Faculty Bibliography

INTRODUCTION/BACKGROUND:Accurate preoperative evaluation of pancreatic cysts is essential. However, cytology and biochemical analysis are often limited by low cellularity, and risk stratification is critical for management. PancreaSeq Genomic Classifier (GC) analyzes cyst fluid for molecular alterations to aid diagnosis and risk assessment. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 219 pancreatic cysts from 206 patients using PancreaSeq GC, integrating molecular findings with cytology, biochemical, imaging, surgical pathology, and follow-up. RESULTS:PancreaSeq GC successfully analyzed 216/219 cysts (99%) and detected alterations in 182 (83%). Among cases with both cytology and molecular data (n = 201), concordance was high in cytologically mucinous neoplasms (94%) and atypical cases (95%). Notably, among cases reported as negative for malignancy or nondiagnostic on cytology (n = 128), PancreaSeq GC identified mucinous neoplasms in 82 cases (64%), demonstrating added value in limited samples. Surgical pathology correlation (n = 24) showed excellent performance for distinguishing mucinous from nonmucinous cysts (area under the curve [AUC] = 0.94, P < 0.001). Risk stratification for detection of any dysplasia yielded an AUC of 0.78 (P = 0.006), and for high-grade dysplasia an AUC of 0.74 (P = 0.046). PancreaSeq GC reliably predicted neuroendocrine tumors, but the sensitivity for focal high-grade dysplasia in mucinous neoplasms and serous cystadenoma was limited. Compared with carcinoembryonic antigen (CEA), cyst fluid glucose showed higher sensitivity but lower specificity for mucinous cyst detection. CONCLUSIONS:PancreaSeq GC provides significant diagnostic and risk-stratification value that complements cytological evaluation, particularly in indeterminate or nondiagnostic cytology specimens and when biochemical data are unavailable. Integration of molecular findings improves cyst classification and dysplasia risk assessment. Multidisciplinary assessment remains essential, given the assay's limited sensitivity for focal high-grade dysplasia and serous cystadenomas.

More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.