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3. Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial

Author

Aamodt, Anne Hege, Adamczewski, Olaf, Alektoror, Kirill, Alexander, März, Alexandrou, Maria, Alias, Quentin, Al-Kuzae, Fadha Elawi, Allard, Julien, Al-Schameri, Rahman, Álvarez, Alberto, Andersen, Grethe, AnkerlundBlaufeldt, Rolf, Antje, Riedel, Appelbohm, Hannes, Argren, Maria, Assmann, Anne, Augustin, Michael, Bach, Elke, Bar, Michal, Barleben, Maria, Baronnet, Flore, Barrios, Andrés, Bavúzová, Xénia, BayThomsen, Rikke, Becker, Sandra, Beer, Sylvia, Behme, Daniel, Bellut, Maximilian, Bendszus, Martin, Berkefeld, Joachim, Bester, Maximillian, Bode, Felix J., Boehme, Christian, Boese, Ramona, Bohmann, Ferdinand, Bonekamp, Susanne, Borggrefe, Jan, Boss, Erendira Gabriela, Boutchakova, Maria, Boxhammer, Elfi, Brandhofe, Annemarie, Breckwoldt, Michael, Brekenfeld, Casper, Brehm, Alex, Brem, Christian, Breuer, Stella, Breyer, Tobias, Brodová, Petra, Broocks, Gabriel, Brosinski, Christoph, Bubel, Nele, Búřil, Jiří, Čábal, Martin, Casado, Laura, de Celis, Elena, Chabert, Emmanuel, Charisse, Daniel, Cheng, Bastian, Chovanec, Vendelín, Cidlinsky, Peter, Cisár, Juraj, Clarençon, Fréderic, Crozier, Sophie, Čurdová, Nina, Damaskinos, Michele, Damgaard, Dorte, Daniš, Martin, Dazinger, Florian, Deb-Chatterji, Milani, Delalic, Asima, Delekta, Agnieszka, Delorme, Stephen, Deutschmann, Hannes, Diamandis, Elie, Diedrichsen, Tove, Doležalová, Irena, Dorn, Franziska, du Mesnil de Rochemont, Richard, DupontHougaard, Kristina, Ebrahimi, Taraneh, Eff, Florian, Eliášová, Ilona, Enriquez, Brian, Ergawy, Mostafa, Essig, Fabian, Falkesgaard, Maiken, Fandler-Höfler, Simon, Fernández, Andrés, Ferré, Jean-Christophe, Ferrier, Anna, Fiehler, Jens, Figlewski, Krystian, Fischer, Sebastian, Fischer, Urs, Flottmann, Fabian, Forbrig, Robert, Förch, Christian, Fromm, Annette, Fuentes, Blanca, Gaedke, Ines, Galczak, Romana, Galijasevic, Malik, Ganser, Bernhard, Gattringer, Thomas, Gawlitza, Matthias, Gelhard, Sarah, Gellißen, Susanne, Gerber, Johannes, Giannakakis, Michail Panagiotis, Gindlhuber, Karin, Gizewski, Elke R., Glodny, Bernhard, Godel, Tim, Goebell, Einar, Goldemund, David, Görtler, Michael, Goyal, Mayank, Grams, Astrid E., Gruber, Joachim, Gruber, Katharina, Günthner-Lengsfeld, Thomas, Haase, Kathrin, Hacker-Ivan, Floriana, Hallerstig, Erika, Hametner, Christian, Hanning, Uta, Haring, Jozef, Haršány, Michal, Haršány, Ján, Hartmann, Christian, Hassler, Eva Maria, Hauptmann, Kristina, Haeusler, Karl Georg, Hecker, Constantin, Hellstern, Victoria, Henkes, Hans, Hernández, Victoria, Herweh, Christian, Hilgenfeld, Tim, Hill, Michael D., Hjort, Niels, HjortJensen, Nina, Hoelter, Maya, Hoffmann, Karl-Titus, Holst, Brigitte, Holtmannspoetter, Markus, Hopf-Jensen, Silke, Hoppe, Julia, Horner, Susanne, HougaardSoerensen, Leif, Hua, Vi Tuan, Hubert, Alexander, Hurtíková, Eva, Jakubíček, Stanislava, Janjic, Tanja, Jaramillo, Kirsten, Jedlitschka, Angela, Jensen, Schiela, Jensen, Märit, Jesser, Jessica, Jestaedt, Leonie, Johnson, Sabine, Jonszta, Tomáš, Kalmar, Peter, Karabegovic, Sanja, Karen, Kollo, Kastrup, Andreas, Katja, Hopp, Keeba, Natalia, Keese, Petra, Kefaloykos, Christina, Keil, Fee, Kellert, Lars, Kellinghaus, Christoph, Kestner, Roxane-Isabelle, Kiechl, Stefan, Killer-Oberpfalzer, Monika, Klepanec, Andrej, Knispel, Casjupea, Knoflach, Michael, Kohler, Sabine, Kohlhase, Konstantin, Kollikowski, Alexander Marco, Kovář, Martin, Krajina, Antonín, Kral, Michael, Krastev, Georgi, Krause, Lars Udo, Kreidenhuber, Rudolf, Křivka, Tomáš, Krkoška, Adam, Kröger, Jan Robert, Kronlage, Moritz, Krukowski, Pawel, Kühn, Julia, Kurča, Egon, Kurka, Natalia, Kuschnerow, Michael, Lachmund, Rita, Lamprecht, Susanne, Lange, Rüdiger, Lauer, Monika, de Leciñana, Alonso, Leder, Sara, Leger, Anne, Lehnen, Nils, Lehrieder, Dominik, Leißner, Maximilian, Leitinger, Markus, Leitner, Ursula, Lenck, Stéphanie, Lenzenweger, Eva, Liebig, Thomas, Lowens, Stephan, Lunzer, Manuel, Maegerlein, Christian, Magyar, Marton, Marques, Leonardo, Matyáš, David, Maurer, Gabriele, Mauritz, Matthias, Maximilian, Thormann, Mayer-Süß, Lukas, Meckel, Stephan, Medek, Oldřich, Meissner, Julius N., Mencl, Pavel, Merkle, Andrea, Mesche, Birte, Michalski, Dominik, Mikulík, Robert, Modrau, Boris, Möhlenbruch, Markus A., Mohr, Alexander, Mönninghoff, Christoph, Moser, Tobias, Mücke, Ramona, Müller-Hülsbeck, Stefan, Müller-Thies-Broussalis, Erasmia, Mutzenbach, Sebastian, Navia, Pedro, Neuberger, Ulf, Neugebauer, Hermann, Neumann, Jens, Nguyên, Anh, Niederkorn, Kurt, Nosál', Vladimír, Novobilský, Richard, Ntoulias, Nikos, Nussbaum, Lukas, Oder, Joanna, Oldag, Andreas, Ondrejkovič, Marián, Otto, Ferdinand, Otto, Dagmar, Paech, Daniel, Pagano, Paolo, Pallesen, Lars-Peder, Panský, Michal, Papanagiotou, Panagiotis, Patrick, Samp, Paukisch, Harald, Pelz, Johann, Petersen, Inga, Petersen, Martina, Petzold, Gabor C., Pfaff, Johannes, Pfeilschifter, Waltraud, Pham, Mirko, Pichler, Alexander, Pierot, Laurent, Pikija, Slaven, PlougmannPovlsen, Jan, Polkowski, Christoph, Polomac, Nenad, Portugaller, Rupert Horst, Poulsen, Marika, Preiß, Michael, Premat, Kévin, Prestsæter, Sjur, Prieto-Pérez, Rocio, Psychogios, Marios, Puetz, Volker, Purrucker, Jan, Rai, Heike, Rauch, Maximilian, Raupach, Jan, Reimann, Gernot, Reimann, Georg, Reitz, Sarah, Renc, Ondřej, Retzlaff, Jasmin, Rigual, Ricardo, Ringleb, Peter Arthur, Rivera-Bengoa, Carlota, Rodríguez, Jorge, Rohde, Stefan, Rohler, Siegfried, Rosso, Charlotte, Roth, Christian, Röttcher, Thomas, Roubec, Martin, Roztočilová, Milada, Rudnicka, Svetlana, Ruiz, Gerardo, Ryan, Stephen, Ryckborst, Karla J., Sandvik, Simen, Schäfer, Jan-Hendrik, Schaller-Paule, Martin, Schell, Maximillian, Schellinger, Peter, Schlemm, Eckhard, Schmid, Florian, Schmidt, Christoph, Schmitz, Marie Louise, Schneider, Claus, Scholtz, Jan-Erik, Schönenberger, Silvia, Schröter, Andreas, Schwarz, Daniel, Schwarz, Stephan, Schwarzenhofer, Daniel, Seifert-Held, Thomas, Seiler, Alexander, Seker, Fatih, Shotar, Eimad, Simonsen, Claus Z., Simonsen, Maria Theresa, Sivák, Jozef, Skagen, Karolina, Skjelland, Mona, Šnajdrová, Alena, Solymosi, Lazlo, Sømark, Jesper, Sonnberger, Michael, Soršák, Jakub, Sourour, Nader, Søyland, Jogrim, Spitzer, Daniel, Sporns, Peter, Städt, Michael, Steidl, Eike, Størdal, Anne Margrethe Kaalaas, Stösser, Sebastian, Strickmann, Sarah, Strýček, Ondřej, Suškevič, Igor, Sýkora, Jan, Tennøe, Bjørn, Thaler, Daniela, Theisen, Sara, Thomalla, Götz, Trendafilov, Petar, Trenkler, Johannes, Trumm, Christoph, Tsogkas, Ioannis, Tunold, Jon-Anders, Tveit, Lars, Ulfert, Christian, Vališ, Kateřina, Vaníček, Jiří, Vassilev, Christine, Vítková, Eva, Voit-Höhne, Heinz-Leonhard, Vojtíšek, Bohuslav, Volderauer, Karoline, Vollherbst, Dominik, Vollmuth, Christoph, Volna, Kamila, Volný, Ondřej, VonWeitzel-Mudersbach, Poul, Vorčák, Martin, Wagner, Marlies, Wathle, Gaute Kjellevold, Weber, Werner, Weber, Anushe, Weiss, Viktor, Weller, Johannes M., Wenger-Alakmeh, Katharina, Weyland, Cyrill, Weymayr, Friedrich, Wießpeiner, Ulrike, Willeit, Johannes, Wittwer, Aymeric, Wollenweber, Frank, Wortmann, Ginette, Wunderlich, Silke, Xiong, Yanyan, You, Se-Jong, ZachoSpeiser, Lasse, Zamani, Mahtab, Zelenak, Kamil, Zeleňáková, Jana, Zubel, Seraphine, Subtil, Fabien, Gizewski, Elke R, Hill, Michael D, Krajina, Antonin, Simonsen, Claus Z, Zeleňák, Kamil, Blauenfeldt, Rolf A, Denis, Angélique, Gerber, Johannes C, Keil, Christiane Fee, Mikkelsen, Ronni, Möhlenbruch, Markus, Münnich, Nico, Petzold, Gabor C, Schell, Maximilian, Vollherbst, Dominik F, and Wick, Wolfgang

Published
2024
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4. MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept studyResearch in context

Author

Alexander M. Kollikowski, Mirko Pham, Alexander G. März, Jörn Feick, Marius L. Vogt, Yanyan Xiong, Marc Strinitz, Christoph Vollmuth, Fabian Essig, Hermann Neugebauer, Karl Georg Haeusler, Christian Hametner, Lena Zimmermann, Guido Stoll, and Michael K. Schuhmann

Subjects
Stroke, Ischaemic stroke, Large-vessel occlusion, Matrix metalloproteinases, MMP-9, MMP-2, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Matrix metalloproteinases (MMPs) are implied in blood–brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). Methods: We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Findings: Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40–94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4–569.6] vs 441 [IQR 223.4–731.5] ng/ml, p

Published
2024
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5. Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke

Author

Lorenzo Barba, Christoph Vollmuth, Samir Abu-Rumeileh, Steffen Halbgebauer, Patrick Oeckl, Petra Steinacker, Alexander M. Kollikowski, Cara Schultz, Judith Wolf, Mirko Pham, Michael K. Schuhmann, Peter U. Heuschmann, Karl Georg Haeusler, Guido Stoll, Hermann Neugebauer, and Markus Otto

Subjects
Medicine, Science
Abstract

Abstract We aimed to assess the prognostic value of serum β-synuclein (β-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic stroke. We measured β-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS). Serum biomarkers were significantly associated with ASPECTS values (β-syn p = 0.0011, GFAP p = 0.0002) but not with NIHSS scores at admission. Patients who received mechanical thrombectomy and intravenous thrombolysis showed lower β-syn (p = 0.029) und NfL concentrations (p = 0.0024) compared to patients who received only mechanical thrombectomy. According to median biomarker levels, patients with high β-syn, NfL or GFAP levels showed, after therapy, lower clinical improvement (i.e., lower 24-h NIHSS change), higher NIHSS scores during hospitalization and higher mRS scores at 3-month follow-up. Elevated serum concentrations of β-syn (p = 0.016), NfL (p = 0.020) or GFAP (p = 0.010) were significantly associated with 3-month mRS of 3–6 vs. 0–2 even after accounting for age, sex and renal function. In patients with moderate-to-severe acute ischemic stroke, serum β-syn, NfL and GFAP levels associated with clinical and radiological scores at different timepoints and were able to predict short- and middle-term clinical outcomes.

Published
2023
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6. MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study

Author

Kollikowski, Alexander M., Pham, Mirko, März, Alexander G., Feick, Jörn, Vogt, Marius L., Xiong, Yanyan, Strinitz, Marc, Vollmuth, Christoph, Essig, Fabian, Neugebauer, Hermann, Haeusler, Karl Georg, Hametner, Christian, Zimmermann, Lena, Stoll, Guido, and Schuhmann, Michael K.

Published
2024
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7. Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study

Author

Andreas Starke, Alexander M. Kollikowski, Vivian Vogt, Guido Stoll, Bernhard Nieswandt, Mirko Pham, David Stegner, and Michael K. Schuhmann

Subjects
blood platelets, GPVI, stroke, biomarker, carotid artery stenosis, thromboembolism, Biology (General), QH301-705.5
Abstract

Background: Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. Methods: We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. Results: Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5–5.0] ng/mL; n = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3–4.2] ng/mL; n = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. Conclusions: Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology.

Published
2024
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8. Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke

Author

Barba, Lorenzo, Vollmuth, Christoph, Abu-Rumeileh, Samir, Halbgebauer, Steffen, Oeckl, Patrick, Steinacker, Petra, Kollikowski, Alexander M., Schultz, Cara, Wolf, Judith, Pham, Mirko, Schuhmann, Michael K., Heuschmann, Peter U., Haeusler, Karl Georg, Stoll, Guido, Neugebauer, Hermann, and Otto, Markus

Published
2023
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9. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial

Author

Aamodt, Anne Hege, Adamczewski, Olaf, Alektoror, Kirill, Alexander, März, Alexandrou, Maria, Alias, Quentin, Al-Kuzae, Fadha Elawi, Allard, Julien, Al-Schameri, Rahman, Álvarez, Alberto, Andersen, Grethe, AnkerlundBlaufeldt, Rolf, Antje, Riedel, Appelbohm, Hannes, Argren, Maria, Assmann, Anne, Augustin, Michael, Bach, Elke, Bar, Michal, Barleben, Maria, Baronnet, Flore, Barrios, Andrés, Bavúzová, Xénia, BayThomsen, Rikke, Becker, Sandra, Beer, Sylvia, Behme, Daniel, Bellut, Maximilian, Bendszus, Martin, Berkefeld, Joachim, Bester, Maximillian, Bode, Felix J., Boehme, Christian, Boese, Ramona, Bohmann, Ferdinand, Bonekamp, Susanne, Borggrefe, Jan, Boss, Erendira Gabriela, Boutchakova, Maria, Boxhammer, Elfi, Brandhofe, Annemarie, Breckwoldt, Michael, Brekenfeld, Casper, Brehm, Alex, Brem, Christian, Breuer, Stella, Breyer, Tobias, Brodová, Petra, Broocks, Gabriel, Brosinski, Christoph, Bubel, Nele, Búřil, Jiří, Čábal, Martin, Casado, Laura, Celis, Elena de, Chabert, Emmanuel, Charisse, Daniel, Cheng, Bastian, Chovanec, Vendelín, Cidlinsky, Peter, Cisár, Juraj, Clarençon, Fréderic, Crozier, Sophie, Čurdová, Nina, Damaskinos, Michele, Damgaard, Dorte, Daniš, Martin, Dazinger, Florian, Deb-Chatterji, Milani, Delalic, Asima, Delekta, Agnieszka, Delorme, Stephen, Deutschmann, Hannes, Diamandis, Elie, Diedrichsen, Tove, Doležalová, Irena, Dorn, Franziska, du Mesnil de Rochemont, Richard, DupontHougaard, Kristina, Ebrahimi, Taraneh, Eff, Florian, Eliášová, Ilona, Enriquez, Brian, Ergawy, Mostafa, Essig, Fabian, Falkesgaard, Maiken, Fandler-Höfler, Simon, Fernández, Andrés, Ferré, Jean-Christophe, Ferrier, Anna, Fiehler, Jens, Figlewski, Krystian, Fischer, Sebastian, Fischer, Urs, Flottmann, Fabian, Forbig, Robert, Förch, Christian, Fromm, Annette, Fuentes, Blanca, Gaedke, Ines, Galczak, Romana, Galijasevic, Malik, Ganser, Bernhard, Gattringer, Thomas, Gawlitza, Matthias, Gelhard, Sarah, Gellißen, Susanne, Gerber, Johannes, Giannakakis, Michail Panagiotis, Gindlhuber, Karin, Gizewski, Elke R., Glodny, Bernhard, Godel, Tim, Goebell, Einar, Goldemund, David, Görtler, Michael, Goyal, Mayank, Grams, Astrid E., Gruber, Joachim, Gruber, Katharina, Günthner-Lengsfeld, Thomas, Haase, Kathrin, Hacker-Ivan, Floriana, Hallerstig, Erika, Hanning, Uta, Haring, Jozef, Haršány, Michal, Haršány, Ján, Hartmann, Christian, Hassler, Eva Maria, Hauptmann, Kristina, Häusler, Karl Georg, Hecker, Constantin, Hellstern, Victoria, Henkes, Hans, Hernández, Victoria, Herweh, Christian, Hilgenfeld, Tim, Hill, Michael D., Hjort, Niels, HjortJensen, Nina, Hoelter, Maya, Hoffmann, Karl-Titus, Holst, Brigitte, Holtmannspoetter, Markus, Hopf-Jensen, Silke, Hoppe, Julia, Horner, Susanne, HougaardSoerensen, Leif, Hua, Vi Tuan, Hubert, Alexander, Hurtíková, Eva, Jakubíček, Stanislava, Janjic, Tanja, Jaramillo, Kirsten, Jedlitschka, Angela, Jensen, Schiela, Jensen, Märit, Jesser, Jessica, Jestaedt, Leonie, Johnson, Sabine, Jonszta, Tomáš, Kalmar, Peter, Karabegovic, Sanja, Karen, Kollo, Kastrup, Andreas, Katja, Hopp, Keeba, Natalia, Keese, Petra, Kefalaykos, Christina, Keil, Fee, Kellert, Lars, Kellinghaus, Christoph, Kestner, Roxane-Isabelle, Kiechl, Stefan, Killer-Oberpfalzer, Monika, Klepanec, Andrej, Knispel, Casjupea, Knoflach, Michael, Kohler, Sabine, Kohlhase, Konstantin, Kollikowski, Alexander Marco, Kovář, Martin, Krajina, Antonín, Kral, Michael, Krastev, Georgi, Krause, Lars Udo, Kreidenhuber, Rudolf, Křivka, Tomáš, Krkoška, Adam, Kröger, Jan Robert, Kronlage, Moritz, Krukowski, Pawel, Kühn, Julia, Kurča, Egon, Kurka, Natalia, Kuschnerow, Michael, Lachmund, Rita, Lamprecht, Susanne, Lange, Rüdiger, Lauer, Monika, Leciñana, Alonso de, Leder, Sara, Leger, Anne, Lehnen, Nils, Lehrieder, Dominik, Leißner, Maximilian, Leitinger, Markus, Leitner, Ursula, Lenck, Stéphanie, Lenzenweger, Eva, Liebig, Thomas, Lowens, Stephan, Lunzer, Manuel, Maegerlein, Christian, Magyar, Marton, Marques, Leonardo, Matyáš, David, Maurer, Gabriele, Mauritz, Matthias, Maximilian, Thormann, Mayer-Süß, Lukas, Meckel, Stephan, Medek, Oldřich, Meissner, Julius N., Mencl, Pavel, Merkle, Andrea, Mesche, Birte, Michalski, Dominik, Mikulík, Robert, Modrau, Boris, Möhlenbruch, Markus A., Mohr, Alexander, Mönninghoff, Christoph, Moser, Tobias, Mücke, Ramona, Müller-Hülsbeck, Stefan, Müller-Thies-Broussalis, Erasmia, Mutzenbach, Sebastian, Navia, Pedro, Neuberger, Ulf, Neugebauer, Hermann, Neumann, Jens, Nguyên, Anh, Niederkorn, Kurt, Nosál', Vladimír, Novobilský, Richard, Ntoulias, Nikos, Nussbaum, Lukas, Oder, Joanna, Oldag, Andreas, Ondrejkovič, Marián, Otto, Ferdinand, Otto, Dagmar, Paech, Daniel, Pagano, Paolo, Pallesen, Lars-Peder, Panský, Michal, Papanagiotou, Panagiotis, Patrick, Samp, Paukisch, Harald, Pelz, Johann, Petersen, Inga, Petersen, Martina, Petzold, Gabor C., Pfaff, Johannes, Pfeilschifter, Waltraud, Pham, Mirko, Pichler, Alexander, Pierot, Laurent, Pikija, Slaven, PlougmannPovlsen, Jan, Polkowski, Christoph, Polomac, Nenad, Portugaller, Rupert Horst, Poulsen, Marika, Preiß, Michael, Premat, Kévin, Prestsæter, Sjur, Prieto-Pérez, Rocio, Psychogios, Marios, Puetz, Volker, Purrucker, Jan, Rai, Heike, Rauch, Maximilian, Raupach, Jan, Reimann, Gernot, Reimann, Georg, Reitz, Sarah, Renc, Ondřej, Retzlaff, Jasmin, Rigual, Ricardo, Ringleb, Peter Arthur, Rivera-Bengoa, Carlota, Rodríguez, Jorge, Rohde, Stefan, Rohler, Siegfried, Rosso, Charlotte, Roth, Christian, Röttcher, Thomas, Roubec, Martin, Roztočilová, Milada, Rudnicka, Svetlana, Ruiz, Gerardo, Ryan, Stephen, Ryckborst, Karla J., Sandvik, Simen, Schäfer, Jan-Hendrik, Schaller-Paule, Martin, Schell, Maximillian, Schellinger, Peter, Schlemm, Eckhard, Schmid, Florian, Schmidt, Christoph, Schmitz, Marie Louise, Schneider, Claus, Scholtz, Jan-Erik, Schönenberger, Silvia, Schröter, Andreas, Schwarz, Daniel, Schwarz, Stephan, Schwarzenhofer, Daniel, Seifert-Held, Thomas, Seiler, Alexander, Seker, Fatih, Shotar, Eimad, Simonsen, Claus Z., Simonsen, Maria Theresa, Sivák, Jozef, Skagen, Karolina, Skjelland, Mona, Šnajdrová, Alena, Solymosi, Lazlo, Sømark, Jesper, Sonnberger, Michael, Soršák, Jakub, Sourour, Nader, Søyland, Jogrim, Spitzer, Daniel, Sporns, Peter, Städt, Michael, Steidl, Eike, Størdal, Anne Margrethe Kaalaas, Stösser, Sebastian, Strickmann, Sarah, Strýček, Ondřej, Suškevič, Igor, Sýkora, Jan, Tennøe, Bjørn, Thaler, Daniela, Theisen, Sara, Thomalla, Götz, Trendafilov, Petar, Trenkler, Johannes, Trumm, Christoph, Tsogkas, Ioannis, Tunold, Jon-Anders, Tveit, Lars, Ulfert, Christian, Vališ, Kateřina, Vaníček, Jiří, Vassilev, Christine, Vítková, Eva, Voit-Höhne, Heinz-Leonhard, Vojtíšek, Bohuslav, Volderauer, Karoline, Vollherbst, Dominik, Vollmuth, Christoph, Volna, Kamila, Volný, Ondřej, VonWeitzel-Mudersbach, Poul, Vorčák, Martin, Wagner, Marlies, Wathle, Gaute Kjellevold, Weber, Werner, Weber, Anushe, Weiss, Viktor, Weller, Johannes M., Wenger-Alakmeh, Katharina, Weyland, Cyrill, Weymayr, Friedrich, Wießpeiner, Ulrike, Willeit, Johannes, Wittwer, Aymeric, Wollenweber, Frank, Wortmann, Ginette, Wunderlich, Silke, Xiong, Yanyan, You, Se-Jong, ZachoSpeiser, Lasse, Zelenak, Kamil, Zeleňáková, Jana, Zubel, Seraphine, Subtil, Fabien, Gizewski, Elke R, Hill, Michael D, Krajina, Antonin, Simonsen, Claus Z, Zeleňák, Kamil, Blauenfeldt, Rolf A, Denis, Angélique, Gerber, Johannes C, Keil, Christiane Fee, Mikkelsen, Ronni, Möhlenbruch, Markus, Münnich, Nico, Petzold, Gabor C, Schell, Maximilian, Vollherbst, Dominik F, and Wick, Wolfgang

Published
2023
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10. Mind–body-medicine in oncology—from patient needs to tailored programs and interventions: a cross-sectional study

Author

Jonas Leonhardt, Marcela Winkler, Anne Kollikowski, Lisa Schiffmann, Anne Quenzer, Hermann Einsele, and Claudia Löffler

Subjects
lifestyle habits, symptom burden, individual mind state, motivational level, stress, Psychology, BF1-990
Abstract

IntroductionNational and international guidelines recommend early integration of evidence-based multimodal interventions and programs, especially with a focus on relaxation techniques and other Mind–Body-based methods to maintain the quality of life of oncology patients, improve treatment tolerability, and promote healthy lifestyle behaviors. Consequently, we aim to understand what drives patients and how they navigate integrative medicine to best advise them. This study aimed to detect possible topics of particular interest to patients and identify the patient groups that could benefit most from further programs. Furthermore, we aimed to investigate if patients are open-minded toward integrative oncology concepts and learn about their motivational level to maintain or change behavior.MethodsBetween August 2019 and October 2020 we surveyed patients undergoing oncological therapy in a university oncological outpatient center using a custom-developed questionnaire based on established Mind–Body Medicine concepts.ResultsWe included 294 patients with various cancers. More than half reported problems sleeping through (61%) and 42% felt stressed frequently, invariably rating this as detrimental to their health. Moreover, a slight majority (52%) felt physically limited due to their disease and only 30% performed defined exercise programs. Women were significantly more likely to feel stressed and reported with alarming frequency that they often feel “everything was up to them.” The 40–65-year-olds reported significantly less restful sleep, more stress and were more dissatisfied with their situation. However, this group already used natural remedies most frequently and was most often motivated to use relaxation techniques in the next 6 months. The lower the perceived individual energy level (EL), the less frequently patients did sport, the more frequently they felt their disease impaired their activity, mostly feeling stressed and tense. We also found significant associations between negative emotions/thoughts and the variables “sleep,” “use of relaxation techniques,” “personal stress perception,” and “successful lifestyle modification.”ConclusionMind–Body programs that focus on patient’s individual resources, with tools to explore impairing patterns of self-perception and cognitive biases, can be a valuable resource for oncology patients and should therefore be part of an integrative medical treatment concept.

Published
2023
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13. Corrigendum: Every fifth patient suffered a high nutritional risk – Results of a prospective patient survey in an oncological outpatient center

Author

Julia Jendretzki, Dorothea Henniger, Lisa Schiffmann, Constanze Wolz, Anne Kollikowski, Alexander Meining, Hermann Einsele, Marcela Winkler, and Claudia Löffler

Subjects
nutritional risk screening, malnutrition, nutritional counseling, oncology outpatients, MUST-Score, nutritional medical needs, Nutrition. Foods and food supply, TX341-641
Published
2023
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14. Every fifth patient suffered a high nutritional risk—Results of a prospective patient survey in an oncological outpatient center

Author

Julia Jendretzki, Dorothea Henniger, Lisa Schiffmann, Constanze Wolz, Anne Kollikowski, Alexander Meining, Hermann Einsele, Marcela Winkler, and Claudia Löffler

Subjects
nutritional risk screening, malnutrition, nutritional counseling, oncology outpatients, MUST-Score, nutritional medical needs, Nutrition. Foods and food supply, TX341-641
Abstract

IntroductionMalnutrition in cancer patients often remains undetected and underestimated in clinical practice despite studies revealing prevalences from 20 to 70%. Therefore, this study aimed to identify patient groups exposed to an increased nutritional risk in a university oncological outpatient center.MethodsBetween May 2017 and January 2018 we screened oncological patients there using the malnutrition universal screening tool (MUST). Qualitative data were collected by a questionnaire to learn about patients’ individual information needs and changes in patients’ diets and stressful personal nutrition restrictions.ResultsWe included 311 patients with various cancers. 20.3% (n = 63) were found to be at high risk of malnutrition, 16.4% (n = 51) at moderate risk despite a mean body mass index (BMI) of 26.5 ± 4.7 kg/m2. The average age was 62.7 (± 11.8) with equal gender distribution (52% women, n = 162). In 94.8% (n = 295) unintended weight loss led to MUST scoring. Patients with gastrointestinal tumors (25%, n = 78) and patients >65 years (22%, n = 68) were at higher risk. Furthermore, there was a significant association between surgery or chemotherapy within six months before survey and a MUST score ≥2 (OR = 3.6). Taste changes, dysphagia, and appetite loss were also particular risk factors (OR = 2.3–3.2). Young, female and normal-weight patients showed most interest in nutrition in cancer. However, only 38% (n = 118) had a nutritional counseling.ConclusionThis study confirms that using the MUST score is a valid screening procedure to identify outpatients at risk of developing malnutrition. Here one in five was at high risk, but only 1% would have been detected by BMI alone. Therefore, an ongoing screening procedure with meaningful parameters should be urgently implemented into the clinical routine of cancer outpatients as recommended in international guidelines.

Published
2022
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15. Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study.

Author

Starke, Andreas, Kollikowski, Alexander M., Vogt, Vivian, Stoll, Guido, Nieswandt, Bernhard, Pham, Mirko, Stegner, David, and Schuhmann, Michael K.

Subjects
ISCHEMIC stroke, CAROTID artery stenosis, STROKE, ENDOVASCULAR surgery, BLOOD platelets
Abstract

Background: Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. Methods: We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. Results: Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5–5.0] ng/mL; n = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3–4.2] ng/mL; n = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. Conclusions: Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke.

Author

Vollmuth, Christoph, Fiessler, Cornelia, Montellano, Felipe A, Kollikowski, Alexander M, Essig, Fabian, Oeckl, Patrick, Barba, Lorenzo, Steinacker, Petra, Schulz, Cara, Ungethüm, Kathrin, Wolf, Judith, Pham, Mirko, Schuhmann, Michael K, Heuschmann, Peter U, Haeusler, Karl Georg, Stoll, Guido, Otto, Markus, and Neugebauer, Hermann

Published
2024
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17. Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice

Author

Michael K. Schuhmann, Michael Bieber, Maximilian Franke, Alexander M. Kollikowski, David Stegner, Katrin G. Heinze, Bernhard Nieswandt, Mirko Pham, and Guido Stoll

Subjects
Ischemic penumbra, Glycoprotein receptor Ib, T-cells, Ischemic stroke, Thrombo-inflammation, middle cerebral artery occlusion, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood. Methods To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1 −/− mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion. Results We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion. Conclusions Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.

Published
2021
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19. The mouse lemurs

Author

Wittkowski, Jennifer, primary, Klein, Annette, additional, Kollikowski, Annika, additional, Scheumann, Marina, additional, Schmidtke, Daniel, additional, Zimmermann, Elke, additional, and Radespiel, Ute, additional

Published
2024
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20. Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion

Author

Axel Haarmann, Christoph Vollmuth, Alexander M. Kollikowski, Peter U. Heuschmann, Mirko Pham, Guido Stoll, Hermann Neugebauer, and Michael K. Schuhmann

Subjects
endoglin, brain endothelium, stroke, shedding, mechanical thrombectomy, hypoxia, Cytology, QH573-671
Abstract

Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.

Published
2023
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22. Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke

Author

Michael K. Schuhmann, Alexander M. Kollikowski, Alexander G. März, Michael Bieber, Mirko Pham, and Guido Stoll

Subjects
Danger-associated molecular patterns, High-mobility group box 1 protein, Calprotectin, Hyper-acute stroke, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Objective: Immune responses are an integral part of the complex reactions to acute cerebral ischemia and contribute to infarct expansion and tissue remodeling. Among damage-associated molecular patterns (DAMPs) the high-mobility group box 1 protein (HMGB1) and calprotectin (S100A8/A9) are released from dying cells and activate the innate immune system. Methods: To assess DAMPs concentrations and related leukocytic infiltration directly and locally in human stroke patients we performed microcatheter sampling from within the core of the occluded vascular compartment before recanalization by mechanical thrombectomy. These samples from the core of a sealed cerebral-ischemic arterial compartment were compared with systemic control samples from the internal carotid artery obtained after recanalization. Results: We found increased plasma levels of total free HMGB1 (+33%) and increased S100A8/A9 (+8%) locally within the ischemic cerebral compartment vs. systemic levels. Local concentrations of HMGB1 were associated with more extensive structural brain infarction on admission. In addition, local ischemic HMGB1 and S100A8/A9 concentrations were associated with the numbers of leukocytes that infiltrate the occluded compartment by collateral pathways. Conclusion: This is the first direct human observation of a local increase in DAMPs concentrations in a uniquely sealed vascular compartment of the ischemic cerebral circulation. These data provide an important pathophysiological link between ischemia-induced cell death and stroke-related inflammation.

Published
2021
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24. First experimental evidence for olfactory species discrimination in two nocturnal primate species (Microcebus lehilahytsara and M. murinus)

Author

Annika Kollikowski, Elke Zimmermann, and Ute Radespiel

Subjects
Medicine, Science
Abstract

Abstract Olfactory communication is highly important for nocturnal mammals, especially for solitary foragers, but knowledge is still limited for nocturnal primates. Mouse lemurs (Microcebus spp.) are nocturnal solitary foragers with a dispersed lifestyle and frequently use chemo-sensory signalling behaviour for governing social interactions. Different mouse lemur species can co-occur in a given forest but it is unknown whether olfaction is involved in species recognition. We first screened 24 captive mouse lemurs (9 M. murinus, 15 M. lehilahytsara) for their olfactory learning potential in an experimental arena and then tested the species discrimination ability with urine odour in an operant conditioning paradigm in four individuals. The majority of the screened animals (75%) did not pass the screening criteria within a 2-week test period. However, all four final test animals, two M. murinus and two M. lehilahytsara, were successfully trained in a 5-step-conditioning process to reliably discriminate conspecific from heterospecific urine odour (requiring an overall median of 293 trials). Findings complement previous studies on the role of acoustic signalling and suggest that olfaction may be an important additional mechanism for species discrimination.

Published
2019
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25. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial

Author

Bendszus, Martin, primary, Fiehler, Jens, additional, Subtil, Fabien, additional, Bonekamp, Susanne, additional, Aamodt, Anne Hege, additional, Fuentes, Blanca, additional, Gizewski, Elke R, additional, Hill, Michael D, additional, Krajina, Antonin, additional, Pierot, Laurent, additional, Simonsen, Claus Z, additional, Zeleňák, Kamil, additional, Blauenfeldt, Rolf A, additional, Cheng, Bastian, additional, Denis, Angélique, additional, Deutschmann, Hannes, additional, Dorn, Franziska, additional, Flottmann, Fabian, additional, Gellißen, Susanne, additional, Gerber, Johannes C, additional, Goyal, Mayank, additional, Haring, Jozef, additional, Herweh, Christian, additional, Hopf-Jensen, Silke, additional, Hua, Vi Tuan, additional, Jensen, Märit, additional, Kastrup, Andreas, additional, Keil, Christiane Fee, additional, Klepanec, Andrej, additional, Kurča, Egon, additional, Mikkelsen, Ronni, additional, Möhlenbruch, Markus, additional, Müller-Hülsbeck, Stefan, additional, Münnich, Nico, additional, Pagano, Paolo, additional, Papanagiotou, Panagiotis, additional, Petzold, Gabor C, additional, Pham, Mirko, additional, Puetz, Volker, additional, Raupach, Jan, additional, Reimann, Gernot, additional, Ringleb, Peter Arthur, additional, Schell, Maximilian, additional, Schlemm, Eckhard, additional, Schönenberger, Silvia, additional, Tennøe, Bjørn, additional, Ulfert, Christian, additional, Vališ, Kateřina, additional, Vítková, Eva, additional, Vollherbst, Dominik F, additional, Wick, Wolfgang, additional, Thomalla, Götz, additional, Adamczewski, Olaf, additional, Alektoror, Kirill, additional, Alexander, März, additional, Alexandrou, Maria, additional, Alias, Quentin, additional, Al-Kuzae, Fadha Elawi, additional, Allard, Julien, additional, Al-Schameri, Rahman, additional, Álvarez, Alberto, additional, Andersen, Grethe, additional, AnkerlundBlaufeldt, Rolf, additional, Antje, Riedel, additional, Appelbohm, Hannes, additional, Argren, Maria, additional, Assmann, Anne, additional, Augustin, Michael, additional, Bach, Elke, additional, Bar, Michal, additional, Barleben, Maria, additional, Baronnet, Flore, additional, Barrios, Andrés, additional, Bavúzová, Xénia, additional, BayThomsen, Rikke, additional, Becker, Sandra, additional, Beer, Sylvia, additional, Behme, Daniel, additional, Bellut, Maximilian, additional, Bendszus, Martin, additional, Berkefeld, Joachim, additional, Bester, Maximillian, additional, Bode, Felix J., additional, Boehme, Christian, additional, Boese, Ramona, additional, Bohmann, Ferdinand, additional, Borggrefe, Jan, additional, Boss, Erendira Gabriela, additional, Boutchakova, Maria, additional, Boxhammer, Elfi, additional, Brandhofe, Annemarie, additional, Breckwoldt, Michael, additional, Brekenfeld, Casper, additional, Brehm, Alex, additional, Brem, Christian, additional, Breuer, Stella, additional, Breyer, Tobias, additional, Brodová, Petra, additional, Broocks, Gabriel, additional, Brosinski, Christoph, additional, Bubel, Nele, additional, Búřil, Jiří, additional, Čábal, Martin, additional, Casado, Laura, additional, Celis, Elena de, additional, Chabert, Emmanuel, additional, Charisse, Daniel, additional, Chovanec, Vendelín, additional, Cidlinsky, Peter, additional, Cisár, Juraj, additional, Clarençon, Fréderic, additional, Crozier, Sophie, additional, Čurdová, Nina, additional, Damaskinos, Michele, additional, Damgaard, Dorte, additional, Daniš, Martin, additional, Dazinger, Florian, additional, Deb-Chatterji, Milani, additional, Delalic, Asima, additional, Delekta, Agnieszka, additional, Delorme, Stephen, additional, Diamandis, Elie, additional, Diedrichsen, Tove, additional, Doležalová, Irena, additional, du Mesnil de Rochemont, Richard, additional, DupontHougaard, Kristina, additional, Ebrahimi, Taraneh, additional, Eff, Florian, additional, Eliášová, Ilona, additional, Enriquez, Brian, additional, Ergawy, Mostafa, additional, Essig, Fabian, additional, Falkesgaard, Maiken, additional, Fandler-Höfler, Simon, additional, Fernández, Andrés, additional, Ferré, Jean-Christophe, additional, Ferrier, Anna, additional, Figlewski, Krystian, additional, Fischer, Sebastian, additional, Fischer, Urs, additional, Forbig, Robert, additional, Förch, Christian, additional, Fromm, Annette, additional, Gaedke, Ines, additional, Galczak, Romana, additional, Galijasevic, Malik, additional, Ganser, Bernhard, additional, Gattringer, Thomas, additional, Gawlitza, Matthias, additional, Gelhard, Sarah, additional, Gerber, Johannes, additional, Giannakakis, Michail Panagiotis, additional, Gindlhuber, Karin, additional, Gizewski, Elke R., additional, Glodny, Bernhard, additional, Godel, Tim, additional, Goebell, Einar, additional, Goldemund, David, additional, Görtler, Michael, additional, Grams, Astrid E., additional, Gruber, Joachim, additional, Gruber, Katharina, additional, Günthner-Lengsfeld, Thomas, additional, Haase, Kathrin, additional, Hacker-Ivan, Floriana, additional, Hallerstig, Erika, additional, Hanning, Uta, additional, Haršány, Michal, additional, Haršány, Ján, additional, Hartmann, Christian, additional, Hassler, Eva Maria, additional, Hauptmann, Kristina, additional, Häusler, Karl Georg, additional, Hecker, Constantin, additional, Hellstern, Victoria, additional, Henkes, Hans, additional, Hernández, Victoria, additional, Hilgenfeld, Tim, additional, Hill, Michael D., additional, Hjort, Niels, additional, HjortJensen, Nina, additional, Hoelter, Maya, additional, Hoffmann, Karl-Titus, additional, Holst, Brigitte, additional, Holtmannspoetter, Markus, additional, Hoppe, Julia, additional, Horner, Susanne, additional, HougaardSoerensen, Leif, additional, Hubert, Alexander, additional, Hurtíková, Eva, additional, Jakubíček, Stanislava, additional, Janjic, Tanja, additional, Jaramillo, Kirsten, additional, Jedlitschka, Angela, additional, Jensen, Schiela, additional, Jesser, Jessica, additional, Jestaedt, Leonie, additional, Johnson, Sabine, additional, Jonszta, Tomáš, additional, Kalmar, Peter, additional, Karabegovic, Sanja, additional, Karen, Kollo, additional, Katja, Hopp, additional, Keeba, Natalia, additional, Keese, Petra, additional, Kefalaykos, Christina, additional, Keil, Fee, additional, Kellert, Lars, additional, Kellinghaus, Christoph, additional, Kestner, Roxane-Isabelle, additional, Kiechl, Stefan, additional, Killer-Oberpfalzer, Monika, additional, Knispel, Casjupea, additional, Knoflach, Michael, additional, Kohler, Sabine, additional, Kohlhase, Konstantin, additional, Kollikowski, Alexander Marco, additional, Kovář, Martin, additional, Krajina, Antonín, additional, Kral, Michael, additional, Krastev, Georgi, additional, Krause, Lars Udo, additional, Kreidenhuber, Rudolf, additional, Křivka, Tomáš, additional, Krkoška, Adam, additional, Kröger, Jan Robert, additional, Kronlage, Moritz, additional, Krukowski, Pawel, additional, Kühn, Julia, additional, Kurka, Natalia, additional, Kuschnerow, Michael, additional, Lachmund, Rita, additional, Lamprecht, Susanne, additional, Lange, Rüdiger, additional, Lauer, Monika, additional, Leciñana, Alonso de, additional, Leder, Sara, additional, Leger, Anne, additional, Lehnen, Nils, additional, Lehrieder, Dominik, additional, Leißner, Maximilian, additional, Leitinger, Markus, additional, Leitner, Ursula, additional, Lenck, Stéphanie, additional, Lenzenweger, Eva, additional, Liebig, Thomas, additional, Lowens, Stephan, additional, Lunzer, Manuel, additional, Maegerlein, Christian, additional, Magyar, Marton, additional, Marques, Leonardo, additional, Matyáš, David, additional, Maurer, Gabriele, additional, Mauritz, Matthias, additional, Maximilian, Thormann, additional, Mayer-Süß, Lukas, additional, Meckel, Stephan, additional, Medek, Oldřich, additional, Meissner, Julius N., additional, Mencl, Pavel, additional, Merkle, Andrea, additional, Mesche, Birte, additional, Michalski, Dominik, additional, Mikulík, Robert, additional, Modrau, Boris, additional, Möhlenbruch, Markus A., additional, Mohr, Alexander, additional, Mönninghoff, Christoph, additional, Moser, Tobias, additional, Mücke, Ramona, additional, Müller-Thies-Broussalis, Erasmia, additional, Mutzenbach, Sebastian, additional, Navia, Pedro, additional, Neuberger, Ulf, additional, Neugebauer, Hermann, additional, Neumann, Jens, additional, Nguyên, Anh, additional, Niederkorn, Kurt, additional, Nosál', Vladimír, additional, Novobilský, Richard, additional, Ntoulias, Nikos, additional, Nussbaum, Lukas, additional, Oder, Joanna, additional, Oldag, Andreas, additional, Ondrejkovič, Marián, additional, Otto, Ferdinand, additional, Otto, Dagmar, additional, Paech, Daniel, additional, Pallesen, Lars-Peder, additional, Panský, Michal, additional, Patrick, Samp, additional, Paukisch, Harald, additional, Pelz, Johann, additional, Petersen, Inga, additional, Petersen, Martina, additional, Petzold, Gabor C., additional, Pfaff, Johannes, additional, Pfeilschifter, Waltraud, additional, Pichler, Alexander, additional, Pikija, Slaven, additional, PlougmannPovlsen, Jan, additional, Polkowski, Christoph, additional, Polomac, Nenad, additional, Portugaller, Rupert Horst, additional, Poulsen, Marika, additional, Preiß, Michael, additional, Premat, Kévin, additional, Prestsæter, Sjur, additional, Prieto-Pérez, Rocio, additional, Psychogios, Marios, additional, Purrucker, Jan, additional, Rai, Heike, additional, Rauch, Maximilian, additional, Reimann, Georg, additional, Reitz, Sarah, additional, Renc, Ondřej, additional, Retzlaff, Jasmin, additional, Rigual, Ricardo, additional, Rivera-Bengoa, Carlota, additional, Rodríguez, Jorge, additional, Rohde, Stefan, additional, Rohler, Siegfried, additional, Rosso, Charlotte, additional, Roth, Christian, additional, Röttcher, Thomas, additional, Roubec, Martin, additional, Roztočilová, Milada, additional, Rudnicka, Svetlana, additional, Ruiz, Gerardo, additional, Ryan, Stephen, additional, Ryckborst, Karla J., additional, Sandvik, Simen, additional, Schäfer, Jan-Hendrik, additional, Schaller-Paule, Martin, additional, Schell, Maximillian, additional, Schellinger, Peter, additional, Schmid, Florian, additional, Schmidt, Christoph, additional, Schmitz, Marie Louise, additional, Schneider, Claus, additional, Scholtz, Jan-Erik, additional, Schröter, Andreas, additional, Schwarz, Daniel, additional, Schwarz, Stephan, additional, Schwarzenhofer, Daniel, additional, Seifert-Held, Thomas, additional, Seiler, Alexander, additional, Seker, Fatih, additional, Shotar, Eimad, additional, Simonsen, Claus Z., additional, Simonsen, Maria Theresa, additional, Sivák, Jozef, additional, Skagen, Karolina, additional, Skjelland, Mona, additional, Šnajdrová, Alena, additional, Solymosi, Lazlo, additional, Sømark, Jesper, additional, Sonnberger, Michael, additional, Soršák, Jakub, additional, Sourour, Nader, additional, Søyland, Jogrim, additional, Spitzer, Daniel, additional, Sporns, Peter, additional, Städt, Michael, additional, Steidl, Eike, additional, Størdal, Anne Margrethe Kaalaas, additional, Stösser, Sebastian, additional, Strickmann, Sarah, additional, Strýček, Ondřej, additional, Suškevič, Igor, additional, Sýkora, Jan, additional, Thaler, Daniela, additional, Theisen, Sara, additional, Trendafilov, Petar, additional, Trenkler, Johannes, additional, Trumm, Christoph, additional, Tsogkas, Ioannis, additional, Tunold, Jon-Anders, additional, Tveit, Lars, additional, Vaníček, Jiří, additional, Vassilev, Christine, additional, Voit-Höhne, Heinz-Leonhard, additional, Vojtíšek, Bohuslav, additional, Volderauer, Karoline, additional, Vollherbst, Dominik, additional, Vollmuth, Christoph, additional, Volna, Kamila, additional, Volný, Ondřej, additional, VonWeitzel-Mudersbach, Poul, additional, Vorčák, Martin, additional, Wagner, Marlies, additional, Wathle, Gaute Kjellevold, additional, Weber, Werner, additional, Weber, Anushe, additional, Weiss, Viktor, additional, Weller, Johannes M., additional, Wenger-Alakmeh, Katharina, additional, Weyland, Cyrill, additional, Weymayr, Friedrich, additional, Wießpeiner, Ulrike, additional, Willeit, Johannes, additional, Wittwer, Aymeric, additional, Wollenweber, Frank, additional, Wortmann, Ginette, additional, Wunderlich, Silke, additional, Xiong, Yanyan, additional, You, Se-Jong, additional, ZachoSpeiser, Lasse, additional, Zelenak, Kamil, additional, Zeleňáková, Jana, additional, and Zubel, Seraphine, additional

Published
2023
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29. An intravascular perspective on hyper-acute neutrophil, T-cell and platelet responses: Similarities between human and experimental stroke

Author

Guido Stoll, Michael K Schuhmann, Bernhard Nieswandt, Alexander M Kollikowski, and Mirko Pham

Subjects
Blood Platelets, Stroke, Neurology, Neutrophils, Signaling Lymphocytic Activation Molecule Family, T-Lymphocytes, Humans, Platelet Membrane Glycoproteins, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

In stroke patients, local sampling of pial blood within the occluded vasculature before recanalization by mechanical thrombectomy emerged as powerful tool enabling insights into ultra-early stroke pathophysiology. Thereby, a strong intravascular inflammatory response hallmarked by hyper-acute neutrophil recruitment, altered lymphocyte composition and platelet activation could be observed. These human findings mirror experimental stroke. Here, neutrophil and T-cell activation are driven by platelets involving engagement of platelet glycoprotein receptor (GP)Ib, GPVI and CD84 as well as α-granule release orchestrating infarct progression. Thus, targeting of early intravascular inflammation may evolve as a new therapeutic strategy to augment the effects of recanalization.

Published
2022
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32. Wie verbreitet sind komplementärmedizinische Verfahren in bayerischen Krankenhäusern? Eine Vollerhebung für Bayern mittels Website-Screening

Author

Anne Kollikowski, Lisa Schiffmann, Katharina Gabriel, Ildikó Gágyor, Peter Heuschmann, Jost Langhorst, Thomas Keil, and Claudia Löffler

Subjects
Public Health, Environmental and Occupational Health, Medizin
Abstract

Zusammenfassung Hintergrund In Deutschland werden komplementärmedizinische Verfahren von bis zu 62% der Patienten genutzt, Art und Ausmaß dieser Versorgungsangebote im stationären Sektor sind jedoch nicht bekannt. Die Zielsetzung der Studie war es, eine Statuserhebung zu komplementärmedizinischen Verfahren mittels Screening der Internetauftritte aller bayerischen Akutkrankenhäuser jeglicher Versorgungsstufe durchzuführen, um das Spektrum der angewendeten komplementärmedizinischen Verfahren zu erfassen. Methoden Im Jahr 2020 wurde nach dem Vier-Augen-Prinzip ein unabhängiges und vollständiges Website-Screening aller bayerischen Akutkrankenhäuser durchgeführt. Angebotene Verfahren aus der Komplementärmedizin wurden in der Gesamtheit sowie getrennt nach Fachgebieten analysiert. Ergebnisse Von 389 bayerischen Krankenhäusern aus der Akutversorgung boten 82% auf ihrer Website mindestens ein und 66% mindestens drei unterschiedliche komplementärmedizinische Verfahren an. Am häufigsten wurden Entspannungstechniken (52%), Akupunktur (44%), Massagen (41%), Bewegungs-, Kunst- und Musiktherapie (33%, 30% bzw. 28%), meditative Bewegungsverfahren wie Yoga (30%) und Aromatherapie (29%) angeboten. Nach Fachgebieten getrennt fanden sich komplementärmedizinische Verfahren mit 87% am häufigsten in der Psychiatrie/Psychosomatik (primär Entspannungsverfahren 69%, Bewegungs- und Kunsttherapie jeweils 60%), sowie mit 72% in der Gynäkologie/Geburtshilfe (primär Akupunktur 64%, Homöopathie 60% und Aromatherapie 41%). Schlussfolgerungen Die große Mehrheit der bayerischen Akutkrankenhäuser scheint laut ihrer Internetauftritte auch komplementärmedizinische Verfahren in der Therapie einzusetzen, insbesondere bei psychischen Indikationen sowie in der Geburtshilfe und Gynäkologie. Wie häufig diese im Klinikalltag tatsächlich zur Anwendung kommen und ob dies sich auch an der aktuellen Evidenz orientiert, sollte in weiteren Studien untersucht werden.

Published
2023

34. [How Common are Complementary Medicine Procedures in Bavarian Acute Care Hospitals? Results of A Bavarian-wide Website Screening]

Author

Anne, Kollikowski, Lisa, Schiffmann, Katharina, Gabriel, Ildikó, Gágyor, Peter, Heuschmann, Jost, Langhorst, Thomas, Keil, and Claudia, Löffler

Abstract

In Germany, complementary medicine is used by up to 62% of patients, but type and extent of in-patient complementary care are not known. The objective of this study was, therefore, to conduct a survey on complementary medicine procedures in Bavarian acute care hospitals by screening the websites of all respective facilities in order to cover a broad range of complementary procedures.In 2020, an independent and comprehensive website screening of all 389 Bavarian acute hospitals, including all departments, was conducted by two independent raters. Complementary medicine procedures offered were analysed in total as well as separately by specialty.Among all 389 Bavarian acute care hospitals, 82% offered at least one and 66% at least three different complementary procedures on their website. Relaxation techniques (52%), acupuncture (44%), massage (41%), movement-, art-, and music therapy (33%, 30%, and 28%), meditative movement therapies like yoga (30%), and aromatherapy (29%) were offered most frequently. Separated by specialty, complementary procedures were most common in psychiatry/psychosomatics (relaxation techniques 69%, movement and art therapy 60% each) at 87%, and in gynaecology/obstetrics (most common acupuncture 64%, homeopathy 60%, and aromatherapy 41%) at 72%.The vast majority of Bavarian acute care hospitals also seem to conduct complementary medicine procedures in therapy, especially for psychological indications and in obstetrics and gynaecology, according to the hospital websites. How often these procedures are used in inpatient or outpatient settings as well as evidence on effectiveness of the applied procedures should be investigated in further studies.In Deutschland werden komplementärmedizinische Verfahren von bis zu 62% der Patienten genutzt, Art und Ausmaß dieser Versorgungsangebote im stationären Sektor sind jedoch nicht bekannt. Die Zielsetzung der Studie war es, eine Statuserhebung zu komplementärmedizinischen Verfahren mittels Screening der Internetauftritte aller bayerischen Akutkrankenhäuser jeglicher Versorgungsstufe durchzuführen, um das Spektrum der angewendeten komplementärmedizinischen Verfahren zu erfassen.Im Jahr 2020 wurde nach dem Vier-Augen-Prinzip ein unabhängiges und vollständiges Website-Screening aller bayerischen Akutkrankenhäuser durchgeführt. Angebotene Verfahren aus der Komplementärmedizin wurden in der Gesamtheit sowie getrennt nach Fachgebieten analysiert.Von 389 bayerischen Krankenhäusern aus der Akutversorgung boten 82% auf ihrer Website mindestens ein und 66% mindestens drei unterschiedliche komplementärmedizinische Verfahren an. Am häufigsten wurden Entspannungstechniken (52%), Akupunktur (44%), Massagen (41%), Bewegungs-, Kunst- und Musiktherapie (33%, 30% bzw. 28%), meditative Bewegungsverfahren wie Yoga (30%) und Aromatherapie (29%) angeboten. Nach Fachgebieten getrennt fanden sich komplementärmedizinische Verfahren mit 87% am häufigsten in der Psychiatrie/Psychosomatik (primär Entspannungsverfahren 69%, Bewegungs- und Kunsttherapie jeweils 60%), sowie mit 72% in der Gynäkologie/Geburtshilfe (primär Akupunktur 64%, Homöopathie 60% und Aromatherapie 41%).Die große Mehrheit der bayerischen Akutkrankenhäuser scheint laut ihrer Internetauftritte auch komplementärmedizinische Verfahren in der Therapie einzusetzen, insbesondere bei psychischen Indikationen sowie in der Geburtshilfe und Gynäkologie. Wie häufig diese im Klinikalltag tatsächlich zur Anwendung kommen und ob dies sich auch an der aktuellen Evidenz orientiert, sollte in weiteren Studien untersucht werden.

Published
2022

36. Every fifth patient suffered a high nutritional risk-Results of a prospective patient survey in an oncological outpatient center

Author

Jendretzki, Julia, Henniger, Dorothea, Schiffmann, Lisa, Wolz, Constanze, Kollikowski, Anne, Meining, Alexander, Einsele, Hermann, Winkler, Marcela, and Löffler, Claudia

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, ddc:610, Food Science
Abstract

IntroductionMalnutrition in cancer patients often remains undetected and underestimated in clinical practice despite studies revealing prevalences from 20 to 70%. Therefore, this study aimed to identify patient groups exposed to an increased nutritional risk in a university oncological outpatient center.MethodsBetween May 2017 and January 2018 we screened oncological patients there using the malnutrition universal screening tool (MUST). Qualitative data were collected by a questionnaire to learn about patients’ individual information needs and changes in patients’ diets and stressful personal nutrition restrictions.ResultsWe included 311 patients with various cancers. 20.3% (n = 63) were found to be at high risk of malnutrition, 16.4% (n = 51) at moderate risk despite a mean body mass index (BMI) of 26.5 ± 4.7 kg/m2. The average age was 62.7 (± 11.8) with equal gender distribution (52% women, n = 162). In 94.8% (n = 295) unintended weight loss led to MUST scoring. Patients with gastrointestinal tumors (25%, n = 78) and patients >65 years (22%, n = 68) were at higher risk. Furthermore, there was a significant association between surgery or chemotherapy within six months before survey and a MUST score ≥2 (OR = 3.6). Taste changes, dysphagia, and appetite loss were also particular risk factors (OR = 2.3–3.2). Young, female and normal-weight patients showed most interest in nutrition in cancer. However, only 38% (n = 118) had a nutritional counseling.ConclusionThis study confirms that using the MUST score is a valid screening procedure to identify outpatients at risk of developing malnutrition. Here one in five was at high risk, but only 1% would have been detected by BMI alone. Therefore, an ongoing screening procedure with meaningful parameters should be urgently implemented into the clinical routine of cancer outpatients as recommended in international guidelines.

Published
2022

37. Progression of cerebral infarction before and after thrombectomy is modified by prehospital pathways

Author

Alexander M. Kollikowski, Guido Stoll, Franziska Weidner, Mirko Pham, Julia Haag, Jörn Feick, Michael K. Schuhmann, Marc Strinitz, Wolfgang Müllges, Alexander G. März, and Franziska Cattus

Subjects
Emergency Medical Services, medicine.medical_specialty, Stroke severity, Infarction, Patient characteristics, Arterial Occlusive Diseases, 030204 cardiovascular system & hematology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Stroke, Ischemic Stroke, Retrospective Studies, Thrombectomy, business.industry, Cerebral infarction, Cerebral Infarction, General Medicine, Methods aspects, medicine.disease, Mechanical thrombectomy, Treatment Outcome, Cardiology, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Large vessel occlusion
Abstract

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent and progression before and after MT in directly admitted (mothership) versus transferred (drip and ship) patients using the Alberta Stroke Program Early CT Score (ASPECTS).MethodsASPECTS of 535 consecutive large vessel occlusion stroke patients eligible for MT between 2015 to 2019 were retrospectively analyzed for differences in the extent of baseline, post-referral, and post-recanalization infarction between the mothership and drip and ship pathways. Time intervals and transport distances of both pathways were analyzed. Multiple linear regression was used to examine the association between infarct progression (baseline to post-recanalization ASPECTS decline), patient characteristics, and logistic key figures.ResultsASPECTS declined during transfer (9 (8–10) vs 7 (6-9), p<0.0001). After multivariable adjustment, only interfacility transfer, preinterventional clinical stroke severity, the degree of angiographic recanalization, and the duration of the thrombectomy procedure remained predictors of infarct progression (R2=0.209, p<0.0001).ConclusionsInfarct progression and postinterventional infarct extent, as assessed by ASPECTS, varied between the drip and ship and mothership pathway, leading to more pronounced infarction in transferred patients. ASPECTS may serve as a radiological measure to monitor the benefit or harm of different prehospital pathways for MT.

Published
2021
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38. Experimental Evaluation of Spontaneous Olfactory Discrimination in Two Nocturnal Primates (Microcebus murinus and M. lehilahytsara)

Author

Ute Radespiel, Selina Jeschke, and Annika Kollikowski

Subjects
Male, 0106 biological sciences, 0301 basic medicine, Microcebus murinus, Physiology, Foraging, Zoology, Lemur, Urine, Olfaction, Nocturnal, 010603 evolutionary biology, 01 natural sciences, Sexual Behavior, Animal, 03 medical and health sciences, Behavioral Neuroscience, Strepsirrhini, Estrus, Species Specificity, Physiology (medical), biology.animal, Animals, Estrous cycle, biology, biology.organism_classification, Sensory Systems, Smell, 030104 developmental biology, Conditioning, Operant, Female, Seasons, Cheirogaleidae
Abstract

Solitary species often employ chemocommunication to facilitate mate localization. In the solitarily foraging, nocturnal mouse lemurs (Microcebus spp.), females advertise their short period of estrus acoustically and by increased scent marking, whereas males search widely for receptive females. Both sexes can be trained by operant conditioning to discriminate conspecific from heterospecific urine scent. However, it is not known, if males during and outside the reproductive season show different spontaneous interest in conspecific female urine, and if urine from estrous females elicits a higher investigation response than that from diestrous females. We established a spontaneous discrimination paradigm and quantified olfactory investigation responses of 21 captive male mouse lemurs of M. lehilahytsara and M. murinus when presenting 1 conspecific and 1 heterospecific female urine odor sample simultaneously. Overall, M. murinus investigated stimuli significantly longer than M. lehilahytsara. Moreover, males of M. murinus showed significantly longer olfactory investigation at conspecific urine samples during but not outside the reproductive season. This indicates that female urinary cues are spontaneously discriminated by male M. murinus and that this discrimination is more relevant during the reproductive season. However, males of both species did not show different responses toward urine samples from estrous versus diestrous females. Finally, male age did not correlate with the overall duration of olfactory investigation, and investigation levels were similar when testing with fresh or frozen urine samples. In conclusion, this new spontaneous discrimination paradigm provides a useful additional tool to study olfactory communication of nocturnal primates from the receiver’s perspective.

Published
2020
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39. Defining cerebral leukocyte populations in local ischemic blood samples from patients with hyperacute stroke

Author

Lena Zimmermann, Mirko Pham, Alexander G März, Alexander M Kollikowski, Guido Stoll, and Michael K Schuhmann

Subjects
Stroke, Leukocyte Count, Neurology, Leukocytes, Humans, Neurology (clinical), Lymphocytes, Cardiology and Cardiovascular Medicine, Brain Ischemia, Ischemic Stroke, Thrombectomy
Abstract

In acute stroke, neuroinflammation can nowadays be analyzed by local cerebral aspiration of pial-ischemic blood during mechanical thrombectomy. Recently, Shaw et al. reported on differences in leukocyte subpopulations within the occluded cerebrovascular compartment. In their study, a main proportion of granulocytes was lost during isolation. By immediate analysis, we found a reproducible increase in absolute local granulocytes without variations in absolute lymphocyte and monocyte numbers. Flow-cytometric phenotyping confirmed a high proportion of granulocytes and a local shift towards CD4+ T cells. Thus, immediate analysis appears to be critical to observe distinct local responses of leukocytes to acute ischemic stroke.

Published
2022

40. A Randomized, Controlled Pilot Study to Evaluate the Immediate Effect of Targeted Exercise Therapy on Cancer-Related Fatigue in Cancer Survivors: The FatiGO Study

Author

Siebert, Stefanie, Kollikowski, Anne, Minto, Carrie-Ann, Byrtus, Franziska, Lesnik, Jennifer, Weis, Joachim, Horneber, Markus, Bloch, Wilhelm, Baumann, Freerk Theeagnus, Salchow, Jannike, Siebert, Stefanie, Kollikowski, Anne, Minto, Carrie-Ann, Byrtus, Franziska, Lesnik, Jennifer, Weis, Joachim, Horneber, Markus, Bloch, Wilhelm, Baumann, Freerk Theeagnus, and Salchow, Jannike

Abstract

Objectives: Cancer-related fatigue (CRF) is a clinically relevant side effect that impairs cancer survivors after treatment cessation. Exercise interventions have proven effective; however, specific exercise modalities remain untested. The purpose of this study was to evaluate the feasibility of daily fatigue screenings and to show the impact of various exercise interventions on CRF. Methods: The randomized controlled pilot study ran for 4 weeks with 3 training sessions per week, in 5 groups: endurance versus strength (moderate- and vigorous-intensity levels for each) compared to a non-active control group. The primary outcome was feasibility; more specifically, it was evaluated whether the documentation with the Numerical Rating Scale (NRS) on a daily basis and the Multidimensional Fatigue Inventory (MFI) on a weekly basis are usable assessments to generate information about CRF. Results: Over the course of the 4-week intervention, 8.3% of the participants (n = 3) dropped out. Thirty-three of the initial 36 participants completed the exercise sessions with an adherence of 95%. Measurements of daily fatigue were collected three times per day, 85% of which were completely filled out. In regard to weekly fatigue, all but one of the questionnaires were submitted (99.5%). Neither during the intervention nor during the tests did any serious adverse events occur within the FatiGO study; hence, the exercise intervention is considered to be feasible for participants. Conclusions: This pilot study showed the feasibility of close-meshed daily fatigue screening. Preliminary data indicate that cancer survivors are able to train in high-intensity ranges with tendencies toward decreased fatigue. Therefore, practicability of the study design is shown. Further results are expected within the prospective multicenter trial.

Published
2022

42. Safety and Effectiveness of the New Generation APERIO® Hybrid Stent-retriever Device in Large Vessel Occlusion Stroke

Author

Marius L. Vogt, Alexander M. Kollikowski, Franziska Weidner, Marc Strinitz, Jörn Feick, Fabian Essig, Hermann Neugebauer, Karl Georg Haeusler, Mirko Pham, and Alexander Maerz

Subjects
Stroke, Treatment Outcome, Humans, Stents, Radiology, Nuclear Medicine and imaging, Neurology (clinical), ddc:610, Brain Ischemia, Retrospective Studies, Thrombectomy
Abstract

Background It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness. Methods Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result. Results A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups. Conclusion In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.

Published
2022
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43. Platelet Activation and Chemokine Release Are Related to Local Neutrophil-Dominant Inflammation During Hyperacute Human Stroke

Author

Alexander M. Kollikowski, Guido Stoll, Alexander G. März, Lena Papp, Bernhard Nieswandt, Michael K. Schuhmann, and Mirko Pham

Subjects
medicine.medical_specialty, Neutrophils, Hemodynamics, Inflammation, Gastroenterology, Internal medicine, medicine, Humans, Platelet, Platelet activation, ddc:610, Stroke, Ischemic Stroke, biology, business.industry, General Neuroscience, Platelet Activation, medicine.disease, Treatment Outcome, Myeloperoxidase, CXCL7, biology.protein, Arterial blood, Neurology (clinical), Chemokines, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

Experimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018–05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (− 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r = − 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.

Published
2022

47. A Randomized, Controlled Pilot Study to Evaluate the Immediate Effect of Targeted Exercise Therapy on Cancer-Related Fatigue in Cancer Survivors: The FatiGO Study

Author

Siebert, Stefanie, primary, Kollikowski, Anne, additional, Minto, Carrie-Ann, additional, Byrtus, Franziska, additional, Lesnik, Jennifer, additional, Weis, Joachim, additional, Horneber, Markus, additional, Bloch, Wilhelm, additional, Baumann, Freerk Theeagnus, additional, and Salchow, Jannike, additional

Published
2022
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48. High Mobility Group Box 1 Protein in Cerebral Thromboemboli

Author

Essig, Fabian, Babilon, Lilith, Vollmuth, Christoph, Kollikowski, Alexander M., Pham, Mirko, Solymosi, László, Haeusler, Karl Georg, Kraft, Peter, Stoll, Guido, and Schuhmann, Michael K.

Subjects
Blood Platelets, HMGB1, acute ischemic stroke, QH301-705.5, Neutrophils, chemical and pharmacologic phenomena, Article, Brain Ischemia, Chemistry, Thromboembolism, platelets, immunohistochemistry, Humans, thromboemboli, ddc:610, Biology (General), HMGB1 Protein, Intracranial Thrombosis, QD1-999
Abstract

High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7% (IQR 0.6–6.2%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.

Published
2021

49. Immune Cells Invade the Collateral Circulation during Human Stroke: Prospective Replication and Extension

Author

Franziska Weidner, Hermann Neugebauer, Jörn Feick, Mirko Pham, Michael K. Schuhmann, Marc Strinitz, Fabian Essig, Guido Stoll, Marius L. Vogt, Alexander M. Kollikowski, and Alexander G. März

Subjects
Male, medicine.medical_specialty, QH301-705.5, leukocytes, Neutrophils, Ischemia, Collateral Circulation, Catalysis, Article, cerebral ischemia, Inorganic Chemistry, Cerebral circulation, mechanical thrombectomy, Immune system, medicine.artery, Internal medicine, large vessel occlusion, medicine, ischemic stroke, Humans, ddc:610, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, Stroke, QD1-999, Spectroscopy, Aged, Aged, 80 and over, business.industry, Organic Chemistry, General Medicine, Cerebral Arteries, Middle Aged, medicine.disease, Collateral circulation, Computer Science Applications, Chemistry, Cohort, Cardiology, Female, Sample collection, Internal carotid artery, business
Abstract

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.

Published
2021

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