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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. © 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.

Cisplatin is a widely used chemotherapeutic agent. However, it is causing nephrotoxic side effects including a reduced glomerular filtration rate and acute kidney injury. Although kidneys can recover to an extent from the treatment, long-term damage is possible. While a lot of research is focusing on short-term effects, little is known about adverse metabolic effects in the process of recovery. In this study, male Han Wistar rats were dosed with a single intraperitoneal injection of 3 mg/kg cisplatin. Urine and kidney samples were harvested 3, 8 and 26 days after administration. Tubular injury was demonstrated through urinary biomarkers. Complementing this, mass spectrometry imaging gives insight on molecular alterations on a spatial level, thus making it well suited to analyze short- and long-term disturbances. Various metabolic pathways seem to be affected, as changes in a wide range of metabolites were observed between treated and control animals. Besides previously reported early changes in kidney metabolism, unprecedented long-term effects were detected including deviation in nucleotides, antioxidants, and phospholipids. Copyright © 2020 Elsevier B.V. All rights reserved.

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 ( 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.

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., New diagnostic strategies are needed to distinguish rarely arising urachal adenocarcinomas (UrC) from other types of adenocarcinomas, as therapy regimes differ. In situ metabolic differences between UrC and colorectal adenocarcinomas were revealed using mass spectrometry imaging combined with digital pathology. A classification accuracy of 87% was achieved, exceeding currently available approaches.

The original version of this article unfortunately contained a mistake. Due to the submission of Table 1 in a separate file, the following citations were missing in the references, leading to an incorrect linking in the table caption. The missing reference are: (A) Sheldon CA, Clayman RV, Gonzalez R, Williams RD, Fraley EE. Malignant urachal lesions. J Urol. 131, 1–8 (1984). (B) Ashley RA, Inman BA, Sebo TJ, Leibovich BC, Blute ML, Kwon ED, et al. Urachal carcinoma: clinicopathologic features and longterm outcomes of an aggressive malignancy. Cancer. 107, 712–720 (2006). (C) Brierley J, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors. In: Brierley J, Gospodarowicz MK, Wittekind C, editors. Chichester, West Sussex, UK, Hoboken, NJ: John Wiley & Sons Inc; 2017. The authors apologize for the mistake. The original article has been corrected.