TY  - JOUR
A1  - Boch, Tobias
A1  - Spiess, Birgit
A1  - Heinz, Werner
A1  - Cornely, Oliver A.
A1  - Schwerdtfeger, Rainer
A1  - Hahn, Joachim
A1  - Krause, Stefan W.
A1  - Duerken, Matthias
A1  - Bertz, Hartmut
A1  - Reuter, Stefan
A1  - Kiehl, Michael
A1  - Claus, Bernd
A1  - Deckert, Peter Markus
A1  - Hofmann, Wolf‐Karsten
A1  - Buchheidt, Dieter
A1  - Reinwald, Mark
T1  - Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis
JF  - Mycoses
N2  - Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.
KW  - antifungal
KW  - aspergillosis
KW  - BAL
KW  - blood
KW  - cerebrospinal fluid
KW  - comparison
KW  - PCR
KW  - Aspergillus
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214065
VL  - 62
IS  - 11
SP  - 1035
EP  - 1042
ER  - 
TY  - JOUR
A1  - Wallaschek, Nina
A1  - Reuter, Saskia
A1  - Silkenat, Sabrina
A1  - Wolf, Katharina
A1  - Niklas, Carolin
A1  - Özge, Kayisoglu
A1  - Aguilar, Carmen
A1  - Wiegering, Armin
A1  - Germer, Christoph-Thomas
A1  - Kircher, Stefan
A1  - Rosenwald, Andreas
A1  - Shannon-Lowe, Claire
A1  - Bartfeld, Sina
T1  - Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids
JF  - PLoS Pathogens
N2  - Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.
KW  - Organoids
KW  - ephitelial cells
KW  - gastrointestinal infections
KW  - cancers and neoplasms
KW  - Epstein-Barr virus
KW  - flow cytometry
KW  - epithelium
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259206
VL  - 17
IS  - 2
ER  -