Donor-recipient risk assessment tools in heart transplant recipients: the Bad Oeynhausen experience.

AIMS: Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions. METHODS AND RESULTS: We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively. CONCLUSIONS: Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.

Porphyrin Dyes for Nonlinear Optical Imaging of Live Cells.

Second harmonic generation (SHG)-based probes are useful for nonlinear optical imaging of biological structures, such as the plasma membrane. Several amphiphilic porphyrin-based dyes with high SHG coefficients have been synthesized with different hydrophilic head groups, and their cellular targeting has been studied. The probes with cationic head groups localize better at the plasma membrane than the neutral probes with zwitterionic or non-charged ethylene glycol-based head groups. Porphyrin dyes with only dications as hydrophilic head groups localize inside HEK293T cells to give SHG, whereas tricationic dyes localize robustly at the plasma membrane of cells, including neurons, in vitro and ex vivo. The copper(II) complex of the tricationic dye with negligible fluorescence quantum yield works as an SHG-only dye. The free-base tricationic dye has been demonstrated for two-photon fluorescence and SHG-based multimodal imaging. This study demonstrates the importance of a balance between the hydrophobicity and hydrophilicity of amphiphilic dyes for effective plasma membrane localization.

A way to stable, highly emissive fluorubine dyes: tuning the electronic properties of azaderivatives of pentacene by introducing substituted pyrazines.

Pentacene and its derivatives are among the most important examples of π-electron-rich molecules used in organic field effect transistors. The replacement of CH groups by nitrogen atoms opens an elegant way to generate highly electron-deficient molecules, known as oligoazaacenes. We describe the synthesis and spectroscopic properties of two novel derivatives of this family, namely the zwitterionic and quinoidal conjugated forms of dihydro-5,6,7,12,13,14-hexaazapentacene (fluorubine). We outline a powerful strategy to tune the electronic properties of these redox-active azaacenes by the selective introduction of substituted pyrazines. Their acidochromic and solvatochromic behaviour is investigated experimentally and interpreted with the help of theoretical calculations. The simple "exchange" of substituents or protonation is shown to significantly alter the spectroscopic and electronic properties of these remarkably stable π-systems. Their exceptional optical properties, such as high fluorescence quantum yields combined with a redox-active behaviour, make them promising candidates for sensor materials. Additional marked features in the solid state, such as herringbone packing in combination with short π-π distances, will open access to electronic materials.

Installation of amine moieties into a polycyclic anodic product derived from 2,4-dimethylphenol.

When 2,4-dimethylphenol is anodically treated, a dehydrotetramer with four contiguous stereocentres is readily obtained on a multi-gram scale. The substitution of a 2,4-dimethyl-phenoxy fragment by several amines was demonstrated, and the best results were obtained with primary amines. Optically pure α-chiral aliphatic amines yield diastereomeric mixtures that can be separated in most cases. The basic amine causes a partial hemiketal-opening of the bisbenzofuran moiety leading to an equilibrium within an α,ß-unsaturated cyclohexenone. This dynamic behaviour occurs on the time scale of NMR spectroscopy and is also found by X-ray analysis providing a consistent picture.

From byproducts to efficient fluorophores: a route to the synthesis of fluorubines.

The reaction of bis(imidoyl) chlorides of oxalic acid with monoalkyl hydrazines leads to substituted Delta(2)-1,2-diazetines, which are versatile building blocks for ring-transformation reactions. One remarkable product originating from side reactions featured by a strong orange/red fluorescence was confirmed as a novel fluorubine derivative. In continuing our studies to substituted oligoazaacenes, we developed several synthetic entries to build up novel fluorubine derivatives, in which particularly aminobridged bis(quinoxaline)s are the key products for cationic hexaazapentacenes. We would like to discuss the possible formation pathways of these fluorubine derivatives, which exhibit interesting photophysical and chemical properties. The structures of all new derivatives were confirmed by common analytical methods (NMR spectroscopy, CV, UV/Vis, mass spectrometry, elemental analysis, and X-ray structural analysis) and will be discussed on selected examples in more detail.