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5. 208P Clinical characteristics and prognostic factors in patients with breast cancer and leptomeningeal metastases: A subanalysis of the German brain metastases in breast cancer registry (BMBC)

Author

E. Laakmann, E. Agostinetto, M. van Ramshorst, F. Schettini, M. Fontes e Sousa, L.V. Matos, A.M. Fitzpatrick, M. Vaz Batista, F. Le Du, K. Riecke, M. Schmidt, T. Neunhöffer, R. Weide, T-W. Park-Simon, C. Denkert, I. Witzel, J. Rey, S. Loibl, and V. Mueller

Subjects
Cancer Research, Oncology
Published
2023

7. Antiinfektive Therapie

Author

D., Adam, W., Christ, D., Hofmann, H., Kemmler, J., Knobloch, N., Lehn, Lemmen, S. W., H., Lode, R., Mertens, Naber, K. G., W., Preiser, K., Riecke, M., Ruhnke, R., Stahlmann, W., Vahlensieck, M., Weiß, Adam, D., editor, Doerr, H. W., editor, Link, H., editor, and Lode, H., editor

Published
2004
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10. Characteristics of patients with brain metastases from HER2-positive breast cancer

Author

Arkadius Polasik, J. Puppe, TW Park-Simon, K Lübbe, M Thill, Julia Rey, C Denkert, V Müller, S Loibl, E Laakmann, I Witzel, Rudolf Weide, Valentina Nekljudova, K Riecke, D. M. Zahm, C Mundhenke, T Hesse, T Fehm, and T Neunhöffer

Subjects
Oncology, medicine.medical_specialty, business.industry, HER2 Positive Breast Cancer, Internal medicine, medicine, business
Published
2021

11. Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry

Author

E, Laakmann, I, Witzel, T, Neunhöffer, T-W, Park-Simon, R, Weide, K, Riecke, A, Polasik, M, Schmidt, J, Puppe, C, Mundhenke, K, Lübbe, T, Hesse, M, Thill, D-M, Zahm, C, Denkert, T, Fehm, V, Nekljudova, J, Rey, S, Loibl, and V, Müller

Subjects
Cancer Research, Oncology, Brain Neoplasms, Receptor, ErbB-2, Humans, Breast Neoplasms, Female, Registries
Abstract

Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital.A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus60 years: hazard ratio (HR) 1.63, P0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

Published
2022

12. 95MO Characteristics of patients with brain metastases from HER2-positive breast cancer

Author

D. M. Zahm, Arkadius Polasik, Volkmar Mueller, E Laakmann, Julia Rey, I Witzel, K Riecke, J. Puppe, Christoph Mundhenke, Martina Schmidt, T. Hesse, Tanja Fehm, Valentina Nekljudova, T Neunhöffer, S. Loibl, TW Park-Simon, Marc Thill, C Denkert, R Weide, and Kristina Lübbe

Subjects
Oncology, medicine.medical_specialty, business.industry, Internal medicine, HER2 Positive Breast Cancer, medicine, Hematology, business
Published
2021

15. Predicting prognosis of breast cancer patients with brain metastases in the BMBC registry – comparison of three different prognostic scores

Author

Arkadius Polasik, Julia Rey, C Mundhenke, S Loibl, T Fehm, T Hesse, Rudolf Weide, E Laakmann, Martina Schmidt, T Neunhöffer, V Mueller, Peter A. Fasching, K Riecke, I Witzel, C Denkert, TW Park-Simon, Valentina Nekljudova, M Thill, and K Lübbe

Subjects
Oncology, medicine.medical_specialty, Breast cancer, business.industry, Internal medicine, medicine, business, medicine.disease
Published
2020

19. Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Author

Valentina Nekljudova, Tjoung Won Park-Simon, Tanja Fehm, T. Hesse, Arkadius Polasik, Peter A. Fasching, K Riecke, Julia Rey, Kristina Lübbe, Isabell Witzel, Volker Möbus, Sibylle Loibl, Carsten Denkert, Rudolf Weide, Christoph Mundhenke, Volkmar Müller, Marcus Schmidt, Marc Thill, Elena Laakmann, and T Neunhöffer

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Neoplasm metastasis, Metastase, Prognose, Context (language use), lcsh:RC254-282, Asymptomatic, Gastroenterology, Article, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, brain metastases, Internal medicine, Brustkrebs, asymptomatic, Medicine, Clinical significance, ddc:610, Treatment outcome, Hirnmetastase, Performance status, business.industry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Metastatic breast cancer, 030104 developmental biology, Risk factors, Oncology, Lead time bias, 030220 oncology & carcinogenesis, Cohort, Breast neoplasms, medicine.symptom, business, DDC 610 / Medicine & health
Abstract

Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80&ndash, 100%: 68.4% vs. 57%, p &lt, 0.001), a lower number of BM (&gt, 1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p &lt, 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p &lt, 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p &lt, 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.

Published
2020

20. 149P Predicting prognosis of breast cancer patients with brain metastases in the BMBC registry: Comparison of three different prognostic scores

Author

Arkadius Polasik, Tanja Fehm, J. Rey, K Riecke, Isabell Witzel, R Weide, T Hesse, K Lübbe, Marc Thill, Christoph Mundhenke, S. Loibl, TW Park-Simon, Marjanka K. Schmidt, T Neunhöffer, C Denkert, Elena Laakmann, Valentina Nekljudova, Peter A. Fasching, and Volkmar Mueller

Subjects
Oncology, medicine.medical_specialty, Breast cancer, business.industry, Internal medicine, Medicine, Hematology, business, medicine.disease
Published
2020

23. An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay

Author

A. Heusener, Peter Ulrich, G. Ehling, M. Hecht, Th. Maurer, K. Riecke, J. Huesler, L. Ullmann, H. van Loveren, A.O. Gamer, Rob J. Vandebriel, and H.-W. Vohr

Subjects
Oncology, medicine.medical_specialty, Validation study, business.industry, Local lymph node assay, Skin sensitization, Oecd guideline, Guideline, Toxicology, Skin irritation, medicine.anatomical_structure, Internal medicine, Immunology, medicine, Inter-laboratory, business, Lymph node
Abstract

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

Published
2005

24. Lactococcosis in Silver Carp

Author

A.W. Dunn, Keith O. Meals, Matt J. Griffin, Sylvie M. A. Quiniou, Frank W. Austin, Patricia S. Gaunt, Alicia M. Jacobs, Dennis K. Riecke, and Lester H. Khoo

Subjects
Silver carp, Hypophthalmichthys, Carps, biology, Lactococcus, Locus (genetics), Aquatic Science, biology.organism_classification, DNA gyrase, Microbiology, Lesion, Lactococcus lactis, Fish Diseases, Mississippi, medicine, bacteria, Animals, medicine.symptom, Ribosomal DNA, Bacteria, Gram-Positive Bacterial Infections
Abstract

An adult Silver Carp Hypophthalmichthys molitrix with a focally extensive skin lesion near the caudal peduncle and mild iridial hemorrhage was submitted to the Aquatic Research and Diagnostic Laboratory (ARDL) in Stoneville, Mississippi, as part of a fish kill investigation. Touch impressions of this musculoskeletal lesion revealed small cocci (∼1 μm) in pairs or chains within an inflammatory milieu. A pure Gram-positive cocci isolate was obtained from the brain, while cultures of the kidney and muscle yielded multiple bacterial colony types, including the Gram-positive cocci seen in the brain. This brain isolate was characterized biochemically and identified as Lactococcus spp. Analysis of the near complete 16S small subunit ribosomal DNA (SSU rDNA) and DNA gyrase subunit B (gyrB) gene sequences revealed the bacterium to be L. lactis subsp. lactis (SSU rDNA: 100% identity, 1,372/1,372 bp; gyrB: 99.7% identity, 1,779/1,785 bp). Comparatively, at the gyrB locus the case isolate shared less than 90% similarity to L. lactis subsp. cremoris (1,599/1,781 bp) and less than 80% homology to L. garvieae (1409/1775 bp). Histopathological examination confirmed a severe meningoencephalitis, a moderate mononuclear myositis, and a mild interstitial nephritis. We believe this represents the first report of a natural infection by L. lactis subsp. lactis in Silver Carp.

Published
2014

25. Textilfarbstoffe - Regulation und experimentelle Studien

Author

C. Lang, Ralf Stahlmann, Thomas Platzek, H. Höcker, T. Wannack, and K. Riecke

Subjects
Public Health, Environmental and Occupational Health
Abstract

In der beim Bundesinstitut fur gesundheitlichen Verbraucherschutz und Veterinarmedizin (BgVV) angesiedelten Arbeitsgruppe “Textilien” wurde erortert, inwieweit Verbraucher beim Tragen von Bekleidungstextilien gesundheitsgefahrdenden Substanzen ausgesetzt sind. Dabei wurde ein Risiko allergischer Reaktionen auf bestimmte Textilfarbstoffe ermittelt. Forschungsbedarf besteht insbesondere im Hinblick auf die Hohe der Exposition, auserdem wurden Lucken in der toxikologischen Prufung aufgezeigt. Daraus ergaben sich Forschungsprojekte zur Migration von Farbstoffen aus Textilien, ein toxikologisches Prufprogramm der Industrie sowie eigene experimentelle Projekte zum Stoffwechsel und zum sensibilisierenden Potential von Farbstoffen, die in Zusammenarbeit mit Universitaten (FU Berlin, TU Berlin, RWTH Aachen) durchgefuhrt werden. In-vitro-Studien mit Bakterien der menschlichen Haut belegen die metabolische Spaltung der Azofarbstoffe zu aromatischen Aminen. Beim Test eines Azofarbstoffs auf ein sensibilisierendes Potential (mouse local lymph node assay) erwies sich ein Metabolit als wirksam. Methodische Variationen wie die Messung der Zellproliferation durch Bestimmung der Zellzahl und die Miteinbeziehung durchflusszytometrischer Methodik sind vielversprechend.

Published
2001

26. An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round

Author

G, Ehling, M, Hecht, A, Heusener, J, Huesler, A O, Gamer, H, van Loveren, Th, Maurer, K, Riecke, L, Ullmann, P, Ulrich, R, Vandebriel, and H-W, Vohr

Subjects
Europe, Mice, Mice, Inbred BALB C, Endpoint Determination, Dermatitis, Allergic Contact, Irritants, Animals, Local Lymph Node Assay, Laboratories, Skin Tests
Abstract

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

Published
2004

28. Cross-reactivity of antibodies on thymic epithelial cells from humans and marmosets by flow-cytometry

Author

K, Riecke, A C, Nogueira, V, Alexi-Meskishvili, and R, Stahlmann

Subjects
Male, Receptors, Lymphocyte Homing, Callithrix, Epithelial Cells, Thymus Gland, Cross Reactions, Flow Cytometry, Antibodies, Xenobiotics, Disease Models, Animal, Epitopes, Animals, Humans, Female, Child
Abstract

Callithrix jacchus, the common marmoset, is particularly suitable for immunological studies in vivo and in vitro since many antibodies directed against epitopes of human cells do also react with their analogues from this non-human primate. We studied the reactivity of antibodies against human epitopes on primary cultures of thymic epithelial cells from marmosets and humans by flow-cytometry after different culture periods. The antibodies against integrins, including CD61, reacted with thymic epithelial cells from both humans and marmosets, as did anti-CD44 and anti-CD106. Antibodies specific for thymic epithelial cells (TE-3, TE-4, TE-8, TE-15, TE-16, TE-19) also bound to cells from marmosets but expression of all epitopes was not observed in all cultures studied. The expression of CD51, CD54, CD58 and CD106 on human cells declined after 4 weeks of culture. Our findings indicate that marmosets are a valuable model for immunological studies of effects of xenobiotics on the thymic epithelium.

Published
2001

29. Federal Funding for Programs to Prevent, Control, and Manage Aquatic Invasive Species

Author

Robert M. Hughes, Kristen H. Ferry, Donna L. Parrish, Philip Moy, Cynthia S. Kolar, Kirk Schroeder, Jill M. Hardiman, Dennis K. Riecke, and Gregory D. Pitchford

Subjects
business.industry, Environmental resource management, Control (management), Business, Aquatic Science, Invasive species, Nature and Landscape Conservation
Published
2013

30. Test systems to identify reproductive toxicants

Author

R. Stahlmann and K. Riecke

Subjects
Male, Urology, Developmental toxicity, Drug Evaluation, Preclinical, Biology, In Vitro Techniques, Bioinformatics, Reproductive cycle, Xenobiotics, chemistry.chemical_compound, Endocrinology, Pregnancy, Animals, Humans, Animal testing, Flexibility (engineering), business.industry, Reproduction, In vitro toxicology, Abnormalities, Drug-Induced, General Medicine, Biotechnology, Fertility, Teratogens, chemistry, Reproductive process, Female, Reproductive toxicity, business, Xenobiotic
Abstract

Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called ‘segment testing protocols’ have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (aciclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

Published
2000

31. [Inpatient treatment costs of exacerbated chronic obstructive lung disease]

Author

K, Riecke, J, Eller, C, Gericke, and H, Lode

Subjects
Adult, Aged, 80 and over, Male, Length of Stay, Middle Aged, Hospital Charges, Berlin, Patient Admission, Costs and Cost Analysis, Humans, Female, Lung Diseases, Obstructive, Prospective Studies, Hospital Costs, Aged
Abstract

Economic aspects are of increasing importance in health care. However, treatment expenditures for most diseases are unknown. We performed a detailed cost analysis for the treatment of the exacerbated chronic obstructive pulmonary disease (ECOPD) in our department. For one year, all patients admitted because of exacerbated chronic obstructive pulmonary disease were included in this study. The workload was assessed for each patient by time keeping. Diagnostic and therapeutic procedures were considered according to the price list of the German hospital association. From 101 patients included into the study, 100 were evaluable. The median duration of inpatient hospitalisation amounted to 18 days (range: 4 to 210 days). Median total cost was DM 7680.- and mean cost DM 11900.-. This consisted of non-medical cost items (36%), personnel expenditures (29%), laboratory tests (14%), respiratory and cardiovascular laboratory (7%), radiology (5%) and pharmacy cost (7%). Endoscopy, external diagnostics and medical reports amounted to 2.8% of the expenditure. Treatment cost correlated with the duration of stay, but hardly with lung function and blood gases, these being independent of age and sex, but significantly higher in case of bronchiectasis, enterobacteriae, cor pulmonale or intensive care. The proportion of the pharmacy expenditures was rather small, and hence this is not a primary target for the realisation of major savings.

Published
1999

32. A

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

33. H

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

34. I

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

35. C

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

36. G

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

37. F

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

38. B

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

39. D

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

40. K

Author

Franz von Bruchhausen, Eberhard Hackenthal, Siegfried Ebel, Ulrike Holzgrabe, August Wilhelm Frahm, M. Albinus, G. Amschler, E. von Angerer, null Arras-Reiter, P. Barth, W. Barthel, K. Bauer, P. Bauer, I. Baumann, J. Beckmann, W. Beil, J. Reitz, K. Binder, F. Bossle, F. Bracher, H. Bräunlich, E. Bretschneider, R. Brigelius-Flohé, K. Brinkmann, F. von Bruchhausen, A. Rüge, W. Christ, M. Cimbollek, R. Daniels, G. Dannhardt, H. Duchstein, S. Ebel, K. Eger, P. Eichhorn, U. Eiben, T. Erker, P. Felfe, A. Frahm, M. Frahm, V. Franke, K. Freundt, D. Geffken, U. Geis, E. Glusa, B. Göber, P. Gobina, W. Golder, M. Goppelt­Strübe, K. Götte, E. Gottstein, G. Greif, A. Grisk, M. Grosam, H. Gustmann, M. Gütschow, E. Hackenthal, A. Häfner, B. Haluszczynski, A. Harder, H. Häusler, D. Heber, M. Heidenreich, G. Heinemeyer, E. Heller, D. von Herrath, J. Hilfenhaus, H. Hoffmann, U. Hoffmann-Schollmayer, B. Hofmann, C. Holpert, U. Holzgrabe, U. Hübner-Steiner, M. Hug, E. Inkmann, A. Jördens, J. Jürgens, B. Kaiser, D. Kalbhen, H. Kemmler, P. Kisser, D. Kleinsorge, C. Klett, S. Klett, M. Klingmüller, H. Klöcking, A. Kramer, B. Krammer, M. Kreher, M. Krüger, M. Kuhn, D. Landsiedel-Maier, P. Lauven, J. Lehmann, M. Lehner, D. Leopoldt, A. Maurer, W. Meindl, K. Menges, P. Mes­singer, F. Meyer, W. Meyerhof, R. Morgenstern, U. Mühlhans, A. Müller, C. Müller, K. Müller, A. Mülsch, C. Nachtsheim, M. Neugebauer, W. Neupert, P. Nickel, P. Nuhn, B. Nürnberg, H. Oelschläger, J. Oertel, M. Oettel, R. Ott, T. Ott, T. Otzen, P. Pachaly, H. Pelzer, K. Petersen, R. Pick, M. Pickert, A. Pies, H. Priewer, O. Queckenberg, G. Radau, E. Reimann, J. Remien, M. Reuß, W. Reuß, J. Richter, P. Richter, K. Riecke, H. Rommelspacher, U. Rose, G. Roth, D. Rothley, G. Rücker, J. Schäfer, J. Schantl, H. Schlager, H. Schleinitz, W. Schlichter, M. Schmauß, H. Schmidhammer, G. Schmidt, T. Schmidt, H. Schmitt, J. Sehräder, T. Schulz, H. Schwilden, M. Serke, G. Skopp, G. Skorka, K. Smolinka, U. Speck, M. Spohn, R. Stahlmann, J. Stasch, C. Steffen, H. Stein, J. Steinmeyer, K. Stiefvater, G. Strippel, K. Surborg, U. Stürig, H. Szelényi, I. Szelényi, A. Täufel, R. Thieroff-Ekerdt, R. Troschütz, H. Ungeheuer, B. Unterhalt, E. Verspohl, S. Vogel, F. Volk, T. Vorwerk, J. Wallmann, H. Weber, M. Wenzel, M. Weyandt-Spangenberg, S. Wich, R. Wintersteiger, B. Wüst, and D. Youssef

Published
1999

41. [Pulmonary melioidosis in a German Southeast Asia tourist]

Author

K, Riecke, S, Wagner, J, Eller, H, Lode, and T, Schaberg

Subjects
Adult, Diagnosis, Differential, Male, Travel, Anti-Infective Agents, Melioidosis, Trimethoprim, Sulfamethoxazole Drug Combination, Pneumonia, Bacterial, Humans, Thailand
Abstract

A patient who returned from a 3-year stay in Thailand and India one year ago, was admitted with fever of 38.5 degrees C and productive cough for the last four weeks. He remembered wounding his foot three years ago in India with contamination by soil. Subsequently, recurrent pustulae appeared on his feet. One such pustule was found on admittance. The clinical examination showed low body weight, without further abnormalities.The blood examinations revealed high inflammation parameters and ruled out any immunodeficiency. Smouldering infiltrates in the upper lobes were found on the chest radiography. Sputum was free of acid fast bacilli and no mycobacterial DNA was detected by polymerase chain reaction. Bronchoscopy showed a normal endobronchal situation, Burkholderia pseudomallei were found to grow from specimens of bronchial mucus.Under the empirical treatment with ampicillin/sulbactam, we could not find any response. After switching to Ceftazidime and trimethoprim/sulfamethoxazol (TMP/SMZ) we observed quick clinical improvement and normalisation of the inflammation parameters and notable radiological response over three weeks. We continued a five months TMP/SMZ therapy after discharge in order to prevent relapses.For travellers and immigrants from Southeast Asia presenting smouldering infiltrations of the upper lobes, one should include Melioidosis in the differential diagnosis.

Published
1997

42. Relationship of Dose and Signal Enhancement Properties of Gadoquatrane, a New Tetrameric, Macrocyclic Gadolinium-Based Contrast Agent, Compared With Gadobutrol: A Randomized Crossover Study in Healthy Adults.

Author

Hofmann BM, Riecke K, Klein S, Klemens MA, Palkowitsch P, Kahn JF, Posch H, Berse M, and Ebert W

Abstract

Objectives: To investigate the signal-enhancement properties of the tetrameric gadolinium-based contrast agent (GBCA) gadoquatrane in relation to the administered dose and compare its properties to those of a standard dose of gadobutrol, as a representative of the currently established macrocyclic GBCAs for magnetic resonance imaging., Materials and Methods: In this randomized, single-blind, 4 × 4 crossover study, 43 healthy adults (19-50 years of age) received 3 single IV injections of gadoquatrane (0.01, 0.03, and 0.06 mmol gadolinium/kg body weight) and 1 injection of gadobutrol (0.1 mmol gadolinium/kg body weight) in randomized sequence with 1-week washout periods between administrations. The relative signal enhancement (RSE) was determined in predefined areas of interest in magnetic resonance image sets of the head-neck region. RSE-vs-dose curves (dose-response curves) were established by linear regression, and comparator-equivalent doses were determined by Bayesian inverse regression analysis. Further, 3 blood samples were taken after each injection for pharmacokinetic analyses, and safety data were assessed., Results: The RSE increased with gadoquatrane dose. A linear function adequately fitted this relationship. In line with the more than 2-fold higher r1 relaxivity of gadoquatrane per gadolinium ion, gadobutrol-equivalent RSE was achieved with gadoquatrane at less than half the gadolinium dose and less than one eighth of the molecule dose.Administration of gadoquatrane and gadobutrol resulted in very similar dose-normalized gadolinium concentrations in plasma, indicating that the pharmacokinetic profiles are essentially the same. Both contrast agents were well tolerated. Adverse events were rare and not dependent on the dose administered., Conclusions: Gadoquatrane has the potential to be an effective GBCA that can be used at substantially lower doses in clinical routine than the currently established macrocyclic GBCAs., Competing Interests: Conflicts of interest and sources of funding: The study was sponsored by Bayer AG. All authors are or were working at Bayer AG or on behalf of Bayer AG., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2024
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43. Differences in patterns of sexual assault among female victims preceding and during the COVID-19 pandemic: an analysis of encounters in an emergency department.

Author

Klasen CM, Teltrop L, Belau MH, Lohner L, Ondruschka B, Riecke K, Reuter S, Schmalfeldt B, Wilmes S, and Witzel I

Subjects
Humans, Female, Retrospective Studies, Adult, Germany epidemiology, Young Adult, Adolescent, Middle Aged, Substance-Related Disorders epidemiology, Coronavirus Infections epidemiology, SARS-CoV-2, Pneumonia, Viral epidemiology, COVID-19 epidemiology, Emergency Service, Hospital statistics & numerical data, Sex Offenses statistics & numerical data, Crime Victims statistics & numerical data, Pandemics
Abstract

The aim of this study was to evaluate how the COVID-19 pandemic may have impacted the number and patterns of sexual assault victims within a German metropolitan city. A retrospective single center analysis of the gynecology examination reports of all women presenting to the emergency department of a university hospital after a sexual offense between 03/2013 and 02/2021 (n = 1167). Comparison of the first year of the pandemic 03/2000-03/2021) to previous years (03/2017-02/2020) and comparison of periods of government-imposed social distancing (03/12/2020-05/23/2020 and 10/23/2020-02/28/2021) with corresponding periods of pre-pandemic years. The overall number of sexual assault cases did not change during the first year of the COVID-19 pandemic. However, during the stay-at-home orders, the number of women presenting to the emergency department decreased by 38% (n=45 vs. 72). Fewer victims filed a police report during the pandemic (49.5% vs. 73.9%, p<0.001) and the lockdown period (50% vs. 76.5%, p<0.001). Less genital injuries after sexual assault were detected during the pandemic (14.3% vs. 25.2%, p<0.02), but there was an increase of illegal substance abuse (19.5% vs. 9.3%, p<0.003). During the stay-at-home orders fewer victims reported alcohol consumption (42.4% vs. 62.5 %, p<0.023). Despite the decrease in sexual offense related police reports, the number of sexual assault cases remained consistent, and the usage of illegal drugs increased during the COVID-19 pandemic. These findings represent the importance of providing support to sexual assault victims, as well as the implementation of preventative measures, especially in times of crisis., (© 2023. The Author(s).)

Published
2024
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44. Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report about a Male Patient with Pectoral Implants.

Author

Riecke K, Steinhilper L, von Bülow C, Schwarz D, Burandt E, Striefler JK, Müller V, Schmalfeldt B, and Witzel I

Abstract

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is still a rare extralymphatic lymphoma. As of March 1, 2023, approximately 1,355 cases of BIA-ALCL have been reported worldwide. However, no such case has yet been described with pectoral implants in male patients. Most patients with BIA-ALCL present with nonspecific implant-associated symptoms such as late-onset seroma, swollen breasts, and deformation of implants., Case Presentation: Here, we describe BIA-ALCL in a 76-year-old male patient who presented with a late-onset seroma in order to raise awareness for BIA-ALCL also in men after esthetic chest surgery with silicone pectoral implants. The patient had undergone augmentation of the pectoralis muscle with implants for esthetic reasons 9 years before. First cytological specimens showed no malignancy. A repeated cytological assessment after 6 weeks from recurring seroma showed characteristic CD30+ T-cell clones. Surgery with complete bilateral capsulectomy and implant removal was performed. Due to the early-stage ALCL being limited only to the capsule and no evidence of systemic disease, adjuvant systemic treatment was not considered necessary., Conclusion: Any persisting late-onset seroma also in male patients with pectoral implants should raise suspicion of ALCL as differential diagnosis and should be assessed with cytological examination., Competing Interests: Prof. Dr. Eike Burandt: advisory boards for Novartis and Daiichi Sankyo, and speaker’s honoria for AstraZeneca, Eisai, and NOGGO. All remaining authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Published
2024
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45. Pharmacokinetics, Safety, and Tolerability of the Novel Tetrameric, High-Relaxivity, Macrocyclic Gadolinium-Based Contrast Agent Gadoquatrane in Healthy Adults.

Author

Hofmann BM, Riecke K, Klein S, Berse M, Rottmann A, Sutter G, and Ebert W

Subjects
Adult, Female, Humans, Male, Double-Blind Method, Magnetic Resonance Imaging, Prospective Studies, Single-Blind Method, Contrast Media adverse effects, Contrast Media pharmacokinetics, Gadolinium adverse effects, Gadolinium pharmacokinetics
Abstract

Objectives: Gadolinium (Gd)-based contrast agents are well established in clinical routine and have been proven safe and effective. However, there is a need for "next-generation" Gd-based contrast agents that would allow lowering the Gd dose used for routine contrast-enhanced magnetic resonance imaging procedures. The objective of this first-in-human study was to investigate the pharmacokinetic profile, safety, and tolerability of gadoquatrane, a novel high-relaxivity Gd-based contrast agent., Materials and Methods: This study was conducted in 2018/2019 as a prospective, randomized, single-blind, single-dose, placebo-controlled, escalating-dose study. Healthy volunteers were randomly assigned (6:2) to intravenous administration of gadoquatrane (0.025 to 0.2 mmol Gd/kg body weight) or placebo. Study procedures included collection of blood samples and excreta for pharmacokinetic analyses and safety assessments., Results: Forty-nine healthy study participants (mean age ± SD, 35 ± 6.3 years; 24 female) were evaluated. The effective half-life of gadoquatrane in plasma was short and similar in all dose groups (1.4-1.7 hours). Plasma concentrations around the lower quantitation limit (0.0318 μmol Gd/L) were reached 15-72 hours after administration. The volume of distribution at steady state was ~0.2 L/kg in all dose groups. The clearance (total and renal) was ~0.1 L/h per kilogram in all groups. Across dose groups, the exposure of gadoquatrane increased dose-proportionally. Metabolite profiling revealed no hint of degradation in vivo or release of free Gd. Seven of 36 participants (19.4%) receiving gadoquatrane and 4 of 13 participants (30.8%) receiving placebo experienced mild or moderate treatment-emergent adverse events. No serious adverse events occurred. The analysis of the Gd concentration-QTc interval relationship indicated no risk of QT/QTc prolongation (>10 milliseconds) with gadoquatrane at clinical dose levels., Conclusions: Gadoquatrane with its high-relaxivity, pharmacokinetic similarity to established Gd-based contrast agents and high tolerability is a promising "next-generation" contrast agent for magnetic resonance imaging., Competing Interests: Conflicts of interest and sources of funding: The study was sponsored by Bayer AG. All authors are or were working at Bayer AG or on behalf of Bayer AG., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2024
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46. Intrathecal Therapy Options for Meningeal Carcinomatosis.

Author

Marowsky M, Müller V, Schmalfeldt B, Riecke K, Witzel I, and Laakmann E

Abstract

Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median survival of these patients is between 3.5 and 4.5 months. Current treatment approaches are based on radiotherapy, systemic and intrathecal therapy. Methotrexate, liposomal cytarabine and trastuzumab are the most common substances used for intrathecal therapy. The aim of this review was to provide an overview of these intrathecal therapy options for meningeal carcinomatosis. A systematic search of the literature was carried out in PubMed using the following search terms: "meningeal metastases", "meningeal carcinomatosis", "leptomeningeal metastasis", "leptomeningeal carcinomatosis", "leptomeningeal disease", "breast cancer", "MTX", "methotrexate", "DepoCyte", "liposomal cytarabine", "trastuzumab" and "anti-HER2". This search resulted in 75 potentially relevant studies, 11 of which were included in this review after meeting the previously determined inclusion and exclusion criteria. The studies differ considerably with regards to study design, cohort size, and dosages of administered drugs. In principle, intrathecal therapy has a tolerable side-effects profile and offers promising results in terms of the median overall survival following treatment with trastuzumab for HER2-positive primary tumors. The focus when treating meningeal carcinomatosis must be on providing a multimodal individual therapeutic approach. However, comprehensive studies which compare the efficacy and side effects of individual pharmaceuticals are lacking. Because of the poor prognosis associated with meningeal carcinomatosis, an approach which treats only the symptoms (best supportive care) should always be considered and discussed with affected patients., Competing Interests: Conflict of Interest MM: no conflict of interest relating to the topic of this review. EL: no conflict of interest relating to the topic of this review. KR: no conflict of interest relating to the topic of this review. IW: no conflict of interest relating to the topic of this review. VM: speaker’s fees: AstraZeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, Medscape. Consultancy services: Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Stemline, ClinSol. Research support to employer: Novartis, Roche, Seagen, Genentech, AstraZeneca. Travel expenses: Roche, Pfizer, Daiichi-Sankyo., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Published
2023
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47. Long-term survival of breast cancer patients with brain metastases: subanalysis of the BMBC registry.

Author

Riecke K, Müller V, Neunhöffer T, Park-Simon TW, Weide R, Polasik A, Schmidt M, Puppe J, Mundhenke C, Lübbe K, Hesse T, Thill M, Wuerstlein R, Denkert C, Decker T, Fehm T, Nekljudova V, Rey J, Loibl S, Laakmann E, and Witzel I

Subjects
Humans, Prognosis, Brain, Triple Negative Breast Neoplasms, Brain Neoplasms therapy, Brain Neoplasms secondary
Abstract

Background: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities., Patients and Methods: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors., Results: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients., Conclusions: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment., Competing Interests: Disclosure IW received speaker’s honoraria from Astra Zeneca, Merck, Pfizer, Roche, Daiichi-Sankyo, Seagen, Gilead and Novartis. KL received speaker’s honoraria from Roche, Novartis, Pfizer, Exact Sciences, MSD, Eisai, Lilly, Seagen, AstraZeneca and Daiichy Sankyo. MS has received personal fees from AstraZeneca, BioNTech, Daiichi-Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and Seagen. His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and Seagen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. SL reports grants, non-financial support and other from Daiichi-Sankyo, during the conduct of the study; grants and other from Abbvie, other from Amgen, grants and other from AstraZeneca, other from BMS, grants and other from Celgene, other from Eirgenix, other from Eisai Europe Ltd, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants from Molecular Health, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Relay Therapeutics, grants, non-financial support and other from Roche, other from Sanofi, non-financial support and other from Seagen, other from Olema Pharmaceutics, outside the submitted work; In addition, SL has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending and a patent Digital Ki67 Evaluator with royalties paid. CD reports advisory role for MSD Oncology, Daiichi-Sankyo, Molecular Health, AstraZeneca, Roche and Lilly; CD received research funding from Myriad Genetics, Roche and German Breast Group; CD owns following patents: VMScope digital pathology software, Patent WO2020109570A1, Patent WO2015114146A1, Patent WO2010076322A1. MT received personal fees from Agendia, Amgen, Art tempi, AstraZeneca, Aurikamed, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Organon, Pfizer, Pierre Fabre, Roche, Seagen, Servier, Streamd Up!, Viatris, Vifor, trial funding from Exact Science and institutional trial honoraria from AstraZeneca, Celgene, Novartis, Roche. VM received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead and Pierre Fabre; consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen and Gilead; Institutional research support from Novartis, Roche, Seagen, Genentech; travel grants: Roche, Pfizer, Daiichi-Sankyo, Gilead. RW received support for advisory, consultancy, speaker and travel grants from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Stemline, Tesaro Bio, Teva, Veracyte and Viatris. TD received Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, IOMEDICO and participated on a Data Safety Monitoring Board or Advisory Board for Novartis, IOMEDICO. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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48. Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry.

Author

Laakmann E, Witzel I, Neunhöffer T, Park-Simon TW, Weide R, Riecke K, Polasik A, Schmidt M, Puppe J, Mundhenke C, Lübbe K, Hesse T, Thill M, Zahm DM, Denkert C, Fehm T, Nekljudova V, Rey J, Loibl S, and Müller V

Subjects
Female, Humans, Receptor, ErbB-2 metabolism, Receptor, ErbB-2 therapeutic use, Registries, Brain Neoplasms secondary, Breast Neoplasms drug therapy
Abstract

Background: Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital., Patients and Methods: A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype., Results: Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups., Conclusions: We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients., Competing Interests: Disclosure MT serves on the advisory board for Amgen, AstraZeneca, AURIKAMED, Becton/Dickinson, Biom‘Up, Celgene, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Lilly, MSD, Norgine, NeoDynamics, Novartis, Onkowissen, Pfizer, pfm Medical, Pierre-Fabre, Roche, RTI Surgical, Seagen and Sysmex; reports manuscript support from Amgen, Celgene, ClearCut, pfm medical, Roche and Servier; support for travel expenses from Amgen, Art Tempi, AstraZeneca, Celgene, Cleracut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Norgine, Novartis, OmniaMed, Pfizer, pfm medical, Roche and RTI Surgical; support for congress expenses from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, NeoDynamics, Novartis, Pfizer and Roche; support for speech expenses: Amgen, Art Tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Eisai, Exact Sciences, Gilead Science, Hexal, I-Med-Institute, Jörg Eickeler, Lilly, MCI, Medtronic, MSD, Novartis, OmniaMed, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, Sysmex, Vifor and Viatris; trial funding support from Endomag and Exact Sciences. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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49. Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry-Comparison of Three Different GPA Prognostic Scores.

Author

Riecke K, Müller V, Weide R, Schmidt M, Park-Simon TW, Möbus V, Mundhenke C, Polasik A, Lübbe K, Hesse T, Laakmann E, Thill M, A Fasching P, Denkert C, Fehm T, Nekljudova V, Rey J, Loibl S, and Witzel I

Abstract

Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients ( n = 197) had triple-negative, 33.4% ( n = 295) luminal A like, 25.1% ( n = 221) luminal B/HER2-enriched like and 19.2% ( n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and low Karnofsky-Performance-Status (KPS) were all associated with worse overall survival (OS) in univariate analysis ( p < 0.001 each). All three GPA-scores were associated with OS. The breast-GPA showed the highest probability of classifying patients with survival above 12 months in the best prognostic group (specificity 68.7% compared with 48.1% for the updated breast-GPA and 21.8% for the original GPA). Sensitivities for predicting 3 months survival were very low for all scores. In this analysis, all GPA-scores showed only moderate diagnostic accuracy in predicting the OS of BC patients with BM.

Published
2021
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50. Targeting the Human Epidermal Growth Factor Receptor Family in Breast Cancer beyond HER2.

Author

Riecke K and Witzel I

Abstract

Currently, the dichotomous definition of human epidermal growth factor receptor 2 (HER2)-positive versus HER2-negative disease undergoing a change through inclusion of the identification of the "HER2-low" category, for which new therapeutic compounds in the form of potent antibody drug conjugates (ADC) may be effective. In addition, resistance to HER2-directed targets has become a clinical challenge and, therefore, strategies to bypass the HER2 receptor are of high interest. These are new HER2 ADCs and tyrosine kinase inhibitors, such as tucatinib or neratinib. The underlying mechanisms of resistance to anti-HER2 therapies and compensatory pathways are complex and a wide range of mechanisms of resistance may coexist in the same cell. Therefore, the combined treatment with agents that interact with HER2-associated downstream signaling pathways like the phosphoinositide-3-kinase (PI3K) and the serine/threonine kinases AKT and mTOR might overcome HER2 resistance. In addition, targeting other members of the HER family is a promising approach to improve outcomes in breast cancer patients. This review gives an overview of treatment strategies in targeting HER2 and other members of the HER family, not only in HER2-positive breast cancer, but also in HER2-low expressing tumors, and of approaches to overcome HER2 resistance., Competing Interests: K.R. has no conflict of interest to declare. I.W. received speakers' honoraria from Amgen, Pfizer, Novartis, Roche, MSD, Daichi Sankyo, and Pierre Fabre Pharma, and institutional (non-personal) funding from MSD., (Copyright © 2020 by S. Karger AG, Basel.)

Published
2020
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