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1. Targeting immune–fibroblast cell communication in heart failure

Author

Amrute, Junedh M., Luo, Xin, Penna, Vinay, Yang, Steven, Yamawaki, Tracy, Hayat, Sikander, Bredemeyer, Andrea, Jung, In-Hyuk, Kadyrov, Farid F., Heo, Gyu Seong, Venkatesan, Rajiu, Shi, Sally Yu, Parvathaneni, Alekhya, Koenig, Andrew L., Kuppe, Christoph, Baker, Candice, Luehmann, Hannah, Jones, Cameran, Kopecky, Benjamin, Zeng, Xue, Bleckwehl, Tore, Ma, Pan, Lee, Paul, Terada, Yuriko, Fu, Angela, Furtado, Milena, Kreisel, Daniel, Kovacs, Atilla, Stitziel, Nathan O., Jackson, Simon, Li, Chi-Ming, Liu, Yongjian, Rosenthal, Nadia A., Kramann, Rafael, Ason, Brandon, and Lavine, Kory J.

Published
2024
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4. The challenges of research data management in cardiovascular science: a DGK and DZHK position paper—executive summary

Author

Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, and Kohl, Peter

Published
2024
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8. Adamts12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts

Author

Hoeft, Konrad, Koch, Lars, Ziegler, Susanne, Zhang, Ling, Luetke, Steffen, Tanzer, Maria C., Mohanta, Debashish, Schumacher, David, Schreibing, Felix, Long, Qingqing, Kim, Hyojin, Klinkhammer, Barbara M., Schikarski, Carla, Maryam, Sidrah, Baens, Mathijs, Hermann, Juliane, Krieg, Sarah, Peisker, Fabian, De Laporte, Laura, Schaefer, Gideon J.L., Menzel, Sylvia, Jankowski, Joachim, Humphreys, Benjamin D., Wahida, Adam, Schneider, Rebekka K., Versele, Matthias, Boor, Peter, Mann, Matthias, Sengle, Gerhard, Hayat, Sikander, and Kramann, Rafael

Subjects
Medical research, Medicine, Experimental, Fibrosis -- Physiological aspects, Proteases -- Physiological aspects, Extracellular matrix -- Physiological aspects, Fibroblasts -- Physiological aspects -- Health aspects, Wounds and injuries -- Physiological aspects
Abstract

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury- responsive fibroblast subset defined by aberrant high JAK/STAT signaling., Introduction Fibrosis represents the uncontrolled replacement of parenchymal tissue by extracellular matrix (ECM) (1). Whereas deposition of ECM sustains tissue integrity immediately after injury, continued deposition of ECM by myofibroblasts [...]

Published
2024
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9. Author Correction: Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9

Author

Schneider, Rebekka K, Schenone, Monica, Ferreira, Monica Ventura, Kramann, Rafael, Joyce, Cailin E, Hartigan, Christina, Beier, Fabian, Brümmendorf, Tim H, Germing, Ulrich, Platzbecker, Uwe, Büsche, Guntram, Knüchel, Ruth, Chen, Michelle C, Waters, Christopher S, Chen, Edwin, Chu, Lisa P, Novina, Carl D, Lindsley, R Coleman, Carr, Steven A, and Ebert, Benjamin L

Published
2024
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11. The role of desmoglein-2 in kidney disease

Author

Xu, Tong, Herkens, Lea, Jia, Ting, Klinkhammer, Barbara M., Kant, Sebastian, Krusche, Claudia A., Buhl, Eva M., Hayat, Sikander, Floege, Jürgen, Strnad, Pavel, Kramann, Rafael, Djudjaj, Sonja, and Boor, Peter

Published
2024
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12. IgA nephropathy

Author

Stamellou, Eleni, Seikrit, Claudia, Tang, Sydney C. W., Boor, Peter, Tesař, Vladimir, Floege, Jürgen, Barratt, Jonathan, and Kramann, Rafael

Published
2023
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16. Deep learning-based bias transfer for overcoming laboratory differences of microscopic images

Author

Thebille, Ann-Katrin, Dietrich, Esther, Klaus, Martin, Gernhold, Lukas, Lennartz, Maximilian, Kuppe, Christoph, Kramann, Rafael, Huber, Tobias B., Sauter, Guido, Puelles, Victor G., Zimmermann, Marina, and Bonn, Stefan

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

The automated analysis of medical images is currently limited by technical and biological noise and bias. The same source tissue can be represented by vastly different images if the image acquisition or processing protocols vary. For an image analysis pipeline, it is crucial to compensate such biases to avoid misinterpretations. Here, we evaluate, compare, and improve existing generative model architectures to overcome domain shifts for immunofluorescence (IF) and Hematoxylin and Eosin (H&E) stained microscopy images. To determine the performance of the generative models, the original and transformed images were segmented or classified by deep neural networks that were trained only on images of the target bias. In the scope of our analysis, U-Net cycleGANs trained with an additional identity and an MS-SSIM-based loss and Fixed-Point GANs trained with an additional structure loss led to the best results for the IF and H&E stained samples, respectively. Adapting the bias of the samples significantly improved the pixel-level segmentation for human kidney glomeruli and podocytes and improved the classification accuracy for human prostate biopsies by up to 14%., Comment: Accepted as a regular conference paper at MIUA 2021

Published
2021
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18. Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Author

Cristoferi, Iacopo, Varol, Hilal, van Baardwijk, Myrthe, Rahiem, Layla, Lila, Karishma A., van den Bosch, Thierry P.P., Baan, Carla C., Hesselink, Dennis A., Kramann, Rafael, Minnee, Robert C., Mustafa, Dana A.M., Reinders, Marlies E.J., Roelen, Dave L., Shahzad-Arshad, Shazia P., Smith, Rex N., Stubbs, Andrew P., Colvin, Robert B., Rosales, Ivy A., and Clahsen-van Groningen, Marian C.

Published
2024
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20. Matrix Metalloproteinase-7 in Urinary Extracellular Vesicles Identifies Rapid Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Author

van Heugten, Martijn H., Blijdorp, Charles J., Arjune, Sita, van Willigenburg, Hester, Bezstarosti, Karel, Demmers, Jeroen A.A., Musterd-Bhaggoe, Usha, Meijer, Esther, Gansevoort, Ron T., Zietse, Robert, Hayat, Sikander, Kramann, Rafael, Müller, Roman-Ulrich, Salih, Mahdi, Hoorn, Ewout J., Blijdorp, Charles, Meijer, Esther, Gansevoort, Ronald, Zietse, Robert, Salih, Mahdi, Hoorn, Ewout, Peters, D.J.M., Losekoot, M., de Fijter, J.W., Vissers, F.W., Drenth, J.P.H., Nijenhuis, T., Wetzels, J., and van Gastel, M.D.A.

Published
2024
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21. Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms

Author

Pritchard, Jessica E., Pearce, Juliette E., Snoeren, Inge A.M., Fuchs, Stijn N.R., Götz, Katrin, Peisker, Fabian, Wagner, Silke, Benabid, Adam, Lutterbach, Niklas, Klöker, Vanessa, Nagai, James S., Hannani, Monica T., Galyga, Anna K., Sistemich, Ellen, Banjanin, Bella, Flosdorf, Niclas, Bindels, Eric, Olschok, Kathrin, Biaesch, Katharina, Chatain, Nicolas, Bhagwat, Neha, Dunbar, Andrew, Sarkis, Rita, Naveiras, Olaia, Berres, Marie-Luise, Koschmieder, Steffen, Levine, Ross L., Costa, Ivan G., Gleitz, Hélène F.E., Kramann, Rafael, and Schneider, Rebekka K.

Published
2024
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23. Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens

Author

Kylies, Dominik, Zimmermann, Marina, Haas, Fabian, Schwerk, Maria, Kuehl, Malte, Brehler, Michael, Czogalla, Jan, Hernandez, Lola C., Konczalla, Leonie, Okabayashi, Yusuke, Menzel, Julia, Edenhofer, Ilka, Mezher, Sam, Aypek, Hande, Dumoulin, Bernhard, Wu, Hui, Hofmann, Smilla, Kretz, Oliver, Wanner, Nicola, Tomas, Nicola M., Krasemann, Susanne, Glatzel, Markus, Kuppe, Christoph, Kramann, Rafael, Banjanin, Bella, Schneider, Rebekka K., Urbschat, Christopher, Arck, Petra, Gagliani, Nicola, van Zandvoort, Marc, Wiech, Thorsten, Grahammer, Florian, Sáez, Pablo J., Wong, Milagros N., Bonn, Stefan, Huber, Tobias B., and Puelles, Victor G.

Published
2023
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24. Defining cardiac functional recovery in end-stage heart failure at single-cell resolution

Author

Amrute, Junedh M., Lai, Lulu, Ma, Pan, Koenig, Andrew L., Kamimoto, Kenji, Bredemeyer, Andrea, Shankar, Thirupura S., Kuppe, Christoph, Kadyrov, Farid F., Schulte, Linda J., Stoutenburg, Dylan, Kopecky, Benjamin J., Navankasattusas, Sutip, Visker, Joseph, Morris, Samantha A., Kramann, Rafael, Leuschner, Florian, Mann, Douglas L., Drakos, Stavros G., and Lavine, Kory J.

Published
2023
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25. Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Author

Miguel, Verónica, Rey-Serra, Carlos, Tituaña, Jessica, Sirera, Belén, Alcalde-Estévez, Elena, Herrero, J. Ignacio, Ranz, Irene, Fernández, Laura, Castillo, Carolina, Sevilla, Lucía, Nagai, James, Reimer, Katharina C., Jansen, Jitske, Kramann, Rafael, Costa, Ivan G., Castro, Ana, Sancho, David, Rodríguez González-Moro, José Miguel, and Lamas, Santiago

Published
2023
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26. Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease

Author

Xu, Yaoxian, Kuppe, Christoph, Perales-Patón, Javier, Hayat, Sikander, Kranz, Jennifer, Abdallah, Ali T., Nagai, James, Li, Zhijian, Peisker, Fabian, Saritas, Turgay, Halder, Maurice, Menzel, Sylvia, Hoeft, Konrad, Kenter, Annegien, Kim, Hyojin, van Roeyen, Claudia R. C., Lehrke, Michael, Moellmann, Julia, Speer, Thimoteus, Buhl, Eva M., Hoogenboezem, Remco, Boor, Peter, Jansen, Jitske, Knopp, Cordula, Kurth, Ingo, Smeets, Bart, Bindels, Eric, Reinders, Marlies E. J., Baan, Carla, Gribnau, Joost, Hoorn, Ewout J., Steffens, Joachim, Huber, Tobias B., Costa, Ivan, Floege, Jürgen, Schneider, Rebekka K., Saez-Rodriguez, Julio, Freedman, Benjamin S., and Kramann, Rafael

Published
2022
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27. Sublethal necroptosis signaling promotes inflammation and liver cancer

Author

Vucur, Mihael, Ghallab, Ahmed, Schneider, Anne T., Adili, Arlind, Cheng, Mingbo, Castoldi, Mirco, Singer, Michael T., Büttner, Veronika, Keysberg, Leonie S., Küsgens, Lena, Kohlhepp, Marlene, Görg, Boris, Gallage, Suchira, Barragan Avila, Jose Efren, Unger, Kristian, Kordes, Claus, Leblond, Anne-Laure, Albrecht, Wiebke, Loosen, Sven H., Lohr, Carolin, Jördens, Markus S., Babler, Anne, Hayat, Sikander, Schumacher, David, Koenen, Maria T., Govaere, Olivier, Boekschoten, Mark V., Jörs, Simone, Villacorta-Martin, Carlos, Mazzaferro, Vincenzo, Llovet, Josep M., Weiskirchen, Ralf, Kather, Jakob N., Starlinger, Patrick, Trauner, Michael, Luedde, Mark, Heij, Lara R., Neumann, Ulf P., Keitel, Verena, Bode, Johannes G., Schneider, Rebekka K., Tacke, Frank, Levkau, Bodo, Lammers, Twan, Fluegen, Georg, Alexandrov, Theodore, Collins, Amy L., Nelson, Glyn, Oakley, Fiona, Mann, Derek A., Roderburg, Christoph, Longerich, Thomas, Weber, Achim, Villanueva, Augusto, Samson, Andre L., Murphy, James M., Kramann, Rafael, Geisler, Fabian, Costa, Ivan G., Hengstler, Jan G., Heikenwalder, Mathias, and Luedde, Tom

Published
2023
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28. Spatial multi-omic map of human myocardial infarction

Author

Kuppe, Christoph, Ramirez Flores, Ricardo O., Li, Zhijian, Hayat, Sikander, Levinson, Rebecca T., Liao, Xian, Hannani, Monica T., Tanevski, Jovan, Wünnemann, Florian, Nagai, James S., Halder, Maurice, Schumacher, David, Menzel, Sylvia, Schäfer, Gideon, Hoeft, Konrad, Cheng, Mingbo, Ziegler, Susanne, Zhang, Xiaoting, Peisker, Fabian, Kaesler, Nadine, Saritas, Turgay, Xu, Yaoxian, Kassner, Astrid, Gummert, Jan, Morshuis, Michiel, Amrute, Junedh, Veltrop, Rogier J. A., Boor, Peter, Klingel, Karin, Van Laake, Linda W., Vink, Aryan, Hoogenboezem, Remco M., Bindels, Eric M. J., Schurgers, Leon, Sattler, Susanne, Schapiro, Denis, Schneider, Rebekka K., Lavine, Kory, Milting, Hendrik, Costa, Ivan G., Saez-Rodriguez, Julio, and Kramann, Rafael

Published
2022
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32. Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease

Author

Wollenhaupt, Julia, Frisch, Janina, Harlacher, Eva, Wong, Dickson W.L., Jin, Han, Schulte, Corinna, Vondenhoff, Sonja, Moellmann, Julia, Klinkhammer, Barbara Mara, Zhang, Li, Baleanu-Curaj, Adelina, Liehn, Elisa A., Speer, Thimoteus, Kazakov, Andrey, Werner, Christian, van der Vorst, Emiel P.C., Selejan, Simina-Ramona, Hohl, Mathias, Böhm, Michael, Kramann, Rafael, Biessen, Erik A.L., Lehrke, Michael, Marx, Nikolaus, Jankowski, Joachim, Maack, Christoph, Boor, Peter, Prates Roma, Leticia, and Noels, Heidi

Published
2022
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34. Mapping the cardiac vascular niche in heart failure

Author

Peisker, Fabian, Halder, Maurice, Nagai, James, Ziegler, Susanne, Kaesler, Nadine, Hoeft, Konrad, Li, Ronghui, Bindels, Eric M. J., Kuppe, Christoph, Moellmann, Julia, Lehrke, Michael, Stoppe, Christian, Schaub, Michael T., Schneider, Rebekka K., Costa, Ivan, and Kramann, Rafael

Published
2022
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35. Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression

Author

Sciacovelli, Marco, Dugourd, Aurelien, Jimenez, Lorea Valcarcel, Yang, Ming, Nikitopoulou, Efterpi, Costa, Ana S. H., Tronci, Laura, Caraffini, Veronica, Rodrigues, Paulo, Schmidt, Christina, Ryan, Dylan Gerard, Young, Timothy, Zecchini, Vincent R., Rossi, Sabrina H., Massie, Charlie, Lohoff, Caroline, Masid, Maria, Hatzimanikatis, Vassily, Kuppe, Christoph, Von Kriegsheim, Alex, Kramann, Rafael, Gnanapragasam, Vincent, Warren, Anne Y., Stewart, Grant D., Erez, Ayelet, Vanharanta, Sakari, Saez-Rodriguez, Julio, and Frezza, Christian

Published
2022
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36. Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease

Author

Jankowski, Vera, Saritas, Turgay, Kjolby, Mads, Hermann, Juliane, Speer, Thimoteus, Himmelsbach, Anika, Mahr, Kerstin, Heuschkel, Marina Augusto, Schunk, Stefan J., Thirup, Soren, Winther, Simon, Bottcher, Morten, Nyegard, Mette, Nykjaer, Anders, Kramann, Rafael, Kaesler, Nadine, Jankowski, Joachim, Floege, Juergen, Marx, Nikolaus, and Goettsch, Claudia

Published
2022
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39. Reply to: Apolipoprotein C3 induces inflammasome activation only in its delipidated form

Author

Zewinger, Stephen, Reiser, Jochen, Jankowski, Vera, Alansary, Dalia, Hahm, Eunsil, Triem, Sarah, Klug, Mira, Schunk, Stefan J., Schmit, David, Kramann, Rafael, Körbel, Christina, Ampofo, Emmanuel, Laschke, Matthias W., Selejan, Simina-Ramona, Paschen, Anna, Herter, Tobias, Gaul, Susanne, Silbernagel, Günther, Sester, Martina, Sester, Urban, Aßmann, Gunter, Bals, Robert, Kostner, Gerhard, Jahnen-Dechent, Willi, Menger, Michael D., Rohrer, Lucia, März, Winfried, Böhm, Michael, Jankowski, Joachim, Kopf, Manfred, Latz, Eicke, Niemeyer, Barbara A., Fliser, Danilo, Laufs, Ulrich, and Speer, Thimoteus

Published
2023
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40. Long-term outcomes of patients with IgA nephropathy in the German CKD cohort.

Author

Stamellou, Eleni, Nadal, Jennifer, Hendry, Bruce, Mercer, Alex, Seikrit, Claudia, Bechtel-Walz, Wibke, Schmid, Matthias, Moeller, Marcus J, Schiffer, Mario, Eckardt, Kai-Uwe, Kramann, Rafael, Floege, Jürgen, and investigators, the GCKD study

Subjects
MAJOR adverse cardiovascular events, RENAL replacement therapy, PROPORTIONAL hazards models, IGA glomerulonephritis, CHRONIC kidney failure
Abstract

Background The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established. Methods From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N  = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model. Results The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1–0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1–0.6 g/g, 0.6–1.4 g/g, 1.4–2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02–4.05], 3.8 (95% CI 1.92–7.5), 5.64 (95% CI 2.58–12.33) and 5.02 (95% CI 2.29–11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11–5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations. Conclusion In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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41. IL-6 in the infarcted heart is preferentially formed by fibroblasts and modulated by purinergic signaling

Author

Alter, Christina, Henseler, Anne-Sophie, Owenier, Christoph, Hesse, Julia, Ding, Zhaoping, Lautwein, Tobias, Bahr, Jasmin, Hayat, Sikander, Kramann, Rafael, Kostenis, Eva, Scheller, Jurgen, and Schrader, Jurgen

Subjects
Interleukin-6 -- Physiological aspects -- Health aspects, Heart attack -- Prognosis -- Development and progression, T cells -- Physiological aspects -- Health aspects, Fibroblasts -- Physiological aspects -- Health aspects, Health care industry
Abstract

Plasma IL-6 is elevated after myocardial infarction (MI) and is associated with increased morbidity and mortality. Which cardiac cell type preferentially contributes to IL-6 expression and how its production is regulated are largely unknown. Here, we studied the cellular source and purinergic regulation of IL-6 formation in a murine MI model. We found that IL- 6, measured in various cell types in post-MI hearts at the protein level and by quantitative PCR and RNAscope, was preferentially formed by cardiac fibroblasts (CFs). Single-cell RNA-Seq (scRNA-Seq) in infarcted mouse and human hearts confirmed this finding. We found that adenosine stimulated fibroblast IL-6 formation via the adenosine receptor A2bR in a Gq-dependent manner. CFs highly expressed Adora2b and rapidly degraded extracellular ATP to AMP but lacked CD73. In mice and humans, scRNA- Seq revealed that Adora2B was also mainly expressed by fibroblasts. We assessed global IL-6 production in isolated hearts from mice lacking CD73 on T cells (CD4-[CD73.sup.-/-]), a condition known to be associated with adverse cardiac remodeling. The ischemia-induced release of IL-6 was strongly attenuated in CD4-[CD73.sup.-/-] mice, suggesting adenosine-mediated modulation. Together, these findings demonstrate that post-MI IL-6 was mainly derived from activated CFs and was controlled by T cell-derived adenosine. We show that purinergic metabolic cooperation between CFs and T cells is a mechanism that modulates IL-6 formation by the heart and has therapeutic potential., Introduction IL-6 is a pleiotropic cytokine that becomes elevated in the acute response to injury (1). After myocardial infarction (MI), serum levels of IL-6 increase rapidly, correlating with the severity [...]

Published
2023
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43. Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury

Author

Billig, Sebastian, primary, Hein, Marc, additional, Kirchner, Celine, additional, Schumacher, David, additional, Habigt, Moriz Aljoscha, additional, Mechelinck, Mare, additional, Fuchs, Dieter, additional, Klinge, Uwe, additional, Theißen, Alexander, additional, Beckers, Christian, additional, Bleilevens, Christian, additional, Kramann, Rafael, additional, and Uhlig, Moritz, additional

Published
2024
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44. Multimodal single-cell profiling reveals cancer crosstalk between macrophages and stromal cells in poor prognostic cholangiocarcinoma patients

Author

Heij, Lara, primary, Hayat, Sikander, additional, Reichel, Konrad, additional, Maryam, Sidrah, additional, O’Rourke, Colm J., additional, Tan, Xiuxiang, additional, van den Braber, Marlous, additional, Verhoeff, Jan, additional, Halder, Maurice, additional, Peisker, Fabian, additional, Wiltberger, Georg, additional, Bednarsch, Jan, additional, Heise, Daniel, additional, Deierl, Julia Campello, additional, Lang, Sven A., additional, Ulmer, Florian, additional, Luedde, Tom, additional, Dahl, Edgar, additional, Jonigk, Danny, additional, Nolting, Jochen, additional, Sivakumar, Shivan, additional, Siveke, Jens, additional, Rocha, Flavio G., additional, Baba, Hideo A., additional, Andersen, Jesper B., additional, Garcia Vallejo, Juan J., additional, Kramann, Rafael, additional, and Neumann, Ulf, additional

Published
2024
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46. The challenges of research data management in cardiovascular science:a DGK and DZHK position paper—executive summary

Author

Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, Kohl, Peter, Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, and Kohl, Peter

Abstract

The sharing and documentation of cardiovascular research data are essential for efficient use and reuse of data, thereby aiding scientific transparency, accelerating the progress of cardiovascular research and healthcare, and contributing to the reproducibility of research results. However, challenges remain. This position paper, written on behalf of and approved by the German Cardiac Society and German Centre for Cardiovascular Research, summarizes our current understanding of the challenges in cardiovascular research data management (RDM). These challenges include lack of time, awareness, incentives, and funding for implementing effective RDM; lack of standardization in RDM processes; a need to better identify meaningful and actionable data among the increasing volume and complexity of data being acquired; and a lack of understanding of the legal aspects of data sharing. While several tools exist to increase the degree to which data are findable, accessible, interoperable, and reusable (FAIR), more work is needed to lower the threshold for effective RDM not just in cardiovascular research but in all biomedical research, with data sharing and reuse being factored in at every stage of the scientific process. A culture of open science with FAIR research data should be fostered through education and training of early-career and established research professionals. Ultimately, FAIR RDM requires permanent, long-term effort at all levels. If outcomes can be shown to be superior and to promote better (and better value) science, modern RDM will make a positive difference to cardiovascular science and practice. The full position paper is available in the supplementary materials.

Published
2024

47. Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort:an investigation using the SPRINT research materials

Author

Emrich, Insa E., Pickering, John W., Götzinger, Felix, Kramann, Rafael, Kunz, Michael, Lauder, Lucas, Papademetriou, Vasilios, Böhm, Michael, Heine, Gunnar H., Mahfoud, Felix, Emrich, Insa E., Pickering, John W., Götzinger, Felix, Kramann, Rafael, Kunz, Michael, Lauder, Lucas, Papademetriou, Vasilios, Böhm, Michael, Heine, Gunnar H., and Mahfoud, Felix

Abstract

Background:Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown. Method:In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events. Results:During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m2 or >60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m2 vs. 73.2 ± 19.4 ml/min/1.73 m2 (P < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: −9.5% (95% confidence interval (CI) −13.0% to −5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: −31.1% (95% CI −32.1% to −30.1%)). Conclusion. Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of

Published
2024

48. Long-term outcomes of adults with FSGS in the German Chronic Kidney Disease cohort.

Author

Stamellou, Eleni, Nadal, Jennifer, Hendry, Bruce, Mercer, Alex, Bechtel-Walz, Wibke, Schiffer, Mario, Eckardt, Kai-Uwe, Kramann, Rafael, Moeller, Marcus J, Floege, Jürgen, and investigators, GCKD study

Subjects
MAJOR adverse cardiovascular events, PROPORTIONAL hazards models, DISEASE risk factors, CHRONIC kidney failure, RENAL replacement therapy
Abstract

Background Focal segmental glomerulosclerosis (FSGS) can lead to kidney failure in adults. This study examines the progression of FSGS in the German Chronic Kidney Disease (GCKD) cohort. Methods The GCKD study (N  = 5217), a prospective cohort, included 159 patients with biopsy-confirmed FSGS recruited from 2010 to 2012. Baseline was defined as the first study visit. Adjudicated endpoints included a composite kidney endpoint (CKE), including an estimated glomerular filtration rate (eGFR) decrease >40%, eGFR <15 ml/min/1.73 m2 or initiation of kidney replacement therapy and combined major adverse cardiovascular events (MACE), including non-fatal myocardial infarction or stroke and all-cause mortality. Associations between baseline demographics, laboratory data, comorbidity and CKE and MACE were analysed using the Cox proportional hazards regression model. Results The mean age at baseline was 52.1 ± 13.6 years, with a disease duration of 4.72 years (quartile 1: 1; quartile 3: 6) before joining the study. The median urinary albumin:creatinine ratio (UACR) at baseline was 0.7 g/g (IQR 0.1;1.8), while mean eGFR was 55.8 ± 23 ml/min/1.73 m2. Based on clinical and pathological features, 69 (43.4%) patients were categorized as primary FSGS, 55 (34.6%) as secondary FSGS and 35 (22%) as indeterminate. Over a follow-up of 6.5 years, 44 patients reached the composite kidney endpoint and 16 individuals had at least one MACE. UACR ≥0.7 g/g was strongly associated with both the composite kidney endpoint {hazard ratio [HR] 5.27 [95% confidence interval (CI) 2.4–11.5]} and MACE [HR 3.37 (95% CI 1.05–10.82)] compared with <0.7 g/g, whereas a higher eGFR at baseline (per 10 ml/min) was protective for both endpoints [HR 0.8 (95% CI 0.68–0.95) and HR 0.63 (95% CI 0.46–0.88), respectively]. Patients with secondary FSGS experienced a greater rate of eGFR decline than patients with primary FSGS. Conclusions Lower eGFR and higher albuminuria are key risk factors for kidney disease progression and cardiovascular events in patients with FSGS. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials

Author

Emrich, Insa E, primary, Pickering, John W, additional, Götzinger, Felix, additional, Kramann, Rafael, additional, Kunz, Michael, additional, Lauder, Lucas, additional, Papademetriou, Vasilios, additional, Böhm, Michael, additional, Heine, Gunnar H, additional, and Mahfoud, Felix, additional

Published
2024
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