CVSnet: A machine learning approach for automated central vein sign assessment in multiple sclerosis

The central vein sign (CVS) is an efficient imaging biomarker for multiple sclerosis (MS) diagnosis, but its application in clinical routine is limited by inter‐rater variability and the expenditure of time associated with manual assessment. We describe a deep learning‐based prototype for automated assessment of the CVS in white matter MS lesions using data from three different imaging centers. We retrospectively analyzed data from 3 T magnetic resonance images acquired on four scanners from two different vendors, including adults with MS (n = 42), MS mimics (n = 33, encompassing 12 distinct neurological diseases mimicking MS) and uncertain diagnosis (n = 5). Brain white matter lesions were manually segmented on FLAIR* images. Perivenular assessment was performed according to consensus guidelines and used as ground truth, yielding 539 CVS‐positive (CVS⁺) and 448 CVS‐negative (CVS^?) lesions. A 3D convolutional neural network (“CVSnet”) was designed and trained on 47 datasets, keeping 33 for testing. FLAIR* lesion patches of CVS⁺/CVS^? lesions were used for training and validation (n = 375/298) and for testing (n = 164/150). Performance was evaluated lesion‐wise and subject‐wise and compared with a state‐of‐the‐art vesselness filtering approach through McNemar's test. The proposed CVSnet approached human performance, with lesion‐wise median balanced accuracy of 81%, and subject‐wise balanced accuracy of 89% on the validation set, and 91% on the test set. The process of CVS assessment, in previously manually segmented lesions, was ~ 600‐fold faster using the proposed CVSnet compared with human visual assessment (test set: 4 seconds vs. 40 minutes). On the validation and test sets, the lesion‐wise performance outperformed the vesselness filter method (P < 0.001). The proposed deep learning prototype shows promising performance in differentiating MS from its mimics. Our approach was evaluated using data from different hospitals, enabling larger multicenter trials to evaluate the benefit of introducing the CVS marker into MS diagnostic criteria.     

Intensive Care of the Multiorgan Donor

Disruption of central feedback regulatory loops leads to specific symptoms at the onset of brain death. Without consistent intensive care, these may cause the death of all organs within a few hours. In order to ensure optimal organ functioning after transplantation, specific minimum requirements must be met in respect of the way in which the multiorgan donor is treated. Standardized guidelines on therapeutic measures and monitoring of the brain-dead patients that are based on the current literature and our own experience will be presented in this paper.     

Antiprotozoal activities of heterocyclic-substituted xanthones from the marine-derived fungus Chaetomium sp

Investigations of the marine-derived fungus Chaetomium sp. led to the isolation of the new natural products chaetoxanthones A, B, and C (1-3). Compounds 1 and 2 are substituted with a dioxane/tetrahydropyran moiety rarely found in natural products. Compound 3 was identified as a chlorinated xanthone substituted with a tetrahydropyran ring. The configurational analysis of these compounds employed CD spectroscopy, modified Mosher's method, and selective NOE gradient measurements. Compound 2 showed selective activity against Plasmodium falciparum with an IC50 value of 0.5 microg/mL without being cytotoxic toward cultured eukaryotic cells. Compound 3 displayed a moderate activity against Trypanosoma cruzi with an IC50 value of 1.5 microg/mL.     

Expression and function of the Fas receptor on human blood and tissue eosinophils

The interaction between activated T cells and eosinophils has been proposed to play an important role in the pathogenesis of allergic diseases. T cell-derived cytokines such as interleukin-5 and granulocyte/macrophage colony-stimulating factor inhibit eosinophil apoptosis and may therefore contribute to the development of tissue and blood eosinophilia in these disorders. Withdrawal of these cytokines leads to eosinophil apoptosis in vitro. In contrast, the mechanisms which actively induce apoptosis in eosinophils are at present not completely understood. In this study, we demonstrate that freshly isolated human eosinophils express mRNA and protein for the Fas receptor. Using anti-Fas monoclonal antibody (mAb), we show that Fas activation accelerates apoptotic eosinophil death in vitro. Moreover, treatment of nasal polyps ex vivo with anti-Fas mAb decreased eosinophilic tissue inflammation. However, we observed that blood as well as tissue eosinophils derived from some eosinophilic donors do not express functional Fas receptors, although Fas protein is normally expressed in these cells. This implies that the susceptibility of the Fas receptor is a matter of regulation in eosinophils as previously observed in other systems. These data suggest that Fas ligand/Fas interactions are involved in the regulation of eosinophil apoptosis and that defects in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases.     

Update on Wilms tumor

This article reviews of the current evidence-based treatment standards for children with Wilms tumor. In this article, a summary of recently completed clinical trials by the Children's Oncology Group is provided, the current diagnostic evaluation and surgical standards are discussed, and the surgical impact on current risk stratification for patients with Wilms tumor is highlighted.