Translational research in sepsis - an ultimate challenge?

In the era of evidence-based medicine, large, randomized, controlled, multicenter studies represent the "summit of evidence". In contrast to specialties like cardiology, the majority of randomized, controlled trials in critical care medicine, however, have failed to demonstrate a survival benefit; notably, despite encouraging results from experimental and phase-II clinical studies. The difficulty in translating our theoretical knowledge into successful multicenter randomized, controlled trials and subsequent treatment recommendations may represent one reason, why the mortality of septic shock still averages between 40-60%, although our knowledge about the underlying pathophysiology has considerably increased and international guidelines have widely been implemented. The present article elucidates some of the difficulties in translating research from bench to bedside

Modulation der Wirksamkeit von Arginin-Vasopressin durch Methylprednisolon am wachen, chronisch-instrumentierten, endotoxämischen Schaf

In der vorliegenden Untersuchung sollte die Nullhypothese, dass die kontinuierliche AVP-Infusion bei endotoxämischen Schafen nicht zu einer Tachyphylaxie führt, widerlegt werden. Es sollte evaluiert werden, ob Methylprednisolon (MP) einer potentiellen Tachyphylaxie entgegenwirken kann. Vierzehn Schafe wurden für die hämodynamische Überwachung instrumentiert und in zwei äquivalente Gruppen (AVP-, Kontrollgruppe) randomisiert. Alle Tiere erhielten eine kontinuierliche Endotoxin-Infusion, die zu einer hypotensiven-hyperdynamen Zirkulation führte. Die kontinuierliche Infusion von 0,04 U/min AVP bewirkte einen Anstieg des arteriellen Mitteldrucks (MAP). Nach 6 h zeigte sich eine Reduktion des Vasopressor-Effekts von AVP. Die Injektion von 30 mg/kg MP führte zu einem Anstieg des MAP in der AVP-Gruppe. Diese Daten legen nahe, dass Glukokortikoide einer Tachyphylaxie gegenüber exogenem AVP in der Endotoxinämie entgegenwirken

Comparison of an automatic analysis and a manual analysis of conjunctival microcirculation in a sheep model of haemorrhagic shock

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis

Testing the universality of free fall with rubidium and ytterbium in a very large baseline atom interferometer

We propose a very long baseline atom interferometer test of Einstein's equivalence principle (EEP) with ytterbium and rubidium extending over 10m of free fall. In view of existing parametrizations of EEP violations, this choice of test masses significantly broadens the scope of atom interferometric EEP tests with respect to other performed or proposed tests by comparing two elements with high atomic numbers. In a first step, our experimental scheme will allow reaching an accuracy in the E\"otv\"os ratio of $7\times 10^{-13}$. This achievement will constrain violation scenarios beyond our present knowledge and will represent an important milestone for exploring a variety of schemes for further improvements of the tests as outlined in the paper. We will discuss the technical realisation in the new infrastructure of the Hanover Institute of Technology (HITec) and give a short overview of the requirements to reach this accuracy. The experiment will demonstrate a variety of techniques which will be employed in future tests of EEP, high accuracy gravimetry and gravity-gradiometry. It includes operation of a force sensitive atom interferometer with an alkaline earth like element in free fall, beam splitting over macroscopic distances and novel source concepts

Comparison of first-line and second-line terlipressin versus sole norepinephrine in fulminant ovine septic shock

The Surviving Sepsis Guidelines suggest the use of vasopressin in case of catecholamine-refractory septic shock. Terlipressin (TP) as a V-1-selective AVP analogue is a potential alternative, though data regarding the first-line administration in septic shock are scarce. The present study explored and compared the effects of first-line vs. second-line infusion of TP or sole norepinephrine regarding organ function, fluid and norepinephrine requirements and survival in fulminant ovine septic shock. Peritoneal sepsis was induced in 23 ewes after laparotomy and faecal withdrawal from the caecum. After onset of shock, causal and supportive sepsis therapy (antibiotics, peritoneal lavage, fluids and open-label norepinephrine) was performed in all animals. Concurrently, animals were randomized to receive 0.9% sodium chloride (control group) or TP (2 mu g.kg(-1).h(-1), first-line group) after shock onset. In the second-line TP group, TP (2 mu g.kg(-1).h(-1)) was started once norepinephrine requirements exceeded 0.5 mu g.kg(-1).min(-1). No significant differences were found between groups regarding survival, haemodynamics as well as fluid-and catecholamine-requirements. Kidney function and electron microscopic kidney injury were comparable between groups. In the present model of fulminant ovine septic shock, first-line TP infusion had no significant effect on fluid and norepinephrine requirements or organ dysfunction as compared to second-line TP infusion or placebo

Quantum Test of the Universality of Free Fall

We simultaneously measure the gravitationally-induced phase shift in two Raman-type matter-wave interferometers operated with laser-cooled ensembles of $^{87}$Rb and $^{39}$K atoms. Our measurement yields an E\"otv\"os ratio of $\eta_{\text{Rb,K}}=(0.3\pm 5.4)\times 10^{-7}$. We briefly estimate possible bias effects and present strategies for future improvements

A new complimentary web-based tool for manual analysis of microcirculation videos: validation of the capillary mapper against the current gold standard AVA 3.2

OBJECTIVE: The aim of the current study was to compare a newly developed web-based freely accessible software program for manual analysis of the microcirculation, the Capillary Mapper (CM), with AVA 3.2 software (AVA; MicroVision Medical B.V., Amsterdam, The Netherlands), which is the current gold standard for analysis of microcirculation videos. METHODS: A web-based software program was developed, which enables manual analysis of videos of the microcirculation to be carried out according to recommendations of the 2018 consensus conference. A set of 50 high quality microcirculation videos was analyzed with AVA and CM with respect to total vessel density, perfused vessel density, proportion of perfused vessels, and the microvascular flow index. RESULTS: Comparison of the mean values derived from manual analysis with CM and AVA revealed no significant differences in microcirculatory variables. Analysis according to Bland and Altman revealed an acceptable bias between manual analysis with the CM and AVA for all variables tested with sufficient limits of agreement. The analysis of intraclass correlation showed "excellent" agreement for all microcirculatory variables analyzed. CONCLUSIONS: The newly developed CM was successfully validated for manual analyses of microcirculation videos against the current gold standard, the software AVA 3.2

Interference of Clocks: A Quantum Twin Paradox

The phase of matter waves depends on proper time and is therefore susceptible to special-relativistic (kinematic) and gravitational time dilation (redshift). Hence, it is conceivable that atom interferometers measure general-relativistic time-dilation effects. In contrast to this intuition, we show that light-pulse interferometers without internal transitions are not sensitive to gravitational time dilation, whereas they can constitute a quantum version of the special-relativistic twin paradox. We propose an interferometer geometry isolating the effect that can be used for quantum-clock interferometry.Comment: 9 Pages, 2 Figure