Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome–associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.
These results indicate that denosumab induces a partial maturation towards the osteoblastic phenotype of the neoplastic cells of GCTB, with production of fibrous and osteoid matrix, but with minor immunophenotypical changes. Finally, we first report an antiangiogenic activity of denosumab in GCTB, possibly mediated by a RANKL-dependent pathway.
Many studies have examined the diagnostic concordance of whole slide imaging (WSI) and light microscopy (LM) for surgical pathology. In cytopathology, WSI use has been more limited, mainly because of technical issues. The aim of this study was to review the literature and determine the overall diagnostic concordance of WSI and LM in cytopathology. A systematic search of PubMed, Scopus, and the Cochrane Library was performed, with data extracted from the included articles. A quality assessment of studies was performed with a modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. The primary outcome was concordance for the diagnoses rendered by WSI and LM as shown by the concordance rate with the original diagnosis, intra‐observer and interobserver concordance with the κ coefficient, or a percentage. Secondary outcomes included the time taken to reach a diagnosis and the quality and perception of WSI. A descriptive survey was provided. Among 1867 publications, a total of 19 studies (1%) were included. Overall, the concordance between WSI and the original diagnosis was 84.1%, the intra‐observer concordance between WSI and LM was 92.5% with a κ coefficient of 0.66, and the interobserver κ coefficient was 0.69. The time to reach a diagnosis was longer with WSI in all studies. The quality of WSI was good, but diagnostic confidence and cytologist preference were higher for LM. In conclusion, the concordance of WSI with LM is acceptable and in line with systematic reviews in surgical pathology. However, the time required for scanning and technical issues represent barriers to complete adoption. It is foreseeable that technical advances and rigorous validation study design will help to improve the diagnostic concordance of WSI with LM in cytopathology.
The application of next generation sequencing (NGS) technology to cytological samples has significantly modified molecular cytopathology practice. Cytological samples represent a valid source of high‐quality DNA for NGS analysis, especially for predicting patients' response to targeted treatments and for refining the risk of malignancy in indeterminate cytological diagnoses. However, several pre‐analytical factors may influence the reliability of NGS clinical analysis. Here, we briefly review the challenges of NGS in cytology practice, focusing on those pre‐analytical factors that may negatively affect NGS success rates and routine diagnostic applications. Finally, we address the future directions of the field.
Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas—originally diagnosed as atypical—in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.
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