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  - 
TY  - JOUR
A1  - Lenz, Dominic
A1  - Pahl, Jens
A1  - Hauck, Fabian
A1  - Alameer, Seham
A1  - Balasubramanian, Meena
A1  - Baric, Ivo
A1  - Boy, Nikolas
A1  - Church, Joseph A.
A1  - Crushell, Ellen
A1  - Dick, Anke
A1  - Distelmaier, Felix
A1  - Gujar, Jidnyasa
A1  - Indolfi, Giuseppe
A1  - Lurz, Eberhard
A1  - Peters, Bianca
A1  - Schwerd, Tobias
A1  - Serranti, Daniele
A1  - Kölker, Stefan
A1  - Klein, Christoph
A1  - Hoffmann, Georg F.
A1  - Prokisch, Holger
A1  - Greil, Johann
A1  - Cerwenka, Adelheid
A1  - Giese, Thomas
A1  - Staufner, Christian
T1  - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency
JF  - Journal of Clinical Immunology
N2  - Purpose
Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system.

Methods
Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system.

Results
Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia.

Conclusion
In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.
KW  - NBAS
KW  - inborn error of immunity
KW  - NK cell deficiency
KW  - B cell deficiency
KW  - vesicle trafficking
KW  - familial hemophagocytic lymphohistiocytosis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308362
SN  - 0271-9142
SN  - 1573-2592
VL  - 41
IS  - 8
ER  -