TY  - JOUR
A1  - Rech, Juergen
A1  - Hueber, Axel J.
A1  - Finzel, Stephanie
A1  - Englbrecht, Matthias
A1  - Haschka, Judith
A1  - Manger, Bernhard
A1  - Kleyer, Arnd
A1  - Reiser, Michaela
A1  - Cobra, Jayme Fogagnolo
A1  - Figueiredo, Camille
A1  - Tony, Hans-Peter
A1  - Kleinert, Stefan
A1  - Wendler, Joerg
A1  - Schuch, Florian
A1  - Ronneberger, Monika
A1  - Feuchtenberger, Martin
A1  - Fleck, Martin
A1  - Manger, Karin
A1  - Ochs, Wolfgang
A1  - Schmitt-Haendle, Matthias
A1  - Lorenz, Hanns-Martin
A1  - Nuesslein, Hubert
A1  - Alten, Rieke
A1  - Henes, Joerg
A1  - Krueger, Klaus
A1  - Schett, Georg
T1  - Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment
JF  - Annals of the Rheumatic Diseases
N2  - Objective 
To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. 

Methods 
MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. 

Results 
Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). 

Conclusions 
MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. 

Trial registration number EudraCT 
2009-015740-42.
KW  - Drug-free remission
KW  - Clinical remission
KW  - Validation
KW  - Synovitis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187519
VL  - 75
IS  - 9
ER  - 
TY  - JOUR
A1  - Stephan, Marlene
A1  - Tascilar, Koray
A1  - Yalcin-Mutlu, Melek
A1  - Hagen, Melanie
A1  - Haschka, Judith
A1  - Reiser, Michaela
A1  - Hartmann, Fabian
A1  - Kleyer, Arnd
A1  - Hueber, Axel J.
A1  - Manger, Bernhard
A1  - Figueiredo, Camille
A1  - Cobra, Jayme Fogagnolo
A1  - Tony, Hans-Peter
A1  - Finzel, Stephanie
A1  - Kleinert, Stefan
A1  - Wendler, Jörg
A1  - Schuch, Florian
A1  - Ronneberger, Monika
A1  - Feuchtenberger, Martin
A1  - Fleck, Martin
A1  - Manger, Karin
A1  - Ochs, Wolfgang
A1  - Schmitt-Haendle, Matthias
A1  - Lorenz, Hannes Martin
A1  - Nüsslein, Hubert
A1  - Alten, Rieke
A1  - Henes, Joerg
A1  - Krüger, Klaus
A1  - Schett, Georg
A1  - Rech, Jürgen
T1  - Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial
JF  - Journal of Clinical Medicine
N2  - Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.
KW  - HAQ
KW  - Rheumatoid Arthritis
KW  - PROM’s
KW  - DMARD
KW  - DAS28
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319349
SN  - 2077-0383
VL  - 12
IS  - 11
ER  - 
TY  - JOUR
A1  - Bousquet, Jean
A1  - Anto, Josep M.
A1  - Bachert, Claus
A1  - Haahtela, Tari
A1  - Zuberbier, Torsten
A1  - Czarlewski, Wienczyslawa
A1  - Bedbrook, Anna
A1  - Bosnic‐Anticevich, Sinthia
A1  - Walter Canonica, G.
A1  - Cardona, Victoria
A1  - Costa, Elisio
A1  - Cruz, Alvaro A.
A1  - Erhola, Marina
A1  - Fokkens, Wytske J.
A1  - Fonseca, Joao A.
A1  - Illario, Maddalena
A1  - Ivancevich, Juan‐Carlos
A1  - Jutel, Marek
A1  - Klimek, Ludger
A1  - Kuna, Piotr
A1  - Kvedariene, Violeta
A1  - Le, LTT
A1  - Larenas‐Linnemann, Désirée E.
A1  - Laune, Daniel
A1  - Lourenço, Olga M.
A1  - Melén, Erik
A1  - Mullol, Joaquim
A1  - Niedoszytko, Marek
A1  - Odemyr, Mikaëla
A1  - Okamoto, Yoshitaka
A1  - Papadopoulos, Nikos G.
A1  - Patella, Vincenzo
A1  - Pfaar, Oliver
A1  - Pham‐Thi, Nhân
A1  - Rolland, Christine
A1  - Samolinski, Boleslaw
A1  - Sheikh, Aziz
A1  - Sofiev, Mikhail
A1  - Suppli Ulrik, Charlotte
A1  - Todo‐Bom, Ana
A1  - Tomazic, Peter‐Valentin
A1  - Toppila‐Salmi, Sanna
A1  - Tsiligianni, Ioanna
A1  - Valiulis, Arunas
A1  - Valovirta, Erkka
A1  - Ventura, Maria‐Teresa
A1  - Walker, Samantha
A1  - Williams, Sian
A1  - Yorgancioglu, Arzu
A1  - Agache, Ioana
A1  - Akdis, Cezmi A.
A1  - Almeida, Rute
A1  - Ansotegui, Ignacio J.
A1  - Annesi‐Maesano, Isabella
A1  - Arnavielhe, Sylvie
A1  - Basagaña, Xavier
A1  - D. Bateman, Eric
A1  - Bédard, Annabelle
A1  - Bedolla‐Barajas, Martin
A1  - Becker, Sven
A1  - Bennoor, Kazi S.
A1  - Benveniste, Samuel
A1  - Bergmann, Karl C.
A1  - Bewick, Michael
A1  - Bialek, Slawomir
A1  - E. Billo, Nils
A1  - Bindslev‐Jensen, Carsten
A1  - Bjermer, Leif
A1  - Blain, Hubert
A1  - Bonini, Matteo
A1  - Bonniaud, Philippe
A1  - Bosse, Isabelle
A1  - Bouchard, Jacques
A1  - Boulet, Louis‐Philippe
A1  - Bourret, Rodolphe
A1  - Boussery, Koen
A1  - Braido, Fluvio
A1  - Briedis, Vitalis
A1  - Briggs, Andrew
A1  - Brightling, Christopher E.
A1  - Brozek, Jan
A1  - Brusselle, Guy
A1  - Brussino, Luisa
A1  - Buhl, Roland
A1  - Buonaiuto, Roland
A1  - Calderon, Moises A.
A1  - Camargos, Paulo
A1  - Camuzat, Thierry
A1  - Caraballo, Luis
A1  - Carriazo, Ana‐Maria
A1  - Carr, Warner
A1  - Cartier, Christine
A1  - Casale, Thomas
A1  - Cecchi, Lorenzo
A1  - Cepeda Sarabia, Alfonso M.
A1  - H. Chavannes, Niels
A1  - Chkhartishvili, Ekaterine
A1  - Chu, Derek K.
A1  - Cingi, Cemal
A1  - Correia de Sousa, Jaime
A1  - Costa, David J.
A1  - Courbis, Anne‐Lise
A1  - Custovic, Adnan
A1  - Cvetkosvki, Biljana
A1  - D'Amato, Gennaro
A1  - da Silva, Jane
A1  - Dantas, Carina
A1  - Dokic, Dejan
A1  - Dauvilliers, Yves
A1  - De Feo, Giulia
A1  - De Vries, Govert
A1  - Devillier, Philippe
A1  - Di Capua, Stefania
A1  - Dray, Gerard
A1  - Dubakiene, Ruta
A1  - Durham, Stephen R.
A1  - Dykewicz, Mark
A1  - Ebisawa, Motohiro
A1  - Gaga, Mina
A1  - El‐Gamal, Yehia
A1  - Heffler, Enrico
A1  - Emuzyte, Regina
A1  - Farrell, John
A1  - Fauquert, Jean‐Luc
A1  - Fiocchi, Alessandro
A1  - Fink‐Wagner, Antje
A1  - Fontaine, Jean‐François
A1  - Fuentes Perez, José M.
A1  - Gemicioğlu, Bilun
A1  - Gamkrelidze, Amiran
A1  - Garcia‐Aymerich, Judith
A1  - Gevaert, Philippe
A1  - Gomez, René Maximiliano
A1  - González Diaz, Sandra
A1  - Gotua, Maia
A1  - Guldemond, Nick A.
A1  - Guzmán, Maria‐Antonieta
A1  - Hajjam, Jawad
A1  - Huerta Villalobos, Yunuen R.
A1  - Humbert, Marc
A1  - Iaccarino, Guido
A1  - Ierodiakonou, Despo
A1  - Iinuma, Tomohisa
A1  - Jassem, Ewa
A1  - Joos, Guy
A1  - Jung, Ki‐Suck
A1  - Kaidashev, Igor
A1  - Kalayci, Omer
A1  - Kardas, Przemyslaw
A1  - Keil, Thomas
A1  - Khaitov, Musa
A1  - Khaltaev, Nikolai
A1  - Kleine‐Tebbe, Jorg
A1  - Kouznetsov, Rostislav
A1  - Kowalski, Marek L.
A1  - Kritikos, Vicky
A1  - Kull, Inger
A1  - La Grutta, Stefania
A1  - Leonardini, Lisa
A1  - Ljungberg, Henrik
A1  - Lieberman, Philip
A1  - Lipworth, Brian
A1  - Lodrup Carlsen, Karin C.
A1  - Lopes‐Pereira, Catarina
A1  - Loureiro, Claudia C.
A1  - Louis, Renaud
A1  - Mair, Alpana
A1  - Mahboub, Bassam
A1  - Makris, Michaël
A1  - Malva, Joao
A1  - Manning, Patrick
A1  - Marshall, Gailen D.
A1  - Masjedi, Mohamed R.
A1  - Maspero, Jorge F.
A1  - Carreiro‐Martins, Pedro
A1  - Makela, Mika
A1  - Mathieu‐Dupas, Eve
A1  - Maurer, Marcus
A1  - De Manuel Keenoy, Esteban
A1  - Melo‐Gomes, Elisabete
A1  - Meltzer, Eli O.
A1  - Menditto, Enrica
A1  - Mercier, Jacques
A1  - Micheli, Yann
A1  - Miculinic, Neven
A1  - Mihaltan, Florin
A1  - Milenkovic, Branislava
A1  - Mitsias, Dimitirios I.
A1  - Moda, Giuliana
A1  - Mogica‐Martinez, Maria‐Dolores
A1  - Mohammad, Yousser
A1  - Montefort, Steve
A1  - Monti, Ricardo
A1  - Morais‐Almeida, Mario
A1  - Mösges, Ralph
A1  - Münter, Lars
A1  - Muraro, Antonella
A1  - Murray, Ruth
A1  - Naclerio, Robert
A1  - Napoli, Luigi
A1  - Namazova‐Baranova, Leyla
A1  - Neffen, Hugo
A1  - Nekam, Kristoff
A1  - Neou, Angelo
A1  - Nordlund, Björn
A1  - Novellino, Ettore
A1  - Nyembue, Dieudonné
A1  - O'Hehir, Robyn
A1  - Ohta, Ken
A1  - Okubo, Kimi
A1  - Onorato, Gabrielle L.
A1  - Orlando, Valentina
A1  - Ouedraogo, Solange
A1  - Palamarchuk, Julia
A1  - Pali‐Schöll, Isabella
A1  - Panzner, Peter
A1  - Park, Hae‐Sim
A1  - Passalacqua, Gianni
A1  - Pépin, Jean‐Louis
A1  - Paulino, Ema
A1  - Pawankar, Ruby
A1  - Phillips, Jim
A1  - Picard, Robert
A1  - Pinnock, Hilary
A1  - Plavec, Davor
A1  - Popov, Todor A.
A1  - Portejoie, Fabienne
A1  - Price, David
A1  - Prokopakis, Emmanuel P.
A1  - Psarros, Fotis
A1  - Pugin, Benoit
A1  - Puggioni, Francesca
A1  - Quinones‐Delgado, Pablo
A1  - Raciborski, Filip
A1  - Rajabian‐Söderlund, Rojin
A1  - Regateiro, Frederico S.
A1  - Reitsma, Sietze
A1  - Rivero‐Yeverino, Daniela
A1  - Roberts, Graham
A1  - Roche, Nicolas
A1  - Rodriguez‐Zagal, Erendira
A1  - Rolland, Christine
A1  - Roller‐Wirnsberger, Regina E.
A1  - Rosario, Nelson
A1  - Romano, Antonino
A1  - Rottem, Menachem
A1  - Ryan, Dermot
A1  - Salimäki, Johanna
A1  - Sanchez‐Borges, Mario M.
A1  - Sastre, Joaquin
A1  - Scadding, Glenis K.
A1  - Scheire, Sophie
A1  - Schmid‐Grendelmeier, Peter
A1  - Schünemann, Holger J.
A1  - Sarquis Serpa, Faradiba
A1  - Shamji, Mohamed
A1  - Sisul, Juan‐Carlos
A1  - Sofiev, Mikhail
A1  - Solé, Dirceu
A1  - Somekh, David
A1  - Sooronbaev, Talant
A1  - Sova, Milan
A1  - Spertini, François
A1  - Spranger, Otto
A1  - Stellato, Cristiana
A1  - Stelmach, Rafael
A1  - Thibaudon, Michel
A1  - To, Teresa
A1  - Toumi, Mondher
A1  - Usmani, Omar
A1  - Valero, Antonio A.
A1  - Valenta, Rudolph
A1  - Valentin‐Rostan, Marylin
A1  - Pereira, Marilyn Urrutia
A1  - van der Kleij, Rianne
A1  - Van Eerd, Michiel
A1  - Vandenplas, Olivier
A1  - Vasankari, Tuula
A1  - Vaz Carneiro, Antonio
A1  - Vezzani, Giorgio
A1  - Viart, Frédéric
A1  - Viegi, Giovanni
A1  - Wallace, Dana
A1  - Wagenmann, Martin
A1  - Wang, De Yun
A1  - Waserman, Susan
A1  - Wickman, Magnus
A1  - Williams, Dennis M.
A1  - Wong, Gary
A1  - Wroczynski, Piotr
A1  - Yiallouros, Panayiotis K.
A1  - Yusuf, Osman M.
A1  - Zar, Heather J.
A1  - Zeng, Stéphane
A1  - Zernotti, Mario E.
A1  - Zhang, Luo
A1  - Shan Zhong, Nan
A1  - Zidarn, Mihaela
T1  - ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice
JF  - Allergy
N2  - Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
KW  - ARIA
KW  - asthma
KW  - CARAT
KW  - digital transformation of health and care
KW  - MASK
KW  - rhinitis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228339
VL  - 76
IS  - 1
SP  - 168
EP  - 190
ER  - 
TY  - JOUR
A1  - Schwaab, Bernhard
A1  - Bjarnason-Wehrens, Birna
A1  - Meng, Karin
A1  - Albus, Christian
A1  - Salzwedel, Annett
A1  - Schmid, Jean-Paul
A1  - Benzer, Werner
A1  - Metz, Matthes
A1  - Jensen, Katrin
A1  - Rauch, Bernhard
A1  - Bönner, Gerd
A1  - Brzoska, Patrick
A1  - Buhr-Schinner, Heike
A1  - Charrier, Albrecht
A1  - Cordes, Carsten
A1  - Dörr, Gesine
A1  - Eichler, Sarah
A1  - Exner, Anne-Kathrin
A1  - Fromm, Bernd
A1  - Gielen, Stephan
A1  - Glatz, Johannes
A1  - Gohlke, Helmut
A1  - Grilli, Maurizio
A1  - Gysan, Detlef
A1  - Härtel, Ursula
A1  - Hahmann, Harry
A1  - Herrmann-Lingen, Christoph
A1  - Karger, Gabriele
A1  - Karoff, Marthin
A1  - Kiwus, Ulrich
A1  - Knoglinger, Ernst
A1  - Krusch, Christian-Wolfgang
A1  - Langheim, Eike
A1  - Mann, Johannes
A1  - Max, Regina
A1  - Metzendorf, Maria-Inti
A1  - Nebel, Roland
A1  - Niebauer, Josef
A1  - Predel, Hans-Georg
A1  - Preßler, Axel
A1  - Razum, Oliver
A1  - Reiss, Nils
A1  - Saure, Daniel
A1  - von Schacky, Clemens
A1  - Schütt, Morten
A1  - Schultz, Konrad
A1  - Skoda, Eva-Maria
A1  - Steube, Diethard
A1  - Streibelt, Marco
A1  - Stüttgen, Martin
A1  - Stüttgen, Michaela
A1  - Teufel, Martin
A1  - Tschanz, Hansueli
A1  - Völler, Heinz
A1  - Vogel, Heiner
A1  - Westphal, Ronja
T1  - Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — part 2
JF  - Journal of Clinical Medicine
N2  - Background: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. Methods: Generation of evidence and search of literature have been described in part 1. Results: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for “distress management” and “lifestyle changes”. PE is able to increase patients’ knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients’ groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. Conclusions: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.
KW  - cardiac rehabilitation
KW  - scientific guidelines
KW  - secondary prevention
KW  - physical activity
KW  - exercise training
KW  - psychological interventions
KW  - education
KW  - gender
KW  - frailty
KW  - migration
KW  - old patients
KW  - young patients
KW  - tele-medicine
KW  - home-based-rehabilitation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242645
SN  - 2077-0383
VL  - 10
IS  - 14
ER  - 
TY  - JOUR
A1  - Dietzsch, Stefan
A1  - Braesigk, Annett
A1  - Seidel, Clemens
A1  - Remmele, Julia
A1  - Kitzing, Ralf
A1  - Schlender, Tina
A1  - Mynarek, Martin
A1  - Geismar, Dirk
A1  - Jablonska, Karolina
A1  - Schwarz, Rudolf
A1  - Pazos, Montserrat
A1  - Weber, Damien C.
A1  - Frick, Silke
A1  - Gurtner, Kristin
A1  - Matuschek, Christiane
A1  - Harrabi, Semi Ben
A1  - Glück, Albrecht
A1  - Lewitzki, Victor
A1  - Dieckmann, Karin
A1  - Benesch, Martin
A1  - Gerber, Nicolas U.
A1  - Obrecht, Denise
A1  - Rutkowski, Stefan
A1  - Timmermann, Beate
A1  - Kortmann, Rolf-Dieter
T1  - Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma—an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial
JF  - Strahlentherapie und Onkologie
N2  - Purpose
In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost.

Patients and methods
A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly.

Results
Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity.

Conclusion
In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed.
KW  - brain tumor
KW  - pediatric
KW  - focal radiotherapy
KW  - quality assurance
KW  - individual case review
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307812
SN  - 0179-7158
SN  - 1439-099X
VL  - 198
IS  - 3
ER  - 
TY  - JOUR
A1  - Schilbach, Karin
A1  - Alkhaled, Mohammed
A1  - Welker, Christian
A1  - Eckert, Franziska
A1  - Blank, Gregor
A1  - Ziegler, Hendrik
A1  - Sterk, Marco
A1  - Müller, Friederike
A1  - Sonntag, Katja
A1  - Wieder, Thomas
A1  - Braumüller, Heidi
A1  - Schmitt, Julia
A1  - Eyrich, Matthias
A1  - Schleicher, Sabine
A1  - Seitz, Christian
A1  - Erbacher, Annika
A1  - Pichler, Bernd J.
A1  - Müller, Hartmut
A1  - Tighe, Robert
A1  - Lim, Annick
A1  - Gillies, Stephen D.
A1  - Strittmatter, Wolfgang
A1  - Röcken, Martin
A1  - Handgretinger, Rupert
T1  - Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation
JF  - OncoImmunology
N2  - Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.
KW  - TH17 cells
KW  - cancer-targeted IL-12
KW  - differentiation
KW  - humanized mice
KW  - immunocytokine
KW  - immunotherapy
KW  - M1/M2 macrophages
KW  - rhabdomyosarcoma
KW  - TH1-induced senescence
KW  - tumor-infiltrating lymphocytes
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154579
VL  - 4
IS  - 7
ER  - 
TY  - JOUR
A1  - Mitchell, Jonathan S.
A1  - Li, Ni
A1  - Weinhold, Niels
A1  - Försti, Asta
A1  - Ali, Mina
A1  - van Duin, Mark
A1  - Thorleifsson, Gudmar
A1  - Johnson, David C.
A1  - Chen, Bowang
A1  - Halvarsson, Britt-Marie
A1  - Gudbjartsson, Daniel F.
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Campo, Chiara
A1  - Einsele, Hermann
A1  - Gregory, Walter A.
A1  - Gullberg, Urban
A1  - Henrion, Marc
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Johnsson, Ellinor
A1  - Jöud, Magnus
A1  - Kristinsson, Sigurdur Y.
A1  - Lenhoff, Stig
A1  - Lenive, Oleg
A1  - Mellqvist, Ulf-Henrik
A1  - Migliorini, Gabriele
A1  - Nahi, Hareth
A1  - Nelander, Sven
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - Rafnar, Thorunn
A1  - Ross, Fiona M.
A1  - da Silva Filho, Miguel Inacio
A1  - Swaminathan, Bhairavi
A1  - Thomsen, Hauke
A1  - Turesson, Ingemar
A1  - Vangsted, Annette
A1  - Vogel, Ulla
A1  - Waage, Anders
A1  - Walker, Brian A.
A1  - Wihlborg, Anna-Karin
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Thorsteinsdottir, Unnur
A1  - Langer, Christian
A1  - Hansson, Markus
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Stefansson, Kari
A1  - Morgan, Gareth J.
A1  - Goldschmidt, Hartmut
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Houlston, Richard S.
T1  - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
JF  - Nature Communications
N2  - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
KW  - Cancer genetics
KW  - Genome-wide association studies
KW  - Myeloma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983
VL  - 7
ER  - 
TY  - JOUR
A1  - Drube, Sebastian
A1  - Weber, Franziska
A1  - Loschinski, Romy
A1  - Beyer, Mandy
A1  - Rothe, Mandy
A1  - Rabenhorst, Anja
A1  - Göpfert, Christiane
A1  - Meininger, Isabel
A1  - Diamanti, Michaela A.
A1  - Stegner, David
A1  - Häfner, Norman
A1  - Böttcher, Martin
A1  - Reinecke, Kirstin
A1  - Herdegen, Thomas
A1  - Greten, Florian R.
A1  - Nieswandt, Bernhard
A1  - Hartmann, Karin
A1  - Krämer, Oliver H.
A1  - Kamradt, Thomas
T1  - Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells
JF  - Oncotarget
N2  - Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2\(^{+}\)-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term "subthreshold IKK activation". This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33. We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo. Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure.
KW  - mast cells
KW  - subthreshold IKK activation
KW  - mitogenic signaling
KW  - NFκB-activation
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143681
VL  - 6
IS  - 7
ER  - 
TY  - JOUR
A1  - Litovkin, Kirill
A1  - Van Eynde, Aleyde
A1  - Joniau, Steven
A1  - Lerut, Evelyne
A1  - Laenen, Annouschka
A1  - Gevaert, Thomas
A1  - Gevaert, Olivier
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
A1  - Gramme, Pierre
A1  - Helleputte, Thibault
A1  - Isebaert, Sofie
A1  - Haustermans, Karin
A1  - Bollen, Mathieu
T1  - DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer
JF  - PLoS ONE
N2  - Background 
Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. 

Methods 
A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. 

Results 
Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort ( HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. 

Conclusions 
Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients.
KW  - CpG island hypermethylation
KW  - radical prostatectomy
KW  - promoter methylation
KW  - receptor beta
KW  - gene
KW  - GSTP1
KW  - biomarkers
KW  - diagnosis
KW  - recurrence
KW  - reveals
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151705
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Kleinschnitz, Christoph
A1  - Grund, Henrike
A1  - Wingler, Kirstin
A1  - Armitage, Melanie E.
A1  - Jones, Emma
A1  - Mittal, Manish
A1  - Barit, David
A1  - Schwarz, Tobias
A1  - Geis, Christian
A1  - Kraft, Peter
A1  - Barthel, Konstanze
A1  - Schuhmann, Michael K.
A1  - Herrmann, Alexander M.
A1  - Meuth, Sven G.
A1  - Stoll, Guido
A1  - Meurer, Sabine
A1  - Schrewe, Anja
A1  - Becker, Lore
A1  - Gailus-Durner, Valerie
A1  - Fuchs, Helmut
A1  - Klopstock, Thomas
A1  - de Angelis, Martin Hrabe
A1  - Jandeleit-Dahm, Karin
A1  - Shah, Ajay M.
A1  - Weissmann, Norbert
A1  - Schmidt, Harald H. H. W.
T1  - Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration
N2  - Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.
KW  - Schlaganfall
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68416
ER  -