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43 results on '"Schuler U"'

1. Prediction of key milk biomarkers in dairy cows through milk mid-infrared spectra and international collaborations

Author

Grelet, C., Larsen, T., Crowe, M.A., Wathes, D.C., Ferris, C.P., Ingvartsen, K.L., Marchitelli, C., Becker, F., Vanlierde, A., Leblois, J., Schuler, U., Auer, F.J., Köck, A., Dale, L., Sölkner, J., Christophe, O., Hummel, J., Mensching, A., Fernández Pierna, J.A., Soyeurt, H., Calmels, M., Reding, R., Gelé, M., Chen, Y., Gengler, N., and Dehareng, F.

Published
2024
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5. The OUTREACH study : oncologists of German university hospitals in rotation on a palliative care unit—evaluation of attitude and competence in palliative care and hospice

Author

Biersching, T., Schweda, A., Oechsle, K., Nauck, F., Schuler, U., Hense, Jörg, Weber, M., Junghanss, C., Kramer, T., Ostgathe, C., Thuss-Patience, P., Van Oorschot, B., Teufel, Martin, Schuler, Martin, Bausewein, C., Tewes, Mitra, Gahr, S., Berendt, J., Benze, G., Rosenbruch, J., Neukirchen, M., Schwarz, J., Reinholz, U., and Roch, C.

Subjects
Medizin
Abstract

Purpose: The effect of the duration of an educational rotation presented at a palliative care unit on the palliative care knowledge gain and the increase of palliative care self-efficacy expectations are unclear. Methods: This national prospective multicenter pre–post survey conducted at twelve German University Comprehensive Cancer Centers prospectively enrolled physicians who were assigned to training rotations in specialized palliative care units for three, six, or twelve months. Palliative care knowledge [in %] and palliative care self-efficacy expectations [max. 57 points] were evaluated before and after the rotation with a validated questionnaire. Results: From March 2018 to October 2020, questionnaires of 43 physicians were analyzed. Physicians participated in a 3- (n = 3), 6- (n = 21), or 12-month (n = 19) palliative care rotation after a median of 8 (0–19) professional years. The training background of rotating physicians covered a diverse spectrum of specialties; most frequently represented were medical oncology (n = 15), and anesthesiology (n = 11). After the rotation, median palliative care knowledge increased from 81.1% to 86.5% (p

Published
2022

9. Abstract

Author

Mache, Ch., Urban, Ch., Sauer, H., Brandesky, G., Meßner, H., Grienberger, H., Becker, H., Slave, I., Hauer, Ch., Pakisch, B., Oberbauer, R., Mokry, M., Ebner, F., Kleinert, R., Schiller, D., Kasparu, H., Schneider, G., Sega, W., Lutz, D., Mader, R. M., Steger, G. G., Sieder, A. E., Ovissi, L., Roth, E., Hamilton, G., Jakesz, R., Rainer, H., Schenk, T., Kornek, G., Schulz, F., Depisch, D., Rosen, H., Sebesta, Ch., Scheithauer, W., Locker, G. J., Czernin, J., Derfler, K., Gnant, M., Schiessel, R., Petru, E., Pickel, H., Heydarfadai, M., Lahousen, M., Haas, J., Sagaster, P., Flamm, J., Umek, H., Essl, R., Teich, G., Micksche, M., Ludwig, H., Ambros, P. F., Lestou, V., Strehl, S., Mann, G., Gadner, H., Eibl, B., Greiter, E., Grünewald, K., Gastl, G., Thaler, J., Aulitzky, W., Lion, T., Henn, T., Gaiger, A., Hofmann, J., Wolf, A., Spitaler, M., Ludescher, Christof, Grunicke, H., Mitterbauer, G., Stangl, E., Geissler, K., Jäger, U., Lechner, K., Mannhalter, C., Haas, Oskar A., Tirita, Anthi, Kahls, P., Haas, O., Hinterberger, W., Linkesch, W., Pober, Michael, Fae, Ingrid, Kyrle, Alexander, Neumeister, Andrea, Panzer, Simon, Kandioler, D., End, A., Grill, R., Karlic, H., Inhauser, T., Chott, A., Pirc-Danoewinata, H., Klepetko, W., Heinz, R., Hopfinger-Limberger, G., Koller, E., Schneider, B., Pittermann, E., Lorber, C., Eichinger, S., Neumann, E., Weidinger, J., Gisslinger, H., Bedford P., Jones D., Cawley J., Catovsky D., Bevan P., Scherrer, R., Bettelheim, P., Knöbl, P., Kyrie, P. A., Lazcika, K., Schwarzinger, I., Sillaber, C., Watzke, H., Dávid, M., Losonczy, H., Matolcsy, A., Papp, M., Prischl, F. C., Schwarzmeier, J. D., Zoubek, Andreas, Harbott, Jochen, Ritterbach, Jutta, Ritter, Jörg, Sillaber, Ch., Agis, H., Spanblöchl, E., Sperr, W. R., Valent, P., Czerwenka, K., Virgolini, I., Li, S. R., Müller, M., Wrann, M., Gaggl, S., Fasching, B., Herold, M., Geissler, D., Nachbaur, D., Huber, Ch., Schwaighofer, H., Pichl, M., Niederwieser, D., Gilly, B., Weissel, H., Lorber, Ch., Schwarzmeier, J., Gasché, C., Reinisch, W., Hilgarth, M., Keil, F., Thomssen, C., Kolb, H. J., Holler, E., Wilmanns, W., Tilg, H., Gächter, A., Panzer-Grümayer, E. R., Majdic, O., Kersey, J. H., Petzer, A. L., Bilgeri, R., Zilian, U., Geisen, F. H., Haun, M., Konwalinka, G., Fuchs, D., Zangerle, R., Artner-Dworzak, E., Weiss, G., Fritsch, P., Tilz, G. P., Dierich, M. P., Wachter, H., Schüller, J., Czejka, M. J., Jäger, W., Meyer, B., Weiss, C., Schernthaner, G., Marosi, Ch., Onderka, E., Schlögl, B., Maca, T., Hanak, R., Mannhalter, Ch., Brenner, B., Mayer, R., Langmann, A., Langmann, G., Slave, J., Poier, E., Stücklschweiger, G., Hackl, A., Fritz, A., Pabinger, I., Willfort, A., Groiss, E., Bernhart, M., Waldner, R., Krieger, O., Nowotny, H., Strobl, H., Michlmayr, G., Mistrik, M., lstvan, L., Kapiotis, S., Laczika, K., Speiser, W., Granena, A., Hermans, J., Zwaan, F., Gratwohl, A., Labar B., Mrsić M., Nemet D., Bogdanić V., Radman I., Zupančić-Šalek Silva, Kovačević-Metelko Jasna, Aurer I., Forstinger, C., Scholten, C., Kier, P., Kalhs, P., Schwinger, W., Slavc, I., Lackner, H., Nussbaumer, W., Fritsch, E., Fink, M., Zechner, O., Kührer, I., Kletter, V., Frey, S., Leitgeb, C., Fritz, E., Silly, H., Brezinschek, R., Kuss, I., Stöger, H., Schmid, M., Samonigg, H., Wilders-Truschnig, M., Schmidt, F., Bauernhofer, T., Kasparek, A. K., Ploner, F., Stoeger, H., Moser, R., Leikauf, W., Klemm, F., Pfeffel, F., Niessner, H., Poschauko, H., Pojer, E., Locker, G. J., Braun, J., Gnant, M. F. X., Michl, I., Pirker, R., Liebhard, A., Zielinski, C., Dittrich, C., Bernát, S. I., Pongrácz, E., Kastner, J., Raderer, M., Jorbenyi, Z., Yilmaz, A., Suardet, L., Lahm, H., Odartchenko, N., Varga, Gy., Sréter, L. A., Oberberg, D., Berdel, W. E., Budiman, R., Brand, C., Berkessy, S., Radványi, G., Pauker, Zs., Nagy, Zs., Karádi, Å., Serti, S., Hainz, R., Kirchweger, P., Prager, C., Prada, J., Neifer, S., Bienzle, U., Kremsner, P., Kämmerer, B., Vetterlein, M., Pohl, W., Letnansky, K., Imre, S. G., Parkas, T., Lakos, Zs., Kiss, A., Telek, B., Felszeghy, E., Kelemen, E., Rak, K., Pfeilstöcker, M., Reisner, R., Salamon, J., Georgopoulos, A., Feistauer, S., Georgopoulos, M., Graninger, W., Klinda, F., Hrubisko, M., Sakalova, A., Weißmann, A., Röhle, R., Fortelny, R., Gutierrez, F., Fritsch, G., Printz, D., Buchinger, P., Buchinger, P., Hoecker, P., Peters, C., Gebauer, E., Katanić, D., Nagy, Á., Szomor, Á., Med. J., Batinić D., Užaervić B., Marušić M., Kovačoević-Metelko Jasminka, Jakić-Razumović Jasminka, Kovačević-Metelko Jasminka, Zuoancić-Šalek Silva, Ihra, G. C., Reinisch, W. W., Hilgarth, M. F., Schwarzmeier, I. D., Várady, E., Molnár, Z. S., Fleischmann, T., Borbényi, Z., Bérczi, M., István, L., Szerafin, L., Jakó, J., Bányai, A., Dankó, K., Szegedi, Gy., Neubauer, M., Frudinger, A., Scholten, Ch., Forstinger, Ch., Dobrić I., Willheim, M., Szépfalusi, Z., Mader, R., Boltz, G., Schwarzmeier, J. D., Nahajevszky, S., Téri, N., Póth, I., Nagy, P., Smanykó, D., Babicz, T., Ujj, Gy., Iványi, J. L., Tóth, F. D., Kiss, J., Konja, J., Petković, I., Kardum, I., Kaštelan, M., Kelečić, J., Feminić, R., Djermanović, M., Bilić, E., Jakovljević, G., Peter, B., Gredelj, G., Senji, P., Thalhammer, F., Floth, A., Etele-Hainz, A., Kainberger, F., Radaszkiewicz, T., Kierner, H., Mód, Anna, Pitlik, E., Gottesman, M., Magócsi, Mária, Sarkadi, B., Knapp, S., Purtscher, B., DelleKarth, G., Jaeger, U., Krieger, O., Berger, W., Elbling, L., Ludescher, C., Hilbe, W., Eisterer, W., Preuß, E., Izraeli, S., Janssen, J. W. G., Walther, J. U., Kovar, H., Ludwig, W. D., Rechavi, G., Bartram, C. R., Rehberger, A., Mittermayer, F., Schauer, E., Kokoschka, E. M., Kammerer, B., Kokron, E., Desser, L., Abdul-Hamid, G., Kroschinksky, F., Luther, Th., Fischer, H., Nowak, R., Wolf, H., Fleischer, J., Wichmann, G., Albercht, S., Adorf, D., Kaboth, W., Nerl, C., Aman, J., Rudolf, G., Peschel, C., Anders, O., Burstein, Ch., Ernst, B., Steiner, H., Konrad, H., Annaloro, U. P., Mozzana, C., Butti, R., Della, C., Volpe A., Soligo D., Uderzo M., Lambertenghi-Deliliers G., Ansari, H., Dickson, D., Hasford, J., Hehlmann, R., Anyanwu, E., Krysa, S., Bülzebrück, H., Vogt-Moykopf, I., Arning, M., Südhoff, Th., Kliche, K. O., Wehmeier, A., Schneider, W., Arnold, R., Bunjes, D., Hertenstein, B., Hueske, D., Stefanic, M., Theobald, M., Wiesneth, M., Heimpel, H., Waldmann, H., Arseniev, L., Bokemeyer, C., Andres, J., Könneke, A., Papageorgiou, E., Kleine, H. -D., Battmer, K., Südmeyer, I., Zaki, M., Schmoll, H. -J., Stangel, W., Poliwoda, H., Link, H., Aul, C., Runde, V., Heyll, A., Germing, U., Gattermann, N., Ebert, A., Feinendegen, L. E., Huhn, D., Bergmann, L., Dönner, H., Hartlapp, J. H., Kreiter, H., Schuhmacher, K., Schalk T., Sparwasser C., Peschel U., Fraaß C. Huber, HIadik, F., Kolbe, K., Irschick, E., Bajko, G., Wozny, T., Hansz, J., Bares, R., Buell, U., Baumann, I., Harms, H., Kuse, R., Wilms, K., Müller-Hermelink, H. K., Baurmann, H., Cherif, D., Berger, R., Becker, K., Zeller, W., Helmchen, U., Hossfeld, D. K., Bentrup, I., Plusczyk, T., Kemkes-Matthes, B., Matthes, K., Bentz, M., Speicher, M., Schröder, M., Moos, M., Döhner, H., Lichter, P., Stilgenbauer, S., Korfel, A., Harnoss, B. -M., Boese-Landgraf, J., May, E., Kreuser, E. -D., Thiel, E., Karacas, T., Jahn, B., Lautenschläger, G., Szepes, S., Fenchel, K., Mitrou, P. S., Hoelzer, D., Heil, G., Lengfelder, E., Puzicha, E., Martin, H., Beyer, J., Kleiner, S., Strohscheer, I., Schwerdtfeger, R., Schwella, N., Schmidt-Wolf, I., Siegert, W., Weyer, C., arzen, G., Risse, G., Miksits, K., Farshidfar, G., Birken, R., Schilling, C. v., Brugger, W., Holldack, J., Mertelsmann, R., Kanz, L., Blanz, J., Mewes, K., Ehninger, G., Zeller, K. -P., Böhme. A., Just G., Bergmann. L., Shah P., Hoelzer D., Stille W., Bohlen, H., Hopff, T., Kapp, U., Wolf, J., Engert, A., Diehl, V., Tesch, H., Schrader, A., van Rhee, J., Köhne-Wömpner, H., Bokemeyer', C., Gonnermann, D., Harstrick, A., Schöffski, P., van Rhee, J., Schuppert, F., Freund, M., Boos, J., Göring, M., Blaschke, G., Borstel, A., Franke, A., Hüller, G., Uhle, R., Weise, W., Brach, Marion A., Gruss, Hans-Jürgen, Herrmann, Friedhelm, deVos, Sven, Brennscheidt, Ulrich, Riedel, Detlev, Klch, Walter, Bonlfer, Renate, Mertelsmann, Roland, Brieaer, J., Appelhans, H., Brückner, S., Siemens, HJ., Wagner, T., Moecklin, W., Mertelsmann, R., Bertz, H., Hecht, T., Mertelsmann, R., Bühl, K., Eichelbaum, M. G., Ladda, E., Schumacher, K., Weimer, A., Bühling, F., Kunz, D., Lendeckel, U., Reinhold, D., Ulmer, A. J., Flad, H. -D., Ansorge, S., Bühring, Hans-Jörg, Broudy¶, Virginia C., Ashman§, Leonie K., Burk, M., Kunecke, H., Dumont, C., Meckenstock, G., Volmer, M., Bucher, M., Manegold, C., Krenpien, B., Fischer, J. R., Drings, P., Bückner, U., Donhuijsen-Ant, R., Eberhardt, B., Westerhausen, M., Busch, F. W., Jaschonek, K., Steinke, B., Calavrezos, A., Hausmann, K., Solbach, M., Woitowitz, H. -P., Hilierdal, G., Heilmann, H. -P., Chen, Z. J., Frickhofen, N., Ellbrück, D., Schwarz, T. F., Körner, K., Wiest, C., Kubanek, B., Seifried, E., Claudé, R., Brücher, J., Clemens, M. R., Bublitz, K., Bieger, O., Schmid, B., Clemetson, K. J., Clemm, Ch., Bamberg, M., Gerl, A., Weißbach, L., Danhauser-Riedl, S., Schick, H. D., Bender, R., Reuter, M., Dietzfelbinger, H., Rastetter, J., Hanauske, A. -R., Decker, Hans-Jochen, Klauck, Sabine, Seizinger, Bernd, Denfeld, Ralf, Pohl, Christoph, Renner, Christoph, Hombach, Andreas, Jung, Wolfram, Schwonzen, Martin, Pfreundschuh, Michael, Derigs, H. Günter, Boswell, H. Scott, Kühn, D., Zafferani, M., Ehrhardt, R., Fischer, K., Schmitt, M., Witt, B., Ho, A. D., Haas, R., Hunstein, W., Dölken, G., Finke, J., Lange, W., Held, M., Schalipp, E., Fauser, A. A., Mertelsmann, R., Donhuijsen, K., Nabavi, D., Leder, L. D., Haedicke, Ch., Freund, H., Hattenberger, S., Dreger, Peter, Grelle, Karen, Schmitz, Norbert, Suttorp, Meinolf, Müller-Ruchholtz, Wolfgang, Löffler, Helmut, Dumoulin, F. L., Jakschies, D., Walther, M., Hunger, P., Deicher, H., von Wussow, P., Dutcher, J. P., Ebell, W., Bender-Götze, C., Bettoni, C., Niethammer, D., Reiter, A., Sauter, S., Schrappe, M., Riehm, H., Niederle, N., Heidersdorf, H., Müller, M. R., Mengelkoch, B., Vanhoefer, U., Stahl, M., Budach, V., loehren, B., Alberti, W., Nowrousian, M. R., Seeber, S., Wilke, H., Stamatis, G., Greschuchna, D., Sack, H., Konietzko, N., Krause, B., Dopfer, R., Schmidt, H., Einsele, H., Müller, C. A., Goldmann, S. F., Grosse-Wilde, H., Waller, H. D., Libal, B., Hohaus, S., Gericke, G., von Eiff, M., Oehme, A., Roth, B., van de Loo, J., von Eiff, K., Pötter, R., Weiß, H., Suhr, B., Koch, P., Roos, H., van de Loo, J., Meuter, V., Heissig, B., Schick, F., Duda, S., Saal, J. G., Klein, R., Steidle, M., Eisner, S., Ganser, A., Seipelt, G., Leonhardt, M., Engelhard, M., Brittinger, G., Gerhartz, H., Meusers, P., Aydemir, Ü., Tintrup, W., Tiemann, H., Lennert, K., Esser, B., Hirsch, F. W., Evers, C., Riess, H., Lübbe, A., Greil, R., Köchling, A., Digel, D., Bross, K. J., Dölken, G., Mertelsmann, R., Gencic S., Ostermann, M., Baum, R. P., Fiebig, H. H., Berger, D. P., Dengler, W. A., Winterhalter, B. R., Hendriks, H., Schwartsmann, G., Pinedo, H. M., Ternes, P., Mertelsmann, R., Dölken, G., Fischbach, W., Zidianakis, Z., Lüke, G., Kirchner, Th., Mössner, J., Fischer, Thomas, Haque, Saikh J., Kumar, Aseem, Rutherford, Michael N., Williams, Bryan R. G., Flohr, T., Decker, T., Thews, A., Hild, F., Dohmen, M., von Wussow, P., Grote-Metke, A., Otremba, B., Fonatsch, C., Binder, T., Imhof, C., Feller, A. C., Fruehauf, S., Moehle, R., Hiddemann Th., Büchner M. Unterhalt, Wörmann, B., Ottmann, O. G., Verbeek, G. W., Seipelt A. Maurer, Geissler, G., Schardt, C., Reutzel, R., Hiddemann, W., Maurer, A., Hess, U., Lindemann, A., Frisch, J., Schulz, G., Mertelsmann, R., Hoelzer, P., Gassmann, W., Sperling, C., Uharek, L., Becher, R., Weh, H. J., Tirier, C., Hagemann, F. G., Fuhr, H. G., Wandt, H., Sauerland, M. C., Gause, A., Spickermann, D., Klein, S., Pfreund-schuh, M., Gebauer, W., Fallgren-Gebauer, E., Geissler, R. G., Mentzel, U., Kleiner, K., Rossol, R., Guba, P., Kojouharoff, G., Gerdau, St., Körholz, D., Klein-Vehne, A., Burdach, St., Gerdemann M., Maurer J., Gerhartz, H. H., Schmetzer, H., Mayer, P., Clemm, C., Hentrich, M., Hartenstein, R., Kohl, P., Gieseler, F., Boege, F., Enttmann, R., Meyer, P., Glass, B., Zeis, M., Loeffler, H., Mueller-Ruchholtz, W., Görg, C., Schwerk, W. B., Köppler, H., Havemann, K., Goldschmitt, J., Goldschmidt, H., Nicolai, M., Richter, Th., Blau, W., Hahn, U., Kappe, R., Leithäuser, F., Gottstein, Claudia, Schön, Gisela, Dünnebacke, Markus, Berthold, Frank, Gramatzki, M., Eger, G., Geiger, M., Burger, R., Zölch, A., Bair, H. J., Becker, W., Griesinger, F., Elfers, H., Griesser, H., Grundner-Culemann, E., Neubauer, V., Fricke, D., Shalitin, C., Benter, T., Mertelsmann, R., Dölken, Gottfried, Mertelsmann, Roland, Günther, W., Schunmm, M., Rieber, P., Thierfelder, S., Gunsilius, E., Kirstein, O., Bommer, M., Serve, H., Hülser, P. -J., Del Valle F., Fischer J. Th., Huberts H., Kaplan E., Haase, D., Halbmayer, W. -M., Feichtinger, Ch., Rubi, K., Fischer, M., Hallek, M., Lepislo, E. M., Griffin, J. D., Emst, T. J., Druker, B., Eder, M., Okuda, K., D.Griffin, J., Kozłowska-Skrzypczak, K., Meyer, B., Reile, D., Scharnofske, M., Hapke, G., Aulenbacher, P., Havemann, K., Becker, N., Scheller, S., Zugmaier, G., Pralle, H., Wahrendorf, J., Heide, Immo, Thiede, Christian, de Kant, Eric, Neubauer, Andreas, Herrmann, Richard, Rochlitz, Christoph, Heiden, B., Depenbrock, H., Block, T., Vogelsang, H., Schneider, P., Fellbaum, Ch., Heidtmann, H. -H., Blings, B., Havemann, K., Fackler-Schwalbe, E., Schlimok, G., Lösch, A., Queißer, W., Löffler, B., Kurrle, E., Chadid, L., Lindemann, A., Mertelsmann, R., Nicolay, U., Gaus, W., Heinemann, V., Jehn, U., Gleixner, B., Wachholz, W., Scholz, P., Plunkett, W., Heinze, B., Novotny, J., Hess, Georg, Gamm, Heinold, Seliger, Barbara, Heuft, H. G., Oettle, H., Zeiler, T., Eckstein, R., Heymanns, J., Havemann, K., Hladik, F., Hoang-Vu, C., Horn, R., Cetin, Y., Scheumann, G., Dralle, H., Köhrle, J., von zur Mühlen, A., Brabant, G., Hochhaus, A., Mende, S., Simon, M., Fonatsch, Ch., Heinze, B., Georgii, A., Hötzl, Ch., Hintermeier-Knabe, R., Kempeni, J., Kaul, M., Hoetzl, Ch., Clemm, Ch., Lauter, H., Hoffknecht, M. M., Eckardt, N., Hoffmann-Fezer, G., Gall, C., Kranz, B., Zengerle, U., Pfoersich, M., Birkenstock, U., Pittenann, E., Heinz, B., Hosten, N., Schörner, W., Kirsch, A., Neumann, K., Felix, R., Humpe, A., Kiss, T., Trümper, L. H., Messner, H. A., Hundt, M., Zielinska-Skowronek, M., Schubert, J., Schmidt, R. E., Huss, R., Storb, R., Deeg, H. J., Issels, R. D., Bosse, D., Abdel-Rahman, S., Jaeger, M., Söhngen, D., Weidmann, E., Schwulera, U., Jakab, I., Fodor, F., Pecze, K., Jaques, G., Schöneberger, H. -J., Wegmann, B., Grüber, A., Bust, K., Pflüger, K. -H., Havemann, K., Faul, C., Wannke, B., Scheurlen, M., Kirchner, M., Dahl, G., Schmits, R., Fohl, C., Kaiser, U., Tuohimaa, P., Wollmer, E., Aumüller, G., Havemann, K., Kolbabek, H., Schölten, C., Popov-Kraupp, B., Emminger, W., Hummel, M., Pawlita, M., v.Kalle, C., Dallenbach, F., Stein, H., Krueger, G. R. F., Müller-Lantzsch, N., Kath, R., Höffken, K., Horn, G., Brockmann, P., Keilholz, U., Stoelben, E., Scheibenbogen, C., Manasterski, M., Tilgen, W., Schlag, P., Görich, J., Kauffmann, G. W., Kempter, B., Rüth, S., Lohse, P., Khalil, R. M., Hültner, L., Mailhammer, R., Luz, A., Hasslinger, M. -A., Omran, S., Dörmer, P., Kienast, J., Kister, K. P., Seifarth, W., Klaassen, U., Werk, S., Reiter, W. W., Klein, G., Beck-Gessert, S., Timpl, R., Hinrichs, H., Lux, E., Döring, G., Scheinichen, D., Döring, G., Wernet, P., Vogeley, K. T., Richartz, G., Südhoff, T., Horstkotte, D., Klocker, J., Trotsenburg, M. v., Schumer, J., Kanatschnig, M., Henning, K., Knauf, W. U., Pottgießer, E., Raghavachar, A., Zeigmeister, B., Bollow, M., Schilling, A., König, H., Koch, M., Volkenandt, M., Seger, Andrea, Banerjee, D., Vogel, J., Bierhoff, E., Heidi, G., Neyses, L., Bertino, J., Kocki, J., Rozynkowa, D. M., M.Rupniewska, Z., Wojcierowski, J., König, V., Hopf, U., Koenigsmann, M., Streit, M., Koeppen, K. M., Martini, I., Poppy, U., Hardel, M., Havemann, K., Havemann, K., Clemm, Ch., Wendt, Th., Gauss, J., Kreienberg, R., Hohenfellner, R., Krieger, O., Istvan, L., Komarnicki, M., Kazmierczak, M., Haertle, D., Korossy, P., Haus, S. Kotlarek, Gabryś, K., Kuliszkiewicz-Janus, M., Krauter, J., Westphal, C., Werner, K., Lang, P., Preissner, K. T., Völler, H., Schröder, K., Uhrig, A., Behles, Ch., Seibt-Jung, H., Besserer, A., Kreutzmann, H., Kröning, H., Kähne, T., Eßbach, U., Kühne, W., Krüger, W. H., Krause, K., Nowicki, B., Stockschläder, M., Peters, S. O., Zander, A. R., Kurowski, V., Schüler, C., Höher, D., Montenarh, M., Lang, W., Schweiger, H., Dölken, Gottfried, Lege, H., Dölken, G., Wex, Th., Frank, K., Hastka, J., Bohrer, M., Leo, R., Peest, D., Tschechne, B., Atzpodien, J., Kirchner, H., Hein, R., Hoffmann, L., Stauch, M., Franks, C. R., Palmer, P. A., Licht, T., Mertelsmann, R., Liersch, T., Vehmeyer, K., Kaboth, U., Maschmeyer, G., Meyer, P., Helmerking, M., Schmitt, J., Adam, D., Prahst, A., Hübner, G., Meisner, M., Seifert, M., Richard, D., Yver, A., Spiekermann, K., Brinkmann, L., Battmer, K., Krainer, M., Löffel, J., Stahl, H., Wust, P., Lübbert, M., Schottelius, A., Mertelsmann, R., Henschler, R., Mertelsmann, R., Mapara, M. Y., Bargou, R., Zugck, C., Krammer, P. H., Dörken, B., Maschek, Hansjörg, Kaloutsi, Vassiliki, Maschek, Hansjörg, Gormitz, Ralf, Meyer, P., Kuntz, B. M. E., Mehl, B., Günther, I., Bülzebruck, H., Menssen, H. D., Mergenthaler, H. -G., Dörmer, P., Heusers, P., Zeller, K. -P., Enzinger, H. M., Neugebauer, T., Klippstein, T., Burkhardt, K. L., Putzicha, E., Möller, Peter, Henne, Christof, Eichelmann, Anette, Brüderlein, Silke, Dhein, Jens, Möstl, M., Krieger, O., Mucke, H., Schinkinger, M., Moiling, J., Daoud, A., Willgeroth, Ch., Mross K., Bewermeier P., Krüger W., Peters S., Berger C., Bohn, C., Edler, L., Jonat, W., Queisser, W., Heidemann, E., Goebel, M., Hamm, K., Markovic-Lipkovski, J., Bitzer, G., Müller, H., Oethinger, M., Grießhammer, M., Tuner, I., Musch E., Malek, M., Peter-Katalinic, J., Hügl, E., Helli, A., Slanicka, M., Filipowicz, A., Nissen, C., Speck, B., Nehls, M. C., Grass, H. -J., Dierbach, H., Mertelsmann, R., Thaller, J., Fiebeler, A., Schmidt, C. A., O'Bryan, J. P., Liu, E., Ritter, M., de Kant, E., Brendel, C., He, M., Dodge, R., George, S., Davey, F., Silver, R., Schiffer, C., Mayer, R., Ball, E., Bloomfield, C., Ramschak, H., Tiran, A., Truschnig-Wilders, M., Nizze, H., Bühring, U., Oelschlägel, U., Jermolow, M., Oertel, J., Weisbach, V., Zingsem, J., Wiens, M., Jessen, J., Osthoff, K., Timm, H., Wilborn, F., Bodak, K., Langmach, K., Bechstein, W., Blumhardt, G., Neuhaus, P., Olek, K., Ottinger, H., Kozole, G., Belka, C., Meusers, P., Hense, J., Papadileris, Stefan, Pasternak, G., Pasternak, L., Karsten, U., Pecherstorfer, M., Zimmer-Roth, I., Poloskey, A., Petrasch, S., Kühnemund, O., Uppenkamp, M., Lütticken, R., Kosco, M., Schmitz, J., Petrides, Petro E., Dittmann, Klaus H., Krieger, O., Pflueger, K. -H., Grueber, A., Schoeneberger, J., Wenzel, E., Havemann, K., Pies, A., Kneba, M., Edel, G., Pohl, S., Bulgay-Mörschel, M., Polzin, R., Issing, W., Clemm, Ch., Schorn, K., Ponta, H., Zöller, M., Hofmann, M., Arch, R., Heider, K. -H., Rudy, W., Tölg, C., Herrlich, P., Prümmer, O., Scherbaum, W. A., Porzsolt, F., Prümmer, O., Krüger, A., Schrezenmeier, H., Schlander, H., Pineo, G., Marin, P., Gluckman, E., Shahidi, N. T., Bacigalupo, A., Ratajczak, M. Z., Gewirtz, A. M., Ratei, R., Borner, K., Bank, U., Bühling, F., Reisbach, G., Bartke, L., Kempkes, B., Kostka, G., Ellwart, X., Birner, A., Bornkamm, G. W., Ullrich, A., Dörmer, P., Henze, G., Parwaresch, R., Müller-Weihrich, S. T., Klingebiel, Th., Odenwald, E., Brandhorst, D., Tsuruo, T., Wetter, O., Renner, C., Pohl, C., Sahin, U., Renner, U., Zeller, K. -P., Repp, R., Valerius, Th., Sendler, A., Kalden, J. R., PIatzer, E., Reuss-Borst, M. A., Bühring, H. J., Reuter, C., der Landwehr, II, U. Auf, der Landwehr, II, U. Auf, Schleyer, E., Rolf, C., Ridwelski, K., Matthias, M., Preiss, R., Riewald, M., Puzo, A., Serke, S., Rohrer, B., Pfeiffer, D., Hepp, H., Romanowski, R., Schött, C., Rüther, U., Rothe, B., Pöllmann, H., Nunnensiek, C., Schöllhammer, T., Ulshöfer, Th., Bader, H., Jipp, P., Müller, H. A. G., Rupp, W., Lüthgens, M., Eisenberger, F., Afflerbach, C., Höller, A., Schwamborn, J. S., Daus, H., Krämer, K., Pees, H., Salat, C., Reinhardt, B., Düll, T., Knabe, H., Hiller, E., Sawinski, K., Schalhorn, A., Kühl, M., Heil, K., Schardt, Ch., Drexler, H. G., Scharf, R. E., Suhijar, D., del Zoppo, G. J., Ruggeri, Z. M., Roll, T., Möhler, T., Giselinger, H., Knäbl, P., Kyrie, P. A., Lazcíka, K., Lechner, X., Scheulen, M. E., Beelen, D. W., Reithmayer, H., Daniels, R., Weiherich, A., Quabeck, K., Schaefer, U. W., Reinhardt J., Grimm M., Unterhalt M., Schliesser, G., Lohmeyer, J., Schlingheider, O., von Eiff, M., Schulze, F., Oehme, C., van de Loo, J., Schlögl E., Bemhart M., Schmeiser, Th., Rozdzinski, E., Kern, W., Reichle, A., Moritz, T., Merk, Bruno, Schmid, R. M., Perkins, N. D., Duckett, C. S., Leung, K., Nabel, G. J., Pawlaczyk-Peter, B., Kellermann-Kegreiß, Schmidt E., Steiert, I., Schmidt-Wolf, G., Schmidt-Wolf, I. G. H., Schlegel, P., Blume, K. G., Chao, N. J., Lefterova, P., Laser, J., Schmitz, G., Rothe, G., Schönfeld, S., Schulz, S., Nyce, J. W., Graf, N., Ludwig, R., Steinhauser, I., Brommer, A. E., Qui, H., Schroeder, M., Grote-Kiehn, J., Bückner, U., Rüger, I., Schröder, J., Meusers, P., Weimar, Ch., Schoch, C., Schröter, G., Stern, H., Buchwald, B., Schick, K., Avril, N., Flierdt, E. v. d., Langhammer, H. R., Pabst, H. W., Alvarado, M., Witte, T., Vogt, H., Schuler, U., Brammer, K., Klann, R. C., Schumm, M., Hahn, J., Günther, W., Wullich, B., Moringlane, J. R., Schöndorf, S., Schwartz, S., Bühring, H. -J., Notter, M., Böttcher, S., Martin, M., Schmid, H., Lübbe, A. S., Leib-Mösch C., Wankmüller, H., Eilbrück, D., Funke, I., Cardoso, M., Duranceyk, H., Seitz, R., Rappe, N., Kraus, H., Egbring, R., Haasberg, M., Havemann, K., Seibach, J., Wollscheid, Ursula, Serke, St., Zimmermann, R., Shirai, T., Umeda, M., Anno, S., Kosuge, T., Katoh, M., Moro, S., Su, C. -Y., Shikoshi, K., Arai, N., Schwieder, G., Silling-Engelhardt, G., Zühlsdorf, M., Aguion-Freire-Innig, E., van de Loo, J., Stockdreher, K., Gatsch, L., Tischler, H. -J., Ringe, B., Diedrich, H., Franzi, A., Kruse, E., Lück, R., Trenn, G., Sykora, J., Wen, T., Fung-Leung, W. P., Mak, T. W., Brady, G., Loke, S., Cossman, J., Gascoyne, R., Mak, T., Urasinski, I., Zdziarska, B., Usnarska-Zubkiewicz, L., Kotlarek-Haus, S., Sciborskl, R., Nowosad, H., Kummer, G., Schleucher, N., Preusser, P., Niebel, W., Achterrath, W., Pott, D., Eigler, F. -W., Venook, A., Stagg, R., Frye, J., Gordon, R., Ring, E., Verschuer, U. v., Baur, F., Heit, W., Corrons, J. L. L. Vives, Vogel, M., Nekarda, H., Remy, W., Bissery, M. C., Aapro, M., Buchwald-Pospiech, A., Kaltwasser, J. P., Jacobi, V., de Vos, Sven, Asano, Yoshinobu, Voss, Harald, Knuth, Alexander, Wiedemann, G., Komischke, B., Horisberger, R., Wussow, P. v., Wanders, L., Senekowitsch, R., Strohmeyer, S., Emmerich, B., Selbach, J., Gutensohn, K., Wacker-Backhaus, G., Winkeimann, M., Send, W., Rösche, J., Weide, R., Parviz, B., Havemann, K., Weidmann, B., Henss, H., Engelhardt, R., Bernards, P., Zeidler, D., Jägerbauer, E., Colajori, E., Kerpel-Fronius, S., Weiss, A., Buchheidt, D., Döring, A., D.Saeger, H., Weissbach, L., Emmler, J., Wermes, R., Meusers, P., Flasshove, M., Skorzec, M., Käding, J., Platow, S., Winkler, Ute, Thorpe, Philip, Winter, S. F., Minna, J. D., Nestor, P. J., Johnson, B. E., Gazdar, A. F., Havemann, K., Carbone, D. P., Wit, M. de, Bittner, S., Hossfeld, D., Wittmann, G., Borchelt, M., Steinhagen-Thiessen, E., Koch, K., Brosch, T., Haas, N., Wölfel, C., Knuth, A., Wölfel, T., Safford, M., Könemann, S., Zurlutter, K., Schreiber, K., Piechotka, K., Drescher, M., Toepker, S., Terstappen, L. W. M. M., Bullerdiek, J., Jox, A., zur Hausen, H., Wolters, B., Stenzinger, W., Woźny, T., Sawiński, K., Kozłowska-Skrzypczak, M., Wussow, P. v., Hochhaus, T., Ansarl, H., Prümmer, O., Zapf, H., Thorban, S., Präuer, H., Zeller, W., Stieglitz, J. v., Dürken, M., Greenshaw, C., Kabisch, H., Reuther, C., Knabbe, C., Lippman, M., Havemann, K., Wellstein, A., Degos, L., Castaigne, S., Fenaux, P., Chomienne, C., Raza, A., Preisler, H. D., PEG Interventional Antimicrobial Strategy Study Group, Interventional Antimicrobial Strategy Study Group of the Paul Ehrlich Society (PEG), and H. Riehm for the BFM study group

Published
1992
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11. State of integration of palliative care at Comprehensive Cancer Centers funded by German Cancer Aid

Author

Berendt, J., Oechsle, K., Thomas, M., van Oorschot, B., Schmitz, A., Radbruch, L., Simon, S. T., Gaertner, J., Thuss-Patience, P., Schuler, U. S., Hense, J., Gog, C., Viehrig, M., Mayer-Steinacker, R., Stachura, P., Stiel, S., Ostgathe, C., Berendt, J., Oechsle, K., Thomas, M., van Oorschot, B., Schmitz, A., Radbruch, L., Simon, S. T., Gaertner, J., Thuss-Patience, P., Schuler, U. S., Hense, J., Gog, C., Viehrig, M., Mayer-Steinacker, R., Stachura, P., Stiel, S., and Ostgathe, C.

Published
2016

12. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation

Author

Schuler U, P. Mackes, Gerhard Ehninger, Holger Hebart, Knut M. Wittkowski, Hermann Einsele, Claudia A. Müller, Thomas Klingebiel, M. Herter, Gerhard Jahn, Silvia Wagner, and Jürgen Löffler

Subjects
Adult, Male, Ganciclovir, medicine.medical_specialty, Neutropenia, Time Factors, Adolescent, Immunology, Cytomegalovirus, Antibodies, Viral, Antiviral Agents, Polymerase Chain Reaction, Biochemistry, Gastroenterology, Betaherpesvirinae, Acute lymphocytic leukemia, Internal medicine, medicine, Humans, Child, Survival rate, Bone Marrow Transplantation, biology, business.industry, Incidence (epidemiology), Cell Biology, Hematology, Middle Aged, biology.organism_classification, medicine.disease, Survival Rate, medicine.anatomical_structure, Cytomegalovirus Infections, DNA, Viral, Chemoprophylaxis, Female, Bone marrow, business, medicine.drug
Abstract

Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P < .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.

Published
1995
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14. Applications of e-SOTER related to major soil threats

Author

Hessel, R., Verzandvoort, S.J.E., Walvoort, D.J.J., Heidema, A.H., Yigini, Y., Schuler, U., Daroussin, J., and Jones, B.

Subjects
Alterra - Soil geography, Life Science, Wageningen Environmental Research, Alterra - Soil physics and land use, CB - Bodemfysica en Landgebruik, Alterra - Bodemgeografie, SS - Soil Physics and Land Use, Alterra - Bodemfysica en landgebruik
Published
2012

15. a Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals

Author

Rieger, C. T., Cornely, O. A., Hoppe-Tichy, T., Kiehl, M., Knoth, H., Thalheimer, M., Schuler, U., Ullmann, A. J., Ehlken, B., Ostermann, H., Rieger, C. T., Cornely, O. A., Hoppe-Tichy, T., Kiehl, M., Knoth, H., Thalheimer, M., Schuler, U., Ullmann, A. J., Ehlken, B., and Ostermann, H.

Abstract

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital providers perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were 51 pound 517 in the IFD group and 30 pound 454 in the control group. Incremental costs of 21 pound 063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.

Published
2012

16. Lack of efficacy of imatinib in a patient with metastatic Leydig cell tumor

Author

Froehner, M., Beuthien-Baumann, B., Dittert, D.-D., Schuler, U., Wirth, M. P., Froehner, M., Beuthien-Baumann, B., Dittert, D.-D., Schuler, U., and Wirth, M. P.

Abstract

Imatinib is a tyrosine kinase inhibitor with activity in gastrointestinal stromal tumor and a variety of other solid and hematological malignancies. Studies in vitro and in a mouse model suggested that the imatinib might also be active in malignant Leydig cell tumor. We report on the—to our knowledge—first treatment experiment with imatinib in a patient with metastatic Leydig cell tumor. Unfortunately, the tumor progressed during treatment.

Published
2006

17. Reduced intensity conditioning before allografting: moderate enthusiasm may be more appropriate

Author

Schuler U

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Immunosuppression, Surgery, Transplantation, surgical procedures, operative, Reduced Intensity Conditioning, Toxicity, medicine, Autogenous bone, Stem cell, business, Preparative Regimen
Abstract

Since the first clinical series of allogeneic bone marrow transplants were reported, the procedure has been associated with a considerable amount of pulmonary complications, among many other problems. Over the last three decades, huge efforts have been devoted to the avoidance and the effective treatment of these complications. In the past, numerous patients did not undergo transplantation, either because they were considered too ill or too old to tolerate these procedure-related side-effects. In this issue of the European Respiratory Journal (ERJ) , Nusair et al. 1 from Jerusalem report on their experience with pulmonary complications as observed after transplants with “nonmyeloablative” conditioning. Stem cell transplantation (SCT) can be divided into three components: the conditioning therapy (chemotherapy with/without irradiation), the source and composition of the graft, and the post-transplant immunosuppression. Modifications of all three components may contribute to the profile of efficacy and toxicity of the procedure. The group from the Hadassah University Hospital in Jerusalem was among the first to develop a procedure that tried to minimise the toxicity of the preparative regimen and relied more on the graft- versus -leukaemia (GVL) effect of the transplanted allogeneic immune system 2. Numerous other centres then followed and this has resulted …

Published
2004
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25. Supportive intervention to improve quality of life (QoL) for patients with soft tissue sarcoma (STS) undergoing palliative treatment: a multicenter, clusterrandomized, controlled trial within the German Interdisciplinary Sarcoma group

Author

Hentschel, L., Richter, S., Kopp, H. -G, Kasper, B., Kunitz, A., Gruenwald, V., Torsten Kessler, Chemnitz, J. M., Pelzer, U., Schuler, U., Freitag, J., Schilling, A., Hornemann, B., Arndt, K., Ehninger, G., Bornhaeuser, M., and Schuler, M. K.

Subjects
Medizin

26. 1606PDQuality of life in patients with soft tissue sarcoma undergoing palliative treatment: A multicenter, cluster-randomized trial within the Germany Interdisciplinary Sarcoma Group (GISG-12).

Author

Hentschel, L, Richter, S, Kopp, H-G, Kasper, B, Kunitz, A, Grünwald, V, Kessler, T, Chemnitz, J-M, Pelzer, U, and Schuler, U S

Subjects
*SARCOMA, *PALLIATIVE treatment, *ISOLATION perfusion, *PALLIATIVE treatment of cancer, *STEM cell transplantation
Published
2018
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27. Contribution of Synthetic Data Generation towards an Improved Patient Stratification in Palliative Care.

Author

Hahn W, Schütte K, Schultz K, Wolkenhauer O, Sedlmayr M, Schuler U, Eichler M, Bej S, and Wolfien M

Abstract

AI model development for synthetic data generation to improve Machine Learning (ML) methodologies is an integral part of research in Computer Science and is currently being transferred to related medical fields, such as Systems Medicine and Medical Informatics. In general, the idea of personalized decision-making support based on patient data has driven the motivation of researchers in the medical domain for more than a decade, but the overall sparsity and scarcity of data are still major limitations. This is in contrast to currently applied technology that allows us to generate and analyze patient data in diverse forms, such as tabular data on health records, medical images, genomics data, or even audio and video. One solution arising to overcome these data limitations in relation to medical records is the synthetic generation of tabular data based on real world data. Consequently, ML-assisted decision-support can be interpreted more conveniently, using more relevant patient data at hand. At a methodological level, several state-of-the-art ML algorithms generate and derive decisions from such data. However, there remain key issues that hinder a broad practical implementation in real-life clinical settings. In this review, we will give for the first time insights towards current perspectives and potential impacts of using synthetic data generation in palliative care screening because it is a challenging prime example of highly individualized, sparsely available patient information. Taken together, the reader will obtain initial starting points and suitable solutions relevant for generating and using synthetic data for ML-based screenings in palliative care and beyond.

Published
2022
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28. Predicting unplanned hospital readmission in palliative outpatients (PRePP) - study protocol of a longitudinal, prospective study to identify informal caregiver-related and structural predictors.

Author

Hentschel L, Wellesen A, Krause LC, von Havranek M, Kramer M, Hornemann B, Bornhäuser M, Schuler U, and Schütte K

Subjects
Humans, Observational Studies as Topic, Outpatients, Prospective Studies, Quality of Life, Caregivers psychology, Patient Readmission
Abstract

Background: Although the majority of German patients in a palliative state prefer to die at home, the actual place of death is most often a hospital. Unplanned hospital readmissions (UHA) not only contradict most patients' preferences but also increase the probability of an aggressive end-of-life treatment. As limited knowledge is available which factors contribute to an UHA, the PRePP-project aims to explore predictors related to informal caregivers (IC) as well as medical and structural factors., Methods: This prospective, observational, mono-centric study will assess structural and medical factors as well as ICs' psychological burden throughout seven study visits. Starting in April 2021 it will consecutively include 240 patients and their respective IC if available. Standardized measures concerning ICs' Quality of Life (WHOQOL-BREF), psychological distress (NCCN-Distress Thermometer), anxiety (GAD-7) and depressiveness (PHQ-9) will be assessed. If participants prefer, assessment via phone, browser-based or paper-based will be conducted. Medical records will provide routinely assessed information concerning patient-related characteristics such as gender, age, duration of hospital stay and medical condition. Nurse-reported data will give information on whether hospitalization and death occurred unexpectedly. Data will be progressed pseudonymized. Multivariable regression models will help to identify predictors of the primary endpoint "unplanned hospital admissions"., Discussion: The PRePP-project is an important prerequisite for a clinical risk assessment of UHAs. Nevertheless, it faces several methodological challenges: as it is a single center study, representativity of results is limited while social desirability might be increased as the study is partly conducted by the treatment team. Furthermore, we anticipated an underrepresentation of highly burdened participants as they might refrain from participation., Trial Registration: This study was retrospectively registered 19 October 2021 at clinicaltrials.gov (NCT05082389). https://clinicaltrials.gov/ct2/show/NCT05082389., (© 2022. The Author(s).)

Published
2022
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29. Deep learning identifies Acute Promyelocytic Leukemia in bone marrow smears.

Author

Eckardt JN, Schmittmann T, Riechert S, Kramer M, Sulaiman AS, Sockel K, Kroschinsky F, Schetelig J, Wagenführ L, Schuler U, Platzbecker U, Thiede C, Stölzel F, Röllig C, Bornhäuser M, Wendt K, and Middeke JM

Subjects
Aged, Female, Humans, Male, Middle Aged, Reproducibility of Results, Retrospective Studies, Staining and Labeling, Bone Marrow Cells pathology, Bone Marrow Examination methods, Deep Learning, Leukemia, Promyelocytic, Acute diagnosis
Abstract

Background: Acute promyelocytic leukemia (APL) is considered a hematologic emergency due to high risk of bleeding and fatal hemorrhages being a major cause of death. Despite lower death rates reported from clinical trials, patient registry data suggest an early death rate of 20%, especially for elderly and frail patients. Therefore, reliable diagnosis is required as treatment with differentiation-inducing agents leads to cure in the majority of patients. However, diagnosis commonly relies on cytomorphology and genetic confirmation of the pathognomonic t(15;17). Yet, the latter is more time consuming and in some regions unavailable., Methods: In recent years, deep learning (DL) has been evaluated for medical image recognition showing outstanding capabilities in analyzing large amounts of image data and provides reliable classification results. We developed a multi-stage DL platform that automatically reads images of bone marrow smears, accurately segments cells, and subsequently predicts APL using image data only. We retrospectively identified 51 APL patients from previous multicenter trials and compared them to 1048 non-APL acute myeloid leukemia (AML) patients and 236 healthy bone marrow donor samples, respectively., Results: Our DL platform segments bone marrow cells with a mean average precision and a mean average recall of both 0.97. Further, it achieves high accuracy in detecting APL by distinguishing between APL and non-APL AML as well as APL and healthy donors with an area under the receiver operating characteristic of 0.8575 and 0.9585, respectively, using visual image data only., Conclusions: Our study underlines not only the feasibility of DL to detect distinct morphologies that accompany a cytogenetic aberration like t(15;17) in APL, but also shows the capability of DL to abstract information from a small medical data set, i. e. 51 APL patients, and infer correct predictions. This demonstrates the suitability of DL to assist in the diagnosis of rare cancer entities. As our DL platform predicts APL from bone marrow smear images alone, this may be used to diagnose APL in regions were molecular or cytogenetic subtyping is not routinely available and raise attention to suspected cases of APL for expert evaluation., (© 2022. The Author(s).)

Published
2022
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30. Reevaluation of reference values for bone marrow differential counts in 236 healthy bone marrow donors.

Author

Parmentier S, Kramer M, Weller S, Schuler U, Ordemann R, Rall G, Schaich M, Bornhäuser M, Ehninger G, and Kroschinsky F

Subjects
Adolescent, Adult, Blood Cell Count methods, Bone Marrow Transplantation methods, Cell Count methods, Cell Count standards, Cohort Studies, Female, Humans, Male, Middle Aged, Random Allocation, Reference Values, Reproducibility of Results, Retrospective Studies, Young Adult, Blood Cell Count standards, Bone Marrow Cells physiology, Bone Marrow Transplantation standards, Living Donors
Abstract

Despite the increasing role of molecular markers, differential counts and morphology of hematopoietic cells in the bone marrow (BM) remain essential diagnostic criteria in hematological diseases. However, the respective reference values for BM myelogram commonly used came from small series with limited numbers of healthy individuals. We evaluated the myelograms of 236 healthy individuals who underwent unrelated bone marrow donation. Health check-ups were performed 4 weeks prior to harvest. Samples for this study, taken from the first aspiration, were stained according to the standard Pappenheim method. Three experienced investigators assessed cellularity, megakaryopoiesis, and differential counts independently. The median donor age was 31 (range 18-51) years. Predonation tests did not reveal any relevant morbidity. Thirty-seven out of 42 hypocellular marrow samples were from younger donors up to 39 years. Content of megakaryocytes was normal in 210 specimens (89%). Gender and body mass index had significant impact on hematopoiesis, whereas age had not. The number of erythroblasts was higher (about 32%) and the proportion granulopoiesis slightly lower (about 50%) compared with previous studies. Differential counts showed also some differences with respect to individual maturation stages in these lines. Interrater comparisons showed greater reliability for the assignment of cells to the different hematopoietic cell lines than for single-cell diagnoses. This study largely confirms the results for cell counts in normal human bone marrow available from previous reports and provides some insights into factors that affect individual cell populations. It also reveals substantial variability among even experienced investigators in cytological diagnoses.

Published
2020
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31. Quality of life and added value of a tailored palliative care intervention in patients with soft tissue sarcoma undergoing treatment with trabectedin: a multicentre, cluster-randomised trial within the German Interdisciplinary Sarcoma Group (GISG).

Author

Hentschel L, Richter S, Kopp HG, Kasper B, Kunitz A, Grünwald V, Kessler T, Chemnitz JM, Pelzer U, Schuler U, Freitag J, Schilling A, Hornemann B, Arndt K, Bornhäuser M, and Schuler MK

Subjects
Humans, Palliative Care, Quality of Life, Trabectedin, Sarcoma drug therapy, Soft Tissue Neoplasms drug therapy
Abstract

Objectives: The choice of drug treatment in advanced soft tissue sarcoma (STS) continues to be a challenge regarding efficacy, quality of life (QoL) and toxicity. Unlike other cancer types, where integrating patient-reported outcomes (PRO) has proven to be beneficial for QoL, there is no such evidence in patients with STS as of now. The YonLife trial aimed to explore the effect of a tailored multistep intervention on QoL, symptoms and survival in patients with advanced STS undergoing treatment with trabectedin as well as identifying predictors of QoL., Design: YonLife is a cluster-randomised, open-label, proof-of-concept study. The intervention incorporates electronic PRO assessment, a case vignette and expert-consented treatment recommendations., Participants: Six hospitals were randomised to the control arm (CA) or interventional arm (IA). Seventy-nine patients were included of whom 40 were analysed as per-protocol analysis set., Primary and Secondary Outcome Measures: The primary end point was the change of Functional Assessment for Cancer Therapy (FACT-G) total score after 9 weeks. Secondary outcomes included QoL (FACT-G subscales), anorexia and cachexia (Functional Assessment of Anorexia/Cachexia Therapy (FAACT)), symptoms (MD Anderson Symptom Inventory (MDASI)), anxiety and depression (HADS), pain intensity and interference (Brief Pain Inventory (BPI)) and survival assessment., Results: After 9 weeks of treatment, QoL declined less in the IA (ΔFACT-G total score: -2.4, 95% CI: -9.2 to 4.5) as compared with CA (ΔFACT-G total score: -3.9; 95% CI:-11.3 to 3.5; p = 0.765). In almost all FACT-G subscales, average declines were lower in IA, but without reaching statistical significance. Smaller adverse trends between arms were observed for MDASI, FAACT, HADS and BPI scales. These trends failed to reach statistical significance. Overall mean survival was longer in IA (648 days) than in CA (389 days, p = 0.110). QoL was predicted by symptom severity, symptom interference, depression and anxiety., Conclusion: Our data suggest a potentially favourable effect of an electronic patient-reported outcomes based intervention on QoL that needs to be reappraised in confirmatory studies., Trial Registration Number: ClinicalTrials.gov Identifier (NCT02204111)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2020
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32. Reliable isolation of human mesenchymal stromal cells from bone marrow biopsy specimens in patients after allogeneic hematopoietic cell transplantation.

Author

Krüger T, Middeke JM, Stölzel F, Mütherig A, List C, Brandt K, Heidrich K, Teipel R, Ordemann R, Schuler U, Oelschlägel U, Wermke M, Kräter M, Herbig M, Wehner R, Schmitz M, Bornhäuser M, and von Bonin M

Subjects
Adult, Aged, Biopsy, Bone Marrow, Collagenases pharmacology, Female, Graft vs Host Disease pathology, Humans, Male, Middle Aged, Tumor Cells, Cultured, Young Adult, Bone Marrow Cells cytology, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Mesenchymal Stem Cells cytology
Abstract

Isolation of mesenchymal stromal cells (MSCs) from pretreated, hematologic patients is challenging. Especially after allogeneic hematopoietic cell transplantation (HCT), standard protocols using bone marrow aspirates fail to reliably recover sufficient cell numbers. Because MSCs are considered to contribute to processes that mainly affect the outcome after transplantation, such as an efficient lymphohematopoietic recovery, extent of graft-versus-host disease as well as the occurrence of leukemic relapse, it is of great clinical relevance to investigate MSC function in this context. Previous studies showed that MSCs can be isolated by collagenase digestion of large bone fragments of hematologically healthy patients undergoing hip replacement or knee surgeries. We have now further developed this procedure for the isolation of MSCs from hematologic patients after allogeneic HCT by using trephine biopsy specimens obtained during routine examinations. Comparison of aspirates and trephine biopsy specimens from patients after allogeneic HCT revealed a significantly higher frequency of clonogenic MSCs (colony-forming unit-fibroblast [CFU-F]) in trephine biopsy specimens (mean, 289.8 ± standard deviation 322.5 CFU-F colonies/1 × 10 6 total nucleated cells versus 4.2 ± 9.9; P < 0.0001). Subsequent expansion of functional MSCs isolated from trephine biopsy specimen was more robust and led to a significantly higher yield compared with control samples expanded from aspirates (median, 1.6 × 10 6 ; range, 0-2.3 × 10 7 P0 MSCs versus 5.4 × 10 4 ; range, 0-8.9 × 10 6 ; P < 0.0001). Using trephine biopsy specimens as MSC source facilitates the investigation of various clinical questions., Competing Interests: Declaration of Competing Interest The project was funded by the Deutsche Forschungsgemeinschaft (Clinician Scientist position and Seed grant within the Centre for Regenerative Therapies Dresden, www.crt-dresden.de). The authors have no conflicts of interest to disclose., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Published
2020
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33. Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients.

Author

Röllig C, Kramer M, Gabrecht M, Hänel M, Herbst R, Kaiser U, Schmitz N, Kullmer J, Fetscher S, Link H, Mantovani-Löffler L, Krümpelmann U, Neuhaus T, Heits F, Einsele H, Ritter B, Bornhäuser M, Schetelig J, Thiede C, Mohr B, Schaich M, Platzbecker U, Schäfer-Eckart K, Krämer A, Berdel WE, Serve H, Ehninger G, and Schuler US

Subjects
Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cytarabine adverse effects, Daunorubicin adverse effects, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Mitoxantrone adverse effects, Remission Induction, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine administration & dosage, Daunorubicin administration & dosage, Leukemia, Myeloid, Acute drug therapy, Mitoxantrone administration & dosage
Abstract

Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA)., Patients and Methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone., Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513)., Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.

Published
2018
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34. Two cycles of risk-adapted consolidation therapy in patients with acute promyelocytic leukemia. Results from the SAL-AIDA2000 trial.

Author

Röllig C, Schäfer-Eckardt K, Hänel M, Kramer M, Schaich M, Thiede C, Oelschlägel U, Mohr B, Wagner T, Einsele H, Krause SW, Bodenstein H, Martin S, Stuhlmann R, Ho AD, Bornhäuser M, Ehninger G, Schuler U, and Platzbecker U

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Drug Administration Schedule, Female, Humans, Leukemia, Promyelocytic, Acute mortality, Male, Middle Aged, Precision Medicine, Risk, Survival Analysis, Young Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Consolidation Chemotherapy methods, Idarubicin administration & dosage, Leukemia, Promyelocytic, Acute drug therapy, Tretinoin administration & dosage
Abstract

The combination of all-trans retinoic acid (ATRA) and idarubicin (AIDA) for induction therapy followed by three cycles of risk-adapted consolidation cycles is considered standard of care for patients with acute promyelocytic leukemia (APL). We report the outcome of 141 patients (median age 51 years; range, 19-82, 31 % ≥60 years) enrolled into the prospective Study Alliance Leukemia (SAL)-AIDA2000 trial, which comprised AIDA-based induction followed by only two courses of risk-adapted consolidation (daunorubicin or mitoxantrone ± cytarabine) followed by 2-year maintenance treatment. The early death rate was 7 % (median age 66 years), and additional 9 % stopped further treatment after induction. The estimated 6-year disease-free survival (DFS) was 80 % in all patients, 84 % in patients ≤60 and 72 % in patients >60 years (p = 0.140). No significant survival differences were observed between the high-risk and the non-high-risk patients (6-year OS 78 vs. 81 %, p = 0.625). Our results confirm the efficacy of a risk-adapted approach in APL patients. Furthermore, long-term outcomes are comparable to the results obtained with three cycles of consolidation. A modification of the number and intensity of conventional consolidation treatment may be a less toxic but equally effective approach and should be considered for further evaluation in randomized clinical trials in APL.

Published
2015
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35. Plasma levels of phospholipase A2-IIA in patients with different types of malignancies: prognosis and association with inflammatory and coagulation biomarkers.

Author

Menschikowski M, Hagelgans A, Schuler U, Froeschke S, Rosner A, and Siegert G

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Blood Coagulation Factors metabolism, C-Reactive Protein metabolism, Female, Humans, Inflammation, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasms blood, Retrospective Studies, Statistics, Nonparametric, Young Adult, Biomarkers, Tumor blood, Group II Phospholipases A2 blood, Neoplasms enzymology
Abstract

It is well-known that the plasma level of group IIA phospholipase A2 (sPLA2-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA2-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin's lymphoma. Plasma levels of sPLA2-IIA are shown to be markedly increased in all types of analysed malignancies in comparison to the normal range (22.8 ± 4.5 μg/L versus <1.9 μg/L). Levels of sPLA2-IIA correlate positively with CRP (p < 0.001), fibrinogen (p < 0.01), FVIII (p < 0.05), and vWF (p < 0.05) and negatively with antithrombin levels (p < 0.05). Kaplan-Meier analyses revealed a statistically prolonged survival time of patients with lower sPLA2-IIA concentrations (<4 μg/L) in comparison to those with elevated concentrations (>4 μg/L) of this enzyme. In conclusion, the study shows that the measurement of plasma sPLA2-IIA levels has prognostic values in patients with different types of malignancies. The association of sPLA2-IIA levels with CRP, fibrinogen, FVIII, and vWF levels supports the importance of inflammatory processes for the up-regulation of sPLA2-IIA during cancer progression.

Published
2013
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36. Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors.

Author

Parmentier S, Schetelig J, Lorenz K, Kramer M, Ireland R, Schuler U, Ordemann R, Rall G, Schaich M, Bornhäuser M, Ehninger G, and Kroschinsky F

Subjects
Adolescent, Adult, Cell Lineage, Cohort Studies, Female, Humans, Male, Middle Aged, Observer Variation, Prognosis, Young Adult, Bone Marrow pathology, Erythropoiesis physiology, Granulocytes pathology, Hematopoiesis physiology, Megakaryocytes pathology, Tissue Donors
Abstract

Background: According to WHO 2008 guidelines, the required percentage of cells manifesting dysplasia in the bone marrow to qualify as significant is 10% or over in one or more hematopoietic cell lineages, but this threshold is controversial. No 'normal' values have been established. Therefore, we investigated dyshematopoiesis in bone marrow aspirate squash preparations of 120 healthy bone marrow donors., Design and Methods: Bone marrow squash slides of 120 healthy unrelated bone marrow donors were examined independently by 4 experienced morphologists. Samples were taken from the first aspiration during the harvest. Bone marrow preparation and assessment were performed according to WHO recommendations and ICSH guidelines., Results: More than 10% dysmyelopoiesis could be detected in 46% of bone marrow aspirate squash preparations with 26% in 2 or more cell lineages and 7% in 3 cell lineages in healthy bone marrow donors. Donors under the age of 30 years exhibited more dysgranulopoietic changes and dysmegakaryopoietic changes (P<0.001) compared to the older donors. Female donors showed more dysgranulopoietic changes than male donors (P = 0.025). The concordance rate between the 4 investigators was modest in dysgranulopoiesis but poor in dyserythropoiesis and dysmegakaryopoiesis., Conclusions: The poor reliability of the 10% cut off was partly related to the proximity of the current criteria to the observed cut-off mean values of the normal population. These findings question the current WHO threshold of the 10% or over necessary for the percentage of cells manifesting dysplasia to be considered significant, and suggest that either a higher threshold would be more appropriate or different thresholds should be set for each lineage.

Published
2012
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37. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial.

Author

Röllig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhäuser M, Platzbecker U, Stuhlmann R, Schuler U, Soucek S, Kramer M, Mohr B, Oelschlaegel U, Stölzel F, von Bonin M, Wermke M, Wandt H, Ehninger G, and Schaich M

Subjects
Aged, Aged, 80 and over, Antimetabolites, Antineoplastic therapeutic use, Cohort Studies, Cytarabine therapeutic use, Daunorubicin therapeutic use, Disease-Free Survival, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute genetics, Male, Middle Aged, Multivariate Analysis, Nuclear Proteins genetics, Nucleophosmin, Prognosis, Proportional Hazards Models, Prospective Studies, Remission Induction, Risk Factors, fms-Like Tyrosine Kinase 3 genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality
Abstract

We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy.

Published
2010
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38. Novel Mutation in Bernard-Soulier Syndrome.

Author

Sandrock K, Knöfler R, Greinacher A, Fürll B, Gerisch S, Schuler U, Gehrisch S, Busse A, and Zieger B

Abstract

BACKGROUND: Bernard-Soulier syndrome (BSS) is a severe congenital bleeding disorder characterized by thrombocytopenia, thrombocytopathy and decreased platelet adhesion. BSS results from genetic alterations of the glycoprotein (GP) Ib/IX/V complex. METHODS: We report on a patient demonstrating typical BSS phenotype (thrombocytopenia with giant platelets, bleeding symptoms). However, BSS was not diagnosed until he reached the age of 39 years. RESULTS: Flow cytometry of the patient's platelets revealed absence of GPIb/IX/V receptor surface expression. In addition, immunofluorescence analysis of patient's platelets demonstrated very faint staining of GPIX. A novel homozygous deletion comprising 11 nucleotides starting at position 1644 of the GPIX gene was identified using molecular genetic analysis. CONCLUSIONS: The novel 11-nucleotide deletion (g.1644&#95;1654del11) was identified as causing the bleeding disorder in the BSS patient. This homozygous deletion includes the last 4 nucleotides of the Kozak sequence as well as the start codon and the following 4 nucleotides of the coding sequence. The Kozak sequence is a region indispensable for the initiation of the protein translation process, thus preventing synthesis of functional GPIX protein in the case of deletion.

Published
2010
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39. Gemtuzumab ozogamicin as part of reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in patients with relapsed acute myeloid leukemia.

Author

Bornhäuser M, Illmer T, Oelschlaegel U, Schetelig J, Ordemann R, Schaich M, Hänel M, Schuler U, Thiede C, Kiani A, Platzbecker U, and Ehninger G

Subjects
Adolescent, Aged, Aminoglycosides adverse effects, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Female, Gemtuzumab, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Recurrence, Salvage Therapy, Survival Analysis, Transplantation, Homologous, Aminoglycosides administration & dosage, Antibodies, Monoclonal administration & dosage, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods
Abstract

Purpose: Gemtuzumab ozogamicin (GO) has been associated with an increased risk of liver sinusoidal obstruction syndrome (SOS) when applied within 3 months of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that GO might be safe and effective as part of a reduced-intensity conditioning regimen as salvage therapy of CD33+ acute myeloid leukemia., Experimental Design: Thirty-one patients with acute myeloid leukemia which relapsed following conventional therapy (n=15), autologous (n=3), or allogeneic (n=13) HCT were included in a prospective phase I/II trial. The preparative regimen contained 6 and 3 mg/m(2) of GO on days -21 and -14 before transplantation, leading to a reduction of marrow blasts in 18 patients (58%). Eight patients received further cytoreductive chemotherapy before conditioning therapy was initiated. Fludarabine-based reduced-intensity (n=11) or nonmyelablative (n=16) conditioning and peripheral blood stem cell infusion from related (n=6) or unrelated (n=21) donors could be done in 27 patients during cytopenia., Results: Primary engraftment occurred in all evaluable patients. Only one case of reversible hepatic sinusoidal obstruction syndrome was documented. Non-relapse mortality until day 100 was 22% (n=6). The probabilities of overall and disease-free survival at 24 months were 39% and 35%, respectively. Relapse of leukemia occurring between 2 and 24 months after transplantation (median, 8 months) was the major reason for treatment failure and death., Conclusion: These data suggest that GO can be combined with reduced-intensity conditioning even after previous autologous or allogeneic HCT.

Published
2008
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40. Improved outcome in central nervous system aspergillosis, using voriconazole treatment.

Author

Schwartz S, Ruhnke M, Ribaud P, Corey L, Driscoll T, Cornely OA, Schuler U, Lutsar I, Troke P, and Thiel E

Subjects
Adult, Aged, Aged, 80 and over, Aspergillosis microbiology, Aspergillosis pathology, Central Nervous System Fungal Infections microbiology, Central Nervous System Fungal Infections pathology, Child, Child, Preschool, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Treatment Outcome, Voriconazole, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Central Nervous System Fungal Infections drug therapy, Pyrimidines therapeutic use, Triazoles therapeutic use
Abstract

The mortality of central nervous system (CNS) aspergillosis approaches 100%, requiring improved therapies. Voriconazole gives superior efficacy and survival in invasive aspergillosis, compared with amphotericin B. Also, in contrast to other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated, retrospectively, the outcome and survival of 81 patients who were treated with voriconazole for definite (n = 48) or probable (n = 33) CNS aspergillosis. Complete and partial responses were recorded in 35% of patients and varied by the underlying disease group: hematologic malignancies (54%), other underlying conditions (50%), chronic immunosuppression (45%), solid organ transplantation (36%), and hematopoietic stem cell transplantation (16%). Thirty-one percent of patients survived CNS aspergillosis for a median observation time of 390 days. There were 31 patients who underwent neurosurgical procedures, including craniotomy/abscess resection (n = 14), abscess drainage (n = 12), ventricular shunt (n = 4), and Ommaya-reservoir (n = 1). Multifactorial analysis revealed that neurosurgery was associated with improved survival (P = .02). Patients who underwent hematopoietic stem cell transplantation had a poorer survival (P = .02), but 7 (22%) of 32 survived for a median of 203 days. We conclude from this large cohort of patients that voriconazole treatment together with neurosurgical management, whenever feasible, is currently the best approach to treat patients with CNS aspergillosis.

Published
2005
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41. Myeloablation by intravenous busulfan and hematopoietic reconstitution with autologous marrow in a canine model.

Author

Deeg HJ, Schuler US, Shulman H, Ehrsam M, Renner U, Yu C, Storb R, and Ehninger G

Subjects
Animals, Blood Cell Count, Bone Marrow Transplantation, Busulfan blood, Busulfan pharmacokinetics, Busulfan toxicity, Dogs, Dose-Response Relationship, Drug, Injections, Intravenous, Leukocyte Count, Models, Biological, Neutrophils drug effects, Platelet Count, Transplantation, Autologous, Busulfan administration & dosage, Hematopoiesis drug effects, Myeloablative Agonists administration & dosage
Abstract

We have previously described pharmacokinetic studies with a dimethylsulfoxide-based intravenous busulfan preparation in a canine model and in preliminary clinical trials. Using the same intravenous busulfan preparation, we carried out a dose escalation study to determine a marrow-ablative dose and to test the ability of autologous marrow to reconstitute hematopoiesis in dogs so treated. Busulfan was given intravenously at doses of 3.75 to 40 mg/kg. Marrow ablation was achieved at 20 mg/kg given either as a single dose or in four daily increments of 5 mg/kg each. There was a relative sparing of lymphocytes. A busulfan dose of 40 mg/kg resulted in severe central nervous system toxicity. Otherwise, nonhematopoietic toxicity was minimal and restricted to mild hepatic abnormalities. Four dogs were given busulfan at 20 mg/kg followed 30 hours later by infusion of autologous marrow, and all showed prompt and complete hematopoietic reconstitution. The area under the curve (AUC) determined by busulfan concentration in plasma over time was dose dependent, ranging from 12 to 100 microg x h/mL for busulfan doses of 3.75-20 mg/kg. There was a suggestion that the plasma half-life increased at the highest busulfan doses used. Intravenous administration of busulfan circumvented differences in bioavailability; nevertheless, considerable variations in the pharmacokinetic parameters were observed between individual animals. Thus, intravenous busulfan can be given safely and is effective in ablating hematopoiesis. However, factors other than absorption influence the AUC, and individualization of dosing may be required even with intravenous administration of the drug.

Published
1999
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43. Stability and pharmacokinetics of m-[131I]iodobenzylguanidine in patients.

Author

Ehninger G, Klingebiel T, Kumbier I, Schuler U, Feine U, Treuner J, and Waller HD

Subjects
3-Iodobenzylguanidine, Child, Child, Preschool, Humans, Iodine Radioisotopes, Iodobenzenes therapeutic use, Neuroblastoma diagnostic imaging, Radionuclide Imaging, Iodobenzenes pharmacokinetics, Neuroblastoma drug therapy
Abstract

A pharmacokinetic study was done to elucidate the body distribution, elimination, and metabolism of m-[131I]iodobenzylguanidine (m-[131I]IBG). For this purpose, an analytical method using solid phase extraction columns was developed. m-[131I]IBG was administered as an i.v. infusion according to different schedules with doses of 7,055 to 13,580 MBq/m2. At the start of the infusion m-[131I]IBG accounted for 93.0 +/- 2.3% (SD; n = 10) of the total radioactivity. At the end of the infusion m-[131I]IBG accounted for 88.0 +/- 7.4%. The non-m-IBG-bound radioactivity was predominantly 131I. The pharmacokinetic parameters (n = 7) are adequately described by a three compartment model. The parameters for m-[131I]IBG were determined with a mean terminal half-life of 37.0 h, a volume of distribution of 307 liters/m2, and an area under the curve value of 1091 kBq x h/ml. The total body clearance was 189 ml/min/m2. The values for 131I showed a terminal half-life of 71.6 h, a volume of distribution of 190 liters/m2, and an area under the curve value of 1537 kBq x h/ml. The total body clearance was 70 ml/min/m2. The selectivity of the m-[131I]IBG treatment might be improved by a reduction of 131I in the infusion fluid and further investigations are warranted.

Published
1987

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