TY  - JOUR
A1  - Dasari, Prasad
A1  - Shopova, Iordana A.
A1  - Stroe, Maria
A1  - Wartenberg, Dirk
A1  - Martin-Dahse, Hans
A1  - Beyersdorf, Niklas
A1  - Hortschansky, Peter
A1  - Dietrich, Stefanie
A1  - Cseresnyés, Zoltán
A1  - Figge, Marc Thilo
A1  - Westermann, Martin
A1  - Skerka, Christine
A1  - Brakhage, Axel A.
A1  - Zipfel, Peter F.
T1  - Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage
JF  - Frontiers in Immunology
N2  - The opportunistic fungal pathogen Aspergillus fumigatus can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first A. fumigatus Factor H-binding protein. Aspf2 recruits several human plasma regulators, Factor H, factor-H-like protein 1 (FHL-1), FHR1, and plasminogen. Factor H contacts Aspf2 via two regions located in SCRs6–7 and SCR20. FHL-1 binds via SCRs6–7, and FHR1 via SCRs3–5. Factor H and FHL-1 attached to Aspf2-maintained cofactor activity and assisted in C3b inactivation. A Δaspf2 knockout strain was generated which bound Factor H with 28% and FHL-1 with 42% lower intensity. In agreement with less immune regulator acquisition, when challenged with complement-active normal human serum, Δaspf2 conidia had substantially more C3b (>57%) deposited on their surface. Consequently, Δaspf2 conidia were more efficiently phagocytosed (>20%) and killed (44%) by human neutrophils as wild-type conidia. Furthermore, Aspf2 recruited human plasminogen and, when activated by tissue-type plasminogen activator, newly generated plasmin cleaved the chromogenic substrate S2251 and degraded fibrinogen. Furthermore, plasmin attached to conidia damaged human lung epithelial cells, induced cell retraction, and caused matrix exposure. Thus, Aspf2 is a central immune evasion protein and plasminogen ligand of A. fumigatus. By blocking host innate immune attack and by disrupting human lung epithelial cell layers, Aspf2 assists in early steps of fungal infection and likely allows tissue penetration.
KW  - complement
KW  - blocking opsonization
KW  - phagocytosis
KW  - acquisition of host regulators
KW  - immune evasion
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197013
SN  - 1664-3224
VL  - 9
IS  - 1635
ER  - 
TY  - JOUR
A1  - Jobs, Alexander
A1  - Vonthein, Reinhard
A1  - König, Inke R.
A1  - Schäfer, Jane
A1  - Nauck, Matthias
A1  - Haag, Svenja
A1  - Fichera, Carlo Federico
A1  - Stiermaier, Thomas
A1  - Ledwoch, Jakob
A1  - Schneider, Alisa
A1  - Valentova, Miroslava
A1  - von Haehling, Stephan
A1  - Störk, Stefan
A1  - Westermann, Dirk
A1  - Lenz, Tobias
A1  - Arnold, Natalie
A1  - Edelmann, Frank
A1  - Seppelt, Philipp
A1  - Felix, Stephan
A1  - Lutz, Matthias
A1  - Hedwig, Felix
A1  - Borggrefe, Martin
A1  - Scherer, Clemens
A1  - Desch, Steffen
A1  - Thiele, Holger
T1  - Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA‐ADHF‐DZHK10 trial
JF  - ESC Heart Failure
N2  - Aims
Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right‐sided haemodynamic congestion. The CAVA‐ADHF‐DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone.

Methods and results
CAVA‐ADHF‐DZHK10 is a randomized, controlled, patient‐blinded, multicentre, parallel‐group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion‐related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N‐terminal pro‐brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints.

Conclusions
CAVA‐ADHF‐DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.
KW  - acute decompensated heart failure
KW  - inferior vena cava
KW  - congestion
KW  - NT‐proBNP
KW  - ultrasound
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212692
VL  - 7
IS  - 3
SP  - 973
EP  - 983
ER  -