Response versus Nonresponse auf einen Volumenbolus bei restriktivem Volumenmanagement bei Leberchirurgie im Rahmen der PHYDELIO-Studie

Einleitung Das perioperative, anästhesiologische Management hat eine große Relevanz für das Outcome und die Mortalität. Alleinig nur mittels eines hämodynamischen Standardmonitorings kardiovaskulärer Parameter können okkulte Hypovolämiezustände nicht sensitiv genug detektieren werden. Der Einsatz eines erweiterten hämodynamischen Monitorings wie zum Beispiel des ösophagealen Dopplermonitorings ermöglicht jedoch die Messung dynamischer Flussparamter. Hieraus resultiert die Möglichkeit einer individuell zielgerichteten Infusionstherapie, welche eine Reduktion der Mortalität und Krankenhausverweildauer zeigt. Gemäß der Volumenreagibilität auf einen Flüssigkeitsbolus anhand der Vorlastreserven der Frank-Starling-Kurve kann zwischen Respondern und Nonrespondern unterschieden werden. Die vorliegende Arbeit untersuchte den Unterschied zwischen Respondern und Nonresponder sowie mögliche klinische Prädiktoren für eine Response auf einen Flüssigkeitsbolus bei restriktivem Volumenmanagement bei leberchirurgischen Patienten. Methoden Die vorliegende Untersuchung war eine retrospektive Subanalyse von 166 Patienten der PHYDELIO-Studie (Perioperative Gabe von Physostigmin bei Leberteilresektion zur Prophylaxe von Delir und postoperativem kognitivem Defizit). Die Gruppeneinteilung definierte sich anhand des Stroke Volume Index (SVI) Anstieges als Reaktion auf einen 200 ml Volumenbolus als Responder (SVI 10%) und Nonresponder (SVI < 10%). Entsprechend des hämodynamischen Algorithmus der PHYDELIO-Studie wurden zwei standardisierte Analysezeitpunkte untersucht: initial nach Narkoseeinleitung (1. Optimierung) und nach Abschluss der Leberteilresektion (2. Optimierung). Die Daten wurden jeweils vor Trial und in Anschluss an die Volumenbolusgabe nach Trial erhoben. Die demografischen, hämodynamischen und laborchemischen Daten der Gruppen wurden deskriptiv im prä- und intraoperativen Verlauf verglichen. In einer Sekundäranalyse wurden Prädiktoren für eine Response mittels binär-logistischer Regression identifiziert. Ergebnisse Zum Zeitpunkt der 1. Optimierung zeigten 72 (43%) Patienten eine positive Response auf einen Volumenbolus und zum Zeitpunkt der 2. Optimierung 96 (58%). Der SVI hatte zu beiden Zeitpunkten vor Trial ein signifikant niedrigeres Niveau in der Gruppe der Responder als in der der Nonresponder (p < 0,001). Zu beiden Zeitpunkten erhielt die Gruppe der Responder weniger Flüssigkeitsvolumen (p = 0,001/ p = 0,022). Eine höhere Gesamtinfusionsmenge stellte einen negativen Prädiktor (p = 0,011) für eine positive Response auf einen Flüssigkeitsbolus zum Zeitpunkt der 1. Optimierung dar. Für den Zeitpunkt der 2. Optimierung ließen sich keine signifikanten klinischen Prädiktoren identifizieren. Zusammenfassung Die Subpopulation der Nonresponder hatte bereits einen größeren Vorlastausgleich vor der Volumenchallenge erfahren. Sie befand sich somit auf einem flacheren Punkt der Frank-Starling-Kurve. Es ließen sich jedoch keine relevanten Unterschiede in den untersuchten klinischen Parametern zwischen der Gruppe der Responder und Nonresponder identifizieren. Des Weiteren ließen sich keine klinisch relevanten prädiktiven Faktoren für eine Response bei restriktivem Volumenmanagement bei Leberchirurgie nachweisen.Introduction Anesthesiological management is of great relevance for outcome, morbidity and mortality. However, occult hypovolemic states cannot be detected sufficiently by today's standard hemodynamic monitoring of cardiovascular parameters. The use of extended hemodynamic monitoring such as esophageal doppler monitoring systems enabels dynamic flow parameters to be measured. This creates the possibility of an individualised goal directed therapy that is related to a reduction in mortality and hospital length of stay. Volume responsiveness to a fluid challenge based on the preload reserves of the Frank-Starling curve allows to distinguish between responders and nonresponders. The aim of this work was to examine the difference between responders and nonresponders and to evaluate possible predictors of fluid responsiveness in liver surgery patients. Methods This study was a retrospective subanalysis of 166 patients within the PHYDELIO trial (perioperative administration of physostigmine for partial liver resection for the prophylaxis of delirium and postoperative cognitive deficit). Patients were classified as responders to a fluid challenge (200 ml), when increases of stroke volume index (SVI) were (SVI 10%) or as nonresponder when increases of SVI were < 10%. According to the hemodynamic algorithm of the PHYDELIO study, two predefined time instances were analysed: initially after induction of anesthesia (Optimisation 1) and after completion of the partial liver resection (Optimisation 2). Before and after fluid administration data was recorded. Demographic, hemodynamic and laboratory chemical data of the subpopulations was descriptively compared. Furthermore, predictors for fluid responsiveness were studied using binary logistic regression. Results Initially 72 (43%) patients showed a positive response to a volume challenge and after resection 96 (58%). The SVI showed a significantly lower level (p < 0,001) in the responders than nonresponders at the 1st optimisation. At both times instances, the group of responders received less fluid volume. As a result, a higher amount of volume was found to be a negative predictor (p = 0,011) for fluid responsiveness after induction of anesthesia. After liver resection no significant predictors could be determined. Conclusion The subpopulation of nonresponders had already experienced a greater preload compensation before the volume challenge and was therefore located on a flatter point on the Frank-Starling curve. However, there was little clinical relevance. No clinically relevant differences could be determined in-between the group of responders and nonresponders. Furthermore, no clinically relevant predictors for fluid responsiveness during liver surgery could be identified

LCA on wastewater and sludge management for local decision-making in Gothenburg – are new LCA method developments enough?

This paper describes an LCA study that was made to inform decision-makers in Gothenburg about two different sludge management options. Incineration of anaerobically digested sludge with recovery of a phosphorus fertiliser product seemed preferable to using pasteurised anaerobically digested sludge in agriculture. Aspects under the control of the decision-makers were important for overall results, and caused the main differences between the studied systems, indicating considerable potential for local improvement efforts. Applying a human toxicity characterisation method with a more sludge specific fate model were important, but not crucial, for the results. However, the results are connected to large uncertainties and remaining challenges are discussed in the paper

Microconstriction Arrays for High-Throughput Quantitative Measurements of Cell Mechanical Properties

AbstractWe describe a method for quantifying the mechanical properties of cells in suspension with a microfluidic device consisting of a parallel array of micron-sized constrictions. Using a high-speed charge-coupled device camera, we measure the flow speed, cell deformation, and entry time into the constrictions of several hundred cells per minute during their passage through the device. From the flow speed and the occupation state of the microconstriction array with cells, the driving pressure across each constriction is continuously computed. Cell entry times into microconstrictions decrease with increased driving pressure and decreased cell size according to a power law. From this power-law relationship, the cell elasticity and fluidity can be estimated. When cells are treated with drugs that depolymerize or stabilize the cytoskeleton or the nucleus, elasticity and fluidity data from all treatments collapse onto a master curve. Power-law rheology and collapse onto a master curve are predicted by the theory of soft glassy materials and have been previously shown to describe the mechanical behavior of cells adhering to a substrate. Our finding that this theory also applies to cells in suspension provides the foundation for a quantitative high-throughput measurement of cell mechanical properties with microfluidic devices

Non-equilibrium dynamics and floral trait interactions shape extant angiosperm diversity.

Why are some traits and trait combinations exceptionally common across the tree of life, whereas others are vanishingly rare? The distribution of trait diversity across a clade at any time depends on the ancestral state of the clade, the rate at which new phenotypes evolve, the differences in speciation and extinction rates across lineages, and whether an equilibrium has been reached. Here we examine the role of transition rates, differential diversification (speciation minus extinction) and non-equilibrium dynamics on the evolutionary history of angiosperms, a clade well known for the abundance of some trait combinations and the rarity of others. Our analysis reveals that three character states (corolla present, bilateral symmetry, reduced stamen number) act synergistically as a key innovation, doubling diversification rates for lineages in which this combination occurs. However, this combination is currently less common than predicted at equilibrium because the individual characters evolve infrequently. Simulations suggest that angiosperms will remain far from the equilibrium frequencies of character states well into the future. Such non-equilibrium dynamics may be common when major innovations evolve rarely, allowing lineages with ancestral forms to persist, and even outnumber those with diversification-enhancing states, for tens of millions of years

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products

Совершенствование организационных структур управления

Материалы IV Республик. науч. конф. студентов, магистрантов и аспирантов, Гомель, 12 мая 2011 г

Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption.

Regulation of body temperature critically depends on thyroid hormone (TH). Recent studies revealed that TH induces browning of white adipose tissue, possibly contributing to the observed hyperthermia in hyperthyroid patients and potentially providing metabolic benefits. Here, we show that browning by TH requires TH-receptor β and occurs independently of the sympathetic nervous system. The beige fat, however, lacks sufficient adrenergic stimulation and is not metabolically activated despite high levels of uncoupling protein 1 (UCP1). Studies at different environmental temperatures reveal that TH instead causes hyperthermia by actions in skeletal muscle combined with a central body temperature set-point elevation. Consequently, the metabolic and thermogenic effects of systemic hyperthyroidism were maintained in UCP1 knockout mice, demonstrating that neither beige nor brown fat contributes to the TH-induced hyperthermia and elevated glucose consumption, and underlining that the mere presence of UCP1 is insufficient to draw conclusions on the therapeutic potential of browning agents