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2. The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

Author

Rijnhout, Tim W. H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C. T. H., Viersen, Victor V. A., van Waes, Oscar J. F., van de Watering, Leo M. G., van der Burg, B. L. S. Borger, Zwaginga, Jaap J., Verhofstad, Michael H. J., and Hoencamp, Rigo

Published
2022
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7. Association of Hospital Volume with Perioperative Mortality of Endovascular Repair of Complex Aortic Aneurysms: A Nationwide Cohort Study

Author

Alberga, Anna J., von Meijenfeldt, Gerdine C. I., Rastogi, Vinamr, de Bruin, Jorg L., Wever, Jan J., van Herwaarden, Joost A., Hamming, Jaap F., Hazenberg, Constantijn E. V. B., van Schaik, Jan, Mees, Barend M. E., van der Laan, Maarten J., Zeebregts, Clark J., Schurink, Geert W. H., Verhagen, Hence J. M., van den Akker, P. J., Akkersdijk, G. P., Akkersdijk, W. L., van Andringa de Kempenaer, M. G., Arts, C. H. P., Avontuur, A. M., Bakker, O. J., Balm, R., Barendregt, W. B., Bekken, J. A., Bender, M. H. M., Bendermacher, B. L. W., van den Berg, M., Beuk, R. J., Blankensteijn, J. D., Bode, A. S., Bodegom, M. E., van der Bogt, K. E. A., Boll, A. P. M., Booster, M. H., Borger van der Burg, B. L. S., de Borst, G. J., Bos-van Rossum, W. T. G. J., Bosma, J., Botman, J. M. J., Bouwman, L. H., Brehm, V., de Bruijn, M. T., de Bruin, J. L., Brummel, P., van Brussel, J. P., Buijk, S. E., Buimer, M. G., Buscher, H. C. J. L., Cancrinus, E., Castenmiller, P. H., Cazander, G., Cuypers, P. W. M., Daemen, J. H. C., Dawson, I., Dierikx, J. E., Dijkstra, M. L., Diks, J., Dinkelman, M. K., Dirven, M., Dolmans, D. E. J. G. J., van Dortmont, L. M. C., Drouven, J. W., van der Eb, M. M., Eefting, D., van Eijck, G. J. W. M., Elshof, J. W. M., Elsman, A. H. P., van der Elst, A., van Engeland, M. I. A., van Eps, G. S., Faber, M. J., de Fijter, W. M., Fioole, B., Fritschy, W. M., Fung Kon Jin, P. H. P., Geelkerken, R. H., van Gent, W. B., Glade, G. J., Govaert, B., Groenendijk, R. P. R., de Groot, H. G. W., van den Haak, R. F. F., de Haan, E. F. A., Hajer, G. F., Hamming, J. F., van Hattum, E. S., Hazenberg, C. E. V. B., Hedeman Joosten, P. P. A., Helleman, J. N., van der Hem, L. G., Hendriks, J. M., van Herwaarden, J. A., Heyligers, J. M. M., Hinnen, J. W., Hissink, R. J., Ho, G. H., den Hoed, P. T., Hoedt, M. T. C., van Hoek, F., Hoencamp, R., Hoffmann, W. H., Hoksbergen, A. W. J., Hollander, E. J. F., Huisman, L. C., Hulsebos, R. G., Huntjens, K. M. B., Idu, M. M., Jacobs, M. J. H. M., van der Jagt, M. F. P., Jansbeken, J. R. H., Janssen, R. J. L., Jiang, H. H. L., de Jong, S. C., Jongbloed-Winkel, T. A., Jongkind, V., Kapma, M. R., Keller, B. P. J. A., Jahrome, A. Khodadade, Kievit, J. K., Klemm, P. L., Klinkert, P., Koedam, N. A., Koelemaij, M. J. W., Kolkert, J. L. P., Koning, G. G., Koning, O. H. J., Konings, R., Krasznai, A. G., Kropman, R. H. J., Kruse, R. R., van der Laan, L., van der Laan, M. J., van Laanen, J. H. H., van Lammeren, G. W., Lamprou, D. A. A., Lardenoije, J. H. P., Lauret, G. J., Leenders, B. J. M., Legemate, D. A., Leij-Dekkers, V. J., Lemson, M. S., Lensvelt, M. M. A., Lijkwan, M. A., van der Linden, F. T. P. M., Lung, P. F. L., Loos, M. J. A., Loubert, M. C., van de Luijtgaarden, K. M., Mahmoud, D. E. A. K., Manshanden, C. G., Mat-Tens, E. C. J. L., Meerwaldt, R., Mees, B. M. E., Menting, T. P., Metz, R., de Mol van Otterloo, J. C. A., Molegraaf, M. J., Montauban van Swijn-Dregt, Y. C. A., Morak, M. J. M., van de Mortel, R. H. W., Mulder, W., Nagesser, S. K., Naves, C. C. L. M., Nederhoed, J. H., Nevenzel, A. M., de Nie, A. J., Nieuwenhuis, D. H., van Nieuwenhuizen, R. C., Nieuwenhui-Zen, J., Nio, D., Oomen, A. P. A., Oranen, B. I., Oskam, J., Palamba, H. W., Peppelenbosch, A. G., van Petersen, A. S., Petri, B. J., Pierie, M. E. N., Ploeg, A. J., Pol, R. A., Ponfoort, E. D., Poyck, P. P. C., Prent, A., ten Raa, S., Raymakers, J. T. F. J., Reichmann, B. L., Reijnen, M. M. P. J., de Ridder, J. A. M., Rijbroek, A., van Rijn, M. J. E., de Roo, R. A., Rouwet, E. V., Saleem, B. R., van Sambeek, M. R. H. M., Samyn, M. G., van't Sant, H. P., van Schaik, J., van Schaik, P. M., Scharn, D. M., Scheltinga, M. R. M., Schepers, A., Schlejen, P. M., Schlösser, F. J. V., Schol, F. P. G., Scholtes, V. P. W., Schouten, O., Schreve, M. A., Schurink, G. W. H., Sikkink, C. J. J. M., te Slaa, A., Smeets, H. J., Smeets, L., Smeets, R. R., de Smet, A. A. E. A., Smit, P. C., Smits, T. M., Snoeijs, M. G. J., Sondakh, A. O., Speijers, M. J., van der Steenhoven, T. J., van Sterkenburg, S. M. M., Stigter, D. A. A., Stokmans, R. A., Strating, R. P., Stultiëns, G. N. M., Sybrandy, J. E. M., Teijink, J. A. W., Telgenkamp, B. J., Testroote, M. J. G., Tha-in, T., The, R. M., Thijsse, W. J., Thomassen, I., Tielliu, I. F. J., van Tongeren, R. B. M., Toorop, R. J., Tournoij, E., Truijers, M., Türkcan, K., Nolthenius, R. P. Tutein, Ünlü, C., Vaes, R. H. D., Vahl, A. C., Veen, E. J., Veger, H. T. C., Veldman, M. G., Verhagen, H. J. M., Verhoeven, B. A. N., Vermeulen, C. F. W., Vermeulen, E. G. J., Vierhout, B. P., van der Vijver-Coppen, R. J., Visser, M. J. T., van der Vliet, J. A., van Vlijmen-van Keulen, C. J., van der Vorst, J. R., Vos, A. W. F., Vos, C. G., Vos, G. A., de Vos, B., Voûte, M. T., Vriens, B. H. R., Vriens, P. W. H. E., de Vries, D. K., de Vries, J. P. P. M., de Vries, M., de Vries, A. C., van der Waal, C., Waasdorp, E. J., de Vries, B. M. Wallis, van Walraven, L. A., van Wanroi, J. L., Warlé, M. C., van Weel, V., van Well, A. M. E., Welten, G. M. J. M., Wever, J. J., Wiersema, A. M., Wikkeling, O. R. M., Willaert, W. I. M., Wille, J., Willems, M. C. M., Willigendael, E. M., Wilschut, E. D., Wisselink, W., Witte, M. E., Wittens, C. H. A., Wong, C. Y., Yazar, O., Yeung, K. K., Zeebregts, C. J. A. M., van Zeeland, M. L. P., Physiology, ACS - Pulmonary hypertension & thrombosis, Surgery, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, VU University medical center, AII - Inflammatory diseases, APH - Digital Health, Medical Biochemistry, ACS - Diabetes & metabolism, AII - Infectious diseases, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
volume-outcome, complex AAA, endovascular, mortality
Abstract

Objective: We evaluate nationwide perioperative outcomes of complex EVAR and assess the volume-outcome association of complex EVAR. Summary of Background Data: Endovascular treatment with fenestrated (FEVAR) or branched (BEVAR) endografts is progressively used for excluding complex aortic aneurysms (complex AAs). It is unclear if a volumeoutcome association exists in endovascular treatment of complex AAs (complex EVAR). Methods: All patients prospectively registered in the Dutch Surgical Aneurysm Audit who underwent complex EVAR (FEVAR or BEVAR) between January 2016 and January 2020 were included. The effect of annual hospital volume on perioperative mortality was examined using multivariable logistic regression analyses. Patients were stratified into quartiles based on annual hospital volume to determine hospital volume categories. Results: We included 694 patients (539 FEVAR patients, 155 BEVAR patients). Perioperative mortality following FEVAR was 4.5% and 5.2% following BEVAR. Postoperative complication rates were 30.1% and 48.7%, respectively. The first quartile hospitals performed

Published
2023

11. The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding:MAFOD—study protocol for a randomized controlled non-inferiority trial

Author

Rijnhout, Tim W.H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C.T.H., Viersen, Victor V.A., van Waes, Oscar J.F., van de Watering, Leo M.G., van der Burg, B. L.S.Borger, Zwaginga, Jaap J., Verhofstad, Michael H.J., Hoencamp, Rigo, Rijnhout, Tim W.H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C.T.H., Viersen, Victor V.A., van Waes, Oscar J.F., van de Watering, Leo M.G., van der Burg, B. L.S.Borger, Zwaginga, Jaap J., Verhofstad, Michael H.J., and Hoencamp, Rigo

Abstract

Background: The Netherlands Armed Forces have been successfully using deep-frozen (− 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. Methods: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. Discussion: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. Trial

Published
2022

12. Clinical Consensus on Diagnosis and Treatment of Patients with Chronic Exertional Compartment Syndrome of the Leg:A Delphi Analysis

Author

Vogels, Sanne, Ritchie, E. D., van der Burg, B. L.S.Borger, Scheltinga, M. R.M., Zimmermann, W. O., Hoencamp, R., Vogels, Sanne, Ritchie, E. D., van der Burg, B. L.S.Borger, Scheltinga, M. R.M., Zimmermann, W. O., and Hoencamp, R.

Abstract

Aim: Defining universally accepted guidelines for the diagnosis and treatment of chronic exertional compartment syndrome (CECS) is hampered by the absence of high-quality scientific research. The aim of this Delphi study was to establish consensus on practical issues guiding diagnosis and treatment of CECS of the leg in civilian and military patient populations. Methods: An international expert group was queried using the Delphi technique with a traditional three-round electronic consultation. Results of previous rounds were anonymously disclosed in the questionnaire of rounds 2 and 3, if relevant. Consensus was defined as > 70% positive or negative agreement for a question or statement. Results: The panel consisted of 27 civilian and military healthcare providers. Consensus was reached on five essential key characteristics of lower leg CECS. The panel achieved partial agreement regarding standardization of the diagnostic protocol, including muscle tissue pressure measurements. Consensus was reached on conservative and surgical treatment regimens. However, the experts did not attain consensus on their approach of postoperative rehabilitation and preferred treatment approach of recurrent or residual disease. A summary of best clinical practice for the diagnosis and management of CECS was formulated by experts working in civilian and military healthcare facilities. Conclusion: The Delphi panel reached consensus on key criteria for signs and symptoms of CECS and several aspects for conservative and surgical treatment. The panel did not agree on the role of ICP values in the diagnostic process, postoperative rehabilitation guidelines protocol, or the preferred treatment approach for recurrent or residual disease. These aspects serve as a first attempt to initiate simple guidelines for clinical practice.

Published
2022

13. Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms: A Nationwide Prospective Cohort Study

Author

Alberga, Anna J., Karthaus, Eleonora G., Wilschut, Janneke A., de Bruin, Jorg L., Akkersdijk, George P., Geelkerken, Robert H., Hamming, Jaap F., Wever, Jan J., Verhagen, Hence J. M., van den Akker, P. J., Akkersdijk, G. P., Akkersdijk, W. L., van Andringa de Kempenaer, M. G., Arts, C. H. P., Avontuur, A. M., Bakker, O. J., Balm, R., Barendregt, W. B., Bekken, J. A., Bender, M. H. M., Bendermacher, B. L. W., van den Berg, M., Beuk, R. J., Blankensteijn, J. D., Bode, A. S., Bodegom, M. E., van der Bogt, K. E. A., Boll, A. P. M., Booster, M. H., Borger van der Burg, B. L. S., de Borst, G. J., Bos-van Rossum, W. T. G. J., Bosma, J., Botman, J. M. J., Bouwman, L. H., Brehm, V., de Bruijn, M. T., de Bruin, J. L., Brummel, P., van Brussel, J. P., Buijk, S. E., Buimer, M. G., Buscher, H. C. J. L., Cancrinus, E., Castenmiller, P. H., Cazander, G., Cuypers, P. H. W. M., Daemen, J. H. C., Dawson, I., Dierikx, J. E., Dijkstra, M. L., Diks, J., Dinkelman, M. K., Dirven, M., Dolmans, D. E. J. G. J., van Dortmont, L. M. C., Drouven, J. W., van der Eb, M. M., Eefting, D., van Eijck, G. J. W. M., Elshof, J. W. M., Elsman, B. H. P., van der Elst, A., van Engeland, M. I. A., van Eps, G. S., Faber, M. J., de Fijter, W. M., Fioole, B., Fritschy, W. M., Jin, P. H. P. F. K., Geelkerken, R. H., van Gent, W. B., Glade, G. J., Govaert, B., Groenendijk, R. P. R., de Groot, H. G. W., van den Haak, R. F. F., de Haan, E. F. A., Hajer, G. F., Hamming, J. F., van Hattum, E. S., Hazenberg, C. E. V. B., Hedeman Joosten, P. P. H. A., Helleman, J. N., van der Hem, L. G., Hendriks, J. M., van Herwaarden, J. A., Heyligers, J. M. M., Hinnen, J. W., Hissink, R. J., Ho, G. H., den Hoed, P. T., Hoedt, M. T. C., van Hoek, F., Hoencamp, R., Hoffmann, W. H., Hoksbergen, A. W. J., Hollander, E. J. F., Huisman, L. C., Hulsebos, R. G., Huntjens, K. M. B., Idu, M. M., Jacobs, M. J. H. M., van der Jagt, M. F. P., Jansbeken, J. R. H., Janssen, R. J. L., Jiang, H. H. L., de Jong, S. C., Jongbloed-Winkel, T. A., Jongkind, V., Kapma, M. R., Keller, B. P. J. A., Jahrome, A. K., Kievit, J. K., Klemm, P. L., Klinkert, P., Koedam, N. A., Koelemaij, M. J. W., Kolkert, J. L. P., Koning, G. G., Koning, O. H. J., Konings, R., Krasznai, A. G., Kropman, R. H. J., Kruse, R. R., van der Laan, L., van der Laan, M. J., van Laanen, J. H. H., van Lammeren, G. W., Lamprou, D. A. A., Lardenoije, J. H. P., Lauret, G. J., Leenders, B. J. M., Legemate, D. A., Leijdekkers, V. J., Lemson, M. S., Lensvelt, M. M. A., Lijkwan, M. A., van der Linden, F. T. H. P. M., Lung, P. F. Liqui, Loos, M. J. A., Loubert, M. C., van de Luijtgaarden, K. M., Mahmoud, D. E. A. K., Manshanden, C. G., Mattens, E. C. J. L., Meerwaldt, R., Mees, B. M. E., Menting, T. P., Metz, R., de Mol van Otterloo, J. C. A., Molegraaf, M. J., Montauban van Swijndregt, Y. C. A., Morak, M. J. M., van de Mortel, R. H. W., Mulder, W., Nagesser, S. K., Naves, C. C. L. M., Nederhoed, J. H., Nevenzel, A. M., de Nie, A. J., Nieuwenhuis, D. H., van Nieuwenhuizen, R. C., Nieuwenhuizen, J., Nio, D., Oomen, A. P. A., Oranen, B. I., Oskam, J., Palamba, H. W., Peppelenbosch, A. G., van Petersen, A. S., Petri, B. J., Pierie, M. E. N., Ploeg, A. J., Pol, R. A., Ponfoort, E. D., Poyck, P. P. C., Prent, A., Raa, S. ten, Raymakers, J. T. F. J., Reichmann, B. L., Reijnen, M. M. P. J., de Ridder, J. A. M., Rijbroek, A., van Rijn, M. J. E., de Roo, R. A., Rouwet, E. V., Saleem, B. R., van Sambeek, M. R. H. M., Samyn, M. G., van ’t Sant, H. P., van Schaik, J., van Schaik, P. M., Scharn, D. M., Scheltinga, M. R. M., Schepers, A., Schlejen, P. M., Schlösser, F. J. V., Schol, F. P. G., Scholtes, V. P. W., Schouten, O., Schreve, M. A., Schurink, G. W. H., Sikkink, C. J. J. M., Slaa, A. te, Smeets, H. J., Smeets, L., Smeets, R. R., de Smet, A. A. E. A., Smit, P. C., Smits, T. M., Snoeijs, M. G. J., Sondakh, A. O., Speijers, M. J., van der Steenhoven, T. J., van Sterkenburg, S. M. M., Stigter, D. A. A., Stokmans, R. A., Strating, R. P., Stultiëns, G. N. M., Sybrandy, J. E. M., Teijink, J. A. W., Telgenkamp, B. J., Testroote, M. J. G., Tha-in, T., The, R. M., Thijsse, W. J., Thomassen, I., Tielliu, I. F. J., van Tongeren, R. B. M., Toorop, R. J., Tournoij, E., Truijers, M., Türkcan, K., Tutein Nolthenius, R. P., Ünlü, C., Vaes, R. H. D., Vahl, A. C., Veen, E. J., Veger, H. T. C., Veldman, M. G., Verhagen, H. J. M., Verhoeven, B. A. N., Vermeulen, C. F. W., Vermeulen, E. G. J., Vierhout, B. P., van der Vijver-Coppen, R. J., Visser, M. J. T., van der Vliet, J. A., van Vlijmen - van Keulen, C. J., van der Vorst, J. R., Vos, A. W. F., Vos, C. G., Vos, G. A., de Vos, B., Voûte, M. T., Vriens, B. H. R., Vriens, P. W. H. E., de Vries, D. K., de Vries, J. P. P. M., de Vries, M., de Vries, A. C., van der Waal, C., Waasdorp, E. J., Wallis de Vries, B. M., van Walraven, L. A., van Wanroi, J. L., Warlé, M. C., van Weel, V., van Well, A. M. E., Welten, G. M. J. M., Wever, J. J., Wiersema, A. M., Wikkeling, O. R. M., Willaert, W. I. M., Wille, J., Willems, M. C. M., Willigendael, E. M., Wilschut, E. D., Wisselink, W., Witte, M. E., Wittens, C. H. A., Wong, C. Y., Yazar, O., Yeung, K. K., Zeebregts, C. J. A. M., van Zeeland, M. L. P., ACS - Microcirculation, Anesthesiology, Physiology, ACS - Pulmonary hypertension & thrombosis, Surgery, ACS - Atherosclerosis & ischemic syndromes, VU University medical center, ACS - Diabetes & metabolism, TechMed Centre, Multi-Modality Medical Imaging, Medical Biochemistry, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, Time Factors, Operative procedure, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Risk Assessment, Blood Vessel Prosthesis Implantation, Postoperative Complications, Risk Factors, Humans, Hospital Mortality, Prospective Studies, Registries, Treatment outcome, Aged, Netherlands, Retrospective Studies, Aged, 80 and over, Endovascular Procedures, Quality of care, Middle Aged, Endovascular procedure, Abdominal aortic aneurysm, Surgery, Female, Trends, Cardiology and Cardiovascular Medicine, Aortic Aneurysm, Abdominal
Abstract

Contains fulltext : 251573.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time. METHODS: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year. RESULTS: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 - 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 - 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 - 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 - 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 - 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 - 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased. CONCLUSION: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.

Published
2022

14. Additional file 2 of The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

Author

Rijnhout, Tim W. H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C. T. H., Viersen, Victor V. A., van Waes, Oscar J. F., van de Watering, Leo M. G., van der Burg, B. L. S. Borger, Zwaginga, Jaap J., Verhofstad, Michael H. J., and Hoencamp, Rigo

Abstract

Additional file 2. Statistical analysis plan.

Published
2022
Full Text
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15. Additional file 3 of The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

Author

Rijnhout, Tim W. H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C. T. H., Viersen, Victor V. A., van Waes, Oscar J. F., van de Watering, Leo M. G., van der Burg, B. L. S. Borger, Zwaginga, Jaap J., Verhofstad, Michael H. J., and Hoencamp, Rigo

Abstract

Additional file 3. Translation of the ethics approval.

Published
2022
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16. A read-across case study on chronic toxicity of branched carboxylic acids (1): Integration of mechanistic evidence from new approach methodologies (NAMs) to explore a common mode of action

Author

Escher SE, Aguayo-Orozco A, Benfenati E, Bitsch A, Braunbeck T, Brotzmann K, Bois F, van der Burg B, Castel J, Exner T, Gadaleta D, Gardner I, Goldmann D, Hatley O, Golbamaki N, Graepel R, Jennings P, Limonciel A, Long A, Maclennan R, Mombelli E, Norinder U, Jain S, Capinha LS, Taboureau OT, Tolosa L, Vrijenhoek NG, van Vugt-Lussenburg BMA, Walker P, van de Water B, Wehr M, White A, Zdrazil B, and Fisher C

Subjects
AOP-network, Liver steatosis, Mechanistic hazard assessment, NAM, Read-across
Abstract

This read-across case study characterises thirteen, structurally similar carboxylic acids demonstrating the application of in vitro and in silico human-based new approach methods, to determine biological similarity. Based on data from in vivo animal studies, the read-across hypothesis is that all analogues are steatotic and so should be considered hazardous. Transcriptomic analysis to determine differentially expressed genes (DEGs) in hepatocytes served as first tier testing to confirm a common mode-of-action and identify differences in the potency of the analogues. An adverse outcome pathway (AOP) network for hepatic steatosis, informed the design of an in vitro testing battery, targeting AOP relevant MIEs and KEs, and Dempster-Shafer decision theory was used to systematically quantify uncertainty and to define the minimal testing scope. The case study shows that the read-across hypothesis is the critical core to designing a robust, NAM-based testing strategy. By summarising the current mechanistic understanding, an AOP enables the selection of NAMs covering MIEs, early KEs, and late KEs. Experimental coverage of the AOP in this way is vital since MIEs and early KEs alone are not confirmatory of progression to the AO. This strategy exemplifies the workflow previously published by the EUTOXRISK project driving a paradigm shift towards NAM-based NGRA.

Published
2022

17. Additional file 1 of The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

Author

Rijnhout, Tim W. H., Noorman, Femke, van der Horst, Robert A., Tan, Edward C. T. H., Viersen, Victor V. A., van Waes, Oscar J. F., van de Watering, Leo M. G., van der Burg, B. L. S. Borger, Zwaginga, Jaap J., Verhofstad, Michael H. J., and Hoencamp, Rigo

Abstract

Additional file 1. SPIRIT Checklist for Trials.

Published
2022
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18. Serious games for professional skills

Author

Bierbooms, J. J. P. A., Feijt, M. A., Ijsselsteijn, W. A., Sluis-Thiescheffe, R. J. W., Weijmans, W., van der Burg, B., Bongers, I. M. B., Wakkary, R., Andersen, K., Tranzo, Scientific center for care and wellbeing, Technological and Social Innovation for Mental Health, Human Technology Interaction, EAISI Health, and EAISI Foundational

Subjects
Final version, Medical education, Field (Bourdieu), 05 social sciences, 020207 software engineering, 02 engineering and technology, Social learning, SDG 3 – Goede gezondheid en welzijn, Mental healthcare, escape room, SDG 3 - Good Health and Well-being, 0202 electrical engineering, electronic engineering, information engineering, Skill enhancement, 0501 psychology and cognitive sciences, Lack of knowledge, Emental health, Serious gaming, Psychology, User needs, 050107 human factors, Professional skills
Abstract

A lack of knowledge and skills is an important barrier in the uptake of technology in mental healthcare. To address this issue, we propose a game-based solution in which mental healthcare professionals can explore and experience the possibilities of eMental Health. Based on extensive user needs research, we arrived at an escape room scenario as a promising solution, allowing a combination of motivated 'hands on' exploration and social learning. Currently, this escape room is being developed in multiple iterations, using input from different co-design sessions with mental healthcare professionals, designers and researchers. A try-out has taken place, based on which the final version is being developed. Subsequently, a field study will be conducted to investigate the user experiences, efficacy, and applicability of the escape room in the practice of mental healthcare.

Published
2020

22. Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment

Author

Drakvik, E., Altenburger, Rolf, Aoki, Y., Backhaus, T., Bahadori, T., Barouki, R., Brack, Werner, Cronin, M.T.D., Demeneix, B., Hougaard Bennekou, S., van Klaveren, J., Kneuer, C., Kolossa-Gehring, M., Lebret, E., Posthuma, L., Reiber, L., Rider, C., Rüegg, J., Testa, G., van der Burg, B., van der Voet, H., Warhurst, A.M., van de Water, B., Yamazaki, K., Öberg, M., Bergman, Å., Drakvik, E., Altenburger, Rolf, Aoki, Y., Backhaus, T., Bahadori, T., Barouki, R., Brack, Werner, Cronin, M.T.D., Demeneix, B., Hougaard Bennekou, S., van Klaveren, J., Kneuer, C., Kolossa-Gehring, M., Lebret, E., Posthuma, L., Reiber, L., Rider, C., Rüegg, J., Testa, G., van der Burg, B., van der Voet, H., Warhurst, A.M., van de Water, B., Yamazaki, K., Öberg, M., and Bergman, Å.

Abstract

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages:•We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures.•Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors.•Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps.•A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as r

Published
2019

23. Consensus on resuscitative endovascular balloon occlusion of the Aorta : A first consensus paper using a Delphi method

Author

van der Burg, B. L. S. Borger, Kessel, B., DuBose, J. J., Hörer, Tal M., Hoencamp, R., van der Burg, B. L. S. Borger, Kessel, B., DuBose, J. J., Hörer, Tal M., and Hoencamp, R.

Abstract

Background: To further strengthen the evidence base on the use of Resuscitative Endovascular Balloon occlusion of the Aorta (REBOA) we performed a Delphi consensus. The aim of this paper is to establish consensus on the indications and contraindications for the use of REBOA in trauma and non-trauma patients based on the existing evidence and expertise. Study Design: A literature review facilitated the design of a three-round Delphi questionnaire. Delphi panelists were identified by the investigators. Consensus was reached when at least 70% of the panelists responded to the survey and more than 70% of respondents reached agreement or disagreement. Results: Panel members reached consensus on potential indications, contra-indications and settings for use of REBOA (excluding the pre hospital environment), physiological parameters for patient selection and indications for early femoral access. Panel members failed to reach consensus on the use of REBOA in patients in extremis (no pulse, no blood pressure) and the use of REBOA in patients with two major bleeding sites. Conclusions: Consensus was reached on indications, contra indications, physiological parameters for patient selection for REBOA and early femoral access. The panel did not reach consensus on the use of REBOA in patients in pre-hospital settings, patients in extremis (no pulse, no blood pressure) and in patients with 2 or more major bleeding sites. Further research should focus on the indications of REBOA in pre hospital settings, patients in near cardiac arrest and REBOA inflation times.

Published
2019
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28. Immediate ecotoxicological effects of short-lived oil spills on marine biota

Author

Brussaard, C.P.D., Peperzak, L., Beggah, S., Wick, L.Y., Wuerz, B., Weber, J., Arey, J.S., Van der Burg, B., Jonas, A., Huisman, J., van der Meer, J.R., Brussaard, C.P.D., Peperzak, L., Beggah, S., Wick, L.Y., Wuerz, B., Weber, J., Arey, J.S., Van der Burg, B., Jonas, A., Huisman, J., and van der Meer, J.R.

Abstract

Marine environments are frequently exposed to oil spills as a result of transportation, oildrilling or fuel usage. Whereas large oil spills and their effects have been widely documented,more common and recurrent small spills typically escape attention. To fill this important gapin the assessment of oil-spill effects, we performed two independent supervised full seareleases of 5 m3of crude oil, complemented by on-board mesocosm studies and sampling ofaccidentally encountered slicks. Using rapid on-board biological assays, we detect highbioavailability and toxicity of dissolved and dispersed oil within 24 h after the spills, occurringfairly deep (8 m) below the slicks. Selective decline of marine plankton is observed, equallyrelevant for early stages of larger spills. Our results demonstrate that, contrary to commonthinking, even small spills have immediate adverse biological effects and their recurrentnature is likely to affect marine ecosystem functioning.

Published
2016

30. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ

Author

Alex, S., Lange, K., Amolo, T., Grinstead, J.S., Haakonsson, A.K., Szalowska, E., Koppen, A., Mudde, K., Haenen, D., Al-Lahham, S., Roelofsen, H., Houtman, R., van der Burg, B., Mandrup, S., Bonvin, A.M.J.J., Kalkhoven, E., Müller, M., Hooiveld, G.J., Kersten, S., NMR Spectroscopy, Dep Scheikunde, Sub NMR Spectroscopy, Sub NMR Spectroscopy, and NMR Spectroscopy

Subjects
Male, Angptl4, Transcription, Genetic, Protein-4, Peroxisome proliferator-activated receptor, Expression, Mice, Transactivation, In-vitro, Plasma, 0302 clinical medicine, ANGPTL4, Taverne, Inhibition, chemistry.chemical_classification, 0303 health sciences, Adipogenesis, digestive, oral, and skin physiology, Inulin, food and beverages, Transcriptional activity, Articles, Cell biology, Ppar-gamma, Biochemistry, 030220 oncology & carcinogenesis, Colonic Neoplasms, lipids (amino acids, peptides, and proteins), HT29 Cells, Transcriptional Activation, Colon, Butyrate, Gut microbiota, Adenocarcinoma, Biology, digestive system, 03 medical and health sciences, Mediator, 3T3-L1 Cells, Cell Line, Tumor, Coactivator, Angiopoietin-Like Protein 4, Animals, Humans, Molecular Biology, 030304 developmental biology, Cell Biology, Fatty Acids, Volatile, digestive system diseases, Mice, Inbred C57BL, PPAR gamma, Nuclear receptor, chemistry, Angiopoietins
Abstract

Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor gamma (PPAR gamma), as demonstrated using PPAR gamma antagonist, PPAR gamma knockdown, and transactivation assays, which show activation of PPAR gamma but not PPAR alpha and PPAR delta by SCFA. At concentrations required for PPAR gamma activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPAR gamma in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPAR gamma modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPAR gamma. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA.

Published
2013

31. Untersuchung von Milch und Milchprodukten

Author

Schwarz, G., Mumm, H., Gerber, D. N., Wawilow, G. m. b. H. M. W., Kogan, R. M., Iochelsson, D. B., Weiss, R., Woiwod, J., Leyko, Z., Cieplinska, H., Mohr, W., Ritterhoff, Münchberg, F., Radeff, T., van der Burg, B., Kyriazidis, K. N., Barrett, W. D., Rutan, H., Keenan, J. A., Barkworth, H., Davies, L. W., Peltzer, J., Schwarz, G., Leibovitch, B., Stoppel, F., Gilcreas, F. W., Davis, W. S., Koppejan, C. A., Kay, H. D., Vuk, M., v. Sandor, Z., Reichard, O., Dagneaux, E. L. K., Clarke, J. O., Cannon, J. H., Coulter, E. W., Goodman, M. S., Greene, W. S., Millstead, K. L., Vandaveer, R. L., Wildman, J. D., Ritter, W., Riedel, W., Mc Dowall, F. H., Mc Dowell, A. K. R., Mohr, W., Wellm, J., Pien, J., Gallup, W. D., Kuhlman, A. H., Waldby, R. M., Konoplewa, J. P., Rosanow, A. A., Leuschen, M. E., Kramer, M. M., Riddell, W. H., Kunerth, B. L., v. Fellenberg, Th., Köster, A., Gould, I. A., Schilowitsch, M. K., Byrylow, D., and Dudenkow, A. J.

Published
1938
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32. Milch

Author

Reiss, F., Herz, Fr. I., Scholler, F., Bolm, F., Vogt, K., Rothenfußer, S., Wedemann, W., Pozzi-Escot, E., Dahlberg, A. O., Kurz, O., Baumann, O., Gahrtz, G., Drost, J., Koestler, G., van der Burg, B., Koppejan, C. A., Müller, Wilhelm, Bang, I., Bakke, A., Horn, D. W., v. Fillinger, F., and Freund, Julius

Published
1925
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33. Untersuchung der Milch

Author

Ilzhöfer, H., Kometiani, P. A., Cvitl, Josefa, Roeder, G., Jeschki, K., Mohr, W., Schulz, M. E., van der Burg, B., Peña, A., and Martin, R.

Published
1933
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34. Nachweis und Bestimmung der Halogene

Author

Dimitroff, M., Spacu, G., Entat, M., Vulquin, E., Herzog, J., van der Burg, B., Koppejan, C. A., Müller, Erich, Fenwick, Florence, Torossian, G., Dean, P. M., Newcomer, E., Watts, O. O., Congdon, L. A., Crabtree, W. B., Coles, H. W., Smith, L. L., Vehalgo, M. L., Doughty, H. W., Jonas, A. J., Oppenheimer, E., Curtman, L. J., Kaufman, C., Kolthoff, J. M., Sasaki, N., Linschoten, J. H., Thüringer, V., Hasselskog, S., Britton, H. T. S., and Hibbard, F. L.

Published
1927
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35. Zur Untersuchung und Beurteilung der Milch

Author

Splittgerber, A., Lührig, Lichtenbelt, A. J., Meillère, G., van der Burg, B., Shaw, R. H., Eckles, C. H., Evenson, O. L., Formenti, C., Porcher, Ch., Gros, L., Bonnema, A. A., van Flyke, L. L., Bosworth, A. W., Hart, E. B., Robertson, T. Br., Arny, H. V., Pratt, T. M., Grimmer, Urbschat, E., Hersey, C. B., Droop Richmond, H., de Graaff, W. C., Walker, W. O., Brodrick-Pittard, N. A., Perking, J., Haensel, E., Malenfant, R., Bordas, Touplain, St. Serkowski, Shimidzu, Y., Sanfelici, R., Hill, R. C., van Driel, C., Vitoux, Kretschmer, E., Feder, E., Baker, J. L., Hulton, H. F. E., Denigès, Carrez, C., v. Fellenberg, Nath Rakshit, J., Brooks, R. O., Wagenaar, M., Fendler, G., Frank, L., Stüber, W., Eldestein, F., Csorka, F. v., Lachs, Hilary, Friedenthal, H., Nottbohm, Weisswange, Dörr, Peotschke, P., Millera, E. H., Doherty, W. M., Elsdon, G. D., Sutcliffe, J. A. L., Tillmans, J., Riffart, H., Desmoulière, E., Kuhn, O., Weller, H., Serger, H., Lowe, W. F., Malacarne, M., van der Harst, J. C., Koers, C. H., Jemma, Gascard, A., and Pégurier, G.

Published
1920
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36. Milch, Fettgemische, Käse

Author

Gerum, J., Pozzi-Escot, E., Großfeld, J., Kuhlmann, J., Grossfeld, J., Bertram, S. H., Bos, H. G., Verhagen, F., Baumann, C., Platon, J. B., Funke, P., Richmond, H. D., Ellison, L. R., Kolthoff, J. M., Panchaud, L., Gronover, A., Türk, F., Strohecker, R., Gerber, V., Drost, T., Pfyl, B., Samter, W., König, W., Kluge, H., Tillmans, J., Luckenbach, W., Grünhut, L., Chelle, L., Hortvet, J., Vollhase, E., Lowe, H., Defrance, P., Rustom, Ahmed, Reiss, F., Scholler, F., Rahn, O., Fonzes-Diacon, Bouin, M., Hanke, Barthel, Chr, Wedemann, W., Koning, C. J., Borinski, P., Hekma, E., Brouwer, E., Tankard, A. R., Letourneur-Hugon, Valin, Scheringa, K., Jörgensen, G., Jessen-Hansen, H., Honegger, Paula, Sutton, R. W., Mc Crae, J., Hurst, H., Weibull, M., Schoonjans, A., Jephcott, H., Siegmund, H. B., Craig, R. S., Hesse, Köhler, Funke, Holwerda, B. J., van der Burg, B., Beythien, A., and Pannwitz, P.

Published
1927
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38. Model Steatogenic Compounds (Amiodarone, Valproic Acid, and Tetracycline) Alter Lipid Metabolism by Different Mechanisms in Mouse Liver Slices

Author

Szalowska, E., van der Burg, B., Man, H.Y., Hendriksen, P.J.M., Peijnenburg, A.A.C.M., Szalowska, E., van der Burg, B., Man, H.Y., Hendriksen, P.J.M., and Peijnenburg, A.A.C.M.

Abstract

Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR) signaling. Application of PPAR reporter assays classified AMI and VA as PPAR¿ and triple PPARa/(ß/d)/¿ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism

Published
2014

43. Evaluation of an alternative in vitro test battery for detecting reproductive toxicants

Author

Piersma, A.H., primary, Bosgra, S., additional, van Duursen, M.B.M., additional, Hermsen, S.A.B., additional, Jonker, L.R.A., additional, Kroese, E.D., additional, van der Linden, S.C., additional, Man, H., additional, Roelofs, M.J.E., additional, Schulpen, S.H.W., additional, Schwarz, M., additional, Uibel, F., additional, van Vugt-Lussenburg, B.M.A., additional, Westerhout, J., additional, Wolterbeek, A.P.M., additional, and van der Burg, B., additional

Published
2014
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45. Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays

Author

Escher, Beate, Allinson, M., Altenburger, Rolf, Bain, P.A., Balaguer, P., Busch, Wibke, Crago, J., Denslow, N.D., Dopp, E., Hilscherova, K., Humpage, A.R., Kumar, A., Grimaldi, M., Jayasinghe, B.S., Jarosova, B., Jia, A., Makarov, S., Maruya, K.A., Medvedev, A., Mehinto, A.C., Mendez, J.E., Poulsen, A., Prochazka, E., Richard, J., Schifferli, A., Schlenk, D., Scholz, Stefan, Shiraishi, F., Snyder, S., Su, G., Tang, J.Y.M., van der Burg, B., van der Linden, S.C., Werner, I., Westerheide, S.D., Wong, C.K.C., Yang, M., Yeung, B.H.Y., Zhang, X., Leusch, F.D.L., Escher, Beate, Allinson, M., Altenburger, Rolf, Bain, P.A., Balaguer, P., Busch, Wibke, Crago, J., Denslow, N.D., Dopp, E., Hilscherova, K., Humpage, A.R., Kumar, A., Grimaldi, M., Jayasinghe, B.S., Jarosova, B., Jia, A., Makarov, S., Maruya, K.A., Medvedev, A., Mehinto, A.C., Mendez, J.E., Poulsen, A., Prochazka, E., Richard, J., Schifferli, A., Schlenk, D., Scholz, Stefan, Shiraishi, F., Snyder, S., Su, G., Tang, J.Y.M., van der Burg, B., van der Linden, S.C., Werner, I., Westerheide, S.D., Wong, C.K.C., Yang, M., Yeung, B.H.Y., Zhang, X., and Leusch, F.D.L.

Abstract

Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.

Published
2013

47. In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PBDEs, and polibrominated bisphenol A compounds

Author

Meerts, I.A.T.M., Letcher, R.J., Hoving, S., Marsh, G., Bergman, A., Lemmen, J.G., van der Burg, B., Brouwer, A., Chemistry and Biology, and Institute for Environmental Studies

Subjects
ER-CALUX, Hydroxylated compounds, endocrine system, WIMEK, SDG 3 - Good Health and Well-being, Polybrominated diphenyl ethers, Estrogenicity, Toxicology, Flame retardants, reproductive and urinary physiology, Toxicologie
Abstract

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50␒nduction (EC50) varying from 2.5 to 7.3 μM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E2), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC50 values of 0.5 μM for 3-monobromobisphenol A). In an ERα-specific, stably transfected human embryonic kidney cell line (293-ERα-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC50 < 0.1 μM and a maximum 35- to 40-fold induction, which was similar to E2. In an analogous ERβ-specific 293-ERβs-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50␒nduction compared to E2), but EC50 values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ERα and ERβ receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.

Published
2001

49. Phyto-estrogen concentration in Trifolium pratense

Author

Toebes, A.H.W., Verkley, J.A.C., Lingeman, H., Ernst, W.H.O., Vethaak, A.D., van der Burg, B., Rijs, G.B.J., Brouwer, A., Ecology and Plant Physiology, and BioAnalytical Chemistry

Published
2000

50. Development of an in vivo assay for oestrogenic potency using transgenic zebrafish

Author

Legler, J., Broekhof, J., Brouwer, A., Murk, A.J., van der Saag, P., Vethaak, A.D., and van der Burg, B.

Subjects
transgenic animals, transgene dieren, WIMEK, oestrogen receptors, ecotoxicologie, Toxicology, fishes, ecotoxicology, aquatic animals, danio rerio, reporter-genen, vissen, biotesten, reporter genes, bioassays, oestrogeenreceptoren, waterdieren, Toxicologie
Published
2000

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