Measurement of CP asymmetry in muon-tagged D0->K-K+ and D0->pi-pi+ decays at LHCb

This thesis presents the measurement of the time-integrated CP asymmetries in D0->K-K+ and D0->pi-pi+ decays. The analysis uses data corresponding to an integrated luminosity of 3 fb^-1 collected at the LHCb experiment in proton-proton collision at centre-of-mass energies of 7 TeV and 8 TeV. The D0 mesons are produced in semileptonic b-hadron decays, where the charge of the accompanying muon determines the initial flavour of the D0 meson. By taking the difference of the observed asymmetries in the selected D0->K-K+ and D0->pi-pi+ samples, production and detection asymmetries cancel. The difference in CP asymmetries between the two final states is measured to be DeltaACP = AcpKK - Acppipi = (+0.14+-0.16(stat)+-0.08(syst))%. In order to obtain a measurement of AcpKK, large samples of Cabibbo-favoured D+ meson decays are used to determine production and detection asymmetries to a high precision. The CP asymmetry is found to be AcpKK = (-0.06+-0.15(stat)+-0.10(syst))%, where the correlation coefficient between DeltaACP and AcpKK is rho=0.28. By combining these results, the CP asymmetry in decays D0->pi-pi+ is derived to be Acppipi = (-0.20+-0.19(stat)+-0.10(syst))%. The results of this thesis show that there is no significant CP violation in D0->K-K+ and D0->pi-pi+ decays at the level of 10^-3

Current clinical practice in using adjunctive extracorporeal blood purification in sepsis and septic shock: results from the ESICM “EXPLORATION” survey

Background: Despite a lack of clear evidence extracorporeal blood purification (EBP) is increasingly used as an adjunctive treatment in septic shock based on its biological plausibility. However, current state of praxis and believes in both efficacy and level of evidence are very heterogeneous. Methods: The "EXPLORATION" (Current Clinical Practice in using adjunctive extracorporeal blood purification in septic shock), a web-based survey endorsed by the European Society of Intensive Care Medicine (ESICM), questioned both the current local clinical practices as well as future perspectives of EBP in sepsis and septic shock. Results: One hundred and two people participated in the survey. The majority of three quarters of participants (74.5%) use adjunctive EBP in their clinical routine with a varying frequency of description. Unselective cytokine adsorption (CA) (37.5%) and therapeutic plasma exchange (TPE) (34.1%) were by far the most commonly used modalities. While the overall theoretical rational was found to be moderate to high by the majority of the participants (74%), the effectively existing clinical evidence was acknowledged to be rather low (66%). Although CA was used most frequently in clinical practice, both the best existing clinical evidence endorsing its current use (45%) as well the highest potential to be explored in future clinical trials (51.5%) was attributed to TPE. Conclusions: Although the majority of participants use EBP techniques in their clinical practice and acknowledge a subjective good theoretical rationale behind it, the clinical evidence is assessed to be limited. While both CA and TPE are by far the most common used technique, both clinical evidence as well as future potential for further exploration in clinical trials was assessed to be the highest for TPE

Plasmapherese bei Sepsis

Trotz der nachvollziehbaren theoretischen Rationale und der biologischen Plausibilität mangelt es bis dato an eindeutiger Evidenz für oder wider extrakorporale Blutreinigungsstrategien. In den letzten 3 Jahren haben allerdings mehrere qualitativ hochwertige Untersuchungen, die sich auf eine vergleichbare Intervention beziehen, darauf hingewiesen, dass die unselektive Entfernung von zirkulierenden Mediatoren bei kritisch kranken Sepsispatienten unerwartet schädlich sein könnte. Der therapeutische Plasmaaustausch (TPE) ist zwar auch eine extrakorporale Behandlung, verfolgt aber einen grundlegend anderen biologischen Ansatz. Hierbei wird das gesamte Plasmavolumen entfernt und zeitgleich mit gesundem Spenderplasma ersetzt. Die Hypothese hinter einem günstigen Effekt des TPE auf die Pathophysiologie der Sepsis basiert hierbei auf der Idee, die Beseitigung übermäßiger schädigender Mediatoren mit der Substitution schützender, aber in der Sepsis verbrauchter Faktoren zu kombinieren. Mehrere rezente Metanalysen, welche die Ergebnisse u. a. des EXCHANGE-Studienprogramms und von retrospektiven Propensity-Score-Analysen der letzten Jahre einbeziehen, finden entsprechend übereinstimmend ein signifikant verbessertes Überleben bei zusätzlich mit TPE behandelten Patienten im septischen Schock. Der Beweis, dass TPE tatsächlich das Überleben von Patienten mit septischem Schock verbessern kann, steht allerdings noch aus