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Bohmann, Ferdinand ; Kurka, Natalia ; Du Mesnil de Rochemont, Richard Klaus Frieder ; Gruber, Katharina ; Guenther, Joachim ; Rostek, Peter ; Rai, Heike ; Zickler, Philipp ; Ertl, Michael ; Berlis, Ansgar ; Poli, Sven ; Mengel, Annerose ; Ringleb, Peter ; Nagel, Simon ; Pfaff, Johannes ; Wollenweber, Frank Arne ; Kellert, Lars ; Herzberg, Moriz ; Köhler, Luzie Katharina ; Häusler, Karl Georg ; Alegiani, Anna ; Schubert, Charlotte ; Brekenfeld, Caspar ; Doppler, Christopher Emanuel Julian ; Onur, Özgür Abdullah ; Kabbasch, Christoph ; Manser, Tanja ; Pfeilschifter, Waltraud
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.
Bohmann, Ferdinand ; Gruber, Katharina ; Kurka, Natalia ; Willems, Laurent Maximilian ; Herrmann, Eva ; Du Mesnil de Rochemont, Richard Klaus Frieder ; Scholz, Peter ; Rai, Heike ; Zickler, Philipp Patrick ; Ertl, Michael ; Berlis, Ansgar ; Poli, Sven ; Mengel, Annerose ; Ringleb, Peter A. ; Nagel, Simon ; Pfaff, Johannes ; Wollenweber, Frank Arne ; Kellert, Lars ; Herzberg, Moriz ; Köhler, Luzie Katharina ; Häusler, Karl Georg ; Alegiani, Anna ; Schubert, Charlotte ; Brekenfeld, Caspar ; Doppler, Christopher Emanuel Julian ; Onur, Özgür Abdullah ; Kabbasch, Christoph ; Manser, Tanja ; Steinmetz, Helmuth ; Pfeilschifter, Waltraud
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.
Klionsky, Daniel ; Petroni, Giulia ; Amaravadi, Ravi K. ; Baehrecke, Eric H. ; Ballabio, Andrea ; Boya, Patricia ; Bravo-San Pedro, José Manuel ; Cadwell, Ken ; Cecconi, Francesco ; Choi, Augustine M. K. ; Choi, Mary E. ; Chu, Charleen T. ; Codogno, Patrice ; Colombo, Maria Isabel ; Cuervo, Ana Maria ; Deretic, Vojo ; Đikić, Ivan ; Elazar, Zvulun ; Eskelinen, Eeva-Liisa ; Fimia, Gian Maria ; Gewirtz, David A. ; Green, Douglas R. ; Hansen, Malene ; Jäättelä, Marja ; Johansen, Terje ; Juhász, Gábor ; Karantza, Vassiliki ; Kraft, Claudine ; Kroemer, Guido ; Ktistakis, Nicholas T. ; Kumar, Sharad ; López Otín, Carlos ; Macleod, Kay F. ; Madeo, Frank ; Martinez, Jennifer ; Meléndez, Alicia ; Mizushima, Noboru ; Münz, Christian ; Penninger, Josef Martin ; Perera, Rushika M. ; Piacentini, Mauro ; Reggiori, Fulvio ; Rubinsztein, David C. ; Ryan, Kevin M. ; Sadoshima, Junichi ; Santambrogio, Laura ; Scorrano, Luca ; Simon, Hans-Uwe ; Simon, Anna Katharina ; Simonsen, Anne ; Stolz, Alexandra ; Tavernarakis, Nektarios ; Tooze, Sharon A. ; Yoshimori, Tamotsu ; Yuan, Junying ; Yue, Zhenyu ; Zhong, Qing ; Galluzzi, Lorenzo ; Pietrocola, Federico
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
Praktiknjo, Michael ; Simón-Talero, Macarena ; Römer, Julia ; Roccarina, Davide ; Martínez, Javier ; Lampichler, Katharina ; Baiges, Anna ; Low, Gavin ; Llop, Elba ; Maurer, Martin H. ; Zipprich, Alexander ; Triolo, Michela ; Maleux, Geert ; Fialla, Annette Dam ; Dam, Claus ; Vidal-González, Judit ; Majumdar, Avik ; Picón, Carmen ; Toth, Daniel ; Darnell, Anna ; Abraldes, Juan G. ; López, Marta ; Jansen, Christian ; Chang, Johannes ; Schierwagen, Robert ; Uschner, Frank Erhard ; Kukuk, Guido ; Meyer, Carsten ; Thomas, Daniel ; Wolter, Karsten ; Straßburg, Christian P. ; Laleman, Wim ; La Mura, Vincenzo ; Ripoll, Cristina ; Berzigotti, Annalisa ; Calleja, José Luis ; Tandon, Puneeta ; Hernández-Gea, Virginia ; Reiberger, Thomas ; Albillos, Agustin ; Tsochatzis, Emmanuel A. ; Krag, Aleksander ; Genescà, Joan ; Trebicka, Jonel
Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
Kurilkin, Aleksey K. ; Arnold, Oliver ; Atomssa, Ermias T. ; Behnke, Claudia ; Belyaev, Alexei V. ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; González-Díaz, Diégo ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Krizek, Filip ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexei ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lang, Simon Martin ; Lapidus, Kirill ; Lebedev, Alexander ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Yurevich, Sergey ; Zanevsky, Yuri V.
We present the results of two-pion production in tagged quasi-free np collisions at a deutron incident beam energy of 1.25 GeV/c measured with the High-Acceptance Di-Electron Spectrometer (HADES) installed at GSI. The specific acceptance of HADES allowed for the first time to obtain high-precision data on π+π− and π−π0 production in np collisions in a region corresponding to large transverse momenta of the secondary particles. The obtained differential cross section data provide strong constraints on the production mechanisms and on the various baryon resonance contributions (∆∆, N(1440), N(1520), ∆(1600)). The invariant mass and angular distributions from the np → npπ+π −and np → ppπ−π0 reactions are compared with different theoretical model predictions.