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2. Validation of the clinical utility of MicroRNA as non-invasive biomarkers of cardiac allograft rejection monitoring: A prospective longitudinal multicenter study

Author

Coutance, G., primary, Racapé, M., additional, Baudry, G., additional, Lecuyer, L., additional, Roubille, F., additional, Blanchart, K., additional, Epailly, E., additional, Vermes, E., additional, Pattier, S., additional, Boignard, A., additional, Gay, A., additional, Jouven, X., additional, Duong, J.-P., additional, and Loupy, A., additional

Published
2024
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3. A new pipeline for the normalization and pooling of metabolomics data

Author

Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, and Sub Inorganic Chemistry and Catalysis

Subjects
Normalization (statistics), Pooling, Computer science, Pipeline (computing), Endocrinology, Diabetes and Metabolism, computer.software_genre, Microbiology, Biochemistry, Generalized linear mixed model, Statistical power, Article, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Cancer epidemiology, Metabolites, Metabolomics, Imputation (statistics), Càncer, Molecular Biology, 030304 developmental biology, Cancer, 0303 health sciences, Cancer och onkologi, Bioinformatics (Computational Biology), Normalization, Technical variability, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Missing data, QR1-502, 3. Good health, Diabetes and Metabolism, Metabolòmica, 030220 oncology & carcinogenesis, Cancer and Oncology, Outlier, Bioinformatik (beräkningsbiologi), Data mining, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, computer
Abstract

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers, imputation of missing data, (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis, (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

Published
2021
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5. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., Tjønneland, A., Truong, T., Lecuyer, L., Boutron-Ruault, M.-C., Katzke, V., Johnson, T.S., Schulze, M.B., Trichopoulou, A., Peppa, E., La Vechia, C., Masala, G., Pala, V., Panico, S., Tumino, R., Ricceri, F., Skeie, G., Ramón Quirós, J., Rodriguez-Barranco, M., Amiano, P., Chirlaque, M.-D., Ardanaz, E., Almquist, M., Hennings, J., Vermeulen, R., Wareham, N.J., Tong, T.Y.N., Aune, D., Byrnes, G., Weiderpass, E., Scalbert, A., Rinaldi, S., Agudo, A., Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., Tjønneland, A., Truong, T., Lecuyer, L., Boutron-Ruault, M.-C., Katzke, V., Johnson, T.S., Schulze, M.B., Trichopoulou, A., Peppa, E., La Vechia, C., Masala, G., Pala, V., Panico, S., Tumino, R., Ricceri, F., Skeie, G., Ramón Quirós, J., Rodriguez-Barranco, M., Amiano, P., Chirlaque, M.-D., Ardanaz, E., Almquist, M., Hennings, J., Vermeulen, R., Wareham, N.J., Tong, T.Y.N., Aune, D., Byrnes, G., Weiderpass, E., Scalbert, A., Rinaldi, S., and Agudo, A.

Abstract

Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods: A nested case–control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

Published
2021

6. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., Tjønneland, A., Truong, T., Lecuyer, L., Boutron-Ruault, M.-C., Katzke, V., Johnson, T.S., Schulze, M.B., Trichopoulou, A., Peppa, E., La Vechia, C., Masala, G., Pala, V., Panico, S., Tumino, R., Ricceri, F., Skeie, G., Ramón Quirós, J., Rodriguez-Barranco, M., Amiano, P., Chirlaque, M.-D., Ardanaz, E., Almquist, M., Hennings, J., Vermeulen, R., Wareham, N.J., Tong, T.Y.N., Aune, D., Byrnes, G., Weiderpass, E., Scalbert, A., Rinaldi, S., Agudo, A., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., Tjønneland, A., Truong, T., Lecuyer, L., Boutron-Ruault, M.-C., Katzke, V., Johnson, T.S., Schulze, M.B., Trichopoulou, A., Peppa, E., La Vechia, C., Masala, G., Pala, V., Panico, S., Tumino, R., Ricceri, F., Skeie, G., Ramón Quirós, J., Rodriguez-Barranco, M., Amiano, P., Chirlaque, M.-D., Ardanaz, E., Almquist, M., Hennings, J., Vermeulen, R., Wareham, N.J., Tong, T.Y.N., Aune, D., Byrnes, G., Weiderpass, E., Scalbert, A., Rinaldi, S., and Agudo, A.

Published
2021

7. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., and Ferrari, P.

Published
2021

8. Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

Author

His, M, Viallon, V, Dossus, L, Schmidt, JA, Travis, RC, Gunter, MJ, Overvad, K, Kyro, C, Tjonneland, A, Lecuyer, L, Rothwell, JA, Severi, G, Johnson, T, Katzke, V, Schulze, MB, Masala, G, Sieri, S, Panico, S, Tumino, R, Macciotta, A, Boer, JMA, Monninkhof, EM, Olsen, KS, Nost, TH, Sandanger, TM, Agudo, A, Sanchez, M-J, Amiano, P, Colorado-Yohar, SM, Ardanaz, E, Vidman, L, Winkvist, A, Heath, AK, Weiderpass, E, Huybrechts, I, Rinaldi, S, His, M, Viallon, V, Dossus, L, Schmidt, JA, Travis, RC, Gunter, MJ, Overvad, K, Kyro, C, Tjonneland, A, Lecuyer, L, Rothwell, JA, Severi, G, Johnson, T, Katzke, V, Schulze, MB, Masala, G, Sieri, S, Panico, S, Tumino, R, Macciotta, A, Boer, JMA, Monninkhof, EM, Olsen, KS, Nost, TH, Sandanger, TM, Agudo, A, Sanchez, M-J, Amiano, P, Colorado-Yohar, SM, Ardanaz, E, Vidman, L, Winkvist, A, Heath, AK, Weiderpass, E, Huybrechts, I, and Rinaldi, S

Abstract

BACKGROUND: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). METHODS: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). RESULTS: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. CONCLUSIONS: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cance

Published
2021

9. Y Prospective analysis of circulating metabolites and endometrial cancer risk

Author

Dossus, L, Kouloura, E, Biessy, C, Viallon, V, Siskos, AP, Dimou, N, Rinaldi, S, Merritt, MA, Allen, N, Fortner, R, Kaaks, R, Weiderpass, E, Gram, IT, Rothwell, JA, Lecuyer, L, Severi, G, Schulze, MB, Nost, TH, Crous-Bou, M, Sanchez, M-J, Amiano, P, Colorado-Yohar, SM, Gurrea, AB, Schmidt, JA, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Mattiello, A, Vermeulen, R, Heath, AK, Christakoud, S, Tsilidis, KK, Travis, RC, Gunter, MJ, Keun, HC, Dossus, L, Kouloura, E, Biessy, C, Viallon, V, Siskos, AP, Dimou, N, Rinaldi, S, Merritt, MA, Allen, N, Fortner, R, Kaaks, R, Weiderpass, E, Gram, IT, Rothwell, JA, Lecuyer, L, Severi, G, Schulze, MB, Nost, TH, Crous-Bou, M, Sanchez, M-J, Amiano, P, Colorado-Yohar, SM, Gurrea, AB, Schmidt, JA, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Mattiello, A, Vermeulen, R, Heath, AK, Christakoud, S, Tsilidis, KK, Travis, RC, Gunter, MJ, and Keun, HC

Abstract

BACKGROUND: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. RESULTS: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95% CI: 1.05-1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80-0.99; OR1SD: 0.89, 95% CI: 0.79-1.00 and OR1SD: 0.91, 95% CI: 0.81-1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02-1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00-1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. CONCLUSION: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

Published
2021

10. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author

Viallon, V, His, M, Rinaldi, S, Breeur, M, Gicquiau, A, Hemon, B, Overvad, K, Tjonneland, A, Rostgaard-Hansen, AL, Rothwell, JA, Lecuyer, L, Severi, G, Kaaks, R, Johnson, T, Schulze, MB, Palli, D, Agnoli, C, Panico, S, Tumino, R, Ricceri, F, Verschuren, WMM, Engelfriet, P, Onland-Moret, C, Vermeulen, R, Nost, TH, Urbarova, I, Zamora-Ros, R, Rodriguez-Barranco, M, Amiano, P, Huerta, JM, Ardanaz, E, Melander, O, Ottoson, F, Vidman, L, Rentoft, M, Schmidt, JA, Travis, RC, Weiderpass, E, Johansson, M, Dossus, L, Jenab, M, Gunter, MJ, Bermejo, JL, Scherer, D, Salek, RM, Keski-Rahkonen, P, Ferrari, P, Viallon, V, His, M, Rinaldi, S, Breeur, M, Gicquiau, A, Hemon, B, Overvad, K, Tjonneland, A, Rostgaard-Hansen, AL, Rothwell, JA, Lecuyer, L, Severi, G, Kaaks, R, Johnson, T, Schulze, MB, Palli, D, Agnoli, C, Panico, S, Tumino, R, Ricceri, F, Verschuren, WMM, Engelfriet, P, Onland-Moret, C, Vermeulen, R, Nost, TH, Urbarova, I, Zamora-Ros, R, Rodriguez-Barranco, M, Amiano, P, Huerta, JM, Ardanaz, E, Melander, O, Ottoson, F, Vidman, L, Rentoft, M, Schmidt, JA, Travis, RC, Weiderpass, E, Johansson, M, Dossus, L, Jenab, M, Gunter, MJ, Bermejo, JL, Scherer, D, Salek, RM, Keski-Rahkonen, P, and Ferrari, P

Abstract

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples' originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

Published
2021

11. Sustainable agriculture: Recognizing the potential of conflict as a positive driver for transformative change

Author

Bohan, D.A., Vanbergen, A.J., Skrimizea, E., Lecuyer, L., Bunnefeld, N., Butler, J.R.A., Fickel, T., Hodgson, I., Holtkamp, C., Marzano, M., Parra, C., Pereira, L., Petit, S., Pound, D., Rodríguez, I., Ryan, P., Staffler, J., Van den Broeck, P., Wittmer, Heidi, Young, J.C., Bohan, D.A., Vanbergen, A.J., Skrimizea, E., Lecuyer, L., Bunnefeld, N., Butler, J.R.A., Fickel, T., Hodgson, I., Holtkamp, C., Marzano, M., Parra, C., Pereira, L., Petit, S., Pound, D., Rodríguez, I., Ryan, P., Staffler, J., Van den Broeck, P., Wittmer, Heidi, and Young, J.C.

Abstract

Transformative changes in agriculture at multiple scales are needed to ensure sustainability, i.e. achieving food security while fostering social justice and environmental integrity. These transformations go beyond technological fixes and require fundamental changes in cognitive, relational, structural and functional aspects of agricultural systems. However, research on agricultural transformations fails to engage deeply with underlying social aspects such as differing perceptions of sustainability, uncertainties and ambiguities, politics of knowledge, power imbalances and deficits in democracy. In this paper, we suggest that conflict is one manifestation of such underlying social aspects. We present an original conceptualization and analytical framework, wherein conflict is recognized as an important motor for redistribution of power and leverage for social learning that—if addressed through a conflict transformation process—could potentially create a step-change in agricultural transformation towards greater sustainability. Our analysis, building on an extensive literature review and empirical case studies from around the world, suggests a novel approach to guide future transdisciplinary research that can support agricultural transformations towards sustainability.

Published
2020

12. Transformation of agricultural landscapes in the Anthropocene: Nature's contributions to people, agriculture and food security

Author

Bohan, D.A., Vanbergen, A., Vanbergen, A.J., Aizen, M.A., Cordeau, S., Garibaldi, L.A., Garratt, M.P.D., Kovács-Hostyánszki, A., Lecuyer, L., Ngo, H.T., Potts, S.G., Settele, Josef, Skrimizea, E., Young, J.C., Bohan, D.A., Vanbergen, A., Vanbergen, A.J., Aizen, M.A., Cordeau, S., Garibaldi, L.A., Garratt, M.P.D., Kovács-Hostyánszki, A., Lecuyer, L., Ngo, H.T., Potts, S.G., Settele, Josef, Skrimizea, E., and Young, J.C.

Abstract

Multiple anthropogenic challenges threaten nature's contributions to human well-being. Agricultural expansion and conventional intensification are degrading biodiversity and ecosystem functions, thereby undermining the natural foundations on which agriculture is itself built. Averting the worst effects of global environmental change and assuring ecosystem benefits, requires a transformation of agriculture. Alternative agricultural systems to conventional intensification exist, ranging from adjustments to efficiency (e.g. sustainable intensification) to a redesign (e.g. ecological intensification, climate-smart agriculture) of the farm management system. These alternatives vary in their reliance on nature or technology, the level of systemic change required to operate, and impacts on biodiversity, landscapes and agricultural production. Different socio-economic, ecological and political settings mean there is no universal solution, instead there are a suite of interoperable practices that can be adapted to different contexts to maximise efficiency, sustainability and resilience. Social, economic, technological and demographic issues will influence the form of sustainable agriculture and effects on landscapes and biodiversity. These include: (1) the socio-technical-ecological architecture of agricultural and food systems and trends such as urbanisation in affecting the mode of production, diets, lifestyles and attitudes; (2) emerging technologies, such as gene editing, synthetic biology and 3D bioprinting of meat; and (3) the scale or state of the existing farm system, especially pertinent for smallholder agriculture. Agricultural transformation will require multifunctional landscape planning with cross-sectoral and participatory management to avoid unintended consequences and ultimately depends on people's capacity to accept new ways of operating in response to the current environmental crisis.

Published
2020

14. NMR metabolomic signatures reveal predictive plasma metabolites associated with long-termrisk of developing breast cancer

Author

Lecuyer, L., Bala, A. V., Deschasaux, M., Bouchemal, N., Triba, M. N., Vasson, M. P., Rossary, A., Demidem, A., Galan, P., Hercberg, S., Partula, V., Le Moyec, L., Srour, B., Fiolet, T., Latino-Martel, P., Kesse-Guyot, E., Zelek, L., Savarin, P., Mathilde Touvier, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Université Paris Nord (Paris 13), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biologie intégrative des adaptations à l'exercice (UBIAE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), ProdInra, Archive Ouverte, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie, Structures, Propriétés de Biomatériaux et d'Agents Thérapeutiques (ancienne affiliation) (CSPBAT), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), UMR 7244, Spectroscopies Biomolécules et Milieux Biologiques (SBMB), Laboratoire CSPBAT, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne, Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris (AP-HP), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Lécuyer, Lucie, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Université Sorbonne Paris Cité (USPC)-Institut Galilée-Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), département de santé publique, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Oncology, approche métabolomique, Magnetic Resonance Spectroscopy, Epidemiology, medicine.disease_cause, mammary malignant tumor, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Cancer, échantillon de plasma, General Medicine, Middle Aged, metabolomics, 3. Good health, 030220 oncology & carcinogenesis, Alimentation et Nutrition, Metabolome, Female, France, étude de cohorte, prospective study, Adult, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Breast cancer, Metabolomics, [SDV.CAN] Life Sciences [q-bio]/Cancer, breast neoplasm, Internal medicine, medicine, Humans, Food and Nutrition, plasma, Creatinine, étude épidémiologique, business.industry, cancer du sein, Case-control study, Odds ratio, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, nuclear magnetic resonance, Logistic Models, 030104 developmental biology, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Carcinogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract

Background Combination of metabolomics and epidemiological approaches opens new perspectives for ground-breaking discoveries. The aim of the present study was to investigate for the first time whether plasma untargeted metabolomic profiles, established from a simple blood draw from healthy women, could contribute to predict the risk of developing breast cancer within the following decade and to better understand the aetiology of this complex disease. Methods A prospective nested case-control study was set up in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort, including 206 breast cancer cases diagnosed during a 13-year follow-up and 396 matched controls. Untargeted nuclear magnetic resonance (NMR) metabolomic profiles were established from baseline plasma samples. Multivariable conditional logistic regression models were computed for each individual NMR variable and for combinations of variables derived by principal component analysis. Results Several metabolomic variables from 1D NMR spectroscopy were associated with breast cancer risk. Women characterized by higher fasting plasma levels of valine, lysine, arginine, glutamine, creatine, creatinine and glucose, and lower plasma levels of lipoproteins, lipids, glycoproteins, acetone, glycerol-derived compounds and unsaturated lipids had a higher risk of developing breast cancer. P-values ranged from 0.00007 [odds ratio (OR)T3vsT1=0.37 (0.23-0.61) for glycerol-derived compounds] to 0.04 [ORT3vsT1=1.61 (1.02-2.55) for glutamine]. Conclusion This study highlighted associations between baseline NMR plasma metabolomic signatures and long-term breast cancer risk. These results provide interesting insights to better understand complex mechanisms involved in breast carcinogenesis and evoke plasma metabolic disorders favourable for carcinogenesis initiation. This study may contribute to develop screening strategies for the identification of at-risk women for breast cancer well before symptoms appear.

Published
2018
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17. Sociodemographic and economic factors are associated with weight gain between before and after cancer diagnosis: results from the prospective population-based NutriNet-Santé cohort

Author

Fassier, P., Zelek, L., Bachmann, P., Touillaud, M., Lecuyer, L., Srour, B., Hercberg, S., Cohen, P., Latino-Martel, P., Mathilde Touvier, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Unité Cancer, environnement et nutrition, Centre Léon Bérard, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), and International Union of Nutritional Sciences (IUNS). INT.

Subjects
breast cancer, cancer diagnosis, socio-demographic factors, [SDV.CAN]Life Sciences [q-bio]/Cancer, weight loss, Weight gain, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background and objectives: While many cancer patients are affected by weight loss, others tend to gain weight, which may impact prognosis and risk of recurrence and of second cancer. The aim of this prospective study was to investigate weight variation between before and after cancer diagnosis and socio-demographic, economic, lifestyle and clinical factors associated with moderate-to-severe weight gain. Methods: 1051 incident cases of first primary cancer were diagnosed in the NutriNet-Santé cohort between 2009 and 2015. Weight was prospectively collected every 6 months since subjects’ inclusion (i.e. an average of 2y before diagnosis). Mean weights before and after cancer diagnosis were compared with paired Student’s t-test. Factors associated with moderate-to-severe weight gain (≥5% of initial weight) were investigated by age and sex-adjusted logistic regression. Results: Weight loss was observed in men (-3.54±4.39kg in those who lost weight, p=0.0002) and in colorectal cancer patients (-3.94±4.40kg,p=0.001). Weight gain was observed in breast and skin cancers (2.83±3.21kg,p=0.04, and 2.96±2.75kg,p=0.04 respectively). Women (OR=1.75[1.06-2.87],p=0.03), younger patients (2.44[1.51-3.70],p

Published
2017
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18. Fasting and restrictive diet to lose weight among cancer survivors: profiles, sources of nutritional information, knowledges and opinions: results from the NutriNet-Santé cohort

Author

Fassier, P., Srour, B., Zelek, L., Touillaud, M., Bachman, P., Cohen, P., Raynard, B., Lecuyer, L., Latino-Martel, P., Mathilde Touvier, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre Léon Bérard [Lyon], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Gustave Roussy (IGR), and International Union of Nutritional Sciences (IUNS). INT.

Subjects
[SDV]Life Sciences [q-bio], cancer survivors, Fasting, nutritional opinions, nutritional knowledges, Diet
Abstract

International audience; Background and objectives: Cancer survivors need to get more actively involved in their disease, notably through their nutritional behavior. For instance restrictive diets may be considered, including fasting practice or restrictive diets to lose weight. For the moment, no previous study has investigated theses both types of restrictive diets among cancer survivors. Aims of this study were to describe profiles of patients having practiced fasting or restrictive diet to lose weight after cancer diagnosis and to investigate knowledges/opinions of these patients and their sources of nutritional information, among cancer survivors in a large web based cohort. Methods: In the NutriNet-Santé cohort, 10,309 cancer survivors received the “Sources of information and knowledges/opinions about nutrition” questionnaire in June 2016. Among them 2,942 completed it in October 2016. Associations were explored by multivariate logistic regression adjusted for socio-professional and lifestyle factors. Results: 4.5% of participants had already practiced fasting practices since their diagnosis. They were more likely to be women (p=0.01), youngers (p=0.03), with higher educational level (p=0.003), lower incomes (p=0.004), to use dietary supplements (p=0.03) and practice higher physical activity (p=0.01). 32.2% of patients had practiced restrictive diet to lose weight since diagnosis with higher proportion of women (p

Published
2017
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19. Quantitative assessment of dietary supplement intake in 77 000 French adults: Impact on nutritional inadequacy, excessive intake, and extent of 'at risk' practices

Author

Fassier, P., Egnell, M., Srour, B., Vasson, M. P., Galan, P., Lecuyer, L., Latino-Martel, P., Hercberg, S., Deschasaux, M., Mathilde Touvier, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Unité de Nutrition, Hôpital Ambroise Paré [AP-HP], International Union of Nutritional Sciences (IUNS). INT., Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne, AP-HP Hôpital Ambroise Paré (Boulogne-Billancourt), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
dietary supplements, education, nutrient inadequacy, drug interactions, tolerable upper intake levels, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, health care economics and organizations
Abstract

Further collaborators: Camille Pouchieu, Emmanuelle Kesse-Guyot; Quantitative assessment of dietary supplement intake in 77 000 French adults: Impact on nutritional inadequacy, excessive intake, and extent of "at risk" practices. 21. International Congress of Nutrition (ICN)

Published
2017
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20. Nutrition and cancer in primary prevention: new insights from circadian regulation

Author

Srour, B., Plancoulaine, S., Andreeva, V., Fassier, P., Lecuyer, L., Galan, P., Deschasaux, M., Latino-Martel, P., Mathilde Touvier, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and International Union of Nutritional Sciences (IUNS). INT.

Subjects
circadian rhythm, [SDV.CAN]Life Sciences [q-bio]/Cancer, cancer risk, feeding time, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, prospective study
Abstract

International audience; Background and objectives: Circadian disruption, resulting from shiftwork, has been classified as probably carcinogenic to humans by the International Agency for Research on Cancer. The biological circadian clock is subject to environmental effects, particularly light exposure and rhythmic food intake. However, the association between circadian nutritional behaviors and cancers has never been well explored. We investigated the prospective associations between time of the last eating episode, number of eating episodes, night-time fasting duration and the nutritional quality of the last eating episode, with overall, breast and prostate cancer risks. Methods: This prospective study included 41,389 men and women of the French population-based NutriNet-Santé cohort (2009-2016) who completed at least three 24h-dietary records during the first two years of follow-up. The risk of developing cancer was compared across different groups using multivariable Cox models. Results: 1,732 first primary incident cancer cases were diagnosed during follow-up, among which 428 breast cancers and 179 prostate cancers. Late eaters (last eating episode after 9:30 pm) had an increased risk of breast cancer (HR=1.48 (1.02-2.17), p=0.03) and prostate cancer (HR=2.20 (1.28-3.78), p=0.004); on the other hand, early eaters (last eating episode before 7 pm) had a lower risk of overall cancers (HR=0.78 (0.63-0.96), p=0.02). No association was observed between the number of eating episodes, nighttime fasting duration and the nutritional quality of the last eating episode, with cancer risk. Conclusions: This large cohort study suggests that circadian disruption associated with late time of last food intake may be involved in carcinogenesis at different locations. Beyond nutritional quality of food intake, targeting time of food intake might be interesting in cancer prevention.

Published
2017
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21. Abstract P5-13-01: Sociodemographic and economic factors are essential determinants of weight gain between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort

Author

Fassier, P, primary, Zelek, L, additional, Partula, V, additional, Lecuyer, L, additional, Srour, B, additional, Bachmann, P, additional, Touillaud, M, additional, Druesne-Pecollo, N, additional, Galan, P, additional, Hercberg, S, additional, Cohen, P, additional, Hoarau, H, additional, Latino-Martel, P, additional, Gonzalez, R, additional, Deschasaux, M, additional, and Touvier, M, additional

Published
2017
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24. Associations entre profils metabolomiques plasmatiques rmn et composition du microbiote intestinal au sein d’une population d’adultes français en bonne santé

Author

Partula, V., Mondot, S., Torres, M., Kesse-Guyot, E., Lécuyer, L., Deschasaux, M., Assmann, K., Latino-Martel, P., Buscail, C., Julia, C., Galan, P., Hercberg, S., Victor-Bala, A., Bouchemal, N., Triba, M., Savarin, P., Rouilly, V., Thomas, S., Quintana-Murci, L., Albert, M., Lantz, O., Duffy, D., and Touvier, M.

Published
2019
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34. Poster session II * Thursday 9 December 2010, 14:00-18:00

Author

Pabari, P. A., primary, Kyriacou, A., additional, Moraldo, M., additional, Unsworth, B., additional, Baruah, R., additional, Sutaria, N., additional, Hughes, A., additional, Mayet, J., additional, Francis, D. P., additional, Uejima, T., additional, Loboz, K., additional, Antonini-Canterin, F., additional, Polombo, C., additional, Carerj, S., additional, Vinereanu, D., additional, Evangelista, A., additional, Leftheriotis, G., additional, Fraser, A. G., additional, Kiotsekoglou, A., additional, Govindan, M., additional, Govind, S. C., additional, Saha, S. K., additional, Camm, A. J., additional, Azcarate, P. M., additional, Castano, S., additional, Rodriguez-Manero, M., additional, Arraiza, M., additional, Levy, B., additional, Barba, J., additional, Rabago, G., additional, Bastarrika, G., additional, Nemes, A., additional, Takacs, R., additional, Varkonyi, T., additional, Gavaller, H., additional, Baczko, I., additional, Forster, T., additional, Wittmann, T., additional, Papp, J. G., additional, Lengyel, C., additional, Varro, A., additional, Tumasyan, L. R., additional, Adamyan, K. G., additional, Savu, O., additional, Mieghem, T., additional, Dekoninck, P., additional, Gucciardo, L., additional, Jurcut, R., additional, Giusca, S., additional, Popescu, B. A., additional, Ginghina, C., additional, Deprest, J., additional, Voigt, J. U., additional, Versiero, M., additional, Galderisi, M., additional, Esposito, R., additional, Rapacciuolo, A., additional, Esposito, G., additional, Raia, R., additional, Morgillo, T., additional, Piscione, F., additional, De Simone, G., additional, Oraby, M. A., additional, Maklady, F. A., additional, Mohamed, E. M., additional, Eraki, A. Z., additional, Zaliaduonyte-Peksiene, D., additional, Tamuleviciute, E., additional, Janenaite, J., additional, Marcinkeviciene, J., additional, Mizariene, V., additional, Bucyte, S., additional, Vaskelyte, J., additional, Trifunovic, D., additional, Nedeljkovic, I., additional, Popovic, D., additional, Ostojic, M., additional, Vujisic-Tesic, B., additional, Petrovic, M., additional, Stankovic, S., additional, Sobic-Saranovic, D., additional, Banovic, M., additional, Dikic-Djordjevic, A., additional, Savino, K., additional, Lilli, A., additional, Grikstaite, E., additional, Giglio, V., additional, Bordoni, E., additional, Maragoni, G., additional, Cavallini, C., additional, Ambrosio, G., additional, Jakovljevic, B., additional, Beleslin, B., additional, Nedeljkovic, M., additional, Petrovic, O., additional, Moral, S., additional, Rodriguez-Palomares, J., additional, Descalzo, M., additional, Marti, G., additional, Pineda, V., additional, Mahia, P., additional, Gutierrez, L., additional, Gonzalez-Alujas, T., additional, Garcia-Dorado, D., additional, Schnell, F., additional, Donal, E., additional, Thebault, C., additional, Bernard, A., additional, Corbineau, H., additional, Le Breton, H., additional, Kochanowski, J., additional, Scislo, P., additional, Piatkowski, R., additional, Roik, M., additional, Marchel, M., additional, Kosior, D., additional, Opolski, G., additional, Lesniak-Sobelga, A. M., additional, Wicher-Muniak, E., additional, Kostkiewicz, M., additional, Olszowska, M., additional, Suchon, E., additional, Klimeczek, P., additional, Banys, P., additional, Pasowicz, M., additional, Tracz, W., additional, Podolec, P., additional, Laynez, A., additional, Hoefsten, D. E., additional, Loegstrup, B. B., additional, Norager, B., additional, Moller, J. E., additional, Flyvbjerg, A., additional, Egstrup, K., additional, Streb, W., additional, Szulik, M., additional, Nowak, J., additional, Markowicz-Pawlus, E., additional, Duszanska, A., additional, Sedkowska, A., additional, Kalarus, Z., additional, Kukulski, T., additional, Spinelli, L., additional, Morisco, C., additional, Assante Di Panzillo, E., additional, Buono, F., additional, Crispo, S., additional, Trimarco, B., additional, Hawary, A. A., additional, Nasr, G. M., additional, Fawzy, M. M., additional, Faber, L., additional, Scholtz, W., additional, Boergermann, J., additional, Wiemer, M., additional, Kleikamp, G., additional, Bogunovic, N., additional, Dimitriadis, Z., additional, Gummert, J., additional, Hering, D., additional, Horstkotte, D., additional, Luca', F., additional, Gelsomino, S., additional, Lorusso, R., additional, Caciolli, S., additional, Carella, R., additional, Bille', G., additional, De Cicco, G., additional, Pazzagli, V., additional, Gensini, G. F., additional, Borowiec, A., additional, Dabrowski, R., additional, Janas, J., additional, Kraska, A., additional, Firek, B., additional, Kowalik, I., additional, Szwed, H., additional, Marcus, K. A., additional, De Korte, C. L., additional, Feuth, T., additional, Thijssen, J. M., additional, Kapusta, L., additional, Dahl, J., additional, Videbaek, L., additional, Poulsen, M. K., additional, Pellikka, P. A., additional, Veien, K., additional, Andersen, L. I., additional, Haghfelt, T., additional, Haberka, M., additional, Mizia - Stec, K., additional, Adamczyk, T., additional, Mizia, M., additional, Chmiel, A., additional, Pysz, P., additional, Sosnowski, M., additional, Gasior, Z., additional, Trusz - Gluza, M., additional, Tendera, M., additional, Niklewski, T., additional, Wilczek, K., additional, Chodor, P., additional, Podolecki, T., additional, Frycz-Kurek, A., additional, Zembala, M., additional, Yurdakul, S., additional, Yildirimturk, O., additional, Tayyareci, Y., additional, Memic, K., additional, Demiroglu, I. C. C., additional, Aytekin, S., additional, Garcia Alonso, C. J., additional, Ferrer Sistach, E., additional, Delgado, L., additional, Lopez Ayerbe, J., additional, Vallejo Camazon, N., additional, Gual Capllonch, F., additional, Espriu Simon, M., additional, Ruyra, X., additional, Caballero Parrilla, A., additional, Bayes Genis, A., additional, Lecuyer, L., additional, Berrebi, A., additional, Florens, E., additional, Noghin, M., additional, Huerre, C., additional, Achouh, P., additional, Zegdi, R., additional, Fabiani, J. N., additional, De Chiara, B., additional, Moreo, A., additional, Musca, F., additional, De Marco, F., additional, Lobiati, E., additional, Belli, O., additional, Mauri, F., additional, Klugmann, S., additional, Caballero, A., additional, Vallejo, N., additional, Gonzalez Guardia, A., additional, Nunez Aragon, R., additional, Bosch, C., additional, Ferrer, E., additional, Pedro Botet, M. 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R., additional, Ribeiro, S., additional, Nunes Diogo, A., additional, Sengupta, P., additional, Di Bella, G., additional, Caracciolo, G., additional, Lentini, S., additional, Kinova, E., additional, Zlatareva, N., additional, Goudev, A., additional, Papagiannis, N., additional, Mpouki, M., additional, Papagianni, A., additional, Vorria, M., additional, Mpenetos, G., additional, Lytra, D., additional, Papadopoulou, E., additional, Sgourakis, P., additional, Malakos, J., additional, Kyriazis, J., additional, Kodali, V., additional, Toole, R., additional, Gopal, A. S., additional, Celutkiene, J., additional, Rudys, A., additional, Grabauskiene, V., additional, Glaveckaite, S., additional, Sadauskiene, E., additional, Lileikiene, Z., additional, Bickauskaite, N., additional, Ciburiene, E., additional, Skorniakov, V., additional, Laucevicius, A., additional, Attenhofer Jost, C. H., additional, Pfyffer, M., additional, Lindquist, R., additional, Santos, J. L. F., additional, Coelho, O. R. 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A., additional, Badano, L. P., additional, Cardillo, M., additional, Del Mestre, L., additional, Gianfagna, P., additional, Proclemer, A., additional, Tschernich, H. D., additional, Mora, B., additional, Base, E., additional, Weber, U., additional, Dumfarth, J., additional, Mukherjee, C., additional, Skaltsiotis, H. S., additional, Kaladaridis, A. K., additional, Bramos, D. B., additional, Kottis, G. K., additional, Antoniou, A. A., additional, Agrios, I. A., additional, Takos, D. T., additional, Vasiladiotis, N. V., additional, Pamboucas, K. P., additional, Toumanidis, S. T. 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Q., additional, Gu, Y., additional, and Tan, R. S., additional

Published
2010
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40. The ICU Trial: a new admission policy for cancer patients requiring mechanical ventilation.

Author

Lecuyer L, Chevret S, Thiery G, Darmon M, Schlemmer B, and Azoulay E

Abstract

Objective: Cancer patients requiring mechanical ventilation are widely viewed as poor candidates for intensive care unit (ICU) admission. We designed a prospective study evaluating a new admission policy titled The ICU Trial.Design: Prospective study.Setting: Intensive care unit.Patients: One hundred eighty-eight patients requiring mechanical ventilation and having at least one other organ failure.Interventions: Over a 3-yr period, all patients with hematologic malignancies or solid tumors proposed for ICU admission underwent a triage procedure. Bedridden patients and patients in whom palliative care was the only cancer treatment option were not admitted to the ICU. Patients at earliest phase of the malignancy (diagnosis <30 days) were admitted without any restriction. All other patients were prospectively included in The ICU Trial, consisting of a full-code ICU admission followed by reappraisal of the level of care on day 5.Measurements and Main Results: Among the 188 patients, 103 survived the first 4 ICU days and 85 died from the acute illness. Hospital survival was 21.8% overall. Among the 103 survivors on day 5, none of the characteristics of the malignancy were significantly different between the 62 patients who died and the 41 who survived. Time course of organ dysfunction over the first 6 ICU days differed significantly between survivors and nonsurvivors. Organ failure scores were more accurate on day 6 than at admission or on day 3 for predicting survival. All patients who required initiation of mechanical ventilation, vasopressors, or dialysis after 3 days in the ICU died.Conclusions: Survival was 40% in mechanically ventilated cancer patients who survived to day 5 and 21.8% overall. If these results are confirmed in future interventional studies, we recommend ICU admission with full-code management followed by reappraisal on day 6 in all nonbedridden cancer patients for whom lifespan-extending cancer treatment is available. [ABSTRACT FROM AUTHOR]

Published
2007
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43. Facilitating biodiversity conservation through partnerships to achieve transformative outcomes.

Author

White RM, Schmook B, Calmé S, Giordano AJ, Hausser Y, Kimmel L, Lecuyer L, Lucherini M, Méndez-Medina C, and Peña-Mondragón JL

Subjects
Mexico, Organizations, Kenya, Conservation of Natural Resources, Biodiversity
Abstract

Conservation biology is a mission-driven discipline that must navigate a new relationship between conservation and science. Because conservation is a social and political as well as an ecological project, conservation biologists must practice interdisciplinarity and collaboration. In a comparative study of 7 cases (Jaguars in the Chaco, Grevy's zebra in Kenya, Beekeeping in Tanzania, Andean cats in Argentina, Jaguars in Mexico, Lobster fishing, and Black bears in Mexico), we examined motivations for collaboration in conservation, who can collaborate in conservation, and how conservation professionals can work well together. In 5 case studies, successful conservation outcomes were prioritized over livelihood benefits. In the other 2 cases, livelihoods were prioritized. All case studies employed participatory approaches. There were multiple external actors, including local and Indigenous communities, nongovernmental organizations, agencies, regional and national governments, and international organizations, which enhanced conservation and wider sustainability outcomes. Key collaboration aspects considered across the case studies were time (mismatch between relationship building and project schedules), trust required for meaningful partnerships, tools employed, and transformative potential for people, nature, and the discipline of conservation biology. We developed guidelines for successful collaboration, including long-term commitment, knowledge integration, multiscalar and plural approaches, cultivation of trust, appropriate engagement, evaluation, supporting students, and efforts for transformation., (© 2022 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Published
2023
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44. Validation of the cutaneous impact location to predict intracranial lesion among elderly admitted to the Emergency Department after a ground-level fall.

Author

Dubucs X, Lecuyer L, Balen F, Houze Cerfon CH, Emond M, Lepage B, Colineaux H, and Charpentier S

Subjects
Aged, Aged, 80 and over, Humans, Emergency Service, Hospital, Retrospective Studies, Brain Injuries, Traumatic complications, Craniocerebral Trauma complications, Craniocerebral Trauma diagnostic imaging
Abstract

Introduction: In the Emergency Departments, almost one out of two head CT scans are carried out for traumatic brain injuries among elderly victims of ground level-falls. Recently, a new predictive factor for intracranial lesions in this population has been suggested: presence and location of cutaneous impact. The aim of this study was to establish determinants of intracranial lesion among older patients admitted to EDs due to ground-level falls with traumatic brain injury using the head cutaneous impact location., Methods: A retrospective, observational and monocentric study of patients admitted to Emergency Department for ground-level falls with traumatic brain injury was carried out between 01 January 2017 and 31 July 2017. The primary outcome was identification of an acute intracranial lesion. A bootstrap procedure was employed to evaluate performance and internal validity of the final model., Results: Among the 1036 patients included, the mean age was 85.6 (SD 7.6) years and 94/1036 (9.1%, 95% CI 7.4-10.9) patients presented with an acute intracranial lesion. Multivariable analysis adjusted by bootstrap shrinkage showed that compared with temporal-parietal or occipital impact, Odds Ratio of intracranial lesions were 0.61 (95% CI 0.39-0.95, p = 0.03) in patients with frontal impact, 0.27 (95% CI 0.12-0.59, p = 0.001) in patients with facial impact and 0.21 (95% CI 0.06-0.77, p = 0.018) in patients without cutaneous impact. Subcutaneous hematoma (OR 1.97, p = 0.007), loss of consciousness (OR 4.66, p<0.001), fall-related amnesia (OR 2.58, p = 2.6), vomiting (OR 2.62, p = 0.002) and altered Glasgow Score (OR 6.79, p<0.001) were as well associated with high risk of intracranial lesion. Taking antiplatelets or anticoagulants were not associated with an increased risk of intracranial lesions. The model discrimination was adequate (C-statistic 0.79; 95% CI 0.73 - 0.85)., Conclusion: Our results establish specific determinants of intracranial lesions among elderly after ground level-falls. The cutaneous impact location may identify patients with high risk of intracranial lesion. Further researches are needed to propose a specific score based on these determinants so as to better target Head CT scan use., Competing Interests: Declaration of Competing Interest Authors assumed no relevant conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2023
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45. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Author

Zamora-Ros R, Lujan-Barroso L, Achaintre D, Franceschi S, Kyrø C, Overvad K, Tjønneland A, Truong T, Lecuyer L, Boutron-Ruault MC, Katzke V, Johnson TS, Schulze MB, Trichopoulou A, Peppa E, La Vechia C, Masala G, Pala V, Panico S, Tumino R, Ricceri F, Skeie G, Quirós JR, Rodriguez-Barranco M, Amiano P, Chirlaque MD, Ardanaz E, Almquist M, Hennings J, Vermeulen R, Wareham NJ, Tong TYN, Aune D, Byrnes G, Weiderpass E, Scalbert A, Rinaldi S, and Agudo A

Abstract

Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking., Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition)., Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis., Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC., Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Published
2021
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46. Assessing physicians' and nurses' experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments.

Author

Boissier F, Seegers V, Seguin A, Legriel S, Cariou A, Jaber S, Lefrant JY, Rimmelé T, Renault A, Vinatier I, Mathonnet A, Reuter D, Guisset O, Cracco C, Durand-Gasselin J, Éon B, Thirion M, Rigaud JP, Philippon-Jouve B, Argaud L, Chouquer R, Papazian L, Dedrie C, Georges H, Lebas E, Rolin N, Bollaert PE, Lecuyer L, Viquesnel G, Leone M, Chalumeau-Lemoine L, Garrouste-Orgeas M, Azoulay E, and Kentish-Barnes N

Subjects
Adult, Attitude of Health Personnel, Female, Humans, Intensive Care Units organization & administration, Intensive Care Units statistics & numerical data, Male, Middle Aged, Nurses statistics & numerical data, Physicians statistics & numerical data, Prospective Studies, Psychometrics instrumentation, Psychometrics methods, Reproducibility of Results, Surveys and Questionnaires, Attitude to Death, Life Change Events, Nurses psychology, Physicians psychology, Psychometrics standards
Abstract

Background: As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient's and/or the relatives' experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study., Methods: Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort., Results: Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002). Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside., Conclusion: We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.

Published
2020
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47. Belatacept-based immunosuppression: A calcineurin inhibitor-sparing regimen in heart transplant recipients.

Author

Launay M, Guitard J, Dorent R, Prevot Y, Prion F, Beaumont L, Kably B, Lecuyer L, Billaud EM, and Guillemain R

Subjects
Adult, Aged, Female, Humans, Immune Tolerance, Male, Middle Aged, Patient Safety, Retrospective Studies, Transplant Recipients, Treatment Outcome, Young Adult, Abatacept therapeutic use, Graft Rejection prevention & control, Heart Transplantation, Immunosuppression Therapy methods, Immunosuppressive Agents therapeutic use
Abstract

Belatacept (BTC) is indicated for prophylaxis of graft rejection in adults receiving a renal transplant (Tx). This retrospective observational study (three centers) included all heart transplant recipients receiving BTC between January 2014 and October 2018. Forty EBV+ patients mean GFR 35 ± 20 mL/min/m 2 were identified, among whom belatacept was initiated during the first 3 months after transplantation in 12 patients, and later in 28 patients. Several patients were multiorgan transplant recipients. Study outcomes were GFR, safety, and changes in immunosuppressive therapy. The main reason for switching to BTC was to preserve renal function, resulting in discontinuation of CNI and changes in immunosuppressive therapy in 76% of cases. At study closeout, 24/40 patients were still on BTC therapy. GFR was improved (+59%, P = .0002*) within 1 month, particularly in the early group. More episodes of rejection were observed among "late" patients (1 death). Sixteen treatment discontinuations were recorded: GFR recovery (n = 4), DSA no longer detectable (n = 1), compliance issues (n = 3), poor venous access (n = 2), multiple infections (n = 1), 1 death (fungal lung infection), and treatment failure (n = 4). Median follow-up was 24 months. Four patients developed de novo DSA (MFI<1500). BTC is an effective alternative immunosuppressive for postoperative transient kidney failure, stabilizing delayed renal function, with acceptable safety profile under careful monitoring., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Published
2020
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48. Building on common ground to address biodiversity conflicts and foster collaboration in environmental management.

Author

Lecuyer L, White RM, Schmook B, and Calmé S

Subjects
Mexico, Biodiversity, Conservation of Natural Resources
Abstract

Conservation biology faces critical challenges that require collaborative approaches, including novel strategies to support interactions among actors in biodiversity conflicts. The goals of this study were to investigate the concept of common ground across multiple issues and to explore its practical application for the support of environmental management. We conceptually defined common ground as the areas of relevance underlying the suite of issues expressed by people regarding environmental management in a particular context. We then empirically tested this in the Calakmul region of Mexico, where the complex socio-historical context and high biodiversity have created environmental management challenges that are now being addressed by a local, multi-stakeholder management board. We conducted 26 open interviews with members of the board and a further round of quantitative prioritisation of issues raised. Using a coding process designed to reveal common ground, we categorized the issues at four levels ranging from coarse to fine (themes, topics, sub-topics and perspectives). We then analysed two levels, topics (n = 14 issues) and sub-topics (n = 51 issues). To do so, we built common ground matrices to identify and analyze common ground among actors and across issues. First, cluster and non-metrical data analyses revealed the diversity of actor positions and the lack of consistent grouping among actors by occupational activity. This demonstrated that focusing on actors' differences might be misleading, and that actors' views were not closely aligned with their roles. Second, we located issues according to their levels of common ground and importance among actors. We showed that by not focusing on single issue conflicts, the identification of common ground across multiple issues can pinpoint synergies. We then proposed a framework for collaboration that prioritizes issues of high importance with greater common ground (e.g. sustainable resource use activities), to support the development of trust and norms of reciprocity among actors, strengthening the potential for future cooperation. By adopting this approach, environmental managers could support the initial stages of collaborative conservation strategies, engaging with other actors to seek common ground, avoid the creation of polarised groups and help effectively manage biodiversity conflicts., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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49. The construction of feelings of justice in environmental management: An empirical study of multiple biodiversity conflicts in Calakmul, Mexico.

Author

Lecuyer L, White RM, Schmook B, Lemay V, and Calmé S

Subjects
Humans, Mexico, Public Opinion, Biodiversity, Emotions, Social Justice
Abstract

A failure to address social concerns in biodiversity conservation can lead to feelings of injustice among some actors, and hence jeopardize conservation goals. The complex socio-cultural and political context of the Calakmul Biosphere Reserve, Mexico, has historically led to multiple biodiversity conflicts. Our goal, in this case study, was to explore perceptions of justice held by local actors in relation to biodiversity conflicts. We then aimed to determine the following: 1) people's definitions of their feelings of justice; 2) the criteria used in this assessment; 3) variability in the criteria influencing them; and 4) implications for environmental management in the region and beyond. We worked with five focus groups, exploring three examples of biodiversity conflict around forest, water and jaguar management with a total of 41 ranchers, farmers and representatives of local producers. Our results demonstrated that people constructed their feelings of justice around four dimensions of justice: recognition (acknowledging individuals' rights, values, cultures and knowledge systems); ecological (fair and respectful treatment of the natural environment), procedural (fairness in processes of environmental management), distributive (fairness in the distribution of costs and benefits). We identified a list of criteria the participants used in their appraisal of justice and sources of variation such as the social scale of focus and participant role, and whom they perceived to be responsible for resource management. We propose a new framework that conceptualizes justice-as-recognition and ecological justice as forms of conditional justices, and procedural and distributive justices as forms of practical justice. Conditional justice allows us to define who is a legitimate source of justice norms and if nature should be integrated in the scope of justice; hence, conditional justice underpins other dimensions of justice. On the other hand, procedural and distributive address the daily practices of fair processes and distribution. We propose that the perception of justice is a neglected but important aspect to include in integrative approaches to managing biodiversity conflicts. Addressing demands of justice in environmental management will require us to consider more than the distribution of costs and benefits among actors. We also need to respect the plurality of fairness perspectives and to recognize the benefits of dialogical approaches to achieve more successful environmental management., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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50. Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

Author

Launay M, Roux A, Beaumont L, Douvry B, Lecuyer L, Douez E, Picard C, Grenet D, Jullien V, Boussaud V, Guillemain R, and Billaud EM

Subjects
Adult, Aged, Antifungal Agents blood, Antifungal Agents pharmacology, Aspergillus drug effects, Cystic Fibrosis immunology, Cystic Fibrosis microbiology, Cystic Fibrosis surgery, Drug Administration Schedule, Drug Interactions, Everolimus blood, Everolimus therapeutic use, Female, Humans, Immunosuppressive Agents blood, Invasive Pulmonary Aspergillosis immunology, Invasive Pulmonary Aspergillosis microbiology, Invasive Pulmonary Aspergillosis surgery, Male, Middle Aged, Prospective Studies, Tablets, Tacrolimus blood, Tacrolimus therapeutic use, Triazoles blood, Triazoles pharmacology, Antifungal Agents pharmacokinetics, Cystic Fibrosis drug therapy, Immunosuppressive Agents therapeutic use, Invasive Pulmonary Aspergillosis prevention & control, Lung Transplantation, Triazoles pharmacokinetics
Abstract

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations ( C 0 ) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) C 0 measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively ( P = 0.001* [asterisk means that statistical test is significant]), and the PSZ C 0 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively ( P < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL C 0 /dose ratio ( C 0 / D ) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution ( P = 0.034*). The ERL C 0 / D was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; P = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients., (Copyright © 2018 American Society for Microbiology.)

Published
2018
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