BACKGROUND Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease process is still lacking. METHODS Autopsies were performed at the Mount Sinai Hospital on 67 COVID-19 positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTS Laboratory results of our COVID-19 cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8 and TNFα. Autopsies revealed large pulmonary emboli in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis and a secondary hemophagocytic lymphohistiocytosis-like syndrome in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 receptor in our samples. CONCLUSIONS We report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome, with hemophagocytosis and a hemophagocytic lymphohistiocytosis-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.

Ovarian cancer is a leading cause of deaths, yet many aspects of the biology of the disease and a routine means of its detection are lacking. We have used protein microarrays and autoantibodies from cancer patients to identify proteins that are aberrantly expressed in ovarian tissue. Sera from 30 cancer patients and 30 healthy individuals were used to probe microarrays containing 5,005 human proteins. Ninety-four antigens were identified that exhibited enhanced reactivity from sera in cancer patients relative to control sera. The differential reactivity of four antigens was tested by using immunoblot analysis and tissue microarrays. Lamin A/C, SSRP1, and RALBP1 were found to exhibit increased expression in the cancer tissue relative to controls. The combined signals from multiple antigens proved to be a robust test to identify cancerous ovarian tissue. These antigens were also reactive with tissue from other types of cancer and thus are not specific to ovarian cancer. Overall our studies identified candidate tissue marker proteins for ovarian cancer and demonstrate that protein microarrays provide a powerful approach to identify proteins aberrantly expressed in disease states.autoantibodies ͉ tissue microarray ͉ tissue marker ͉ differential expression ͉ cancer antigen

These data suggest that intra-arterial (90)Y microspheres can be used as a bridge to transplantation, surgical resection, or RFA.

We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series.

The regulation of proliferation and cell death is vital for homeostasis, but the mechanism that coordinately balances these events in rheumatoid arthritis (RA) remains largely unknown. In RA, the synovial lining thickens in part through increased proliferation and/or decreased synovial fibroblast cell death. Here we demonstrate that the anti-apoptotic protein, Bcl-2, is highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68-negative, fibroblast-like synoviocyte population. To determine the importance of endogenous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was employed. Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA and osteoarthritis synovial tissues. In addition, Ad-Rbz-Bcl-2-induced mitochondrial permeability transition, cytochrome c release, activation of caspases 9 and 3, and DNA fragmentation. The general caspase inhibitor zVAD.fmk blocked caspase activation, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation, but not loss of transmembrane potential or viability, indicating that cell death was independent of caspase activation. Ectopically expressed Bcl-xL inhibited Ad-Rbz-Bcl-2-induced mitochondrial permeability transition and apoptosis in Ad-Rbz-Bcl-2-transduced cells. Thus, forced down-regulation of Bcl-2 does not induce a compensatory mechanism to prevent loss of mitochondrial integrity and cell death in human fibroblasts.