically removed for pathology examination in order to rule out liposarcoma. Histopathology demonstrated mature adipocytes, entrapped myocytes with hypertrophy, and interstitial fibrosis foci confirming the diagnosis of lipoma.