TY - JOUR A1 - Stangl, Stephanie A1 - Popp, Maria A1 - Reis, Stefanie A1 - Sitter, Magdalena A1 - Saal-Bauernschubert, Lena A1 - Schießer, Selina A1 - Kranke, Peter A1 - Choorapoikayil, Suma A1 - Weibel, Stephanie A1 - Meybohm, Patrick T1 - Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes JF - Systematic Reviews N2 - Background Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. Methods We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. Results Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the ‘blood and lymphatic system’ domain, followed by “adverse event” (77%) and “need for further resources” (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting. Conclusion This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. Systematic review registration PROSPERO CRD42020214247 KW - iron deficiency KW - iron deficiency anemia KW - core outcome set KW - outcome reporting KW - data harmonization KW - preoperative setting KW - perioperative setting KW - surgery Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357213 VL - 13 ER - TY - JOUR A1 - López, Cristina A1 - Kleinheinz, Kortine A1 - Aukema, Sietse M. A1 - Rohde, Marius A1 - Bernhart, Stephan H. A1 - Hübschmann, Daniel A1 - Wagener, Rabea A1 - Toprak, Umut H. A1 - Raimondi, Francesco A1 - Kreuz, Markus A1 - Waszak, Sebastian M. A1 - Huang, Zhiqin A1 - Sieverling, Lina A1 - Paramasivam, Nagarajan A1 - Seufert, Julian A1 - Sungalee, Stephanie A1 - Russell, Robert B. A1 - Bausinger, Julia A1 - Kretzmer, Helene A1 - Ammerpohl, Ole A1 - Bergmann, Anke K. A1 - Binder, Hans A1 - Borkhardt, Arndt A1 - Brors, Benedikt A1 - Claviez, Alexander A1 - Doose, Gero A1 - Feuerbach, Lars A1 - Haake, Andrea A1 - Hansmann, Martin-Leo A1 - Hoell, Jessica A1 - Hummel, Michael A1 - Korbel, Jan O. A1 - Lawerenz, Chris A1 - Lenze, Dido A1 - Radlwimmer, Bernhard A1 - Richter, Julia A1 - Rosenstiel, Philip A1 - Rosenwald, Andreas A1 - Schilhabel, Markus B. A1 - Stein, Harald A1 - Stilgenbauer, Stephan A1 - Stadler, Peter F. A1 - Szczepanowski, Monika A1 - Weniger, Marc A. A1 - Zapatka, Marc A1 - Eils, Roland A1 - Lichter, Peter A1 - Loeffler, Markus A1 - Möller, Peter A1 - Trümper, Lorenz A1 - Klapper, Wolfram A1 - Hoffmann, Steve A1 - Küppers, Ralf A1 - Burkhardt, Birgit A1 - Schlesner, Matthias A1 - Siebert, Reiner T1 - Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma JF - Nature Communications N2 - Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing. KW - cancer genomics KW - lymphocytes KW - lymphoid tissues KW - oncology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237281 VL - 10 ER - TY - JOUR A1 - Weibel, Stephanie A1 - Pace, Nathan L. A1 - Schaefer, Maximilian S. A1 - Raj, Diana A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Kienbaum, Peter A1 - Eberhart, Leopold H. J. A1 - Kranke, Peter T1 - Drugs for preventing postoperative nausea and vomiting in adults after general anesthesia: An abridged Cochrane network meta-analysis JF - Journal of Evidence-Based Medicine N2 - Objective In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form. Methods We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia. Results 585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies’ overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing. Conclusions There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation. KW - systematic review, KW - antiemetics KW - network meta-analysis KW - postoperative nausea and vomiting KW - vomiting Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259470 VL - 14 IS - 3 ER - TY - JOUR A1 - Schuler, Michael A1 - Murauer, Kathrin A1 - Stangl, Stephanie A1 - Grau, Anna A1 - Gabriel, Katharina A1 - Podger, Lauren A1 - Heuschmann, Peter U. A1 - Faller, Hermann T1 - Pre-post changes in main outcomes of medical rehabilitation in Germany: protocol of a systematic review and meta-analysis of individual participant and aggregated data JF - BMJ Open N2 - Introduction Multidisciplinary, complex rehabilitation interventions are an important part of the treatment of chronic diseases. However, little is known about the effectiveness of routine rehabilitation interventions within the German healthcare system. Due to the nature of the social insurance system in Germany, randomised controlled trials examining the effects of rehabilitation interventions are challenging to implement and scarcely accessible. Consequently, alternative pre-post designs can be employed to assess pre-post effects of medical rehabilitation programmes. We present a protocol of systematic review and meta-analysis methods to assess the pre-post effects of rehabilitation interventions in Germany. Methods and analysis The respective study will be conducted within the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic literature review will be conducted to identify studies reporting the pre-post effects (start of intervention vs end of intervention or later) in German healthcare. Studies investigating the following disease groups will be included: orthopaedics, rheumatology, oncology, pulmonology, cardiology, endocrinology, gastroenterology and psychosomatics. The primary outcomes of interest are physical/mental quality of life, physical functioning and social participation for all disease groups as well as pain (orthopaedic and rheumatologic patients only), blood pressure (cardiac patients only), asthma control (patients with asthma only), dyspnoea (patients with chronic obstructive pulmonary disease only) and depression/anxiety (psychosomatic patients only). We will invite the principal investigators of the identified studies to provide additional individual patient data. We aim to perform the meta-analyses using individual patient data as well as aggregate data. We will examine the effects of both study-level and patient-level moderators by using a meta-regression method. Ethics and dissemination Only studies that have received institutional approval from an ethics committee and present anonymised individual patient data will be included in the meta-analysis. The results will be presented in a peer-reviewed publication and at research conferences. A declaration of no objection by the ethics committee of the University of Würzburg is available (number 20180411 01). KW - medical rehabilitation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201929 VL - 9 IS - 5 ER - TY - JOUR A1 - Couch, Fergus J. A1 - Wang, Xianshu A1 - McGuffog, Lesley A1 - Lee, Andrew A1 - Olswold, Curtis A1 - Kuchenbaecker, Karoline B. A1 - Soucy, Penny A1 - Fredericksen, Zachary A1 - Barrowdale, Daniel A1 - Dennis, Joe A1 - Gaudet, Mia M. A1 - Dicks, Ed A1 - Kosel, Matthew A1 - Healey, Sue A1 - Sinilnikova, Olga M. A1 - Lee, Adam A1 - Bacot, Françios A1 - Vincent, Daniel A1 - Hogervorst, Frans B. L. A1 - Peock, Susan A1 - Stoppa-Lyonnet, Dominique A1 - Jakubowska, Anna A1 - Radice, Paolo A1 - Schmutzler, Rita Katharina A1 - Domchek, Susan M. A1 - Piedmonte, Marion A1 - Singer, Christian F. A1 - Friedman, Eitan A1 - Thomassen, Mads A1 - Hansen, Thomas V. O. A1 - Neuhausen, Susan L. A1 - Szabo, Csilla I. A1 - Blanco, Ingnacio A1 - Greene, Mark H. A1 - Karlan, Beth Y. A1 - Garber, Judy A1 - Phelan, Catherine M. A1 - Weitzel, Jeffrey N. A1 - Montagna, Marco A1 - Olah, Edith A1 - Andrulis, Irene L. A1 - Godwin, Andrew K. A1 - Yannoukakos, Drakoulis A1 - Goldgar, David E. A1 - Caldes, Trinidad A1 - Nevanlinna, Heli A1 - Osorio, Ana A1 - Terry, Mary Beth A1 - Daly, Mary B. A1 - van Rensburg, Elisabeth J. A1 - Hamann, Ute A1 - Ramus, Susan J. A1 - Toland, Amanda Ewart A1 - Caligo, Maria A. A1 - Olopade, Olufunmilayo I. A1 - Tung, Nadine A1 - Claes, Kathleen A1 - Beattie, Mary S. A1 - Southey, Melissa C. A1 - Imyanitov, Evgeny N. A1 - Tischkowitz, Marc A1 - Janavicius, Ramunas A1 - John, Esther M. A1 - Kwong, Ava A1 - Diez, Orland A1 - Kwong, Ava A1 - Balmaña, Judith A1 - Barkardottir, Rosa B. A1 - Arun, Banu K. A1 - Rennert, Gad A1 - Teo, Soo-Hwang A1 - Ganz, Patricia A. A1 - Campbell, Ian A1 - van der Hout, Annemarie H. A1 - van Deurzen, Carolien H. M. A1 - Seynaeve, Caroline A1 - Garcia, Encarna B. Gómez A1 - van Leeuwen, Flora E. A1 - Meijers-Heijboer, Hanne E. J. A1 - Gille, Johannes J. P. A1 - Ausems, Magreet G. E. M. A1 - Blok, Marinus J. A1 - Ligtenberg, Marjolinjin J. L. A1 - Rookus, Matti A. A1 - Devilee, Peter A1 - Verhoef, Senno A1 - van Os, Theo A. M. A1 - Wijnen, Juul T. A1 - Frost, Debra A1 - Ellis, Steve A1 - Fineberg, Elena A1 - Platte, Radke A1 - Evans, D. Gareth A1 - Izatt, Luise A1 - Eeles, Rosalind A. A1 - Adlard, Julian A1 - Eccles, Diana M. A1 - Cook, Jackie A1 - Brewer, Carole A1 - Douglas, Fiona A1 - Hodgson, Shirley A1 - Morrison, Patrick J. A1 - Side, Lucy E. A1 - Donaldson, Alan A1 - Houghton, Catherine A1 - Rogers, Mark T. A1 - Dorkins, Huw A1 - Eason, Jacqueline A1 - Gregory, Helen A1 - McCann, Emma A1 - Murray, Alex A1 - Calender, Alain A1 - Hardouin, Agnès A1 - Berthet, Pascaline A1 - Delnatte, Capucine A1 - Nogues, Catherine A1 - Lasset, Christine A1 - Houdayer, Claude A1 - Leroux,, Dominique A1 - Rouleau, Etienne A1 - Prieur, Fabienne A1 - Damiola, Francesca A1 - Sobol, Hagay A1 - Coupier, Isabelle A1 - Venat-Bouvet, Laurence A1 - Castera, Laurent A1 - Gauthier-Villars, Marion A1 - Léoné, Mélanie A1 - Pujol, Pascal A1 - Mazoyer, Sylvie A1 - Bignon, Yves-Jean A1 - Zlowocka-Perlowska, Elzbieta A1 - Gronwald, Jacek A1 - Lubinski,, Jan A1 - Durda, Katarzyna A1 - Jaworska, Katarzyna A1 - Huzarski, Tomasz A1 - Spurdle, Amanda B. A1 - Viel, Alessandra A1 - Peissel, Bernhard A1 - Bonanni, Bernardo A1 - Melloni, Guilia A1 - Ottini, Laura A1 - Papi, Laura A1 - Varesco, Liliana A1 - Tibiletti, Maria Grazia A1 - Peterlongo, Paolo A1 - Volorio, Sara A1 - Manoukian, Siranoush A1 - Pensotti, Valeria A1 - Arnold, Norbert A1 - Engel, Christoph A1 - Deissler, Helmut A1 - Gadzicki, Dorothea A1 - Gehrig, Andrea A1 - Kast, Karin A1 - Rhiem, Kerstin A1 - Meindl, Alfons A1 - Niederacher, Dieter A1 - Ditsch, Nina A1 - Plendl, Hansjoerg A1 - Preisler-Adams, Sabine A1 - Engert, Stefanie A1 - Sutter, Christian A1 - Varon-Mateeva, Raymenda A1 - Wappenschmidt, Barbara A1 - Weber, Bernhard H. F. A1 - Arver, Brita A1 - Stenmark-Askmalm, Marie A1 - Loman, Niklas A1 - Rosenquist, Richard A1 - Einbeigi, Zakaria A1 - Nathanson, Katherine L. A1 - Rebbeck, Timothy R. A1 - Blank, Stephanie V. A1 - Cohn, David E. A1 - Rodriguez, Gustavo C. A1 - Small, Laurie A1 - Friedlander, Michael A1 - Bae-Jump, Victoria L. A1 - Fink-Retter, Anneliese A1 - Rappaport, Christine A1 - Gschwantler-Kaulich, Daphne A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Lindor, Noralane M. A1 - Kaufman, Bella A1 - Paluch, Shani Shimon A1 - Laitman, Yael A1 - Skytte, Anne-Bine A1 - Gerdes, Anne-Marie A1 - Pedersen, Inge Sokilde A1 - Moeller, Sanne Traasdahl A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Vijai, Joseph A1 - Sarrel, Kara A1 - Robson, Mark A1 - Kauff, Noah A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Ozcelik, Hilmi A1 - Ejlertsen, Bent A1 - Nielsen, Finn C. A1 - Jønson, Lars A1 - Andersen, Mette K. A1 - Ding, Yuan Chun A1 - Steele, Linda A1 - Foretova, Lenka A1 - Teulé, Alex A1 - Lazaro, Conxi A1 - Brunet, Joan A1 - Pujana, Miquel Angel A1 - Mai, Phuong L. A1 - Loud, Jennifer T. A1 - Walsh, Christine A1 - Lester, Jenny A1 - Orsulic, Sandra A1 - Narod, Steven A. A1 - Herzog, Josef A1 - Sand, Sharon R. A1 - Tognazzo, Silvia A1 - Agata, Simona A1 - Vaszko, Tibor A1 - Weaver, Joellen A1 - Stravropoulou, Alexandra V. A1 - Buys, Saundra S. A1 - Romero, Atocha A1 - de la Hoya, Miguel A1 - Aittomäki, Kristiina A1 - Muranen, Taru A. A1 - Duran, Mercedes A1 - Chung, Wendy K. A1 - Lasa, Adriana A1 - Dorfling, Cecilia M. A1 - Miron, Alexander A1 - Benitez, Javier A1 - Senter, Leigha A1 - Huo, Dezheng A1 - Chan, Salina B. A1 - Sokolenko, Anna P. A1 - Chiquette, Jocelyne A1 - Tihomirova, Laima A1 - Friebel, Tara M. A1 - Agnarsson, Bjarne A. A1 - Lu, Karen H. A1 - Lejbkowicz, Flavio A1 - James, Paul A. A1 - Hall, Per A1 - Dunning, Alison M. A1 - Tessier, Daniel A1 - Cunningham, Julie A1 - Slager, Susan L. A1 - Chen, Wang A1 - Hart, Steven A1 - Stevens, Kristen A1 - Simard, Jacques A1 - Pastinen, Tomi A1 - Pankratz, Vernon S. A1 - Offit, Kenneth A1 - Easton, Douglas F. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. T1 - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk JF - PLOS Genetics N2 - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. KW - common variants KW - susceptibility alleles KW - genetic variants KW - modifiers KW - ZNF365 KW - investigators KW - population KW - consortium KW - selection KW - subtypes Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947 SN - 1553-7404 VL - 9 IS - 3 ER - TY - JOUR A1 - Schmitt, Jana A1 - Backes, Christina A1 - Nourkami-Tutdibi, Nasenien A1 - Leidinger, Petra A1 - Deutscher, Stephanie A1 - Beier, Markus A1 - Gessler, Manfred A1 - Graf, Norbert A1 - Lenhof, Hans-Peter A1 - Keller, Andreas A1 - Meese, Eckart T1 - Treatment-independent miRNA signature in blood of wilms tumor patients JF - BMC Genomics N2 - Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment. KW - miRNA Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124034 VL - 13 IS - 379 ER - TY - JOUR A1 - Gerszten, Peter C. A1 - Sahgal, Arjun A1 - Sheehan, Jason P. A1 - Kersh, Ronald A1 - Chen, Stephanie A1 - Flickinger, John C. A1 - Quader, Mubina A1 - Fahim, Daniel A1 - Grills, Inga A1 - Shin, John H. A1 - Winey, Brian A1 - Oh, Kevin A1 - Sweeney, Reinhart A. A1 - Guckenberger, Matthias T1 - A multi-national report on methods for institutional credentialing for spine radiosurgery JF - Radiation Oncology N2 - Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program. KW - cyberknife radiosurgery KW - advanced technology KW - conformal radiotherapy KW - clinical trials KW - quality assurance KW - credentialing KW - spine tumors KW - stereotactic body radiotherapy KW - spine Radiosurgery KW - paraspinal tumors KW - intensity modulated radiotherapy KW - ACR practice guidelines KW - radiation therapy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131485 VL - 8 IS - 158 ER - TY - JOUR A1 - Weibel, Stephanie A1 - Basse-Luesebrink, Thomas Christian A1 - Hess, Michael A1 - Hofmann, Elisabeth A1 - Seubert, Carolin A1 - Langbein-Laugwitz, Johanna A1 - Gentschev, Ivaylo A1 - Sturm, Volker Jörg Friedrich A1 - Ye, Yuxiang A1 - Kampf, Thomas A1 - Jakob, Peter Michael A1 - Szalay, Aladar A. T1 - Imaging of Intratumoral Inflammation during Oncolytic Virotherapy of Tumors by \(^{19}\)F-Magnetic Resonance Imaging (MRI) JF - PLoS ONE N2 - Background Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate \(^{19}\)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy. Methodology/Principal Findings The Vaccinia virus strain GLV-1h68 was used as an oncolytic agent for the treatment of different tumor models. Systemic application of PFC emulsions followed by \(^1H\)/\(^{19}\)F MRI of mock-infected and GLV-1h68-infected tumor-bearing mice revealed a significant accumulation of the \(^{19}\)F signal in the tumor rim of virus-treated mice. Histological examination of tumors confirmed a similar spatial distribution of the \(^{19}\)F signal hot spots and \(CD68^+\)-macrophages. Thereby, the \(CD68^+\)-macrophages encapsulate the GFP-positive viral infection foci. In multiple tumor models, we specifically visualized early inflammatory cell recruitment in Vaccinia virus colonized tumors. Furthermore, we documented that the \(^{19}\)F signal correlated with the extent of viral spreading within tumors. Conclusions/Significance These results suggest \(^{19}\)F MRI as a non-invasive methodology to document the tumor-associated host immune response as well as the extent of intratumoral viral replication. Thus, \(^{19}\)F MRI represents a new platform to non-invasively investigate the role of the host immune response for therapeutic outcome of oncolytic virotherapy and individual patient response. KW - inflammation KW - fluorescence microscopy KW - oncolytic viruses KW - fluorescence imaging KW - macrophages KW - magnetic resonance imaging KW - histology KW - in vivo imaging Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130311 VL - 8 IS - 3 ER - TY - JOUR A1 - Szalay, Aladar A A1 - Weibel, Stephanie A1 - Hofmann, Elisabeth A1 - Basse-Luesebrink, Thomas Christian A1 - Donat, Ulrike A1 - Seubert, Carolin A1 - Adelfinger, Marion A1 - Gnamlin, Prisca A1 - Kober, Christina A1 - Frentzen, Alexa A1 - Gentschev, Ivaylo A1 - Jakob, Peter Michael T1 - Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer JF - Journal of Translational Medicine N2 - Background Malignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options. Methods In this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma. Results We demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment. Conclusions Here, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer. KW - Oncolytic virotherapy KW - Malignant effusion KW - Lung cancer KW - VEGF KW - Lungenkrebs KW - Vascular endothelial Growth Factor Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96016 UR - http://www.translational-medicine.com/content/11/1/106 ER - TY - JOUR A1 - Schleicher, Ulrike A1 - Paduch, Katrin A1 - Debus, Andrea A1 - Obermeyer, Stephanie A1 - König, Till A1 - Kling, Jessica C. A1 - Ribechini, Eliana A1 - Dudziak, Diana A1 - Mougiakakos, Dimitrios A1 - Murray, Peter J. A1 - Ostuni, Renato A1 - Körner, Heinrich A1 - Bogdan, Christian T1 - TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection JF - Cell Reports N2 - Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1) expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control. KW - TNF Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164897 VL - 15 IS - 5 ER - TY - JOUR A1 - Hornick, Thomas A1 - Richter, Anett A1 - Harpole, William Stanley A1 - Bastl, Maximilian A1 - Bohlmann, Stephanie A1 - Bonn, Aletta A1 - Bumberger, Jan A1 - Dietrich, Peter A1 - Gemeinholzer, Birgit A1 - Grote, Rüdiger A1 - Heinold, Bernd A1 - Keller, Alexander A1 - Luttkus, Marie L. A1 - Mäder, Patrick A1 - Motivans Švara, Elena A1 - Passonneau, Sarah A1 - Punyasena, Surangi W. A1 - Rakosy, Demetra A1 - Richter, Ronny A1 - Sickel, Wiebke A1 - Steffan‐Dewenter, Ingolf A1 - Theodorou, Panagiotis A1 - Treudler, Regina A1 - Werchan, Barbora A1 - Werchan, Matthias A1 - Wolke, Ralf A1 - Dunker, Susanne T1 - An integrative environmental pollen diversity assessment and its importance for the Sustainable Development Goals JF - Plants, People, Planet N2 - Societal Impact Statement Pollen relates to many aspects of human and environmental health, which protection and improvement are endorsed by the United Nations Sustainable Development Goals. By highlighting these connections in the frame of current challenges in monitoring and research, we discuss the need of more integrative and multidisciplinary pollen research related to societal needs, improving health of humans and our ecosystems for a sustainable future. Summary Pollen is at once intimately part of the reproductive cycle of seed plants and simultaneously highly relevant for the environment (pollinators, vector for nutrients, or organisms), people (food safety and health), and climate (cloud condensation nuclei and climate reconstruction). We provide an interdisciplinary perspective on the many and connected roles of pollen to foster a better integration of the currently disparate fields of pollen research, which would benefit from the sharing of general knowledge, technical advancements, or data processing solutions. We propose a more interdisciplinary and holistic research approach that encompasses total environmental pollen diversity (ePD) (wind and animal and occasionally water distributed pollen) at multiple levels of diversity (genotypic, phenotypic, physiological, chemical, and functional) across space and time. This interdisciplinary approach holds the potential to contribute to pressing human issues, including addressing United Nations Sustainable Development Goals, fostering social and political awareness of these tiny yet important and fascinating particles. KW - aerobiology KW - allergy KW - diversity KW - environmental monitoring KW - food safety KW - paleoecology KW - palynology KW - pollination Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276487 VL - 4 IS - 2 SP - 110 EP - 121 ER - TY - JOUR A1 - Stangl, Stephanie A1 - Haas, Kirsten A1 - Eichner, Felizitas A. A1 - Grau, Anna A1 - Selig, Udo A1 - Ludwig, Timo A1 - Fehm, Tanja A1 - Stübner, Tanja A1 - Rashid, Asarnusch A1 - Kerscher, Alexander A1 - Bargou, Ralf A1 - Hermann, Silke A1 - Arndt, Volker A1 - Meyer, Martin A1 - Wildner, Manfred A1 - Faller, Hermann A1 - Schrauder, Michael G. A1 - Weigel, Michael A1 - Schlembach, Ulrich A1 - Heuschmann, Peter U. A1 - Wöckel, Achim T1 - Development and proof-of-concept of a multicenter, patient-centered cancer registry for breast cancer patients with metastatic disease — the “Breast cancer care for patients with metastatic disease” (BRE-4-MED) registry JF - Pilot and Feasibility Studies N2 - Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus oncontrolling for disease symptoms and maintaining high quality of life. Information on individual needs of patients andtheir relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or arenot routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adaptedfor these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered “Breast cancer care for patients with metastatic disease”(BRE-4-MED)registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germanycomprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information includingroutine data from established Cancer Registries in different federal states, treating physicians in hospital as well as inoutpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancerregistry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-basedquestionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitorneeds, progression, and therapy change of individual patients. Patient’s acceptance and feasibility of data collection inclinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018.In total n= 31 patients were included in the pilot study, n= 22 patients were followed up after 1 month. Recordlinkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n= 7 participants. The feasibility of the registry concept in clinical routine waspositively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needsof family members, and raising clinical parameters from primary and secondary data sources as well as m-healthapplications are feasible and accepted in an incurable cancer collective. KW - Metastatic breast cancer KW - Patient-centered registry KW - Patient’s needs KW - m-Health KW - Health care service research Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229149 VL - 6 ER - TY - JOUR A1 - Postema, Merel C. A1 - Hoogman, Martine A1 - Ambrosino, Sara A1 - Asherson, Philip A1 - Banaschewski, Tobias A1 - Bandeira, Cibele E. A1 - Baranov, Alexandr A1 - Bau, Claiton H.D. A1 - Baumeister, Sarah A1 - Baur‐Streubel, Ramona A1 - Bellgrove, Mark A. A1 - Biederman, Joseph A1 - Bralten, Janita A1 - Brandeis, Daniel A1 - Brem, Silvia A1 - Buitelaar, Jan K. A1 - Busatto, Geraldo F. A1 - Castellanos, Francisco X. A1 - Cercignani, Mara A1 - Chaim‐Avancini, Tiffany M. A1 - Chantiluke, Kaylita C. A1 - Christakou, Anastasia A1 - Coghill, David A1 - Conzelmann, Annette A1 - Cubillo, Ana I. A1 - Cupertino, Renata B. A1 - de Zeeuw, Patrick A1 - Doyle, Alysa E. A1 - Durston, Sarah A1 - Earl, Eric A. A1 - Epstein, Jeffery N. A1 - Ethofer, Thomas A1 - Fair, Damien A. A1 - Fallgatter, Andreas J. A1 - Faraone, Stephen V. A1 - Frodl, Thomas A1 - Gabel, Matt C. A1 - Gogberashvili, Tinatin A1 - Grevet, Eugenio H. A1 - Haavik, Jan A1 - Harrison, Neil A. A1 - Hartman, Catharina A. A1 - Heslenfeld, Dirk J. A1 - Hoekstra, Pieter J. A1 - Hohmann, Sarah A1 - Høvik, Marie F. A1 - Jernigan, Terry L. A1 - Kardatzki, Bernd A1 - Karkashadze, Georgii A1 - Kelly, Clare A1 - Kohls, Gregor A1 - Konrad, Kerstin A1 - Kuntsi, Jonna A1 - Lazaro, Luisa A1 - Lera‐Miguel, Sara A1 - Lesch, Klaus‐Peter A1 - Louza, Mario R. A1 - Lundervold, Astri J. A1 - Malpas, Charles B A1 - Mattos, Paulo A1 - McCarthy, Hazel A1 - Namazova‐Baranova, Leyla A1 - Nicolau, Rosa A1 - Nigg, Joel T. A1 - Novotny, Stephanie E. A1 - Oberwelland Weiss, Eileen A1 - O'Gorman Tuura, Ruth L. A1 - Oosterlaan, Jaap A1 - Oranje, Bob A1 - Paloyelis, Yannis A1 - Pauli, Paul A1 - Picon, Felipe A. A1 - Plessen, Kerstin J. A1 - Ramos‐Quiroga, J. Antoni A1 - Reif, Andreas A1 - Reneman, Liesbeth A1 - Rosa, Pedro G.P. A1 - Rubia, Katya A1 - Schrantee, Anouk A1 - Schweren, Lizanne J.S. A1 - Seitz, Jochen A1 - Shaw, Philip A1 - Silk, Tim J. A1 - Skokauskas, Norbert A1 - Soliva Vila, Juan C. A1 - Stevens, Michael C. A1 - Sudre, Gustavo A1 - Tamm, Leanne A1 - Tovar‐Moll, Fernanda A1 - van Erp, Theo G.M. A1 - Vance, Alasdair A1 - Vilarroya, Oscar A1 - Vives‐Gilabert, Yolanda A1 - von Polier, Georg G. A1 - Walitza, Susanne A1 - Yoncheva, Yuliya N. A1 - Zanetti, Marcus V. A1 - Ziegler, Georg C. A1 - Glahn, David C. A1 - Jahanshad, Neda A1 - Medland, Sarah E. A1 - Thompson, Paul M. A1 - Fisher, Simon E. A1 - Franke, Barbara A1 - Francks, Clyde T1 - Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets JF - Journal of Child Psychology and Psychiatry N2 - Objective Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait. KW - attention‐deficit KW - hyperactivity disorder KW - brain asymmetry KW - brain laterality KW - structural MRI KW - large‐scale data Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239968 VL - 62 IS - 10 SP - 1202 EP - 1219 ER - TY - JOUR A1 - Forchert, Leandra A1 - Potapova, Ekaterina A1 - Panetta, Valentina A1 - Dramburg, Stephanie A1 - Perna, Serena A1 - Posa, Daniela A1 - Resch‐Marat, Yvonne A1 - Lupinek, Christian A1 - Rohrbach, Alexander A1 - Grabenhenrich, Linus A1 - Icke, Katja A1 - Bauer, Carl‐Peter A1 - Hoffman, Ute A1 - Forster, Johannes A1 - Zepp, Fred A1 - Schuster, Antje A1 - Wahn, Ulrich A1 - Keil, Thomas A1 - Lau, Susanne A1 - Vrtala, Susanne A1 - Valenta, Rudolf A1 - Matricardi, Paolo Maria T1 - Der p 23‐specific IgE response throughout childhood and its association with allergic disease: A birth cohort study JF - Pediatric Allergy and Immunology N2 - Background The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross‐sectional studies. We longitudinally analysed the trajectory of Der p 23‐specific IgE antibody (sIgE) levels throughout childhood and youth, their early‐life determinants and their clinical relevance for allergic rhinitis and asthma. Methods We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. Results Der p 23‐sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23‐sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. Conclusions Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23‐sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens. KW - asthma KW - birth cohort KW - childhood KW - Der p 23 KW - house dust mite allergy KW - IgE Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287181 VL - 33 IS - 7 ER - TY - JOUR A1 - Wiegering, Armin A1 - Matthes, Niels A1 - Mühling, Bettina A1 - Koospal, Monika A1 - Quenzer, Anne A1 - Peter, Stephanie A1 - Germer, Christoph-Thomas A1 - Linnebacher, Michael A1 - Otto, Christoph T1 - Reactivating p53 and Inducing Tumor Apoptosis (RITA) Enhances the Response of RITA-Sensitive Colorectal Cancer Cells to Chemotherapeutic Agents 5-Fluorouracil and Oxaliplatin JF - Neoplasia N2 - Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n = 9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n = 5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC\(_{50}\)< 3.0 μmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents. KW - colorectal carcinoma KW - reactivating p53 and inducing tumor apoptosis (RITA) KW - chemotherapy KW - 5-fluorouracil KW - oxaliplatin Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171067 VL - 19 IS - 4 ER - TY - JOUR A1 - Stangl, Stephanie A1 - Rauch, Sebastian A1 - Rauh, Jürgen A1 - Meyer, Martin A1 - Müller‐Nordhorn, Jacqueline A1 - Wildner, Manfred A1 - Wöckel, Achim A1 - Heuschmann, Peter U. T1 - Disparities in Accessibility to Evidence-Based Breast Cancer Care Facilities by Rural and Urban Areas in Bavaria, Germany JF - Cancer N2 - Background Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care. Methods Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof‐of‐concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population‐based Cancer Registry of Bavaria were linked at the district level. Results Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho‐oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes. Conclusions Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high‐quality health care to all inhabitants, regardless of residence. KW - accessibility KW - breast cancer KW - evidence‐based medicine KW - geographic information science KW - health care service research Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239854 VL - 127 IS - 13 SP - 2319 EP - 2332 ER - 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 - Gerhard-Hartmann, Elena A1 - Goergen, Helen A1 - Bröckelmann, Paul J. A1 - Mottok, Anja A1 - Steinmüller, Tabea A1 - Grund, Johanna A1 - Zamò, Alberto A1 - Ben-Neriah, Susana A1 - Sasse, Stephanie A1 - Borchmann, Sven A1 - Fuchs, Michael A1 - Borchmann, Peter A1 - Reinke, Sarah A1 - Engert, Andreas A1 - Veldman, Johanna A1 - Diepstra, Arjan A1 - Klapper, Wolfram A1 - Rosenwald, Andreas T1 - 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial JF - British Journal of Haematology N2 - High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment. KW - fluorescence in situ hybridisation KW - major histocompatibility complex KW - immune checkpoint blockade KW - classical Hodgkin lymphoma KW - CD274 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258358 VL - 196 IS - 1 ER - TY - JOUR A1 - Riemer, Manuel A1 - Kranke, Peter A1 - Helf, Antonia A1 - Mayer, Debora A1 - Popp, Maria A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting JF - BMC Anesthesiology N2 - Background: Selective outcome reporting in clinical trials introduces bias in the body of evidence distorting clinical decision making. Trial registration aims to prevent this bias and is suggested by the International Committee of Medical Journal Editors (ICMJE) since 2004. Methods: The 585 randomized controlled trials (RCTs) published between 1965 and 2017 that were included in a recently published Cochrane review on antiemetic drugs for prevention of postoperative nausea and vomiting were selected. In a retrospective study, we assessed trial registration and selective outcome reporting by comparing study publications with their registered protocols according to the ‘Cochrane Risk of bias’ assessment tool 1.0. Results: In the Cochrane review, the first study which referred to a registered trial protocol was published in 2004. Of all 585 trials included in the Cochrane review, 334 RCTs were published in 2004 or later, of which only 22% (75/334) were registered. Among the registered trials, 36% (27/75) were pro- and 64% (48/75) were retrospectively registered. 41% (11/27) of the prospectively registered trials were free of selective outcome reporting bias, 22% (6/27) were incompletely registered and assessed as unclear risk, and 37% (10/27) were assessed as high risk. Major outcome discrepancies between registered and published high risk trials were a change from the registered primary to a published secondary outcome (32%), a new primary outcome (26%), and different outcome assessment times (26%). Among trials with high risk of selective outcome reporting 80% favoured at least one statistically significant result. Registered trials were assessed more often as ‘overall low risk of bias’ compared to non-registered trials (64% vs 28%). Conclusions: In 2017, 13 years after the ICMJE declared prospective protocol registration a necessity for reliable clinical studies, the frequency and quality of trial registration in the field of PONV is very poor. Selective outcome reporting reduces trustworthiness in findings of clinical trials. Investigators and clinicians should be aware that only following a properly registered protocol and transparently reporting of predefined outcomes, regardless of the direction and significance of the result, will ultimately strengthen the body of evidence in the field of PONV research in the future. KW - clinical trial KW - postoperative nausea and vomiting KW - selective outcome reporting KW - systematic review KW - trial registration Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265518 VL - 21 ER - TY - JOUR A1 - Schlesinger, Tobias A1 - Weibel, Stephanie A1 - Steinfeldt, Thorsten A1 - Sitter, Magdalena A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Intraoperative management of combined general anesthesia and thoracic epidural analgesia: A survey among German anesthetists JF - Acta Anaesthesiologica Scandinavica N2 - Background Evidence concerning combined general anesthesia (GA) and thoracic epidural analgesia (EA) is controversial and the procedure appears heterogeneous in clinical implementation. We aimed to gain an overview of different approaches and to unveil a suspected heterogeneity concerning the intraoperative management of combined GA and EA. Methods This was an anonymous survey among Members of the Scientific working group for regional anesthesia within the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) conducted from February 2020 to August 2020. Results The response rate was 38%. The majority of participants were experienced anesthetists with high expertise for the specific regimen of combined GA and EA. Most participants establish EA in the sitting position (94%), prefer early epidural initiation (prior to skin incision: 80%; intraoperative: 14%) and administer ropivacaine (89%) in rather low concentrations (0.2%: 45%; 0.375%: 30%; 0.75%: 15%) mostly with an opioid (84%) in a bolus-based mode (95%). The majority reduce systemic opioid doses intraoperatively if EA works sufficiently (minimal systemic opioids: 58%; analgesia exclusively via EA: 34%). About 85% manage intraoperative EA insufficiency with systemic opioids, 52% try to escalate EA, and only 25% use non-opioids, e.g. intravenous ketamine or lidocaine. Conclusions Although, consensus seems to be present for several aspects (patient's position during epidural puncture, main epidural substance, application mode), there is considerable heterogeneity regarding systemic opioids, rescue strategies for insufficient EA, and hemodynamic management, which might explain inconsistent results of previous trials and meta-analyses. KW - analgesics KW - enhanced recovery after surgery KW - multimodal treatments KW - perioperative care KW - epidural analgesia Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258286 VL - 65 IS - 10 ER - TY - JOUR A1 - Reis, Stefanie A1 - Popp, Maria A1 - Schmid, Benedikt A1 - Stegemann, Miriam A1 - Metzendorf, Maria-Inti A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: a systematic review and meta-analysis JF - Journal of Clinical Medicine N2 - Background: COVID-19 patients are at high thrombotic risk. The safety and efficacy of different anticoagulation regimens in COVID-19 patients remain unclear. Methods: We searched for randomised controlled trials (RCTs) comparing intermediate- or therapeutic-dose anticoagulation to standard thromboprophylaxis in hospitalised patients with COVID-19 irrespective of disease severity. To assess efficacy and safety, we meta-analysed data for all-cause mortality, clinical status, thrombotic event or death, and major bleedings. Results: Eight RCTs, including 5580 patients, were identified, with two comparing intermediate- and six therapeutic-dose anticoagulation to standard thromboprophylaxis. Intermediate-dose anticoagulation may have little or no effect on any thrombotic event or death (RR 1.03, 95% CI 0.86–1.24), but may increase major bleedings (RR 1.48, 95% CI 0.53–4.15) in moderate to severe COVID-19 patients. Therapeutic-dose anticoagulation may decrease any thrombotic event or death in patients with moderate COVID-19 (RR 0.64, 95% CI 0.38–1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95% CI 0.86–1.12). The risk of major bleedings may increase independent of disease severity (RR 1.78, 95% CI 1.15–2.74). Conclusions: Certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic-dose anticoagulation, but the risk for bleeding is increased. KW - anticoagulant therapy KW - coronavirus disease 2019 KW - thrombosis KW - bleeding KW - death Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252285 SN - 2077-0383 VL - 11 IS - 1 ER - TY - JOUR A1 - Hackenbroich, Samantha A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Include or not to include conference abstracts in systematic reviews? Lessons learned from a large Cochrane network meta-analysis including 585 trials JF - Systematic Reviews N2 - Background Systematic reviews attempt to gather all available evidence. Controversy exists regarding effort and benefit of including study results presented at conferences only. We recently published a Cochrane network meta-analysis (NMA) including 585 randomized controlled trials comparing drugs for prevention of postoperative nausea and vomiting (PONV). Studies published as conference abstracts only were excluded. This study aimed to include all eligible studies published as abstracts only, assessing their added value regarding reporting quality and effect on the review’s interpretation. Methods Conference abstracts were searched in the review’s excluded studies and conference proceedings of anaesthesiologic societies. We assessed their reporting quality regarding review’s eligibility criteria, Cochrane ‘risk of bias’ assessment tool 1.0, and adherence to CONSORT (Consolidated Standards of Reporting Trials) for abstracts. Abstracts were included in sensitivity NMA, and impact on the NMA structure was investigated. Results We identified 90 abstracts. A total of 14% (13/90) were eligible. A total of 86% (77/90) are awaiting classification due to insufficient reporting of review’s eligibility criteria. In abstracts awaiting classification, sufficient information was missing on standardization of anaesthesia in 71% (55/77), age of participants in 56% (43/77), and outcome details in 46% (36/77). A total of 73% (66/90) of abstracts lacked sufficient information on 15/25 data extraction items. Reported study characteristics of abstracts were comparable to included studies of the review. A total of 62% (56/90) of abstract trials were assessed as overall high risk of bias due to poor reporting. Median adherence to CONSORT for abstracts was 24% (IQR, 18 to 29%). Six of the 13 eligible abstracts reported relevant outcome data in sufficient detail for NMA on seven outcomes of the Cochrane review. Inclusion of abstracts did not substantially change the network structure, network effect estimates, ranking of treatments, or the conclusion. Certainty of evidence for headache on palonosetron use was upgraded from very low to low. Conclusions Most conference abstracts on PONV were insufficiently reported regarding review’s narrow inclusion criteria and could not be included in NMA. The resource-intensive search and evaluation of abstracts did not substantially extent the full-text evidence base of the review, given the few adequately reported abstracts. Conferences should oblige authors to adhere to CONSORT for abstracts. KW - systemic reviews KW - conference abstracts KW - meta-analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299660 VL - 11 IS - 1 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 - Huflage, Henner A1 - Kunz, Andreas Steven A1 - Hendel, Robin A1 - Kraft, Johannes A1 - Weick, Stefan A1 - Razinskas, Gary A1 - Sauer, Stephanie Tina A1 - Pennig, Lenhard A1 - Bley, Thorsten Alexander A1 - Grunz, Jan-Peter T1 - Obesity-related pitfalls of virtual versus true non-contrast imaging — an intraindividual comparison in 253 oncologic patients JF - Diagnostics N2 - Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m\(^2\)) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m\(^2\) (n = 110), pre-obese: 25–29.9 kg/m\(^2\) (n = 73), and obese: >30 kg/m\(^2\) (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDI\(_{vol}\) than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R\(^2\) = 0.738) and SECT (R\(^2\) = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1%) compared with non-obese (0%) and pre-obese patients (4.1%). Conclusion: DECT facilitates a 30.8% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients. KW - dual-energy CT KW - dual-source CT KW - virtual non-contrast KW - radiation dose KW - spectral CT KW - obesity Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313519 SN - 2075-4418 VL - 13 IS - 9 ER - TY - JOUR A1 - Huflage, Henner A1 - Grunz, Jan-Peter A1 - Patzer, Theresa Sophie A1 - Pannenbecker, Pauline A1 - Feldle, Philipp A1 - Sauer, Stephanie Tina A1 - Petritsch, Bernhard A1 - Ergün, Süleyman A1 - Bley, Thorsten Alexander A1 - Kunz, Andreas Steven T1 - Potential of unenhanced ultra-low-dose abdominal photon-counting CT with tin filtration: a cadaveric study JF - Diagnostics N2 - Objectives: This study investigated the feasibility and image quality of ultra-low-dose unenhanced abdominal CT using photon-counting detector technology and tin prefiltration. Materials and Methods: Employing a first-generation photon-counting CT scanner, eight cadaveric specimens were examined both with tin prefiltration (Sn 100 kVp) and polychromatic (120 kVp) scan protocols matched for radiation dose at three different levels: standard-dose (3 mGy), low-dose (1 mGy) and ultra-low-dose (0.5 mGy). Image quality was evaluated quantitatively by means of contrast-to-noise-ratios (CNR) with regions of interest placed in the renal cortex and subcutaneous fat. Additionally, three independent radiologists performed subjective evaluation of image quality. The intraclass correlation coefficient was calculated as a measure of interrater reliability. Results: Irrespective of scan mode, CNR in the renal cortex decreased with lower radiation dose. Despite similar mean energy of the applied x-ray spectrum, CNR was superior for Sn 100 kVp over 120 kVp at standard-dose (17.75 ± 3.51 vs. 14.13 ± 4.02), low-dose (13.99 ± 2.6 vs. 10.68 ± 2.17) and ultra-low-dose levels (8.88 ± 2.01 vs. 11.06 ± 1.74) (all p ≤ 0.05). Subjective image quality was highest for both standard-dose protocols (score 5; interquartile range 5–5). While no difference was ascertained between Sn 100 kVp and 120 kVp examinations at standard and low-dose levels, the subjective image quality of tin-filtered scans was superior to 120 kVp with ultra-low radiation dose (p < 0.05). An intraclass correlation coefficient of 0.844 (95% confidence interval 0.763–0.906; p < 0.001) indicated good interrater reliability. Conclusions: Photon-counting detector CT permits excellent image quality in unenhanced abdominal CT with very low radiation dose. Employment of tin prefiltration at 100 kVp instead of polychromatic imaging at 120 kVp increases the image quality even further in the ultra-low-dose range of 0.5 mGy. KW - spectral shaping KW - tin prefiltration KW - abdominal imaging KW - ultra-low-dose CT KW - urinary calculi KW - photon-counting Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304122 SN - 2075-4418 VL - 13 IS - 4 ER - TY - JOUR A1 - Pennig, Lenhard A1 - Hoyer, Ulrike Cornelia Isabel A1 - Krauskopf, Alexandra A1 - Shahzad, Rahil A1 - Jünger, Stephanie T. A1 - Thiele, Frank A1 - Laukamp, Kai Roman A1 - Grunz, Jan-Peter A1 - Perkuhn, Michael A1 - Schlamann, Marc A1 - Kabbasch, Christoph A1 - Borggrefe, Jan A1 - Goertz, Lukas T1 - Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage JF - Neuroradiology N2 - Purpose To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH). Methods Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 ± 185.4 mm3, 13.0% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared. Results In the test set, the detection sensitivity of the DLM-Ens (85.7%) was comparable to the radiologists (reader 1: 91.2%, reader 2: 86.5%, and reader 3: 86.5%; Fleiss κ of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6%, reader 2: 97.6%,and reader 3: 96.0%; overall P=.024; Fleiss κ of 0.878), especially for secondary aneurysms (88.2% of the additional aneurysms provided by the DLM). Conclusion Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment. KW - aneurysms KW - aneurysmal subarachnoid hemorrhage KW - CT angiography KW - deep learning KW - convolutional neural networks Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308117 SN - 0028-3940 SN - 1432-1920 VL - 63 IS - 12 ER -