INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic of coronavirus disease 2019 (COVID-19) is a global health crisis. Possible pancreatic involvement has recently been observed in these patients; however, its significance is unclear. The aim of this study was to evaluate the association of significantly elevated lipase with disease outcomes. METHODS: Data about demographics, symptoms, laboratory values, and clinical outcomes were collected for 1,003 consecutive patients testing positive for COVID-19. Elevated lipase was defined as greater than 3 times the upper limit of normal (>3 × ULN). Baseline characteristics among patients with or without elevated lipase were compared using Fisher exact test or Student t -test for categorical or numerical variables, respectively. Logistic regression was used to evaluate the association of lipase levels with primary clinical outcomes (intensive care unit admission and intubation) adjusted for age, sex, body mass index, history of diabetes, and hypertension. RESULTS: Of 1,003 patients with COVID-19, 83 had available lipase levels and were all admitted to the hospital. Of 83, 14 (16.8%) had elevated lipase (>3 × ULN), which was associated with higher rates of leukocytosis ( P < 0.001) and abnormal liver enzymes ( P < 0.01). Compared with lower lipase levels (<3 × ULN), patients with elevated lipase had higher rates of ICU admission (92.9% vs 32.8%; P < 0.001) and intubation (78.6% vs 23.5%; P 0.002). In a multivariable-adjusted model, higher lipase levels were significantly associated with admission to the ICU and rate of intubation. DISCUSSION: Lipase elevation is seen in COVID-19 and is associated with worse disease outcomes.

BACKGROUND & AIMS Experimental studies in acute pancreatitis (AP) suggest strong association of acinar cell injury with cathepsin-B dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death have not been studied. In this study, we have explored, for the first time, intra-acinar events downstream of trypsin activation which lead to acinar cell death. METHODS Acinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen-7 or cathepsin-B deleted) were stimulated with supramaximal caerulein and cytosolic activity of cathepsin-B and trypsin was evaluated. Permeabilzed acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin-B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis. RESULTS Both in vitro and in vivo studies suggest that during AP cathepsin-B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin-B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin-B into the cytosol can lead to cell death through necrosis. CONCLUSIONS This is the first report which defines the role of trypsin in AP and demonstrates that cytosolic cathepsin-B but not trypsin activates cell death pathways. This is also the first report to suggest that trypsin is requisite for AP only because it causes release of cathepsin-B into the cytosol.

Morphine treatment worsens the severity of acute pancreatitis and delays resolution and regeneration. Considering our results, the safety of morphine for analgesia during acute pancreatitis should be re-evaluated in future human studies.

Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased (i) ductal to acinar gene expression ratios, (ii) epithelial cells proliferation and (iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo. KRAS mutations induced a protumorigenic phenotype in macrophages. Altered macrophages decreased epithelial pigment epithelial derived factor (PEDF) expression and induced a cancerous phenotype. We validated our findings using annotated patient samples from The Cancer Genome Atlas (TCGA) and in our human PDA specimens. Epithelium-macrophage cross-talk occurs early in pancreatic carcinogenesis where KRAS directly induces cancer-related phenotypes in epithelium, and also promotes a protumorigenic phenotype in macrophages, in turn augmenting neoplastic growth.

Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.

In the current study, we have characterized the global miRNA expression profile in mouse pancreatic acinar cells and during acute pancreatitis using next-generation RNA sequencing. We identified 324 known and six novel miRNAs that are expressed in mouse pancreatic acinar cells. In the basal state, miR-148a-3p, miR-375-3p, miR-217-5p, and miR-200a-3p were among the most abundantly expressed, whereas miR-24-5p and miR-421-3p were the least abundant. Treatment of acinar cells with caerulein (100 nM) and taurolithocholic acid 3-sulfate [TLC-S (250 μM)] induced numerous changes in miRNA expression profile. In particular, we found significant overexpression of miR-21-3p in acini treated with caerulein and TLC-S. We further looked at the expression of miR-21-3p in caerulein, l-arginine, and caerulein + LPS-induced acute pancreatitis mouse models and found 12-, 21-, and 50-fold increased expression in the pancreas, respectively. In summary, this is the first comprehensive analysis of global miRNA expression profile of mouse pancreatic acinar cells in normal and disease conditions. Our analysis shows that miR-21-3p expression level correlates with the severity of the disease.

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Our study indicates that Minnelide is very effective as a therapeutic option against CRPC at a dose that is currently tolerated by patients in the ongoing clinical trials. Prostate 77: 584-596, 2017. © 2017 Wiley Periodicals, Inc.