CME: Sekundäre hämophagozytische Lymphohistiozytose

CME: Acquired Hemophagocytic Lymphohistiocytosis Abstract. Acquired hemophagocytic lymphohistiocytosis comprises a heterogenous group of hyperinflammatory immunoreactions often resulting in uncontrolled immune responses, mainly throughout proliferation of cytotoxic T cells and hemophagocytosis by macrophages. Hemophagocytic lymphohistiocytosis is often underdiagnosed, contributing to its high morbidity and mortality. A systematic diagnostic approach and the use of established diagnostic criteria should lead to an early diagnosis, which is crucial for any therapeutic attempt to achieve a curative state of the disease

Sca-1 is a marker for cell plasticity in murine pancreatic epithelial cells and induced by IFN-β in vitro

BACKGROUND & AIMS: Sca-1 is a surface marker for murine hematopoietic stem cells (HSCs) and type-I interferon is a key regulator for Lin$^{-}$Sca-1$^{+}$ HSCs expansion through Ifnar/Stat-1/Sca-1-signaling. In this study we aimed to characterize the role and regulation of Sca-1$^{+}$ cells in pancreatic regeneration. METHODS: To characterize Sca-1 in vivo, immunohistochemistry and immunofluorescence staining of Sca-1 was conducted in normal pancreas, in cerulein-mediated acute pancreatitis, and in Kras-triggered cancerous lesions. Ifnar/Stat-1/Sca-1-signaling was studied in type-I IFN-treated epithelial explants of adult wildtype, Ifnar$^{-}$$^{/-}$, and Stat-1$^{-}$$^{/}$$^{-}$ mice. Sca-1 induction was analyzed by gene expression and FACS analysis. After isolation of pancreatic epithelial Lin$^{-}$Sca-1$^{+}$cells, pancreatosphere-formation and immunofluorescence-assays were carried out to investigate self-renewal and differentiation capabilities. RESULTS: Sca-1$^{+}$ cells were located in periacinar and periductal spaces and showed an enrichment during cerulein-induced acute pancreatitis (23.2/100 μm$^{2}$ ± 4.9 SEM) and in early inflammation-mediated carcinogenic lesions of the pancreas of Kras$^{G12D}$ mice (35.8/100 μm$^{2}$ ± SEM 1.9) compared to controls (3.6/100 μm$^{2}$ ± 1.3 SEM). Pancreatic Lin$^{-}$Sca-1$^{+}$ cells displayed a small population of 1.46% ± 0.12 SEM in FACS. In IFN-β treated pancreatic epithelial explants, Sca-1 expression was increased, and Lin$^{-}$Sca-1$^{+}$ cells were enriched in vitro (from 1.49% ± 0.36 SEM to 3.85% ± 0.78 SEM). Lin$^{-}$Sca-1$^{+}$ cells showed a 12 to 51-fold higher capacity for clonal self-renewal compared to Lin$^{-}$Sca-1$^{-}$ cells and generated cells express markers of the acinar and ductal compartment. CONCLUSIONS: Pancreatic Sca-1$^{+}$ cells enriched during parenchymal damage showed a significant capacity for cell renewal and in vitro plasticity, suggesting that corresponding to the type I interferon-dependent regulation of Lin$^{-}$Sca-1$^{+}$ hematopoietic stem cells, pancreatic Sca-1$^{+}$ cells also employ type-I-interferon for regulating progenitor-cell-homeostasis

Performance of two-dimensional shear wave elastography and transient elastography compared to liver biopsy for staging of liver fibrosis

BACKGROUND: Staging of liver fibrosis traditionally relied on liver histology, however transient elastography (TE) and more recently two-dimensional shear wave elastography (2D-SWE) evolved to non-invasive alternatives. Hence, we evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system using liver biopsy as reference and compared the performance to TE. METHODS: In total, 108 adult patients with chronic liver disease undergoing liver biopsy, 2D-SWE and TE were enrolled prospectively at the University Hospital Zurich. Diagnostic accuracies were evaluated using the area under the receiver operating characteristic (AUROC) analysis, and optimal cutoff values by Youden's index RESULTS: Diagnostic accuracy of 2D-SWE was good for significant (≥F2; AUROC 85.2%, 95% confidence interval (95%CI):76.2-91.2%) as well as severe fibrosis (≥F3; AUROC 86.8%, 95%CI:78.1-92.4%) and excellent for cirrhosis (AUROC 95.6%, 95%CI:89.9-98.1%), compared to histology. TE performed equally well (significant fibrosis: 87.5%, 95%CI:77.7-93.3%; severe fibrosis: 89.7%, 95%CI:82.0-94.3%; cirrhosis: 96%, 95%CI:90.4-98.4%), and accuracy was not statistically different to 2D-SWE. 2D-SWE optimal cutoff values were 6.5, 9.8 and 13.1 kPa for significant fibrosis, severe fibrosis, and cirrhosis, respectively. CONCLUSIONS: Performance of 2D-SWE was good to excellent and well comparable with TE, supporting the application of this 2D-SWE system in the diagnostic workup of chronic liver disease

Performance of two-dimensional shear wave elastography and transient elastography compared to liver biopsy for staging of liver fibrosis.

BACKGROUND Staging of liver fibrosis traditionally relied on liver histology, however transient elastography (TE) and more recently two-dimensional shear wave elastography (2D-SWE) evolved to non-invasive alternatives. Hence, we evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system using liver biopsy as reference and compared the performance to TE. METHODS In total, 108 adult patients with chronic liver disease undergoing liver biopsy, 2D-SWE and TE were enrolled prospectively at the University Hospital Zurich. Diagnostic accuracies were evaluated using the area under the receiver operating characteristic (AUROC) analysis, and optimal cutoff values by Youden's index RESULTS: Diagnostic accuracy of 2D-SWE was good for significant (≥F2; AUROC 85.2%, 95% confidence interval (95%CI):76.2-91.2%) as well as severe fibrosis (≥F3; AUROC 86.8%, 95%CI:78.1-92.4%) and excellent for cirrhosis (AUROC 95.6%, 95%CI:89.9-98.1%), compared to histology. TE performed equally well (significant fibrosis: 87.5%, 95%CI:77.7-93.3%; severe fibrosis: 89.7%, 95%CI:82.0-94.3%; cirrhosis: 96%, 95%CI:90.4-98.4%), and accuracy was not statistically different to 2D-SWE. 2D-SWE optimal cutoff values were 6.5, 9.8 and 13.1 kPa for significant fibrosis, severe fibrosis, and cirrhosis, respectively. CONCLUSIONS Performance of 2D-SWE was good to excellent and well comparable with TE, supporting the application of this 2D-SWE system in the diagnostic workup of chronic liver disease