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Aims: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.
Methods and results: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.
Conclusion: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
Mit der Neuregelung der Studienplatzverteilung von 2005 haben die Universitäten in Deutschland die Möglichkeit, bis zu 60% der Studienplätze nach universitätseigenen Kriterien zu vergeben. Implizit wird vom Gesetzgeber und der öffentlichen Meinung gefordert, nicht-leistungsbezogene Kriterien und Persönlichkeitsmerkmale verstärkt zur Bewerberauswahl einzusetzen (Motivation, Identifikation, Vermeidung von Fehlvorstellungen). Da in Anbetracht der Bewerberzahlen mündliche Auswahlgespräche als ungeeignet erscheinen, wurde vom Fachbereich Medizin der Johann Wolfgang Goethe Universität ein Fragebogen entworfen, um nichtschulische Leistungen zu erfassen. Dieser Fragebogen wurde am Beginn des Wintersemesters 2005/2006 von allen Studienanfängern der JWG-Universität Frankfurt und der Medizinischen Universität Innsbruck ausgefüllt. Entgegen der initialen Erwartungen der Verfasser gaben nur etwa 15% Prozent Medizin-spezifische berufliche Vorerfahrungen an (Rettungsdienst, Ausbildung als Krankenschwester/pfleger oder ähnliches); dagegen wurden von etwa 60% angegeben, mindestens ein Musikinstrument zu spielen oder länger sportlich aktiv gewesen zu sein. Die Zusammenstellung der Selbstangaben zeigt, dass Medizin-relevante Vorkenntnisse nur bei einem kleinen Anteil der Studienbewerber in größerem Umfang vorhanden sind. Aufgrund der großen Streuung in der Art und Dauer der angegebenen Vorleistungen sollte die Erhebung von Parametern zur Beurteilung von soft skills, z.B. durch Online-Fragebogen, als (Vor)Selektionsinstrument nur sehr vorsichtig eingesetzt werden.
Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2–3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period.
Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the “door-to-needle” time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire.
Interventions: We are applying a multi-level intervention in cooperation with three “STREAM multipliers” from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2–3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings.
Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.
Background: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care.
Methods: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the ‘door-to-needle’ time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm.
Results: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25–43 min) to 33 min (IQR 23–39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (−21 min, simulation-naive: 95 min, IQR 69–111 vs. simulation-experienced: 74 min, IQR 51–92, p = 0.04).
Conclusion: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.