418 results on '"Christine Schmitz"'
Search Results
2. Christine Schmitz: Juvenal
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Franco Bellandi
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- 2021
3. Christine Schmitz: Juvenal.
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Bellandi, Franco, primary
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- 2021
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4. Die kosmische Dimension in den Tragödien Senecas (Untersuchungen zur antiken Literatur und Geschichte. 39.) Christine Schmitz
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Müller, Hildegund
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- 2002
5. Die kosmische Dimension in den Tragödien Senecas Christine Schmitz
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Giancotti, Francesco
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- 1997
6. Christine Schmitz (Hrsg.), Mythos im Alltag - Alltag im Mythos. Die Banalität des Alltags in unterschiedlichen literarischen Verwendungskontexten
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Schmitz, Dietmar
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Rezension zu: Christine Schmitz (Hrsg.), Mythos im Alltag - Alltag im Mythos. Die Banalität des Alltags in unterschiedlichen literarischen Verwendungskontexten. Wilhelm Fink Verlag: Paderborn 2010. (ISBN 3-978-7705-4959-7f)., Forum Classicum, Nr. 1 (2011): Forum Classicum
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- 2017
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7. Das Satirische in Juvenals Satiren Christine Schmitz
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Winkler, Martin M.
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- 2003
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8. Profile of Christine Schmitz Treasurer of Virginia Gildersleeve International Fund
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Foreign securities ,Financial planners ,State finance ,Financial planning ,Long term care ,Long term care insurance ,Health insurance industry ,General interest ,News, opinion and commentary - Abstract
New York NY: Following is the Profile of Christine Schmitz Treasurer of Virginia Gildersleeve International Fund: Christine Schmitz has a B.M. from Peabody Conservatory of Music of the Johns Hopkins [...]
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- 2017
9. Impact of complete surgical resection on outcome in aggressive non‐Hodgkin lymphoma treated with immunochemotherapy
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Christine Schmitz, Jan Rekowski, Stefan P. Müller, Navid Farsijani, Bernd Hertenstein, Christiane Franzius, Ulla vonVerschuer, Paul La Rosée, Martin Freesmeyer, Stefan Wilop, Thomas Krohn, Aruna Raghavachar, Arnold Ganser, Frank M. Bengel, Gabriele Prange‐Krex, Frank Kroschinsky, Jörg Kotzerke, Aristoteles Giagounidis, Ulrich Dührsen, and Andreas Hüttmann
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Lymphoma ,B‐cell ,lymphoma ,T‐cell ,positron emission tomography ,prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Surgical resection is considered to be of purely diagnostic value in aggressive lymphoma. Evidence for an impact on outcome is scant and restricted to retrospective observations. Methods In the “Positron Emission Tomography‐guided Therapy of Aggressive non‐Hodgkin Lymphomas” (PETAL) trial, patients with a negative baseline positron emission tomography (PET) scan were documented in a prospective observational substudy. Baseline PET‐negative patients with the absence of lymph node enlargement on computed tomography and a negative bone marrow biopsy were considered to have undergone complete lymphoma resection. Results Eighty‐two of 1,041 patients (7.9%) had a negative baseline PET scan, and 67 were included in this analysis. All were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), plus rituximab for CD20‐positive lymphomas. Among 52 patients with diffuse large B‐cell lymphoma (DLBCL), 48 had completely resected disease. Their outcome tended to be better than that of 115 baseline PET‐positive stage I DLBCL patients treated in the main part of the PETAL trial (2‐year progression‐free survival 92.7% [95% confidence interval 84.7‐100] versus 88.4% [82.5‐94.3], P = .056; 2‐year overall survival 92.7% [84.7‐100] versus 93.7% [89.2‐98.2], P = .176), but this was restricted to patients below the age of 60 years (2‐year progression‐free survival 100% versus 92.2% [84.8‐99.6], P = .031; 2‐year overall survival 100% versus 95.9% [90.2‐100], P = .075). In peripheral T‐cell lymphoma, eight of 11 patients had completely resected disease. In contrast to DLBCL, complete resection was not associated with improved outcome compared to the control. Conclusion Young patients with early stage DLBCL may benefit from complete lymphoma resection prior to immunochemotherapy.
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- 2020
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10. Interview: Christine Schmitz on doctors seeking to help Uganda mutilation victims
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Doctors Without Borders ,Physicians - Abstract
To listen to this broadcast, click here: http://www.npr.org/templates/story/story.php?storyId=5060108 DEBBIE ELLIOTT, host: For almost two decades, the people of northern Uganda have been brutalized by war. During the worst of the […]
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- 2005
11. Juvenal
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Christine Schmitz and Christine Schmitz
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- 2019
12. Synergism and phytotoxicity: The effects of tank‐mix additives on the biological efficacy of Cu 2+ against Venturia inaequalis and Podosphaera leucotricha
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Christine Schmitz, Eike Luedeling, and Shyam Pariyar
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Agronomy and Crop Science - Published
- 2023
13. Anfänge und Enden: Narrative Potentiale des antiken und nachantiken Epos
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Christine Schmitz, Jan Telg genannt Kortmann, Angela Jöne and Christine Schmitz, Jan Telg genannt Kortmann, Angela Jöne
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- 2017
14. Lateinische Epik
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Christine Schmitz
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- 2023
15. Reinduction therapy with everolimus in combination with dexamethasone, high‐dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD‐R3i)
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Horst Müller, Heinz Haverkamp, Peter Borchmann, Andreas Viardot, Jan-Michel Heger, Christine Schmitz, Bastian von Tresckow, Michael Fuchs, Dennis A. Eichenauer, Vladan Vucinic, Andreas Engert, Stephanie Sasse, Max S. Topp, Paul J Bröckelmann, Annette Plütschow, Sarah Gillessen, Boris Böll, Sven Borchmann, Carsten Kobe, and Andreas Hüttmann
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Randomization ,medicine.medical_treatment ,Medizin ,Kaplan-Meier Estimate ,Dexamethasone ,Young Adult ,Refractory ,Recurrence ,Germany ,DHAP ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Everolimus ,Neoplasm Staging ,Chemotherapy ,business.industry ,Remission Induction ,Cytarabine ,Induction Chemotherapy ,Hematology ,Middle Aged ,Prognosis ,Hodgkin Disease ,Regimen ,Drug Resistance, Neoplasm ,Positron-Emission Tomography ,Retreatment ,Female ,Cisplatin ,Neoplasm Grading ,business ,medicine.drug - Abstract
Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.
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- 2021
16. A tumor volume and performance status model to predict outcome before treatment in diffuse large B-cell lymphoma
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Catherine Thieblemont, Loic Chartier, Ulrich Dührsen, Umberto Vitolo, Sally F. Barrington, Jan M. Zaucha, Laetitia Vercellino, Maria Gomes Silva, Ines Patrocinio-Carvalho, Pierre Decazes, Pierre-Julien Viailly, Herve Tilly, Alina Berriolo-Riedinger, Oliver Casasnovas, Andreas Hüttmann, Hajira Ilyas, N. George Mikhaeel, Joel Dunn, Anne-Ségolène Cottereau, Christine Schmitz, Lale Kostakoglu, Joseph N. Paulson, Tina Nielsen, Michael Meignan, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), King‘s College London, Guy's and St Thomas' Hospital [London], Medical University of Gdańsk, Service de Médecine Nucléaire [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], University of Virginia, Genentech, Inc. [San Francisco], F. Hoffmann-La Roche [Basel], CHU Henri Mondor, and leboeuf, Christophe
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Clinical Trials as Topic ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Medizin ,Humans ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hematology ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,Tumor Burden - Abstract
Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use factors for risk stratification that inadequately identify patients at high risk of refractory disease or relapse before initial treatment. A model associating 2 risk factors, total metabolic tumor volume (TMTV) >220 cm3 (determined by fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography) and performance status (PS) ≥2, identified as prognostic in 301 older patients in the REMARC trial (#NCT01122472), was validated in 2174 patients of all ages treated in 2 clinical trials, PETAL (Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas; N = 510) and GOYA (N = 1315), and in real-world clinics (N = 349) across Europe and the United States. Three risk categories, low (no factors), intermediate (1 risk factor), and high (2 risk factors), significantly discriminated outcome in most of the series. Patients with 2 risk factors had worse outcomes than patients with no risk factors in the PETAL, GOYA, and real-world series. Patients with intermediate risk also had significantly worse outcomes than patients with no risk factors. The TMTV/Eastern Cooperative Oncology Group-PS combination outperformed the International Prognostic Index with a positive C-index for progression-free survival and overall survival in most series. The combination of high TMTV > 220 cm3 and ECOG-PS ≥ 2 is a simple clinical model to identify aggressive LBCL risk categories before treatment. This combination addresses the unmet need to better predict before treatment initiation for aggressive LBCL the patients likely to benefit the most or not at all from therapy.
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- 2022
17. Synergism and phytotoxicity: the effects of tank-mix additives on the biological efficacy of Cu2+againstVenturia inaequalisandPodosphaera leucotricha
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Christine Schmitz, Eike Luedeling, and Shyam Pariyar
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SummaryThe wetting behaviour of the spray and biological efficacy of Cu2+active ingredients in agrochemical formulations may be enhanced by tank-mix additives. We investigated how three BREAK-THRU®additives (BT301: biodegradable, BT133 and BT420: bio-based and biodegradable) as tank-mix with commercial copper preparations influence the spray distribution, leaf uptake and biological efficacy of copper additive mixtures against apple scab and apple powdery mildew under controlled conditions. We quantified the synergetic effects of these additives in foliar applications. In addition, we determined the phytotoxic potential and evaluated impacts on photosynthetic activity, non-photochemical quenching and ROS activity. The additives BT301 and BT420 strongly reduced surface tension and contact angle of copper treatments. The fluorescence observations revealed that BT301 achieved better spreading of copper formulation with more complete coverage of the leaf surface than BT420 and BT133, whereas “coffee-ring” spreading was observed with BT133. The additive BT301 showed an increase in relative fluorescence area, indicating higher ROS production as a signal of intra-cellular tissue activity. The photochemical efficiency of photosystem II (Fv/Fm) was not negatively influenced by copper or additive treatment. Thus, we observed no phytotoxic effects of copper-additive mixtures on apple leaves at treatment doses of 4 g Cu2+L-1. All copper treatments reduced apple scab infestations significantly, by 53-76%. Interestingly, addition of BT301 to copper preparations showed the strongest biological efficacy (83% reduction) againstV. inaequalis, whereas addition of BT420 showed the strongest effect againstP. leucotricha(89% infection reduction). The synergetic effects of additives on the biological efficacy without phytotoxic effects on plants may have potential for reducing copper loads in horticultural production systems.
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- 2022
18. Optimal timing and criteria of interim PET in DLBCL: A comparative study of 1692 patients
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Sanne E Wiegers, Stefan P. Müller, N. G. Mikhaeel, Robert Carr, Luca Ceriani, Annika Loft, Tamás Györke, Martin Hutchings, Jakoba J Eertink, Pieternella J. Lugtenburg, Emanuele Zucca, Ulrich Dührsen, Ronald Boellaard, Christine Schmitz, Simone Pieplenbosch, Andreas Hüttmann, H.C.W. de Vet, Sally F. Barrington, S. Czibor, J. M. Zijlstra, L. Kostakoglu, Coreline N. Burggraaff, Otto S. Hoekstra, Stefano Fanti, Martijn W. Heymans, Eertink JJ, Burggraaff CN, Heymans MW, Dührsen U, Hüttmann A, Schmitz C, Müller S, Lugtenburg PJ, Barrington SF, Mikhaeel NG, Carr R, Czibor S, Györke T, Ceriani L, Zucca E, Hutchings M, Kostakoglu L, Loft A, Fanti S, Wiegers SE, Pieplenbosch S, Boellaard R, Hoekstra OS, Zijlstra JM, de Vet HCW., Hematology, VU University medical center, Internal medicine, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life
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Oncology ,medicine.medical_specialty ,Medizin ,Context (language use) ,Standardized uptake value ,DLBCL, interim PET ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Randomized controlled trial ,Fluorodeoxyglucose F18 ,law ,Prednisone ,Internal medicine ,Humans ,Medicine ,Lymphoid Neoplasia ,business.industry ,Proportional hazards model ,Hazard ratio ,Hematology ,Prognosis ,Vincristine ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,medicine.drug - Abstract
Interim 18F-fluorodeoxyglucose positron emission tomography (Interim- 18F-FDG-PET,hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-celllymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determinethe optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL.Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (DSUVmax ). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects oftiming and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using DSUVmax , respectively. DSUVmax identified a larger proportion of poor respondersthan DS5 did. For all criteria, the negative predictive value was >80%, and positivepredictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs,2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOPtherapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Goodresponse at I-PET2 is suggested for de-escalation trials, and poor response using DSUVmax atI-PET4 is suggested for randomized trials that are evaluating new therapies
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- 2021
19. Seneca
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Otto Zwierlein, Rainer Jakobi, Rebekka Junge, Christine Schmitz and Otto Zwierlein, Rainer Jakobi, Rebekka Junge, Christine Schmitz
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- 2015
20. Antike und Mittelalter
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Otto Zwierlein, Rainer Jakobi, Rebekka Junge, Christine Schmitz and Otto Zwierlein, Rainer Jakobi, Rebekka Junge, Christine Schmitz
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- 2015
21. Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation
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Veronica Estrada, Nicole Brazda, Christine Schmitz, Silja Heller, Heinrich Blazyca, Rudolf Martini, and Hans Werner Müller
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Trauma ,Axon regeneration ,Biomatrix ,Complete spinal cord transection ,Chronic Spinal Cord Injury ,Locomotor improvement ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. According to axon regeneration-supporting effects, the biopolymers could be ranked in the order PEG > > alginate-hydrogel > Matrigel™. Even after complete chronic transection, the PEG-bridge allowed long-distance axon regeneration through the grafted area and for, at least, 1 cm beyond the lesion/graft border. As revealed by electron microscopy, bundles of regenerating axons within the matrix area received myelin ensheathment from Schwann cells. The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8 months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI.
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- 2014
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22. Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: Post-hoc analysis from the PETAL trial
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Ulrich Dührsen, Jan Rekowski, Andreas Hüttmann, Stefan P. Müller, Karl-Heinz Jöckel, Maher Hanoun, Christine Schmitz, Marcus Brinkmann, Ronald Boellaard, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and CCA - Imaging and biomarkers
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Medizin ,Standardized uptake value ,Risk Assessment ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,hemic and lymphatic diseases ,Internal medicine ,Post-hoc analysis ,medicine ,Humans ,Positron emission ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,030104 developmental biology ,Positron emission tomography ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
Background Valid prognostic tools are needed to guide risk-adjusted treatment approaches in patients with diffuse large B-cell lymphoma (DLBCL). Methods We assessed total metabolic tumor volume (TMTV) and standardized uptake value (SUV)-based interim positron emission tomography (iPET) response in 510 patients with DLBCL participating in the positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL) trial (NCT00554164). TMTV was analyzed with a relative (SUV41max) and a fixed thresholding method (SUV4), and iPET was evaluated using the ΔSUVmax procedure. We determined associations between TMTV and international prognostic index (IPI) factors using Welch's t-test, investigated effects of TMTV, iPET response, and the IPI factors on time to progression (TTP), progression-free survival (PFS), and overall survival (OS) by Cox regression, and estimated the outcome using Kaplan–Meier curves. Findings TMTV was associated with all IPI factors except age. Irrespective of the thresholding method used, TMTV and iPET response were correlated with TTP, PFS, and OS, and remained the only independent outcome predictors in Cox regression analysis. By dichotomizing TMTV (cut-off: 328 cm³ by SUV41max) and iPET response (cut-off: 66% SUVmax reduction), we defined three groups at different risk of treatment failure (low [57.1% of patients]: low TMTV/good iPET response; intermediate [37.8%]: high TMTV/good iPET response or low TMTV/poor iPET response; and high [5.1%]: high TMTV/poor iPET response), with corresponding 2-year probabilities of 93.8% vs. 67.3% vs. 38.5% for TTP, 90.9% vs. 62.5% vs. 29.9% for PFS, and 95.5% vs. 77.4% vs. 37.1% for OS. Interpretation The PET-based risk model proposed may help identify patients who may benefit from treatment modifications or novel approaches.
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- 2020
23. Synergetic effects of tank-mix additives on the foliar uptake of Ca2+ and biological activity of Cu2+ against Venturia inaequalis and Podosphaera leucotricha
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Christine Schmitz, Eike Luedeling, and Shyam Pariyar
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- 2022
24. Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index
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N. George Mikhaeel, Martijn W. Heymans, Jakoba J. Eertink, Henrica C.W. de Vet, Ronald Boellaard, Ulrich Dührsen, Luca Ceriani, Christine Schmitz, Sanne E. Wiegers, Andreas Hüttmann, Pieternella J. Lugtenburg, Emanuele Zucca, Gerben J.C. Zwezerijnen, Otto S. Hoekstra, Josée M. Zijlstra, Sally F. Barrington, Hematology, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Hematology laboratory, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, AII - Infectious diseases, and CCA - Cancer Treatment and quality of life
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Cancer Research ,Medizin ,Prognosis ,Disease-Free Survival ,Tumor Burden ,Oncology ,SDG 3 - Good Health and Well-being ,Fluorodeoxyglucose F18 ,Positron-Emission Tomography ,hemic and lymphatic diseases ,parasitic diseases ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Retrospective Studies - Abstract
PURPOSE Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model. METHODS PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times. RESULTS The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm3. MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3% v 58.0% and 3-year OS 51.5% v 66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities. CONCLUSION A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.
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- 2022
25. Flauberts Salammbô
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Evi Ziegler c, Alexander Arweiler, Karin Westerwelle, Christine Schmitz, Martin Hose, Bardo Maria Gauly, Therese Fuhrer, D. S. Levene, o Edv Fotowerk Huber, and Pia Claudia Doering
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- 2021
26. Das Satirische in Juvenals Satiren
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Christine Schmitz and Christine Schmitz
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- 2011
27. Die 'Annahme' öffentlicher Urkunden nach Art. 59 Abs. 1 EuErbVO
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Christine Schmitz and Christine Schmitz
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Erbfälle mit Auslandsbezug gewinnen zunehmend an Bedeutung, damit einhergehend auch der Einsatz öffentlicher Urkunden in Erbschaftsangelegenheiten. Zur Förderung von deren Freizügigkeit wurde in der seit 2015 geltenden Europäischen Erbrechtsverordnung erstmals die'Annahme'öffentlicher Urkunden geregelt. Christine Schmitz untersucht diese neue Regelungsmethode. Dabei arbeitet sie zunächst den Anwendungsbereich der Norm heraus und nimmt in diesem Rahmen eine verordnungsautonome Qualifikation des deutschen Erbscheins vor. Darauf aufbauend ermittelt sie das neue Konzept der grenzüberschreitenden Beweiskraftwirkung. Hierbei zeigt die Autorin, dass es sich nicht um eine Inhaltsanerkennung, sondern um eine verfahrensrechtliche Kollisionsnorm und eine Wirkungserstreckung der formellen Beweiskraft öffentlicher Urkunden handelt. Weiterhin untersucht sie den zentralen Begriff der formellen Beweiskraft, für den sie abschließend eine verordnungsautonome Definition vorschlägt.
- Published
- 2020
28. Serologic response to meningococcal vaccination in patients with cold agglutinin disease (CAD) in the novel era of complement inhibition
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Alexander Röth, Dörte Herich-Terhürne, Amin T. Turki, Ulrich Dührsen, Andreas Hüttmann, Martin Bommer, Ferras Alashkar, Ulrich Vogel, Christine Schmitz, and Colin Vance
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Male ,Asplenia ,Cold agglutinin disease ,030231 tropical medicine ,Medizin ,Meningococcal Vaccines ,Neisseria meningitidis ,medicine.disease_cause ,03 medical and health sciences ,Classical complement pathway ,0302 clinical medicine ,Conjugate vaccine ,medicine ,Animals ,Humans ,Serologic Tests ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public Health, Environmental and Occupational Health ,Complement System Proteins ,Middle Aged ,Eculizumab ,medicine.disease ,Haemolysis ,Antibodies, Bacterial ,Meningococcal Infections ,Vaccination ,Infectious Diseases ,Immunology ,Molecular Medicine ,Female ,Anemia, Hemolytic, Autoimmune ,Rabbits ,business ,medicine.drug - Abstract
Cold agglutinin disease (CAD) is a rare, potentially life-threatening acquired autoimmune hemolytic anemia characterized by hemagglutination and hemolysis due to immunoglobulin-mediated (usually IgMκ) classic complement pathway activation. Complement inhibition (CI) represents a novel treatment option to control hemolysis. Due to CI patients (pts) are susceptible to encapsulated bacteria e.g. N. meningitidis. Therefore, meningococcal vaccination on CI is mandatory. In this study serologic response to the tetravalent conjugate vaccine Menveo® was analyzed in CAD pts on eculizumab treatment (DECADE trial) using rabbit serum as complement source (rSBA). Protective rSBA titers varied for meningococcal serogroups and over time reflecting an early decline to even non-protective rSBA titers. These data highlight the importance of serologic analyses under chronic CI. Currently, re-vaccination with a tetravalent meningococcal conjugate vaccine every 3 years is recommended on chronic CI. However, re-vaccination on CI might further rely on serologic analyses, implying even early booster vaccinations similar to adults with (functional) asplenia.
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- 2019
29. Immunosuppressive therapy (IST) in adult patients with acquired aplastic anemia (AA): A single‐center experience over the past 15 years
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Dörte Herich-Terhürne, Colin Vance, Maren Oelmüller, Ferras Alashkar, Alexander Röth, Christine Schmitz, Amin T. Turki, and Ulrich Dührsen
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Adult ,Erythrocyte Indices ,Male ,medicine.medical_specialty ,Medizin ,Single Center ,Severity of Illness Index ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Recurrence ,Internal medicine ,medicine ,Humans ,Aplastic anemia ,Acquired aplastic anemia ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,Aged, 80 and over ,Immunosuppression Therapy ,Hematology ,business.industry ,Bone marrow failure ,Anemia, Aplastic ,Horse ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cyclosporine ,Drug Therapy, Combination ,Female ,business ,Immunosuppressive Agents ,030215 immunology - Abstract
Objective Immunosuppressive therapy (IST) with horse anti-thymocyte globulin (hATG) and cyclosporine (CsA) is considered one of the first-line therapies in patients (pts) with acquired aplastic anemia (AA). Methods In our single-center, retrospective analysis response rates (RRs) to ATG/CsA at a minimum of 6 mo were evaluated in 67 treatment-naive (TN) AA pts (52.2% (35/67) females; median age 45 y (range 18-89 y)) being treated at the West German Cancer Center at the Department of Hematology at the University Hospital of Essen between April 2000 and December 2015. Results Overall 6 mo RRs in TN pts following ATG/CsA were 67.2% (45/67) (5-year OS: 79.5%). In TN hATG-treated pts 6 mo RRs were 75.5% (37/49) (5-year OS: 81%) compared to 44.4% (8/18) (5-year OS 73.5%) following rabbit ATG (rATG). Response to ATG/CsA was dependent of age, absolute reticulocyte count (ARC), and disease severity. Six mo RRs to salvage ATG/CsA in relapsed/refractory (R/R) pts were 37.5% (6/16). Conclusion Our data independently confirm the findings of previous studies that hATG/CsA is superior to rATG/CsA in TN pts. The lack of hATG availability should not result in abstaining it from an indicated ATG therapy, even though ATGAM® is not registered in Germany.
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- 2019
30. Interim FDG PET analysis performed by Neural Networks to predict the outcome of patients with aggressive B-cell lymphoma
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Manuel Weber, Ulrich Dührsen, P Sandach, Ken Herrmann, Christian Reinhardt, R Seifert, Christine Schmitz, C Rischpler, M Schäfers, B von Tresckow, David Kersting, and Andreas Hüttmann
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Oncology ,medicine.medical_specialty ,Artificial neural network ,business.industry ,Interim ,Internal medicine ,Medicine ,business ,B-cell lymphoma ,medicine.disease ,Outcome (game theory) - Published
- 2021
31. Interim PET in Diffuse Large B-Cell Lymphoma
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Dirk Hasenclever, Lars Kurch, Thomas Georgi, Regine Kluge, Andreas Hüttmann, Osama Sabri, Ulrich Dührsen, Jan Rekowski, and Christine Schmitz
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Adult ,Percentile ,Treatment response ,Poor responder ,Medizin ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Positive predicative value ,Positron Emission Tomography Computed Tomography ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,PET-CT ,business.industry ,Middle Aged ,medicine.disease ,Interim pet ,Predictive value ,Hodgkin Disease ,030220 oncology & carcinogenesis ,Lymphoma, Large B-Cell, Diffuse ,business ,Nuclear medicine ,Diffuse large B-cell lymphoma - Abstract
In diffuse large B-cell lymphoma, early assessment of treatment response by 18F-FDG PET may trigger treatment modification. Reliable identification of good and poor responders is important. We compared 3 competing methods of interim PET evaluation. Methods: Images from 449 patients participating in the "PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas" trial were reanalyzed by applying the visual Deauville score and the SUV-based qPET (q = quantitative) and ΔSUVmax scales to interim PET scans performed after 2 cycles of chemotherapy. qPET relates residual lymphoma 18F-FDG uptake to physiologic liver uptake, converting the ordinal Deauville scale into a continuous scale and permitting a direct comparison with the continuous ΔSUVmax scale, which is based on SUVmax changes between baseline and interim scans. Positive and negative predictive values were calculated for progression-free survival. Results: When established thresholds were used to distinguish between good and poor responders (visual Deauville score 1-3 vs. 4-5; ΔSUVmax > 66% vs. ≤ 66%), the positive predictive value was significantly lower with Deauville than ΔSUVmax (38.4% vs. 56.6%; P = 0.03). qPET and ΔSUVmax were strongly correlated on the log scale (Pearson r = 0.75). When plotted along corresponding percentiles, the positive predictive value curves for qPET and ΔSUVmax were superimposable, with low values up to the 85th percentile and a steep rise thereafter. The recommended threshold of 66% SUVmax reduction for the identification of poor responders was equivalent to qPET = 2.26, corresponding to score 5 on the visual Deauville scale. The negative predictive value curves were also superimposable but remained flat between 80% and 70%. Conclusion: Continuous scales are better suited for interim PET-based outcome prediction than the ordinal Deauville scale. qPET and ΔSUVmax essentially carry the same information. The proportion of poor-risk patients identified is less than 15%.
- Published
- 2021
32. Interim PET Evaluation in Diffuse Large B-Cell Lymphoma Using Published Recommendations : Comparison of the Deauville 5-Point Scale and the ΔSUVmₐₓ Method
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Fonyuy Nyuyki, Daniëlle M. E. van Assema, Thomas Krohn, Matthias Weckesser, Lilli Geworski, A. Hertel, Jan Rekowski, Christine Schmitz, Lars Kurch, Frank M. Bengel, Christiane Franzius, Ingo Brink, Jens Holzinger, Karl-Heinz Jöckel, Ulrich Dührsen, Dirk Hasenclever, Andreas Hüttmann, Jörg Kotzerke, Martin Freesmeyer, Uwe Haberkorn, Stefan P. Müller, and VU University medical center
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Proportional hazards model ,Concordance ,Hazard ratio ,Medizin ,medicine.disease ,Interim pet ,Spearman's rank correlation coefficient ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Cutoff ,Radiology, Nuclear Medicine and imaging ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
The value of interim 18F-FDG PET/CT (iPET)-guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the change-in-SUV max (DSUV max) approach-2 methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas trial, iPET scans of 596 patients originally evaluated using the DSUV max method were available for post hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUV max approach is characterized as a relative reduction of the SUV max between baseline and iPET staging of less than or equal to 66%. We investigated the 2 methods' correlation and concordance by Spearman rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the prespecified cutoffs. Time-dependent receiver-operating-characteristic curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and DSUV max approach differed in their iPET-based prognosis. The ΔSUV max approach outperformed the Deauville score in terms of discrimination performance-most likely because of a high number of false-positive decisions by the Deauville score. Cutoff-independent discrimination performance remained low for both methods, but cutoff-related analyses showed promising results. Both favored the ΔSUV max approach, for example, for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval, 2.22-4.46) for ΔSUV max and 1.70 (95% confidence interval, 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUV max criterion of a relative reduction in SUV max of less than or equal to 66% should be considered as an alternative.
- Published
- 2021
33. Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma
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Joanne Soo, Florian Scherer, Andrea Garofalo, Brian Sworder, Mark Roschewski, Jason R. Westin, Davide Rossi, Olivier Casasnovas, Michael C. Jin, Wyndham H. Wilson, Stefan Alig, Charles Macaulay, Michel Meignan, Ash A. Alizadeh, Mohammad Shahrokh Esfahani, David M. Kurtz, Ulrich Dührsen, Gianluca Gaidano, Alexander F.M. Craig, Maximilian Diehn, Barzin Y. Nabet, Christine Schmitz, and Andreas Hüttmann
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Treatment interval ,Medizin ,Circulating Tumor DNA ,Young Adult ,Text mining ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,ORIGINAL REPORTS ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,Clinical trial ,Circulating tumor DNA ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma - Abstract
PURPOSE Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias. PATIENTS AND METHODS We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome. RESULTS Short DTI was associated with advanced-stage disease ( P < .001) and higher IPI ( P < .001). We also found an inverse correlation between DTI and TMTV ( RS = −0.37; P < .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all P < .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels ( P < .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI ( P < .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; −DTI: 1.1 [1.0 to 1.2]). CONCLUSION Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.
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- 2021
34. Juvenal
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Christine Schmitz and Christine Schmitz
- Abstract
Juvenal (ca. 60-140 n. Chr.) ist der letzte bedeutende Repräsentant der römischen Verssatire. Die Art, wie er sich in diese dynamische Gattung eingeschrieben hat, war prägend für die nachfolgende Satire, die als Schreibmodus unabhängig von formalen Charakteristika wie dem Hexameter fortlebt. Die Einführung bietet einen Überblick über literaturtheoretische und sozialhistorische Fragen, die für das Verständnis der Satiren Juvenals zentral sind: das Verhältnis zwischen historischem Autor und textimmanentem Sprecher (persona-Theorie), die nicht mehr funktionierende Klient-Patron-Beziehung (amicitia), rollenabweichendes Verhalten von Männern und Frauen der sozialen und politischen Elite, Konzepte von Homosexualität etc.
- Published
- 2023
35. Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma:A subgroup analysis of the PETAL trial
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Heinz Dürk, Arnold Ganser, Jan Rekowski, Andreas Hertel, Bernd Hertenstein, Lars Kurch, Matthias Sandmann, Winfried Brenner, Christiane Kreisel-Büstgens, Christiane Franzius, Wolfram Klapper, Matthias Weckesser, Aristoteles Giagounidis, Martin Freesmeyer, Thomas Krohn, Volker Runde, Dirk Behringer, Michael Heike, Stefan P. Müller, Frank Kroschinsky, Regina Moeller, Rolf Larisch, Hubertus Hautzel, Christine Schmitz, Gerhard Heil, Rolf M. Mesters, Ulrich Dührsen, Karl-Heinz Jöckel, Ferras Alashkar, Helga Bernhard, Dietmar Wacker, Uwe M. Martens, Stefan Mahlmann, Stefan Wilop, Jörg Kotzerke, Ronald Boellaard, Paul La Rosée, Gabriele Prange-Krex, Andreas Hüttmann, Heinz Gert Hoeffkes, Uwe Haberkorn, Guido Trenn, Dieter Hoelzer, Marcus Brinkmann, Frank M. Bengel, Radiology and nuclear medicine, and CCA - Imaging and biomarkers
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Population ,Medizin ,Standardized uptake value ,Subgroup analysis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Anaplastic lymphoma kinase ,Humans ,Prospective cohort study ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Hazard ratio ,Lymphoma, T-Cell, Peripheral ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Peripheral T-cell lymphoma ,Lymphoma ,Survival Rate ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Female ,Radiopharmaceuticals ,business ,030215 immunology ,Follow-Up Studies - Abstract
The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4. For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4, and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4. At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.
- Published
- 2020
36. FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma—An Updated Overview
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Jirka Grosse, Christian Baues, Carsten Kobe, Peter Borchmann, Conrad-Amadeus Voltin, Markus Dietlein, Christine Schmitz, Dirk Hellwig, and Jasmin Mettler
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,hodgkin lymphoma ,positron emission tomography ,medicine.medical_treatment ,Medizin ,Review ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,response assessment ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Metabolic tumor volume ,staging ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Lymphoma ,Response assessment ,diffuse large b-cell lymphoma ,Total lesion glycolysis ,030104 developmental biology ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,Radiology ,business ,Diffuse large B-cell lymphoma - Abstract
Since the mid-1990s, 18F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future.
- Published
- 2020
37. Metabolic tumor volume, cancer cell fraction, and prognosis - the case of T-cell/histiocyte-rich large B-cell lymphoma
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Christine Schmitz, Andreas Hüttmann, Jan Rekowski, Wolfram Klapper, Stefan P. Müller, Ulrich Dührsen, and Sarah Reinke
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Cancer Research ,T-Lymphocytes ,Medizin ,Aggressive lymphoma ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Survival analysis ,Histiocyte ,medicine.diagnostic_test ,business.industry ,Histiocytes ,Hematology ,medicine.disease ,Prognosis ,Lymphoma ,Tumor Burden ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Lymphoma, Large B-Cell, Diffuse ,T-Cell/Histiocyte-Rich Large B-Cell Lymphoma ,business ,Tomography, X-Ray Computed ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare aggressive lymphoma characterized by a paucity of neoplastic B-cells and a majority of reactive T-cells with or without histiocytes. In the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' trial (clinicaltrials.gov NCT00554164; EudraCT 2006-001641-33), its frequency was less than 3%. While cancer cell content by quantitative histology was 10-times lower, baseline total metabolic tumor volume (TMTV) by 18-fluorodesoxyglucose positron emission tomography was 10-times higher in THRLBCL than in diffuse large B-cell lymphoma (DLBCL). When THRLBCL and DLBCL populations were matched for TMTV, the survival curves were superimposable. However, when the populations were matched for cancer cell volume by multiplying TMTV by cancer cell fraction, outcome in THRLBCL was worse than in DLBCL. Whether genetic differences between cancer cells, tumor-promoting properties of non-neoplastic cells, or both are responsible for inferior cancer cell volume-related outcome in THRLBCL, remains to be elucidated.
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- 2020
38. Supporting data for positron emission tomography-based risk modelling using a fixed-instead of a relative thresholding method for total metabolic tumor volume determination
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Marcus Brinkmann, Maher Hanoun, Ronald Boellaard, Andreas Hüttmann, Stefan P. Müller, Karl-Heinz Jöckel, Ulrich Dührsen, Jan Rekowski, Christine Schmitz, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Brain Imaging, and Radiology and nuclear medicine
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Medizin ,Standardized uptake value ,Agreement ,PETAL trial ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Research article ,030304 developmental biology ,TMTV determination ,0303 health sciences ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,Fixed thresholding method ,Hazard ratio ,Metabolic tumor volume ,Medicine and Dentistry ,Positron emission tomography scanning ,Thresholding ,Positron emission tomography ,DLBCL ,business ,Risk assessment ,Nuclear medicine ,030217 neurology & neurosurgery - Abstract
Total metabolic tumor volume (TMTV) was measured in 510 patients with DLBCL participating in the PETAL trial. The present data provide information about the prognostic impact of total metabolic tumor volume using the fixed standardized uptake value (SUV4) instead of the relative SUV41max thresholding method. A Bland-Altman plot was created to compare both methods. For TMTV assessed by the SUV4 method a Cox regression was applied to determine its effect on time to progression, progression-free survival, and overall survival. Kaplan-Meier curves and corresponding hazard ratios were used to estimate the effect of TMTV alone or in combination with interim positron emission tomography response on patients’ survival. The data relate to the research article entitled “Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: post-hoc analysis from the PETAL trial” [1].
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- 2020
39. Fertility preservation and fulfillment of parenthood after treatment of hematological malignancies : results from the ‘Aftercare in Blood Cancer Survivors’ (ABC) study
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Ulrich Dührsen, Dietrich W. Beelen, Karl-Heinz Jöckel, Hildegard Lax, Christine Schmitz, Nils Lehmann, Julia Baum, and Tanja Gromke
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Infertility ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Allogeneic transplantation ,Treatment-related infertility ,Adolescent ,media_common.quotation_subject ,Medizin ,Aftercare ,Fertility ,Blood cancer ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Cancer Survivors ,Hematological malignancy ,Surgical oncology ,Surveys and Questionnaires ,medicine ,Humans ,Fertility preservation ,media_common ,Aged ,business.industry ,Fertility Preservation ,Posttreatment parenthood ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Childlessness ,Hematologic Neoplasms ,Surgery ,Female ,Original Article ,business ,030215 immunology ,Cohort study - Abstract
Purpose Treatment of hematological malignancies carries the risk of lasting sterility. We aimed to identify fertility-related unmet needs. Methods The ‘Aftercare in Blood Cancer Survivors’ study is a cohort study of hematological patients who were in treatment-free remission for ≥ 3 years or stable under continuous oral medication. Female patients age 18–45 years and male patients age 18–65 years without a history of pre-treatment infertility were asked to answer a structured questionnaire including questions addressing fertility issues. Multivariable analyses were performed to detect risk factors. Results Of 1562 study participants, 1031 met the inclusion criteria for the fertility sub-study. A high proportion of patients (72.4%) received information about the risk of losing fertility, but only a minority (15%) took steps to preserve it. Female and older patients were less likely to be informed. A post-treatment wish for parenthood was expressed by 19.3% of patients. It was strongly associated with childlessness at time of diagnosis and could be fulfilled by 29.4%. Fulfillment of desired parenthood increased with increasing time from diagnosis and was low after allogeneic transplantation. Conclusions Female and older hematological patients are less likely to be informed about fertility-related issues than other patients. With societal changes towards first parenthood at higher age, the proportion of patients desiring a child after treatment is likely to increase. Fulfillment of desired parenthood remains challenging, especially after allogeneic transplantation. Implications for cancer survivors In patients likely to express a wish for post-treatment parenthood, fertility-related issues should routinely be addressed before gonadotoxic treatment is started.
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- 2020
40. Etoposide combined with FLAG salvage therapy is effective in multiple relapsed / refractory acute myeloid leukemia
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Richard Noppeney, Jonas Westhus, Christine Schmitz, Maher Hanoun, Ulrich Dührsen, and Michael Flasshove
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Oncology ,medicine.medical_specialty ,business.industry ,Medizin ,Salvage therapy ,Myeloid leukemia ,Hematology ,General Medicine ,Fludarabine ,Transplantation ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cytarabine ,FLAG (chemotherapy) ,business ,Etoposide ,030215 immunology ,medicine.drug - Abstract
Managing acute myeloid leukemia (AML) is often hampered by repeated failure to achieve complete remission as well as recurrent relapse that causes an emergent need for alternative salvage therapies. The efficacy of most salvage therapies is based on anthracycline combinations. In highly pretreated patients who are not eligible for anthracycline-based protocols therapeutic alternatives are limited. For this particular group we evaluated the efficacy and safety of fludarabine, cytarabine, granulocyte colony-stimulating factor (FLAG) in combination with etoposide (FLAG-Eto) in 36 patients. The complete remission rate (CR) was 25.7% with a median overall survival of 6 months (95% CI 4.5–7.7). The median disease-free survival for CR/CRi/MLFS (CR/CR with incomplete hematological recovery/morphologic leukemia-free state) patients was 8 months (95% CI 0.6–15.5). The mortality rate on day 30 was 8% and increased on day 60 to 17%. Our results show meaningful anti-leukemic activity of the FLAG-Eto regimen with a moderate toxicity profile in heavily pretreated relapsed/refractory AML patients enabling consolidating allogeneic stem cell transplantation.
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- 2020
41. Die »Annahme« öffentlicher Urkunden nach Art. 59 Abs. 1 EuErbVO
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Christine Schmitz
- Published
- 2020
42. Dimethylarginine dimethylaminohydrolase1 is an organ-specific mediator of end organ damage in a murine model of hypertension.
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Karsten Sydow, Christine Schmitz, Eike-Christin von Leitner, Robin von Leitner, Anna Klinke, Dorothee Atzler, Christian Krebs, Hartwig Wieboldt, Heimo Ehmke, Edzard Schwedhelm, Thomas Meinertz, Stefan Blankenberg, Rainer H Böger, Tim Magnus, Stephan Baldus, and Ulrich Wenzel
- Subjects
Medicine ,Science - Abstract
The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular and overall mortality. Moreover, elevated ADMA plasma concentrations are associated with the extent of hypertension. However, data from small-sized clinical trials and experimental approaches using murine transgenic models have revealed conflicting results regarding the impact of ADMA and its metabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) in the pathogenesis of hypertension.Therefore, we investigated the role of ADMA and DDAH1 in hypertension-induced end organ damage using the uninephrectomized, deoxycorticosterone actetate salt, and angiotensin II-induced hypertension model in human DDAH1 (hDDAH1) overexpressing and wild-type (WT) mice. ADMA plasma concentrations differed significantly between hDDAH1 and WT mice at baseline, but did not significantly change during the induction of hypertension. hDDAH1 overexpression did not protect against hypertension-induced cardiac fibrosis and hypertrophy. In addition, the hypertension-induced impairment of the endothelium-dependent vasorelaxation of aortic segments ex vivo was not significantly attenuated by hDDAH1 overexpression. However, hDDAH1 mice displayed an attenuated hypertensive inflammatory response in renal tissue, resulting in less hypertensive renal injury.Our data reveal that hDDAH1 organ-specifically modulates the inflammatory response in this murine model of hypertension. The lack of protection in cardiac and aortic tissues may be due to DDAH1 tissue selectivity and/or the extent of hypertension by the used combined model. However, our study underlines the potency of hDDAH1 overexpression in modulating inflammatory processes as a crucial step in the pathogenesis of hypertension, which needs further experimental and clinical investigation.
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- 2012
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43. Combining PET Radiomic Features with MYC Gene Rearrangement Results in High Prediction of Outcome in Diffuse Large B-Cell Lymphoma
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Jakoba J Eertink, Josée M. Zijlstra, Bauke Ylstra, Sanne E Wiegers, Daphne de Jong, Julia Richter, Wolfram Klapper, Christine Schmitz, Matias Mendeville, Otto S. Hoekstra, Pieternella J. Lugtenburg, G.J.C. Zwezerijnen, Martine E D Chamuleau, Ronald Boellaard, Henrica C.W. de Vet, Ulrich Dührsen, and Andreas Hüttmann
- Subjects
Immunology ,medicine ,Cancer research ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Diffuse large B-cell lymphoma ,MYC Gene Rearrangement - Abstract
Introduction Genetic abnormalities, such as MYC oncogene rearrangements, contribute to the outcome heterogeneity in diffuse large B-cell lymphoma (DLBCL) patients. These rearrangements occur in 10-15% of DLBCL patients and have been associated with a poor prognosis. Recently, radiomics features extracted from PET/CT scans have shown to be predictive of outcome. The aim of this study was to investigate if the ability to predict outcome in DLBCL can be improved by combining different clinical, radiomics and genetic features. Methods 323 DLBCL patients from the HOVON-84, HOVON-130, and PETAL trials with a baseline PET/CT scan and a minimum follow-up of two years were included. MYC status was assessed using Fluorescence in situ hybridization (FISH). 245 patients were MYC negative, whereas 25 patients had a MYC rearrangement and 57 patients had MYC and BCL2 and/or BCL6 rearrangements. Lesions were delineated using a semi-automated preselection of 18F-FDG avid structures defined by a SUV4.0 threshold using the ACCURATE tool. Next, 5 conventional PET features (maximum standardized uptake value (SUV max), SUV peak, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis and 18 dissemination features were extracted. Dissemination features were pertaining to distance between lesions, differences in uptake between lesions and differences in volume between lesions. Logistic regression with backward feature selection was used to predict 2-year time to progression, defined as time from baseline PET/CT to progression. We tested the predictive value of 4 models. 1) a clinical model using individual components of the international prognostic index (IPI): Ann Arbor stage (categorical), WHO performance status (categorical), lactate dehydrogenase (LDH) levels (dichotomous) and age (continuous), 2) a model that included clinical and genetic predictors: MYC status (categorical) and IPI components, 3) a model that included radiomics features: 5 conventional PET and 18 dissemination features and 4) a model that combined clinical and genetic predictors with radiomics features. Model performance was assessed using repeated cross-validation (5-fold, 1000 repeats) yielding the cross-validated area under the curve of the receiver-operator-characteristics curve (CV-AUC). To match prevalence of MYC-positive patients with real-world prevalence (Rosenwald et al, JCO 2019) all 245 MYC-negative patients were used for each repeat, and 10 MYC-FISH_positive DLBCL patients and 20 patients with MYC and BCL2 and/or BCL6 rearrangements were selected using random stratified sampling. Regression coefficients were averaged over all folds to calculate the probability of progression for all patients. High- and low-risk groups were defined based on prevalence of events and the diagnostic performance was assessed using positive- and negative predictive values. Results The highest model performance for the clinical model was observed when combining Ann Arbor stage, LDH and extranodal involvement and yielded in a CV-AUC of 0.69 (95% confidence interval (CI): 0.52-0.83). MYC status combined with WHO performance status, LDH and extranodal involvement yielded an improved CV-AUC of 0.71 (95% CI: 0.52-0.86). The highest model performance for the radiomics model was observed for MTV combined with the maximum distance between the largest lesion and any other lesions (Dmax bulk), the maximum difference in SUV peak between two lesions (DSUVpeak patient) and the maximum difference in volume between two lesions (DVol patient) yielding a CV-AUC of 0.77 (95% CI: 0.62-0.90). The optimal combined model included MYC status, WHO performance status, LDH, MTV, Dmax patient, DSUVpeak patient and DVol patient after backward feature selection and yielded a CV-AUC of 0.77 (95% CI: 0.60 - 0.90). The positive predictive value was highest for the combined model (53.0%) and increased by 20% compared to the optimal clinical model (33.1%). Negative predictive values were comparable between models and ranged between 85.8-88.1%. Conclusions Prediction models using 18F-FDG PET/CT radiomics features at baseline aids in identifying DLBCL patients at high risk for relapse. The positive predictive value increased when radiomics features were added to the clinical and genetic parameters. Therefore, radiomics features can increase the efficiency of clinical trials by only selecting poor prognosis patients. Figure 1 Figure 1. Disclosures Chamuleau: Gilead: Research Funding; Genmab: Research Funding; Celgene: Research Funding. Lugtenburg: Incyte: Honoraria; Regeneron: Honoraria; Genmab: Honoraria; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Other: Non-financial support; Travel support; Roche: Honoraria, Research Funding. Dührsen: CPT Cellex Patient Treatment: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hüttmann: Celgene: Honoraria; Gilead: Honoraria; Lead Discovery Center GmbH: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Richter: HTG Molecular Diagnostics, Inc.: Current Employment, Research Funding. Klapper: Regeneron: Consultancy, Research Funding; Amgen: Research Funding; Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Zijlstra: Takeda: Research Funding.
- Published
- 2021
44. Corrigendum to ‘Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: Post-hoc analysis from the PETAL trial’ [Eur J Canc 124 (January 2020) 25–36]
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Maher Hanoun, Stefan P. Müller, Karl-Heinz Jöckel, Marcus Brinkmann, Ulrich Dührsen, Jan Rekowski, Andreas Hüttmann, Ronald Boellaard, and Christine Schmitz
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Cancer Research ,Oncology ,medicine.diagnostic_test ,business.industry ,Positron emission tomography ,Post-hoc analysis ,Medicine ,Regret ,business ,Nuclear medicine ,Risk assessment ,medicine.disease ,Diffuse large B-cell lymphoma - Abstract
The authors regret that they confused the colours of the time-to-progression curves in Figure 4C and Figure 4D. The correct Figure 4 appears below. [Figure presented] The authors would like to apologise for any inconvenience caused.
- Published
- 2020
45. Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP : results from the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' (PETAL) trial
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Bernd Hertenstein, Lars Kurch, Roland Schroers, Andreas Hüttmann, Thomas Krohn, Georg Maschmeyer, Ariane Dienst, Heinz-Gert Höffkes, Ingo Brink, Gabriele Prange-Krex, Aruna Raghavachar, Alfred Klein, Christine Schmitz, Andreas Schwarzer, Gabriele Pöpperl, Wolfram Klapper, Andreas Hertel, Martin Griesshammer, Stefan P. Müller, Matthias Weckesser, Ralph Naumann, Heike Steiniger, Matthias Grube, Wolfgang Römer, Dieter Hoelzer, Marcus Brinkmann, Jan Dürig, Christiane Franzius, Thomas Südhoff, Frank M. Bengel, Holger Nückel, Claudia Ose, Ulrich Dührsen, Karl-Heinz Jöckel, Jan Rekowski, Thomas Höhler, Aristoteles Giagounidis, Arnold Ganser, Dennis Hahn, Paul La Rosée, Helga Bernhard, Jörg Kotzerke, Frank Kroschinsky, Hubertus Hautzel, Dirk Behringer, Jochen Schütte, Tobias Gaska, Rolf M. Mesters, Ferras Alashkar, Jens Holzinger, Stefan Wilop, Jörg Marienhagen, and Martin Freesmeyer
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Lymphoma, B-Cell ,Adolescent ,Follicular lymphoma ,Medizin ,CHOP ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Fluorodeoxyglucose F18 ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,B-cell lymphoma ,Cyclophosphamide ,Aged ,Aged, 80 and over ,business.industry ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Lymphoma ,Survival Rate ,Doxorubicin ,Vincristine ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Prednisone ,Female ,Rituximab ,Primary mediastinal B-cell lymphoma ,business ,Diffuse large B-cell lymphoma ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Standard first-line treatment of aggressive B cell lymphoma comprises six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus eight doses of rituximab (R). Whether adding two doses of rituximab to six cycles of R-CHOP is of therapeutic benefit has not been systematically investigated. The Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial investigated the ability of [18F]-fluorodesoxyglucose PET scanning to guide treatment in aggressive non-Hodgkin lymphomas. Patients with B cell lymphomas and a negative interim scan received six cycles of R-CHOP with or without two extra doses of rituximab. For reasons related to trial design, only about a third underwent randomization between the two options. Combining randomized and non-randomized patients enabled subgroup analyses for diffuse large B cell lymphoma (DLBCL; n = 544), primary mediastinal B cell lymphoma (PMBCL; n = 37), and follicular lymphoma (FL) grade 3 (n = 35). With a median follow-up of 52 months, increasing the number of rituximab administrations failed to improve outcome. A non-significant trend for improved event-free survival was seen in DLBCL high-risk patients, as defined by the International Prognostic Index, while inferior survival was observed in female patients below the age of 60 years. Long-term outcome in PMBCL was excellent. Differences between FL grade 3a and FL grade 3b were not apparent. The results were confirmed in a Cox proportional hazard regression model and a propensity score matching analysis. In conclusion, adding two doses of rituximab to six cycles of R-CHOP did not improve outcome in patients with aggressive B cell lymphomas and a fast metabolic treatment response.
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- 2019
46. Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial : correlation with interim PET and outcome
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Martin-Leo Hansmann, Selina Gärtner, Wolfram Klapper, Peter Möller, Hans-Heinrich Wacker, Jan Rekowski, Julia Richter, Andreas Rosenwald, Andreas Hüttmann, Sylvia Hartmann, Ulrich Dührsen, Christoph Thorns, Alfred C. Feller, Christine Schmitz, and Stefan P. Müller
- Subjects
Male ,Medizin ,lcsh:RC254-282 ,Medical research ,Correspondence ,Humans ,Medicine ,ddc:610 ,Cancer genetics ,medicine.diagnostic_test ,business.industry ,Lymphoma, Non-Hodgkin ,Hematology ,Translational research ,Prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Interim pet ,Treatment Outcome ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Lymphoma, Large B-Cell, Diffuse ,Nuclear medicine ,business ,Diffuse large B-cell lymphoma - Abstract
No abstract available
- Published
- 2019
47. Mythos im Alltag – Alltag im Mythos : Die Banalität des Alltags in unterschiedlichen literarischen Verwendungskontexten
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Christine Schmitz, Durs Grünbein, Felix Mundt, Siegmar Döpp, Philipp Fondermann, Nina Otto, Christine Schmitz, Durs Grünbein, Felix Mundt, Siegmar Döpp, Philipp Fondermann, and Nina Otto
- Published
- 2019
48. Interim PET-Based Outcome Prediction in Diffuse Large B-Cell Lymphoma Patients Participating in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) Trial : Comparison of the Delta SUV Max Method and the Deauville 5-Point Scale
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Christine Schmitz, Ulrich Duehrsen, Andreas Hüttmann, Stefan P. Müller, Karl-Heinz Jöckel, and Jan Rekowski
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Oncology ,medicine.medical_specialty ,Receiver operating characteristic ,Proportional hazards model ,business.industry ,Concordance ,Immunology ,Hazard ratio ,Medizin ,Standardized uptake value ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Confidence interval ,Internal medicine ,Medicine ,business ,Diffuse large B-cell lymphoma ,Survival analysis - Abstract
Introduction: The recently published randomized PETAL trial (JCO 36:2024, 2018) aimed at improving outcome of aggressive non-Hodgkin lymphomas by changing therapy based on the response to the first 2 cycles of standard (R-)CHOP as assessed by interim PET (iPET). Outcome remained unaffected by treatment changes, which provided an opportunity to use the study to define the prognostic value of iPET. This report details the iPET results in the subgroup of patients (pts.) with diffuse large B-cell lymphoma (DLBCL), by comparing the deltaSUVmax method (J Nucl Med 48:1626, 2007) used in the course of the trial, with the Deauville 5-point scale (DS) which has been recommended for iPET-based outcome prediction in DLBCL (JCO 32:3048, 2014). With deltaSUVmax, a positive iPET indicating insufficient treatment response is defined as a reduction of the maximum standardized uptake value (SUV) by 2) or the liver (DS >3) on the same interim scan. Methods: iPET scans for a post-hoc investigation using the Deauville criteria were available from 597 of 609 DLBCL pts. treated in the PETAL trial. For the binary cut-off variables of deltaSUVmax and DS, concordance and Spearman correlation were calculated and hazard ratios (HR) regarding event-free (EFS), overall (OS), progression-free survival (PFS), and time to progression (TTP) were determined by Cox regression. Time-dependent receiver operating characteristic (ROC) analysis (Biometrics 56:337-44, 2000) for the raw values of deltaSUVmax and DS yielded area under the curve (AUC), sensitivity, specificity, and predictive values that were accompanied with median and 95% confidence intervals (CI) obtained from a simple bootstrap with 1,000 repetitions. The integrated Brier score was used as a measure of model calibration. Results: The numbers of DLBCL pts. with a positive iPET scan were 62 for deltaSUVmax, 408 for DS >2, and 278 for DS >3. Concordance between a positive iPET according to deltaSUVmax and the DS cut-offs was 40.4% and 60.1%, and Spearman correlation was 0.17 and 0.24, respectively. HRs for a positive iPET according to deltaSUVmax were higher than for the two DS cut-offs in any time-to-event endpoint: 3.13 [CI: 2.22 - 4.46] in EFS as compared to 1.36 [0.99 - 1.85] for DS >2 and 1.38 [1.05 - 1.81] for DS >3; 3.48 [2.29 - 5.27] in OS versus 1.56 [1.03 - 2.36] and 1.91 [1.33 - 2.73]; 3.06 [2.11 - 4.43] in PFS compared to 1.22 [0.88 - 1.69] and 1.34 [1.00 - 1.80]; and 3.04 [1.97 - 4.67] versus 1.28 [0.88 - 1.88] and 1.46 [1.04 - 2.07] in TTP. ROC analysis confirmed this tendency as AUCs were higher for deltaSUVmax than for DS in all four endpoints (Table 1). Also, the difference of predictive values of the two markers favored deltaSUVmax over DS >3 in EFS (Figure 1). Similar results were obtained in the remaining endpoints and for DS >2. Calibration assessed by the Brier score was slightly better for deltaSUVmax than for DS in EFS, PFS, and TTP, and was equal in OS. Of note, when investigating the survival curves in subgroups defined by both deltaSUVmax and DS >3, pts. with negative deltaSUVmax but positive DS showed similar survival as pts. with deltaSUVmax and DS both negative, presumably indicating DS false-positives (Figure 2). The same was true for deltaSUVmax positive/DS negative pts. whose unfavorable survival curve resembled that of double-positive pts.. Conclusion: DeltaSUVmax seems to be a more potent prognostic factor than DS in terms of discrimination and calibration with respect to EFS, OS, PFS, and TTP. Superior performance was shown for raw values as well as for dichotomized variables. The DS appeared unreliable due to a high number of false-positive results. Although the AUCs for deltaSUVmax were relatively low, it still seems to be a good prognostic tool with regard to HRs. Given its high positive predictive value, it may be a suitable tool to select poor-prognosis pts. in first-line for treatment approaches that have so far been reserved for later lines of therapy. Disclosures Hüttmann: Roche: Other: Travel expenses; Celgene: Other: Travel expenses. Duehrsen:Amgen: Research Funding; Gilead: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.
- Published
- 2018
49. Positron emission tomography-guided therapy of Aggressive Non-Hodgkin Lymphomas (PETAL): A multicenter, randomized phase III trial
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Georg Maschmeyer, Martin Griesshammer, Stefan P. Müller, Helga Bernhard, Johannes Matschke, Dieter Hoelzer, Marcus Brinkmann, Aristoteles Giagounidis, André Scherag, J. rg Kotzerke, Heinz-Gert Höffkes, Gabriele Prange-Krex, Rolf M. Mesters, Wolfgang E. Berdel, Andreas Hertel, Ingo Brink, Uwe Haberkorn, Aruna Raghavachar, Christine Schmitz, Dorothea Kofahl-Krause, Thorsten Pöppel, Jan Dürig, Lilli Geworski, Bernd Hertenstein, Lars Kurch, Christiane Franzius, Martin Freesmeyer, Jan Rekowski, Frank Kroschinsky, Claudia Ose, Henrike Thomssen, Stefan Wilop, Paul La Rosée, Dirk Behringer, Jens Holzinger, Andreas Hüttmann, Tobias Gaska, Ulrich Dührsen, Frank M. Bengel, Andreas Bockisch, Karl-Heinz Jöckel, Daniëlle M. E. van Assema, Wolfram Klapper, Matthias Weckesser, Thomas Krohn, and VU University medical center
- Subjects
Male ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Medizin ,CHOP ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Fluorodeoxyglucose F18 ,Prednisone ,immune system diseases ,Positron Emission Tomography Computed Tomography ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Fluorodeoxyglucose ,business.industry ,Lymphoma, Non-Hodgkin ,Hazard ratio ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,Treatment Outcome ,Oncology ,Doxorubicin ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Female ,Rituximab ,business ,030215 immunology ,medicine.drug - Abstract
Purpose Interim positron emission tomography (PET) using the tracer, [18F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt’s lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.
- Published
- 2018
50. T. GEUE, JUVENAL AND THE POETICS OF ANONYMITY (Cambridge Classical Studies). Cambridge: Cambridge University Press, 2017. Pp. xiii + 352. <scp>isbn</scp>9781108416344. £75.00
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Christine Schmitz
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Archeology ,History ,Literature and Literary Theory ,Visual Arts and Performing Arts ,Poetics ,Philosophy ,Classics ,Anonymity - Published
- 2019
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