Articles: cations.
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SARS-CoV-2 vaccine ChAdOx1 nCov-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models and analysis of VITT patient samples we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. ⋯ Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drive thrombosis in VITT. The data support a two-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.
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The clinical and pathologic diagnosis of hypersensitivity pneumonitis has been confounded by conflicting definitions, with two recent guidelines suggesting that hypersensitivity pneumonitis simply be diagnosed as nonfibrotic or fibrotic. Nonfibrotic hypersensitivity pneumonitis is usually characterized by a bronchiolocentric chronic interstitial inflammatory infiltrate, frequently but by no means always with associated granulomas or giant cells. Fibrotic hypersensitivity pneumonitis may take the form of interstitial fibrosis confined to the peribronchiolar regions, or fibrotic nonspecific interstitial pneumonia, or a process similar to and sometimes indistinguishable from usual interstitial pneumonia/idiopathic interstitial fibrosis, but the exact pathologic features that favor a diagnosis of fibrotic hypersensitivity pneumonitis are disputed. ⋯ Clinical and CT features are crucial to the diagnosis of hypersensitivity pneumonitis: sparing of the lung bases, centrilobular nodules, air-trapping, or the triple density sign with fibrosis favor a diagnosis of fibrotic hypersensitivity pneumonitis. At this point there are no molecular tests that reliably separate fibrotic hypersensitivity pneumonitis from other forms of interstitial lung disease. Currently the separation of fibrotic hypersensitivity pneumonitis from usual interstitial pneumonia is crucial to treatment (immunosuppressives for the former, anti-fibrotics for the latter) but this approach is changing and all progressive fibrosing interstitial pneumonias will probably be treated with antifibrotics in the future.
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Editorial Comment Retraction Of Publication
Commentary: "Zooming in" on Glioblastoma: Understanding Tumor Heterogeneity and Its Clinical Implications in the Era of Single-Cell Ribonucleic Acid Sequencing.
This article has been withdrawn due to an error that caused the article to be duplicated. The definitive version of this article is published under DOI 10.1093/neuros/nyab288.