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1.
Clin Cardiol ; 45(10): 1029-1035, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35864729

ABSTRACT

OBJECTIVES: We aimed to assess the relationship of left atrial appendage (LAA) fibrosis with atrial fibrillation (AF) and postoperative events in patients receiving coronary artery bypass graft surgery (CABG). BACKGROUND: Increased atrial fibrosis has been associated with AF and worse outcome following catheter ablation. Only limited data exists focusing on the impact of LAA fibrosis on AF after CABG. METHODS: LAA tissue from 164 CABG-patients was stained with Masson-Goldner trichrome. The histological landscape was scanned and segmented into superpixels for software analysis (QuPath). A classification algorithm was extensively trained to detect fibrotic superpixels for quantification. In 43 propensity score matched pairs with AF or sinus rhythm (SR), LAA fibrosis was compared. Moreover, subgroups of mitral valve regurgitation (MR) were analyzed as follows: SR, SR + MR, AF and AF + MR. The predictive value of LAA fibrosis postoperative stroke, postoperative AF and mortality was assessed. RESULTS: Fibrotic remodeling (%) showed no significant difference for the total cohort between the SR and AF group (SR: 30.8 ± 11.4% and AF: 33.8 ± 16.0%, respectively, p = .32). However, significant fibrotic remodeling was observed for SR and AF subgroups (SR: 27.2 ± 12.2% vs. AF: 35.3 ± 13.7%; respectively, p = .049) and between SR and SR + MR subgroups (SR: 27.2 ± 12.2% vs. SR + MR: 34.9 ± 9.1%, respectively, p = .027). LAA fibrosis was not significantly associated with postoperative stroke, postoperative AF or overall mortality (all p > .05). CONCLUSION: LAA fibrosis may contribute to an individual arrhythmia substrate for AF in patients with AF but also in those with SR and coincidence of MR. LAA fibrosis was not found to be predictive for clinical events in patients after CABG.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Mitral Valve Insufficiency , Stroke , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/etiology , Coronary Artery Bypass/adverse effects , Fibrosis , Humans , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery , Stroke/etiology
2.
J Cancer Res Clin Oncol ; 148(2): 351-360, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34839410

ABSTRACT

PURPOSE: Most cancer-related deaths worldwide are associated with lung cancer. Subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (AC) and squamous cell carcinoma (SqCC) is of importance, as therapy regimes differ. However, conventional staining and immunohistochemistry have their limitations. Therefore, a spatial metabolomics approach was aimed to detect differences between subtypes and to discriminate tumor and stroma regions in tissues. METHODS: Fresh-frozen NSCLC tissues (n = 35) were analyzed by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) of small molecules (< m/z 1000). Measured samples were subsequently stained and histopathologically examined. A differentiation of subtypes and a discrimination of tumor and stroma regions was performed by receiver operating characteristic analysis and machine learning algorithms. RESULTS: Histology-guided spatial metabolomics revealed differences between AC and SqCC and between NSCLC tumor and tumor microenvironment. A diagnostic ability of 0.95 was achieved for the discrimination of AC and SqCC. Metabolomic contrast to the tumor microenvironment was revealed with an area under the curve of 0.96 due to differences in phospholipid profile. Furthermore, the detection of NSCLC with rarely arising mutations of the isocitrate dehydrogenase (IDH) gene was demonstrated through 45 times enhanced oncometabolite levels. CONCLUSION: MALDI-MSI of small molecules can contribute to NSCLC subtyping. Measurements can be performed intraoperatively on a single tissue section to support currently available approaches. Moreover, the technique can be beneficial in screening of IDH-mutants for the characterization of these seldom cases promoting the development of treatment strategies.


Subject(s)
Carcinoma, Non-Small-Cell Lung/classification , Lung Neoplasms/classification , Metabolomics/methods , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Cytological Techniques/methods , Female , Germany , Humans , Immunohistochemistry/methods , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Machine Learning , Male , Middle Aged , Mutation , Neoplasm Staging , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
4.
Lab Invest ; 101(9): 1281-1288, 2021 09.
Article in English | MEDLINE | ID: mdl-34021261

ABSTRACT

Urachal adenocarcinomas (UrC) are rare but aggressive. Despite being of profound therapeutic relevance, UrC cannot be differentiated by histomorphology alone from other adenocarcinomas of differential diagnostic importance. As no reliable tissue-based diagnostic biomarkers are available, we aimed to detect such by integrating mass-spectrometry imaging-based metabolomics and digital pathology, thus allowing for a multimodal approach on the basis of spatial information. To achieve this, a cohort of UrC (n = 19) and colorectal adenocarcinomas (CRC, n = 27) as the differential diagnosis of highest therapeutic relevance was created, tissue micro-arrays (TMAs) were constructed, and pathological data was recorded. Hematoxylin and eosin (H&E) stained tissue sections were scanned and annotated, enabling an automized discrimination of tumor and non-tumor areas after training of an adequate algorithm. Spectral information within tumor regions, obtained via matrix-assisted laser desorption/ionization (MALDI)-Orbitrap-mass spectrometry imaging (MSI), were subsequently extracted in an automated workflow. On this basis, metabolic differences between UrC and CRC were revealed using machine learning algorithms. As a result, the study demonstrated the feasibility of MALDI-MSI for the evaluation of FFPE tissue in UrC and CRC with the potential to combine spatial metabolomics data with annotated histopathological data from digitalized H&E slides. The detected Area under the curve (AUC) of 0.94 in general and 0.77 for the analyte taurine alone (diagnostic accuracy for taurine: 74%) makes the technology a promising tool in this differential diagnostic dilemma situation. Although the data has to be considered as a proof-of-concept study, it presents a new adoption of this technology that has not been used in this scenario in which reliable diagnostic biomarkers (such as immunohistochemical markers) are currently not available.


Subject(s)
Metabolomics/methods , Molecular Imaging/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Urinary Bladder Neoplasms , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Humans , Male , Metabolome/physiology , Middle Aged , Multivariate Analysis , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
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