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The Leipzig Health Atlas - A Research Data Repository utilizing i2b2 and tranSMART: Poster
Management of health information systems

Abstract

Not specified

Authors: Salma El-Oualydy, Matthias Löbe, Frank Meineke, Alfred Winter

Date Published: 2018

Publication Type: Misc

Age, ocular magnification, and circumpapillary retinal nerve fiber layer thickness.
LIFE Adult

Abstract (Expand)

Optical coherence tomography (OCT) manufacturers graphically present circumpapillary retinal nerve fiber layer thickness (cpRNFLT) together with normative limits to support clinicians in diagnosing … ophthalmic diseases. The impact of age on cpRNFLT is typically implemented by linear models. cpRNFLT is strongly location-specific, whereas previously published norms are typically restricted to coarse sectors and based on small populations. Furthermore, OCT devices neglect impacts of lens or eye size on the diameter of the cpRNFLT scan circle so that the diameter substantially varies over different eyes. We investigate the impact of age and scan diameter reported by Spectralis spectral-domain OCT on cpRNFLT in 5646 subjects with healthy eyes. We provide cpRNFLT by age and diameter at 768 angular locations. Age/diameter were significantly related to cpRNFLT on 89%/92% of the circle, respectively (pointwise linear regression), and to shifts in cpRNFLT peak locations. For subjects from age 42.1 onward but not below, increasing age significantly decreased scan diameter (r=-0.28, p<0.001), which suggests that pathological cpRNFLT thinning over time may be underestimated in elderly compared to younger subjects, as scan diameter decrease correlated with cpRNFLT increase. Our detailed numerical results may help to generate various correction models to improve diagnosing and monitoring optic neuropathies.

Authors: M. Wang, T. Elze, D. Li, N. Baniasadi, K. Wirkner, T. Kirsten, J. Thiery, M. Loeffler, C. Engel, F. G. Rauscher

Date Published: 25th Dec 2017

Publication Type: Journal article

Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group.
GLA - German Lymphoma Alliance

Abstract (Expand)

To study if obesity is a risk factor in elderly patients (>60 years) with aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with rituximab in the RICOVER-60 trial were analysed … in a retrospective study with regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body weight (BMI < 18.5), 38% were normal weight (18.5 </= BMI < 25), 42% were overweight (25 </= BMI < 30) and 19% were obese (BMI >/= 30). Event-free (EFS), progression-free (PFS) and overall survival (OS) according to BMI showed no significant differences for all and for male patients. EFS (P = 0.041), PFS (P = 0.038) and OS (P = 0.031) were significantly better for female non-obese patients. A multivariate analysis adjusted for International Prognostic Index risk factors confirmed these results, with the following hazard ratios (HR) for obesity (BMI >/= 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4 (not significant); male patients - 1.2/1.2/1.0 (not significant) and female patients - 1.7 (P = 0.032)/1.9 (P = 0.022)/2.0 (P = 0.017). In conclusion, obesity is a risk factor that influences treatment outcome in elderly female patients with aggressive B-cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone). The inferior outcomes in obese female patients may be due to faster rituximab clearance in obese females.

Authors: K. Hohloch, B. Altmann, M. Pfreundschuh, M. Loeffler, N. Schmitz, F. Zettl, M. Ziepert, L. Trumper

Date Published: 2nd Dec 2017

Publication Type: Not specified

Human Diseases: obesity, B-cell lymphoma

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

Background: The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods: We analysed patient … characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results: TF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (</=12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. Conclusion: MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

Authors: B. Glass, A. J. Dohm, L. H. Truemper, M. Pfreundschuh, A. Bleckmann, G. G. Wulf, A. Rosenwald, M. Ziepert, N. Schmitz

Date Published: 1st Dec 2017

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using … 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P \textless 5 \times 10-8 with ten variants at nine new loci. At P \textless 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Authors: Roger L. Milne, Karoline B. Kuchenbaecker, Kyriaki Michailidou, Jonathan Beesley, Siddhartha Kar, Sara Lindström, Shirley Hui, Audrey Lemaçon, Penny Soucy, Joe Dennis, Xia Jiang, Asha Rostamianfar, Hilary Finucane, Manjeet K. Bolla, Lesley McGuffog, Qin Wang, Cora M. Aalfs, Marcia Adams, Julian Adlard, Simona Agata, Shahana Ahmed, Habibul Ahsan, Kristiina Aittomäki, Fares Al-Ejeh, Jamie Allen, Christine B. Ambrosone, Christopher I. Amos, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Bernd Auber, Paul L. Auer, Margreet G. E. M. Ausems, Jacopo Azzollini, François Bacot, Judith Balmaña, Monica Barile, Laure Barjhoux, Rosa B. Barkardottir, Myrto Barrdahl, Daniel Barnes, Daniel Barrowdale, Caroline Baynes, Matthias W. Beckmann, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Yves-Jean Bignon, Kathleen R. Blazer, Marinus J. Blok, Carl Blomqvist, William Blot, Kristie Bobolis, Bram Boeckx, Natalia V. Bogdanova, Anders Bojesen, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Aniko Bozsik, Angela R. Bradbury, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Brigitte Bressac-de Paillerets, Carole Brewer, Louise Brinton, Per Broberg, Angela Brooks-Wilson, Joan Brunet, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Jinyoung Byun, Qiuyin Cai, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Federico Canzian, Olivier Caron, Angel Carracedo, Brian D. Carter, J. Esteban Castelao, Laurent Castera, Virginie Caux-Moncoutier, Salina B. Chan, Jenny Chang-Claude, Stephen J. Chanock, Xiaoqing Chen, Ting-Yuan David Cheng, Jocelyne Chiquette, Hans Christiansen, Kathleen B. M. Claes, Christine L. Clarke, Thomas Conner, Don M. Conroy, Jackie Cook, Emilie Cordina-Duverger, Sten Cornelissen, Isabelle Coupier, Angela Cox, David G. Cox, Simon S. Cross, Katarina Cuk, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Francesca Damiola, Hatef Darabi, Rosemarie Davidson, Kim de Leeneer, Peter Devilee, Ed Dicks, Orland Diez, Yuan Chun Ding, Nina Ditsch, Kimberly F. Doheny, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Isabel Dos-Santos-Silva, Stéphane Dubois, Pierre-Antoine Dugué, Martine Dumont, Alison M. Dunning, Lorraine Durcan, Miriam Dwek, Bernd Dworniczak, Diana Eccles, Ros Eeles, Hans Ehrencrona, Ursula Eilber, Bent Ejlertsen, Arif B. Ekici, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, Laura Fachal, Laurence Faivre, Peter A. Fasching, Ulrike Faust, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, William D. Foulkes, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Pragna Gaddam, Marilie D. Gammon, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, José A. García-Sáenz, Mia M. Gaudet, Marion Gauthier-Villars, Andrea Gehrig, Vassilios Georgoulias, Anne-Marie Gerdes, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Paul Goodfellow, Mark H. Greene, Grethe I. Grenaker Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Daphne Gschwantler-Kaulich, Pascal Guénel, Qi Guo, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Emily Hallberg, Ute Hamann, Nathalie Hamel, Susan Hankinson, Thomas v. O. Hansen, Patricia Harrington, Steven N. Hart, Jaana M. Hartikainen, Catherine S. Healey, Alexander Hein, Sonja Helbig, Alex Henderson, Jane Heyworth, Belynda Hicks, Peter Hillemanns, Shirley Hodgson, Frans B. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Bob Hoover, John L. Hopper, Chunling Hu, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, David J. Hunter, Evgeny N. Imyanitov, Claudine Isaacs, Motoki Iwasaki, Louise Izatt, Anna Jakubowska, Paul James, Ramunas Janavicius, Wolfgang Janni, Uffe Birk Jensen, Esther M. John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Karin Kast, Renske Keeman, Michael J. Kerin, Carolien M. Kets, Machteld Keupers, Sofia Khan, Elza Khusnutdinova, Johanna I. Kiiski, Sung-Won Kim, Julia A. Knight, Irene Konstantopoulou, Veli-Matti Kosma, Vessela N. Kristensen, Torben A. Kruse, Ava Kwong, Anne-Vibeke Lænkholm, Yael Laitman, Fiona Lalloo, Diether Lambrechts, Keren Landsman, Christine Lasset, Conxi Lazaro, Loic Le Marchand, Julie Lecarpentier, Andrew Lee, Eunjung Lee, Jong Won Lee, Min Hyuk Lee, Flavio Lejbkowicz, Fabienne Lesueur, Jingmei Li, Jenna Lilyquist, Anne Lincoln, Annika Lindblom, Jolanta Lissowska, Wing-Yee Lo, Sibylle Loibl, Jirong Long, Jennifer T. Loud, Jan Lubinski, Craig Luccarini, Michael Lush, Robert J. MacInnis, Tom Maishman, Enes Makalic, Ivana Maleva Kostovska, Kathleen E. Malone, Siranoush Manoukian, JoAnn E. Manson, Sara Margolin, John W. M. Martens, Maria Elena Martinez, Keitaro Matsuo, Dimitrios Mavroudis, Sylvie Mazoyer, Catriona McLean, Hanne Meijers-Heijboer, Primitiva Menéndez, Jeffery Meyer, Hui Miao, Austin Miller, Nicola Miller, Gillian Mitchell, Marco Montagna, Kenneth Muir, Anna Marie Mulligan, Claire Mulot, Sue Nadesan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Dieter Niederacher, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Robert L. Nussbaum, Edith Olah, Olufunmilayo I. Olopade, Janet E. Olson, Curtis Olswold, Kai-Ren Ong, Jan C. Oosterwijk, Nick Orr, Ana Osorio, V. Shane Pankratz, Laura Papi, Tjoung-Won Park-Simon, Ylva Paulsson-Karlsson, Rachel Lloyd, Inge Søkilde Pedersen, Bernard Peissel, Ana Peixoto, Jose I. A. Perez, Paolo Peterlongo, Julian Peto, Georg Pfeiler, Catherine M. Phelan, Mila Pinchev, Dijana Plaseska-Karanfilska, Bruce Poppe, Mary E. Porteous, Ross Prentice, Nadege Presneau, Darya Prokofieva, Elizabeth Pugh, Miquel Angel Pujana, Katri Pylkäs, Brigitte Rack, Paolo Radice, Nazneen Rahman, Johanna Rantala, Christine Rappaport-Fuerhauser, Gad Rennert, Hedy S. Rennert, Valerie Rhenius, Kerstin Rhiem, Andrea Richardson, Gustavo C. Rodriguez, Atocha Romero, Jane Romm, Matti A. Rookus, Anja Rudolph, Thomas Ruediger, Emmanouil Saloustros, Joyce Sanders, Dale P. Sandler, Suleeporn Sangrajrang, Elinor J. Sawyer, Daniel F. Schmidt, Minouk J. Schoemaker, Fredrick Schumacher, Peter Schürmann, Lukas Schwentner, Christopher Scott, Rodney J. Scott, Sheila Seal, Leigha Senter, Caroline Seynaeve, Mitul Shah, Priyanka Sharma, Chen-Yang Shen, Xin Sheng, Hermela Shimelis, Martha J. Shrubsole, Xiao-Ou Shu, Lucy E. Side, Christian F. Singer, Christof Sohn, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Christa Stegmaier, Dominique Stoppa-Lyonnet, Grzegorz Sukiennicki, Harald Surowy, Christian Sutter, Anthony Swerdlow, Csilla I. Szabo, Rulla M. Tamimi, Yen Y. Tan, Jack A. Taylor, Maria-Isabel Tejada, Maria Tengström, Soo H. Teo, Mary B. Terry, Daniel C. Tessier, Alex Teulé, Kathrin Thöne, Darcy L. Thull, Maria Grazia Tibiletti, Laima Tihomirova, Marc Tischkowitz, Amanda E. Toland, Rob A. E. M. Tollenaar, Ian Tomlinson, Ling Tong, Diana Torres, Martine Tranchant, Thérèse Truong, Kathy Tucker, Nadine Tung, Jonathan Tyrer, Hans-Ulrich Ulmer, Celine Vachon, Christi J. van Asperen, David van den Berg, Ans M. W. van den Ouweland, Elizabeth J. van Rensburg, Liliana Varesco, Raymonda Varon-Mateeva, Ana Vega, Alessandra Viel, Joseph Vijai, Daniel Vincent, Jason Vollenweider, Lisa Walker, Zhaoming Wang, Shan Wang-Gohrke, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Jelle Wesseling, Alice S. Whittemore, Juul T. Wijnen, Walter Willett, Robert Winqvist, Alicja Wolk, Anna H. Wu, Lucy Xia, Xiaohong R. Yang, Drakoulis Yannoukakos, Daniela Zaffaroni, Wei Zheng, Bin Zhu, Argyrios Ziogas, Elad Ziv, Kristin K. Zorn, Manuela Gago-Dominguez, Arto Mannermaa, Håkan Olsson, Manuel R. Teixeira, Jennifer Stone, Kenneth Offit, Laura Ottini, Sue K. Park, Mads Thomassen, Per Hall, Alfons Meindl, Rita K. Schmutzler, Arnaud Droit, Gary D. Bader, Paul D. P. Pharoah, Fergus J. Couch, Douglas F. Easton, Peter Kraft, Georgia Chenevix-Trench, Montserrat García-Closas, Marjanka K. Schmidt, Antonis C. Antoniou, Jacques Simard

Date Published: 1st Dec 2017

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The aim of this analysis in a pilot study population was to investigate whether we can verify seemingly harmful lifestyle factors such as nicotine and alcohol indulgence, obesity, and physical …l inactivity, as well as a low socioeconomic status for increased cancer prevalence in a cohort of BRCA 1 and 2 mutation carriers. METHODS The analysis data are derived from 68 participants of the lifestyle intervention study LIBRE-1, a randomized, prospective trial that aimed to test the feasibility of a lifestyle modification in BRCA 1 and 2 mutation carriers. At study entry, factors such as medical history, lifestyle behavior, and socioeconomic status were retrospectively documented by interview and the current BMI was determined by clinical examination. The baseline measurements were compared within the cohort, and presented alongside reference values for the German population. RESULTS Study participants indicating a higher physical activity during their adolescence showed a significantly lower cancer prevalence (p = 0.019). A significant difference in cancer occurrence was observed in those who smoked prior to the disease, and those who did not smoke (p \textless 0.001). Diseased mutation carriers tended to have a lower BMI compared to non-diseased mutation carriers (p = 0.079), whereas non-diseased revealed a significantly higher physical activity level than diseased mutation carriers (p = 0.046). DISCUSSION The present data in this small cohort of 68 mutation carriers suggest that smoking and low physical activity during adolescence are risk factors for developing breast cancer in women with BRCA1 or BRCA2 mutation. Further data of the ongoing LIBRE 2 study are necessary to confirm these findings in a larger cohort of 600 mutation carriers.

Authors: Sabine Grill, Maryam Yahiaoui-Doktor, Ricarda Dukatz, Jacqueline Lammert, Mirjam Ullrich, Christoph Engel, Katharina Pfeifer, Maryam Basrai, Michael Siniatchkin, Thorsten Schmidt, Burkhard Weisser, Kerstin Rhiem, Nina Ditsch, Rita Schmutzler, Stephan C. Bischoff, Martin Halle, Marion Kiechle

Date Published: 1st Dec 2017

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Urine Biomarkers of Tubular Renal Cell Damage for the Prediction of Acute Kidney Injury After Cardiac Surgery-A Pilot Study
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVE To evaluate the perioperative course of urine levels of the renal damage biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) …) and to evaluate the predictive value of elevated TIMP-2 \times IGFBP7 concentrations to predict acute kidney injury (AKI) early after cardiac on-pump surgery. DESIGN Prospective, observational cohort study. SETTING University hospital. PARTICIPANTS The study comprised 110 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) between January and March 2014. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Urinary TIMP-2 \times IGFBP7 levels were quantified using a commercially available kit at the following measurement points: before surgery, 1 hour after starting CPB, 4 hours after weaning from CPB, and 24 hours after weaning from CPB (time points 1-4). Postoperative AKI was defined according to Kidney Disease Improving Global Outcomes criteria. AKI after cardiac surgery was diagnosed in 9 patients (8%). The perioperative course of TIMP-2 \times IGFBP7 was significantly different in patients with and without postoperative AKI (p \textless 0.001). TIMP-2 \times IGFBP7 levels were significantly higher in patients with AKI 1 hour after CPB start and 24 hours after weaning from CPB (p \textless 0.05). TIMP-2 \times IGFBP7 levels \textgreater0.40 (ng/mL)(2)/1,000 measured at 1 hour after starting CPB were found to be the optimal cut-off, with a sensitivity of 0.778 and a specificity of 0.641. The negative predictive value was 0.972. CONCLUSIONS Urine levels of TIMP-2 \times IGFBP7 are predictive for AKI at an early time point (1 hour after starting CPB). Renal damage biomarkers such as TIMP-2 and IGFBP7 might be recommended as a supplement to traditionally used criteria of AKI prediction.

Authors: Tanja Mayer, Daniel Bolliger, Markus Scholz, Oliver Reuthebuch, Michael Gregor, Patrick Meier, Martin Grapow, Manfred D. Seeberger, Jens Fassl

Date Published: 1st Dec 2017

Publication Type: Journal article

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