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128 results on '"Weinhold, Leonie"'

1. The effect of isolation precautions on care processes and medical outcomes in patients colonized with MRSA

Author

Labus, David, Weinhold, Leonie, and Heller, Joerg

Subjects
methicillin-resistant staphylococcus aureus, patient isolation, infection control, outcome and process assessment (health care), diagnostic techniques and procedures, patient safety, Medicine, Public aspects of medicine, RA1-1270, Microbiology, QR1-502
Abstract

Background: Isolation precautions used in methicillin-resistant (MRSA) infection control are effective in inhibiting pathogen transmission, but may cause unintended consequences in medical care. In addition, while costs attributed to MRSA are known to be substantial, little is known about their reimbursement in the German Diagnosis Related Groups (G-DRG) payment system. The aim of our study was to examine the effect of isolation precautions used in MRSA infection control on care processes, patient outcomes and deliver reliable data on MRSA-attributed reimbursement.Methods: A retrospective, matched cohort study of inpatients admitted to a general care teaching hospital in Bad Neuenahr, Germany, between January 1, 2016, and December 31, 2017 was performed. Patients isolated for MRSA colonization were matched to non-isolated controls based on age, gender, MRSA-adjusted Patient Clinical Complexity Level (Ma-PCCL) and Major Diagnostic Category (MDC). Main outcome measures on care processes and patient outcomes included adverse events, patient complaints, 30-day readmission rates, length of stay, type of discharge, and performance of instrument-based diagnostics. MRSA-attributed reimbursement was measured by conducting two separate G-DRG groupings, one with inclusion of MRSA-related codes and one without. Results: A total of 26,059 patients were admitted to Maria Hilf Hospital in Bad Neuenahr, Germany, during the study period. We identified 304 patients isolated for MRSA colonization. Compared to non-isolated matched controls, those on isolation precautions for MRSA colonization acquired about 45% more pressure ulcers and experienced significant delays in the performance of radiological diagnostics and echocardiographs. Patients isolated for MRSA colonization received about 49% fewer echocardiographs and had about 38% fewer abdominal ultrasound exams performed compared to non-isolated matched controls. A non-significant tendency towards fewer discharges to rehabilitation clinics and higher mortality rates were observed in patients isolated for MRSA colonization. Reimbursements were negligibly affected when MRSA-related codes were integrated by the grouper.Conclusion: Isolation precautions are associated with adverse consequences for care processes. These consequences need to be mitigated in order to justify placing patients at risk.

Published
2019
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2. Accounting for Time Dependency in Meta-Analyses of Concordance Probability Estimates

Author

Schmid, Matthias, Friede, Tim, Klein, Nadja, and Weinhold, Leonie

Subjects
Statistics - Methodology
Abstract

Recent years have seen the development of many novel scoring tools for disease prognosis and prediction. To become accepted for use in clinical applications, these tools have to be validated on external data. In practice, validation is often hampered by logistical issues, resulting in multiple small-sized validation studies. It is therefore necessary to synthesize the results of these studies using techniques for meta-analysis. Here we consider strategies for meta-analyzing the concordance probability for time-to-event data ("C-index"), which has become a popular tool to evaluate the discriminatory power of prediction models with a right-censored outcome. We show that standard meta-analysis of the C-index may lead to biased results, as the magnitude of the concordance probability depends on the length of the time interval used for evaluation (defined e.g. by the follow-up time, which might differ considerably between studies). To address this issue, we propose a set of methods for random-effects meta-regression that incorporate time directly as covariate in the model equation. In addition to analyzing nonlinear time trends via fractional polynomial, spline, and exponential decay models, we provide recommendations on suitable transformations of the C-index before meta-regression. Our results suggest that the C-index is best meta-analyzed using fractional polynomial meta-regression with logit-transformed C-index values. Classical random-effects meta-analysis (not considering time as covariate) is demonstrated to be a suitable alternative when follow-up times are small. Our findings have implications for the reporting of C-index values in future studies, which should include information on the length of the time interval underlying the calculations.

Published
2022

3. Deselection of Base-Learners for Statistical Boosting -- with an Application to Distributional Regression

Author

Strömer, Annika, Staerk, Christian, Klein, Nadja, Weinhold, Leonie, Titze, Stephanie, and Mayr, Andreas

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

We present a new procedure for enhanced variable selection for component-wise gradient boosting. Statistical boosting is a computational approach that emerged from machine learning, which allows to fit regression models in the presence of high-dimensional data. Furthermore, the algorithm can lead to data-driven variable selection. In practice, however, the final models typically tend to include too many variables in some situations. This occurs particularly for low-dimensional data (p

Published
2022

5. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín

Published
2023
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7. A Random Forest Approach for Modeling Bounded Outcomes

Author

Weinhold, Leonie, Schmid, Matthias, Wright, Marvin N., and Berger, Moritz

Subjects
Statistics - Methodology
Abstract

Random forests have become an established tool for classification and regression, in particular in high-dimensional settings and in the presence of complex predictor-response relationships. For bounded outcome variables restricted to the unit interval, however, classical random forest approaches may severely suffer as they do not account for the heteroscedasticity in the data. A random forest approach is proposed for relating beta distributed outcomes to explanatory variables. The approach explicitly makes use of the likelihood function of the beta distribution for the selection of splits during the tree-building procedure. In each iteration of the tree-building algorithm one chooses the combination of explanatory variable and splitting rule that maximizes the log-likelihood function of the beta distribution with the parameter estimates derived from the nodes of the currently built tree. Several simulation studies demonstrate the properties of the method and compare its performance to classical random forest approaches as well as to parametric regression models., Comment: 19 pages, 5 figures

Published
2019

10. Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis.

Author

Koch, Teresa, Fabian, Rachel, Weinhold, Leonie, Koch, Franz‐W., Barakat, Saman, Castro‐Gomez, Sergio, Grehl, Torsten, Bernsen, Sarah, and Weydt, Patrick

Subjects
AMYOTROPHIC lateral sclerosis, PHYSIOLOGY, VITAL capacity (Respiration), TROPONIN, CYTOPLASMIC filaments
Abstract

Objective: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. Methods: In this retrospective observation, we analyzed two independent hospital‐based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49). Results: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = −0.45, p = 0.001) and slow vital capacity % (r = −0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62–0.84) and <50% (AUC 0.80, 95% CI 0.68–0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61–0.83) and <50% (AUC 0.79, 95% CI 0.67–0.91). Interpretation: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function. [ABSTRACT FROM AUTHOR]

Published
2024
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12. A Statistical Model for the Analysis of Beta Values in DNA Methylation Studies

Author

Weinhold, Leonie, Wahl, Simone, and Schmid, Matthias

Subjects
Statistics - Methodology
Abstract

Background: The analysis of DNA methylation is a key component in the development of personalized treatment approaches. A common way to measure DNA methylation is the calculation of beta values, which are bounded variables of the form M = (M + U) that are generated by Illumina's 450k BeadChip array. The statistical analysis of beta values is considered to be challenging, as traditional methods for the analysis of bounded variables, such as M-value regression and beta regression, are based on regularity assumptions that are often too strong to adequately describe the distribution of beta values. Results: We develop a statistical model for the analysis of beta values that is derived from a bivariate gamma distribution for the signal intensities M and U. By allowing for possible correlations between M and U, the proposed model explicitly takes into account the data-generating process underlying the calculation of beta values. Conclusion: The proposed model can be used to improve the identification of associations between beta values and covariates such as clinical variables and lifestyle factors in epigenome-wide association studies. It is as easy to apply to a sample of beta values as beta regression and M-value regression.

Published
2016

14. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín

Published
2021
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17. Deep Learning Super-Resolution Reconstruction for Fast and Motion-Robust T2-weighted Prostate MRI

Author

Bischoff, Leon M., primary, Peeters, Johannes M., additional, Weinhold, Leonie, additional, Krausewitz, Philipp, additional, Ellinger, Jörg, additional, Katemann, Christoph, additional, Isaak, Alexander, additional, Weber, Oliver M., additional, Kuetting, Daniel, additional, Attenberger, Ulrike, additional, Pieper, Claus C., additional, Sprinkart, Alois M., additional, and Luetkens, Julian A., additional

Published
2023
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20. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Böhmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kähönen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M., Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Jr, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hägg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Räikkönen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Jr, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.

Published
2019
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21. Low Serum Vitamin D Status Is Associated with Incident Alzheimer’s Dementia in the Oldest Old

Author

Melo van Lent, Debora, primary, Egert, Sarah, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Weinhold, Leonie, additional, Wagner-Thelen, Holger, additional, Stoffel-Wagner, Birgit, additional, Bickel, Horst, additional, Wiese, Birgitt, additional, Weyerer, Siegfried, additional, Pentzek, Michael, additional, Jessen, Frank, additional, Schmid, Matthias, additional, Maier, Wolfgang, additional, Scherer, Martin, additional, Riedel-Heller, Steffi G., additional, Ramirez, Alfredo, additional, and Wagner, Michael, additional

Published
2022
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23. Evaluation of the Perioperative and Postoperative Course of Surgery for Pineal Germinoma in the SIOP CNS GCT 96 Trial

Author

Shabo, Ehab, primary, Czech, Thomas, additional, Nicholson, James C., additional, Mallucci, Conor, additional, Mottolese, Carmine, additional, Piatelli, Gianluca, additional, Frappaz, Didier, additional, Murray, Matthew Jonathan, additional, Faure-Conter, Cecile, additional, Garrè, Maria Luisa, additional, Sarikaya-Seiwert, Sevgi, additional, Weinhold, Leonie, additional, Haberl, Hannes, additional, and Calaminus, Gabriele, additional

Published
2022
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24. Validation of the web-based self-administered 24-h dietary recall myfood24-Germany: comparison with a weighed dietary record and biomarkers

Author

Koch, Stefanie A. J., Conrad, Johanna, Cade, Janet E., Weinhold, Leonie, Alexy, Ute, and Nöthlings, Ute

Subjects
Male, Potassium intake, Dietary assessment, Concordance, Medicine (miscellaneous), Diet Surveys, Animal science, Germany, Surveys and Questionnaires, Humans, Medicine, Web-based 24-h dietary recall, Internet, Nutrition and Dietetics, business.industry, Validation study, Reproducibility of Results, Myfood24, Original Contribution, Protein intake, Diet Records, Diet, Nutrition Assessment, Dietary recall, Method comparison, Mental Recall, Biomarker (medicine), Female, Energy Intake, business, Biomarkers, Kappa
Abstract

Purpose We aimed to validate myfood24-Germany, a web-based 24-h dietary recall (24HDR), by comparing its performance with a weighed dietary record (WDR) and biomarkers. Methods 97 adults (77% female) completed a 3-day WDR with a 24-h urine collection on day 3, followed by at least one 24HDR with myfood24-Germany (corresponding to day 3 of the WDR). Intake of energy and 32 nutrients assessed by myfood24-Germany and the WDR for the same day were compared (method comparison). Intakes of protein and potassium assessed by myfood24-Germany/WDR were compared with intake estimated from urinary biomarkers for protein and potassium (biomarker comparison). Results In the method comparison, significant correlations were found for energy and all tested nutrients (range 0.45–0.87). There was no significant difference between both methods in the assessed mean energy and macronutrient intake. However, myfood24-Germany underestimated mean intake of 15 nutrients. In the biomarker comparison, protein intake reported by myfood24-Germany/WDR was on average 10%/8% lower than estimated by biomarker. There was no significant difference in mean potassium intake assessed by myfood24-Germany/WDR and biomarker. However, a shared bias in the assessment of potassium intake was observed for both instruments. Concordance correlation coefficients (pc) and weighted Kappa coefficients (κ) confirmed good agreement with the biomarker estimates for myfood24-Germany/WDR in case of protein (pc = 0.58/0.66, κ = 0.51/0.53) and moderate agreement in case of potassium (pc = 0.44/0.51; κ = 0.30/0.33). Conclusion Our results suggest that myfood24-Germany is of comparable validity to traditional dietary assessment methods.

Published
2021

25. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Böhmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kähönen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M., Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Jr, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hägg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Räikkönen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Jr, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.

Published
2018
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27. Lymphocyte transformation test for drug allergy detection: When does it work?

Author

Glässner, Andreas, Dubrall, Diana, Weinhold, Leonie, Schmid, Matthias, and Sachs, Bernhardt

Subjects
Drug Hypersensitivity, Drug Hypersensitivity Syndrome, Eosinophilia, Hypersensitivity, Humans, lymphocyte transformation test, Random-effects meta-regression analyse, drug allergy detection, Lymphocyte Activation
Abstract

BACKGROUND: The lymphocyte transformation test (LTT) is an in vitro test system for the detection of a sensitization in the context of allergies to drugs. Its reported sensitivity varies largely and seems to be affected by different parameters. In review articles, the average LTT performance was often calculated by combining overall mean sensitivities of various published studies, but without considering different patient characteristics or varying patient numbers per publication. OBJECTIVE: To investigate the impact of different patient-specific and methodological parameters on the sensitivity of the LTT based on data on the level of the individual patient extracted from single studies. METHODS: We performed an advanced literature search in PubMed and screened the identified publications according to previously defined inclusion criteria. In total, individual patient data from 721 patients were extracted from 30 studies. Random-effects meta-regression analyses were performed. RESULTS: The analysis indicate that the enzyme-linked immunosorbent assay–based read-out is more sensitive compared with the classical radioactivity method (enzyme-linked immunosorbent assay: 80% vs radioactivity: 66%; P = .08). Interestingly, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome is associated with a higher probability of a positive LTT test result compared with other investigated clinical phenotypes (“drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome” vs “bullous reaction”; odds ratio, 2.52; P value = .003). Our analysis also revealed an impact of the time to testing period after the occurrence of the allergic event (“< 2 weeks” vs “2 weeks-2 months”; odds ratio, 2.12; P value = .03). CONCLUSION: The read-out method and relevant clinical parameters affect the sensitivity of the LTT. These findings are based on a meta-analysis providing a higher level of evidence than a single study or previous reviews not considering individual patient data.

Published
2022

28. Erratum to ‘Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma’ [Eur J Cancer 170 (2022) 209-235, (S0959804922001629), (10.1016/j.ejca.2022.03.018)]

Author

Budde, Axel, Baust, Katja, Weinhold, Leonie, Bernstein, Mark, Bielack, Stefan, Dhooge, Catharina, Hjorth, Lars, Janeway, Katherine A., Jenney, Meriel, Krailo, Mark D., Marina, Neyssa, Nagarajan, Rajaram, Smeland, Sigbjørn, Sydes, Matthew R., De Vos, Patricia, Whelan, Jeremy, Wiener, Andreas, Calaminus, Gabriele, and Schmid, Matthias

Subjects
Medizin
Abstract

The publisher regrets that errors appear in Table 2a in the printed article. These errors have now been corrected online, and the correct version of Table 2a is given here.[Formula presented] We also note that a Multimedia component was included with the online article in error. This has now been removed from the online article. We can confirm that there are no additional Supplementary Data files to appear with this article. The publisher would like to apologise for any inconvenience caused.

Published
2022

29. Low Serum Vitamin D Status Is Associated with Incident Alzheimer's Dementia in the Oldest Old.

Author

Melo van Lent, Debora, Egert, Sarah, Wolfsgruber, Steffen, Kleineidam, Luca, Weinhold, Leonie, Wagner-Thelen, Holger, Stoffel-Wagner, Birgit, Bickel, Horst, Wiese, Birgitt, Weyerer, Siegfried, Pentzek, Michael, Jessen, Frank, Schmid, Matthias, Maier, Wolfgang, Scherer, Martin, Riedel-Heller, Steffi G., Ramirez, Alfredo, and Wagner, Michael

Abstract

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer's dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies. [ABSTRACT FROM AUTHOR]

Published
2023
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30. ACKT - ein neuer Score zur Vorhersage einer postoperativen invasiven Beatmung nach chirurgischer Behandlung von geriatrischen Meningeompatienten

Author

Scharnböck, Elisa, Weinhold, Leonie, Potthoff, Anna-Laura, Schäfer, Niklas, Heimann, Muriel, Lehmann, Felix, Güresir, Erdem, Bode, Christian, Jacobs, Andreas H., Vatter, Hartmut, Herrlinger, Ulrich, Schneider, Matthias, and Schuss, Patrick

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk-benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Published
2021
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31. Einfluss von Komorbiditäten und Frailty auf frühes Shuntversagen bei geriatrischen Patienten mit Normaldruck-Hydrozephalus

Author

Kilinc, Fatma, Hadjiathanasiou, Alexis, Behmanesh, Bedjan, Güresir, Erdem, Heimann, Muriel, Konczalla, Jürgen, Scharnböck, Elisa, Schneider, Matthias, Weinhold, Leonie, Seifert, Volker, Vatter, Hartmut, Schuss, Patrick, and Gessler, Florian

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Older patients are considered to bear a higher perioperative risk. Since idiopathicnormal pressure hydrocephalus (NPH) predominantly concerns older patients, identifying risk factorsfor early shunt failure for preoperative risk/benefit assessment is indispensable for indication and/orconsultation[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Published
2021

35. Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

Author

Melo van Lent, Debora, primary, Egert, Sarah, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Weinhold, Leonie, additional, Wagner-Thelen, Holger, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Ramirez, Alfredo, additional, Schmid, Matthias, additional, Scherer, Martin, additional, Riedel-Heller, Steffi G., additional, and Wagner, Michael, additional

Published
2021
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36. PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment

Author

KLEINEIDAM, Luca, Chouraki, Vincent, Próchnicki, Tomasz, van der Lee, Sven, Madrid‑Márquez, Laura, Wagner-Thelen, Holger, Karaca, Ilker, WEINHOLD, Leonie, Wolfsgruber, Steffen, Boland, Anne, Martino Adami, Pamela, Lewczuk, Piotr, POPP, Julius, Brosseron, Frederic, Jansen, Iris, HULSMAN, Marc, Kornhuber, Johannes, Peters, Oliver, Berr, Claudine, Heun, Reinhard, Frölich, Lutz, Tzourio, Christophe, Dartigues, Jean-François, Hüll, Michael, Espinosa, Ana, Hernández, Isabel, de Rojas, Itziar, ORELLANA, Adelina, VALERO, Sergi, STRINGA, Najada, Van Schoor, Natasja, Huisman, Martijn, Scheltens, Philip, For The Alzheimer'S Disease Neuroimaging Initiative, (ADNI), Rüther, Eckart, Deleuze, Jean-François, Wiltfang, Jens, Tarraga, Lluis, Schmid, Matthias, Scherer, Martin, Riedel-Heller, Steffi, Heneka, Michael, Amouyel, Philippe, Jessen, Frank, Boada, Merce, Maier, Wolfgang, Schneider, Anja, González‑Pérez, Antonio, van der Flier, Wiesje, Wagner, Michael, Lambert, Jean-Charles, Holstege, Henne, Saez, Mª Eugenia, Latz, Eicke, Ruiz, Agustin, Ramirez, Alfredo, University Hospital Bonn, Universität zu Köln, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Amsterdam UMC, Vrije Universiteit Amsterdam [Amsterdam] (VU), Centro andaluz de estudios bioinformáticos - Andalusian Bioinformatics Research Centre [Sevilla] (CAEBi), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universitätsklinikum Erlangen [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Bialystok, Lausanne University Hospital, University hospital of Zurich [Zurich], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universität Heidelberg [Heidelberg], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert-Ludwigs-Universität Freiburg, Universitat Internacional de Catalunya [Barcelona] (UIC), Instituto de Salud Carlos III [Madrid] (ISC), University Medical Center Göttingen (UMG), Universidade de Aveiro, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Universität Leipzig [Leipzig], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Open Access funding provided by Projekt DEAL. This publication was funded in part by the German Federal Ministry of Education and Research (BMBF) (grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434, grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). Analyses were also funded by the German Federal Ministry of Education and Research (BMBF 01EA1410A) within the project 'Diet-Body-Brain: from epidemiology to evidence-based communication'. Part of the work was funded by the JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A). Part of the analysis was funded by the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case–control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica, Inc., Biogen, Bristol-Myers Squibb Company, CereSpir, Inc., Cogstate, Eisai Inc., ElanPharmaceuticals, Inc., Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development, LLC., Johnson and Johnson Pharmaceutical Research and Development LLC., Lumosity, Lundbeck, Merck and Co., Inc., Meso Scale Diagnostics, LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. The Three-City Study genotyping and analysis was funded by the GENMED Labex, the Joint Programming Initiative on Neurodegenerative Diseases Research (JPND, PERADES project), the Institute Pasteur de Lille, the University of Lille, and the Nord-Pas de Calais Regional Council. This work also benefited from the Lille Métropole Communauté Urbaine Council, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). In addition, the Three-City Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. Additional funding for the 3C Study was also obtained from the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM 'Cohortes et collections de données biologiques' programme. Lille Génopôle received an unconditional grant from Eisai. Fundacio ACE cohort receives support from the Innovative Medicines Initiative 2 Joint Undertaking which receives support from the European Union’s Horizon 2020 research and innovation programme (ADAPTED Grant No. 115975). A. Ruiz’s research is also supported by Instituto de Salud Carlos III (ISCIII) grants PI13/02434, PI16/01861, and PI19/01301. Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-'Una manera de Hacer Europa'), by Fundación bancaria 'La Caixa' and Grifols SA (GR@ACE project). For the Longitudinal Aging Study Amsterdam (LASA) supports was largely obtained from a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The data collection in 2012–2013 was financially supported by the Netherlands Organization for Scientific Research (NWO) in the framework of the project 'New Cohorts of young old in the twenty-first century' (File Number 480-10-014). Genotyping using Axiom-NL array was financially supported by EMGO+ Research Institute. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. JW is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/04501/2013), at the University of Aveiro, Portugal. JP was supported by a grant from the Swiss National Science Foundation (320030L_141179)., Universität zu Köln = University of Cologne, Amsterdam UMC - Amsterdam University Medical Center, Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Leipzig, Alzheimer's Disease Neuroimaging Initiative (ADNI), Kleineidam, L., Karaca, I., Heneka, M.T., Maier, W., Schneider, A., Wagner, M., Chouraki, V., Amouyel, P., Lambert, J.C., Próchnicki, T., Latz, E., van der Lee, S.J., Jansen, I.E., Hulsman, M., Scheltens, P., van der Flier, W.M., Holstege, H., Madrid-Márquez, L., González-Pérez, A., Sáez, M.E., Wagner-Thelen, H., Martino Adami, P.V., Jessen, F., Ramirez, A., Weinhold, L., Schmid, M., Wolfsgruber, S., Brosseron, F., Boland, A., Deleuze, J.F., Lewczuk, P., Kornhuber, J., Popp, J., Peters, O., Berr, C., Heun, R., Frölich, L., Tzourio, C., Dartigues, J.F., Hüll, M., Espinosa, A., Hernández, I., de Rojas, I., Orellana, A., Valero, S., Ruiz, A., Tarraga, L., Boada, M., Stringa, N., van Schoor, N.M., Huisman, M., Rüther, E., Wiltfang, J., Scherer, M., Riedel-Heller, S., Neurology, Human genetics, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, APH - Methodology, Sociology, and The Social Context of Aging (SoCA)

Subjects
Apolipoprotein E, Male, pathology [Cognitive Dysfunction], Cognitive decline, genetics [Alzheimer Disease], Disease, SEPIA, pathology [Alzheimer Disease], 0302 clinical medicine, Cognition, genetics [Amyloid beta-Peptides], Medicine, Aged, 80 and over, 0303 health sciences, education.field_of_study, Microglia, physiology [Cognition], Middle Aged, medicine.anatomical_structure, Disease Progression, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], analysis [Biomarkers], Alzheimer’s disease, Amyloid, Phospholipase C gamma 2, Population, tau Proteins, Pathology and Forensic Medicine, PLCG2, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Alzheimer Disease, Humans, Cognitive Dysfunction, ddc:610, education, Mild cognitive impairment, HEALTHY, 030304 developmental biology, Aged, metabolism [Phospholipase C gamma], Original Paper, Amyloid beta-Peptides, TREM2, business.industry, Phospholipase C gamma, genetics [Cognitive Dysfunction], metabolism [tau Proteins], cerebrospinal fluid [tau Proteins], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunology, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aβ1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.

Published
2020

37. ACKT: A Proposal for a Novel Score to Predict Prolonged Mechanical Ventilation after Surgical Treatment of Meningioma in Geriatric Patients

Author

Scharnböck, Elisa, primary, Weinhold, Leonie, additional, Potthoff, Anna-Laura, additional, Schäfer, Niklas, additional, Heimann, Muriel, additional, Lehmann, Felix, additional, Güresir, Erdem, additional, Bode, Christian, additional, Jacobs, Andreas H., additional, Vatter, Hartmut, additional, Herrlinger, Ulrich, additional, Schneider, Matthias, additional, and Schuss, Patrick, additional

Published
2020
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38. Impact of Comorbidities and Frailty on Early Shunt Failure in Geriatric Patients With Normal Pressure Hydrocephalus

Author

Hadjiathanasiou, Alexis, primary, Kilinc, Fatma, additional, Behmanesh, Bedjan, additional, Bernstock, Joshua, additional, Güresir, Erdem, additional, Heimann, Muriel, additional, Konczalla, Jürgen, additional, Scharnböck, Elisa, additional, Schneider, Matthias, additional, Weinhold, Leonie, additional, Seifert, Volker, additional, Vatter, Hartmut, additional, Gessler, Florian, additional, and Schuss, Patrick, additional

Published
2020
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40. Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases

Author

Schneider, Matthias, primary, Heimann, Muriel, additional, Schaub, Christina, additional, Eichhorn, Lars, additional, Potthoff, Anna-Laura, additional, Giordano, Frank A., additional, Güresir, Erdem, additional, Ko, Yon-Dschun, additional, Landsberg, Jennifer, additional, Lehmann, Felix, additional, Radbruch, Alexander, additional, Schwab, Katjana S., additional, Weinhold, Leonie, additional, Weller, Johannes, additional, Wispel, Christian, additional, Herrlinger, Ulrich, additional, Vatter, Hartmut, additional, Schäfer, Niklas, additional, and Schuss, Patrick, additional

Published
2020
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42. Vergleich des Outcome von Arthrodese und Revisionsendoprothese nach fehlgeschlagener Kniegelenksendoprothese bei periprothetischer Infektion

Author

Gathen, Martin, Gravius, Sascha, Randau, Thomas, Wimmer, Matthias D., Weinhold, Leonie, Plöger, Milena, and Friedrich, Max

Subjects
Arthrodese, Revisionsendoprothese, ddc: 610, 610 Medical sciences, Medicine, Periprothetische Infektion
Abstract

Fragestellung: Die periprothetische Infektion des Kniegelenkes eine der schwerwiegende Komplikationen nach Kniegelenkersatz. Ausgeprägte Knochen- und Weichteildestruktionen, insbesondere der Zustand des Streckapparates, können die erneute Implantation einer Revisionsprothese unmöglich[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

Published
2018

43. Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study

Author

Scholtes, Cathy, primary, Baust, Katja, additional, Weinhold, Leonie, additional, Creutzig, Ursula, additional, Gnekow, Astrid, additional, Hinz, Andreas, additional, Kaatsch, Peter, additional, Kreitz, Kiana, additional, Langer, Thorsten, additional, Rutkowski, Stefan, additional, Singer, Susanne, additional, Spix, Claudia, additional, Teske, Carmen, additional, Schmid, Matthias, additional, Dilloo, Dagmar, additional, and Calaminus, Gabriele, additional

Published
2019
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44. Prospective Associations between Single Foods, Alzheimer’s Dementia and Memory Decline in the Elderly

Author

Fischer, Karina, primary, Melo van Lent, Debora, additional, Wolfsgruber, Steffen, additional, Weinhold, Leonie, additional, Kleineidam, Luca, additional, Bickel, Horst, additional, Scherer, Martin, additional, Eisele, Marion, additional, van den Bussche, Hendrik, additional, Wiese, Birgitt, additional, König, Hans-Helmut, additional, Weyerer, Siegfried, additional, Pentzek, Michael, additional, Röhr, Susanne, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Schmid, Matthias, additional, Riedel-Heller, Steffi, additional, and Wagner, Michael, additional

Published
2018
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47. The betaboost package—a software tool for modelling bounded outcome variables in potentially high-dimensional epidemiological data.

Author

Mayr, Andreas, Weinhold, Leonie, Hofner, Benjamin, Titze, Stephanie, Gefeller, Olaf, and Schmid, Matthias

Subjects
*REGRESSION analysis, *STATISTICAL software, *STATISTICAL learning, *EPIDEMIOLOGY, *COMPUTER software
Abstract

Motivation To provide an integrated software environment for model fitting and variable selection in regression models with a bounded outcome variable. Implementation The proposed modelling framework is implemented in the add-on package betaboost of the statistical software environment R. General features The betaboost methodology is based on beta-regression, which is a state-of-the-art method for modelling bounded outcome variables. By combining traditional model fitting techniques with recent advances in statistical learning and distributional regression, betaboost allows users to carry out data-driven variable and/or confounder selection in potentially high-dimensional epidemiological data. The software package implements a flexible routine to incorporate linear and non-linear predictor effects in both the mean and the precision parameter (relating inversely to the variance) of a beta-regression model. Availability The software is hosted publicly at [ http://github.com/boost-R/betaboost ] and has been published under General Public License (GPL) version 3 or newer. [ABSTRACT FROM AUTHOR]

Published
2018
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48. ACKT: A Proposal for a Novel Score to Predict Prolonged Mechanical Ventilation after Surgical Treatment of Meningioma in Geriatric Patients.

Author

Scharnböck, Elisa, Weinhold, Leonie, Potthoff, Anna-Laura, Schäfer, Niklas, Heimann, Muriel, Lehmann, Felix, Güresir, Erdem, Bode, Christian, Jacobs, Andreas H., Vatter, Hartmut, Herrlinger, Ulrich, Schneider, Matthias, and Schuss, Patrick

Subjects
*C-reactive protein, *CONFIDENCE intervals, *MANN Whitney U Test, *ARTIFICIAL respiration, *RISK assessment, *MENINGIOMA, *DESCRIPTIVE statistics, *LOGISTIC regression analysis, *OLD age
Abstract

Simple Summary: Meningiomas are most commonly benign intracranial tumors, and surgical resection represents the treatment modality of choice. However, especially for patients of higher age and with increasing comorbidities, brain surgery might be accompanied by the need for postoperative prolonged intensive care, which might impair intended operative benefit. In the present study, we therefore analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential effects on mortality after meningioma resection in patients aged 70 years and older. We found that patients with postoperative PMV exhibited a profoundly increased probability to die within 1 year after surgery. Based on these findings, we identified risk factors for postoperative PMV occurrence and developed an easy-to-use score which allows us to estimate the risk of PMV occurrence preliminary to the surgical resection. We believe that this score might help to more sufficiently guide patients in the course of risk–benefit assessment and preoperative counseling. Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk–benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection. Between 2009 and 2019, 261 patients aged ≥ 70 years were surgically treated for intracranial meningioma at our institution. PMV was defined as postoperative invasive ventilation of >7 days. Postoperative PMV was present in 17 of 261 geriatric meningioma patients (7%). Twenty-five geriatric patients (10%) died within 1 year after surgery. A scoring system ("ACKT") based on the variables of age, preoperative C-reactive protein (CRP) value, Karnofsky performance scale and tumor size supports prediction of postoperative PMV (sensitivity 73%, specificity 84%). PMV is significantly associated with increased mortality after surgical treatment of meningiomas in geriatric patients. Furthermore, we suggest a novel score ("ACKT") to preoperatively estimate the risk of PMV occurrence, which might help to guide future risk–benefit assessment and patient counseling in the geriatric meningioma population. [ABSTRACT FROM AUTHOR]

Published
2021
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49. New insights on the genetic etiology of Alzheimer’s and related dementia

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris, Andrade, Victor, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Grenier-Boley, Benjamin, Campos-Martin, Rafael, Holmans, Peter A., Boland, Anne, Kleineidam, Luca, Damotte, Vincent, van der Lee, Sven J., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Costa, Marcos R, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Boada, Mercè, Aarsland, Dag, García-González, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Belén Pastor, Ana, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizzarro, Alessandra, Alcolea, Daniel, Blesa, Rafael, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bresner, Catherine, Brookes, Keeley J., Brusco, Luis Ignacio, Bûrger, Katharina, Bullido, María J., Burholt, Vanessa, Bush, William S., Calero, Miguel, Dufouil, Carole, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chillotti, Caterina, Brodaty, Henry, Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Buiza-Rueda, Dolores, Ewers, Michael, Tagliavini, Fabrizio, Nielsen, Sune Fallgaard, Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Hardy, John, Ferrari, Raffaele, Ferreira, Catarina B, Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fortea, Juan, Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Frank-García, Ana, Froelich, Lutz, Galimberti, Daniela, García-Alberca, Jose Maria, Garcia-Madrona, Sebastian, García-Ribas, Guillermo, Chene, Geneviève, Ghidoni, Roberta, Giegling, Ina, Giaccone, Giorgio, Goldhardt, Oliver, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Johansson, Charlotte, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kuksa, Pavel P., Kunkle, Brian W., Lage, Carmen, Laukka, Erika J, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Satizabal, Claudia L., Lerch, Ondrej, Lleó, Alberto, Lopez, Rogelio, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Martín Montes, Angel, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Periñán, Maria Teresa, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermín, Morgan, Kevin, Nöthen, Markus M., Muchnik, Carolina, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Caffarra, Paolo, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A.L., Pineda, Juan A, Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M, Reinders, Marcel J.T., Riedel-Heller, Steffi, Riederer, Peter, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Mehrabian, Shima, Sánchez-Juan, Pascual, Sánchez-Valle, Raquel, Sando, Sigrid B, Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Sha, Jin, Shadrin, Alexey A, Skrobot, Olivia, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Tartari, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Tegos, Thomas, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Van Broeckhoven, Christine, van der Lugt, Aad, Van Dongen, Jasper, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zhao, Yi, Zulaica, Miren, Serrano-Rios, Manuel, Seripa, Davide, Stordal, Eystein, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles

Subjects
0303 health sciences, Microglia, Amyloid, business.industry, Disease, medicine.disease, Bioinformatics, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Genetic etiology, Medicine, Dementia, Egfr signaling, business, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, and the failure to find effective treatments suggests that the underlying pathology remains poorly understood. Due to its strong heritability, deciphering the genetic landscape of AD and related dementia (ADD) is a unique opportunity to advance our knowledge. We completed a meta-analysis of genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases and 401,577 controls) with the most promising signals followed-up in 25,392 independent AD cases and 276,086 controls. We report 75 risk loci for ADD, including 42 novel ones. Pathway-enrichment analyses confirm the involvement of amyloid/Tau pathways, highlight the role of microglia and its potential interaction with APP metabolism. Numerous genes exhibited differential expression or splicing in AD-related conditions and gene prioritization implies EGFR signaling and TNF-α pathway through LUBAC complex. We also generated a novel polygenic risk score strongly associated with the risk of future dementia or progression from mild cognitive impairment to dementia. In conclusion, by more than doubling the number of loci associated with ADD risk, our study offers new insights into the pathophysiological processes underlying AD and offers additional therapeutic entry-points and tools for translational genomics.

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50. Evaluation of the Perioperative and Postoperative Course of Surgery for Pineal Germinoma in the SIOP CNS GCT 96 Trial

Author

Ehab Shabo, Thomas Czech, James C. Nicholson, Conor Mallucci, Carmine Mottolese, Gianluca Piatelli, Didier Frappaz, Matthew Jonathan Murray, Cecile Faure-Conter, Maria Luisa Garrè, Sevgi Sarikaya-Seiwert, Leonie Weinhold, Hannes Haberl, Gabriele Calaminus, Czech, Thomas [0000-0001-8112-2795], Nicholson, James C [0000-0001-9494-0199], Murray, Matthew Jonathan [0000-0002-4480-1147], Weinhold, Leonie [0000-0002-9194-9427], Calaminus, Gabriele [0000-0002-7893-7982], and Apollo - University of Cambridge Repository

Subjects
Cancer Research, perioperative course, Oncology, pineal germinoma, biopsy, resection, SIOP CNS GCT 96 trial
Abstract

Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.

Published
2022
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