Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options

Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Effekte einer 6-tägigen Höhenexposition auf die Gefäßbarriere Vorläufige Ergebnisse der DLR EFA-Studie

Einleitung: Ein schneller Aufstieg in große Höhe führt in den ersten 2-5 Tagen zur akuten Höhenkrankheit (AHK), deren Mechanismen nur unzureichend verstanden sind. In Tierund klinischen Studien kam es durch Hypoxie und Inflammation zum Zusammenbruch der Gefäßbarriere bestehend aus einer endothelialen Mikroschicht aus Proteoglykanen (Glycocalyx). Daraus folgte eine erhöhte Gefäßpermeabilität mit Ödembildung und Proteinurie. Die Glycocalyx erholte sich in einer dieser Studien innerhalb von 5 Tagen und zeigte damit eine vergleichbare zeitliche Dynamik wie die AHK. Im Rahmen der AHK ist das Verhalten der endothelialen Glycocalyx allerdings bisher nicht erforscht worden. Hypothesen: Eine 6-tägige Höhenexposition führt zu Hypoxämie, Albuminurie, Bildung peripherer Ödeme und einer Erhöhung der Blutkonzentration der (endothelialen) Glycocalyxfragmente Syndecan-1, Heparansulfat, und Hyaluronan und des Inflammationsmarkers CRP im Vergleich zu den Ausgangswerten in Meereshöhe. Methodik: Aktiver, zweitägiger Aufstieg von 9 gesunden Probanden (4�) zur Capanna Regina Margherita (4554 m, Monte Rosa Massiv, Italien) mit anschließendem 6-tägigem Aufenthalt. Tägliche Messung der peripheren Sauerstoffsättigung und Quantifizierung der akuten Höhenkrankheit mittels Lake Louise Fragebogen (LLS), tägliche 24hUrinsammlung zur quantitativen Bestimmung der Albuminausscheidung und tägliche Blutabnahmen zur späteren Analyse der genannten Glycocalyxfragmente und des CRP. Ergebnisse: Die Höhenexposition führte im Probandenkollektiv nach 48 h zu einer maximalen Hypoxämie mit einer peripheren Sättigung von 76 ±4% und zur Höhenkrankheit (max. 5,5 ±1,8 Punkte im LLS nach der ersten Nacht in 4554 m). Alle Probanden zeigten klinisch periphere Ödeme. Am 5. Tag in der Höhe war das Albumin im Urin signifikant gegenüber dem Ausgangswert in 70 Meter über Meereshöhe erhöht. Syndecan-1, Heparansulfat und Hyaluronan waren in der Höhe signifikant gegenüber den Ausgangswerten erhöht. Schlussfolgerungen: Die in dieser Höhenstudie gefundenen peripheren Ödeme in Kombination mit der erhöhten Albuminausscheidung im Urin, sprechen für eine Erhöhung der Durchlässigkeit der Gefäßbarriere. Die erhöhte Konzentration an Glycocalyx-Bestandteilen im Blut in der Höhe deutet auf eine Fragmentierung der endothelialen Glycocalyx als Pathomechanismus hin. Die bekannten Trigger der Glycocalyx-Fragmentierung, Hypoxämie und eine systemische Inflammationsreaktion, könnten in diesem Fall eine Rolle gespielt haben. Förderung: Die Studie wurde durch programmatische Mittel des DLR Instituts für Luft- und Raumfahrtmedizin und durch Fördermittel der Deutschen Gesellschaft für Berg- und Expeditionsmedizin (BExMed) finanziert

Intraoperative transfusion practices in Europe

BACKGROUND: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. METHODS: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. RESULTS: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl(-1) and increased to 9.8 (1.8) g dl(-1) after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). CONCLUSION: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl(-1)), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. CLINICAL TRIAL REGISTRATION: NCT 01604083