Die präoperative Nierenfunktion und der EuroSCORE II als Prädiktoren für Komplikationen und Mortalität nach elektiven kardiochirurgischen Eingriffen

Die Abschätzung der postoperativen 30-Tage-Mortalität nach einer Herzoperation erfolgt seit 2012 anhand des EuroSCORE II. Dieser umfasst insgesamt 18 Risikofaktoren wie Alter, Geschlecht, Art des Eingriffes und den kardialen Zustand Auf der Basis einer prospektiven Kohortenstudie zwischen 02/2010 und 03/2011 sollte die prognostische Wertigkeit der eingehenden Risikofaktoren für die postoperative Mortalität und Komplikationen im Vergleich zum präoperativ gemessenen Cystatin C untersucht werden, In die Studie gingen 860 Patienten ein. Endpunkte waren die postoperative Mortalität, ein akutes Nierenversagen und eine nicht-okklusive Darmischämie. Ein postoperatives akutes Nierenversagen trat in 26,2 % auf, nicht-okklusive Darmischämie in 9,1 % und Tod in 3,1 %. Der EuroSCORE II überschätzte die Mortalität mit 6,2% und wies damit eine prädiktorische Wertigkeit in der ROC-Analyse mit einer AUC von 0,761 auf. Eine einzelne präoperative Bestimmung des Cystatin C erwies sich als prädiktorisch wenigstens gleichwertig (AUC 0,770). Im Hinblick auf die Komplikationen NOD und ANV war das Cystatin C dem EuroSCORE II sogar überlegen. Im Gegensatz hierzu erwiesen sich einige der Risikoparameter, die in den EuroSCORE II eingehen als wenig prädiktiv für Komplikationen oder Outcome. Interessanterweise zeigte das in den EuroSCORE II eingehende Kreatinin, bzw. die GFR auf Basis der Berechnung nach Cockrofft-Gault eine geringere prädiktorische Kapazität für die Endpunkte als das Cystatin C. Die Nierenfunktion als guter Prädiktor für Outcome und Komplikationen nach kardiochirurgischem Eingriff ist seit langem bekannt. Eine mögliche Erklärung für die unterschiedliche prädiktorische Wertigkeit von Cystatin C und Kreatinin wäre, dass durch das Cystatin C die renale Funktion exakter abgebildet wird und damit eine bessere Prädiktion verbunden sein könnte. Dies würde letztlich auch erklären können, weshalb das Cystatin C eine dem 18 Parameter umfassenden EuroSCORE II vergleichbare prognostische Wertigkeit für das Auftreten von Komplikationen und outcome nach kardiochirurgischen Eingriffen aufweist.The EuroSCORE II has been used since 2012 to predict early mortality in cardiosurgical patients. It is based on a specific range of risk factors including age, gender, type of surgical intervention and heart function. A prospective cohort study was carried out from 02/2010 to 03/2011 with the aim to determine the prognostic significance of the included risk factors when it comes to predicting postsurgical mortality as well as complications compared to measuring the cystatin C pre-surgery. The study included 860 patients. The endpoints were postoperative mortality, acute renal failure and non-occlusive bowel ischemia. Postoperative renal failure occurred in 26.2% of the patients, non-occlusive bowel ischemia in 9.1% and death in 3.1% of patients. The EuroSCORE II overestimated the mortality by 6.2% and delivered a predictive significance in the ROC analysis with 0.761 AUC. The individual preoperative measurement of cystatin C proved to be of similar accuracy with AUC 0.770. If cystatin C was used to predict the outcome in cases of renal failure or non-occlusive bowel ischemia it was even superior to the EuroSCORE II. At the same time it was found that a number of risk factors that are included in the EuroSCORE II had very little significance in predicting complications or outcome. Interestingly, it was found that the creatinine that is included in the EuroSCORE II or the GFR using the Cockroft-Gauck method, had a less accurate predictive significance than the cystatin C. It has been known for some time that the renal function can be used as a valid predictor for outcome and complications following a cardiac surgical intervention. The difference in the predictive significance of cystatin C and creatinine could be explained with the fact that cystatin C more closely mirrors the renal function and therefore offers a better prediction. This could also explain why the cystatin C on its own has a similar prognostic significance to the EuroSCORE II including its 18 parameters when looking to predict outcome and complications of post-cardiac interventions

Microplastics are not important for the cycling and bioaccumulation of organic pollutants in the oceans – but should microplastics be considered POPs themselves?

The role of microplastic particles in the cycling and bioaccumulation of persistent organic pollutants (POPs) is discussed. Five common concepts, sometimes misconceptions, about the role of microplastics are reviewed. While there is ample evidence that microplastics accumulate high concentrations of POPs, this does not result in microplastics being important for the global dispersion of POPs. Similarly, there is scant evidence that microplastics are an important transfer vector of POPs into animals, but possibly for plastic additives (flame retardants). Last, listing microplastics as POPs could help reduce their environmental impact

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/-mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals\u27 lifespans. METHODS. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety. RESULTS. At 12 weeks, statistically significant median (IQR) reductions in the Epidermolysis Bullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0% (2.9%-30%; P = 0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB-c) score of 18.2% (1.9%-39.8%; P = 0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%-42.9%; P = 0.033) and 25.0% (-8.4% to 46.4%; P = 0.168), respectively. Three adverse events were considered related to the cell product: 1 mild lymphadenopathy and 2 hypersensitivity reactions. The latter 2 were serious but resolved without sequelae shortly after withdrawal of treatment. CONCLUSION. This trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5+ MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation

Plastics in the marine environment are reservoirs for antibiotic and metal resistance genes

Plastics have been accumulated offshore and in the deep oceans at an unprecedented scale. Microbial communities have colonized the plastisphere, which has become a reservoir for both antibiotic and metal resistance genes (ARGs and MRGs). This is the first analysis of the diversity, abundance, and co-occurrence of ARGs and MRGs, and their relationships within the microbial community, using metagenomic data of plastic particles observed in the North Pacific Gyre obtained from the National Centre for Biotechnology Information Sequence Read Archive database. The abundance of ARGs and MRGs in microbial communities on the plastics were in the ranges 7.07 x 10(-4)-1.21 x 10(-2) and 5.51 x 10(-3)-4.82 x 10(-2) copies per 16S rRNA, respectively. Both the Shannon-Wiener indices and richness of ARGs and MRGs in plastics microbiota were significantly greater than those of ARGs and MRGs in seawater microbiota in the North Pacific Gyre via one-way analysis of variance. Multidrug resistance genes and multi-metal resistance genes were the main classes of genes detected in plastic microbiota. There were no significant differences in the abundance or diversity of ARGs and MRGs between macroplastics biota and microplastics biota, indicating that particle size had no effect on resistance genes. Procrustes analysis suggested that microbial community composition was the determining factor of the ARG profile but not for MRG. Some ARGs and MRGs had a higher incidence of non-random co-occurrence, suggesting that the co-effects of selection for antibiotic or metal resistance are important factors influencing the resistome of the microbiota on the plastic particles

The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis.

N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis

Microplastic-Associated Biofilms: A Comparison of Freshwater and Marine Environments

Microplastics (<5 mm particles) occur within both engineered and natural freshwater ecosystems, including wastewater treatment plants, lakes, rivers, and estuaries. While a significant proportion of microplastic pollution is likely sequestered within freshwater environments, these habitats also constitute an important conduit of microscopic polymer particles to oceans worldwide. The quantity of aquatic microplastic waste is predicted to dramatically increase over the next decade, but the fate and biological implications of this pollution are still poorly understood. A growing body of research has aimed to characterize the formation, composition, and spatiotemporal distribution of microplastic-associated (“plastisphere”) microbial biofilms. Plastisphere microorganisms have been suggested to play significant roles in pathogen transfer, modulation of particle buoyancy, and biodegradation of plastic polymers and co-contaminants, yet investigation of these topics within freshwater environments is at a very early stage. Here, what is known about marine plastisphere assemblages is systematically compared with up-to-date findings from freshwater habitats. Through analysis of key differences and likely commonalities between environments, we discuss how an integrated view of these fields of research will enhance our knowledge of the complex behavior and ecological impacts of microplastic pollutants