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3. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Author

Vandriel, S, Li, L, She, H, Wang, J, Gilbert, M, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, Spinner, N, Loomes, K, Piccoli, D, D'Antiga, L, Nicastro, E, Sokal, A, Demaret, T, Ebel, N, Feinstein, J, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, S, Romero, R, Kim, K, Baek, W, Hardikar, W, Shankar, S, Roberts, A, Evans, H, Jensen, M, Kavan, M, Sundaram, S, Chaidez, A, Karthikeyan, P, Sanchez, M, Cavalieri, M, Verkade, H, Lee, W, Squires, J, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, R, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, H, Bernabeu, J, Alam, S, Kelly, D, Carvalho, E, Ferreira, C, Indolfi, G, Quiros-Tejeira, R, Bulut, P, Calvo, P, Anal, Z, Valentino, P, Desai, D, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, R, Wolters, V, Tamara, M, Zizzo, A, Garcia, J, Schwarz, K, Beretta, M, Sandahl, T, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, C, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, R, Hansen, B, Kamath, B, Vandriel S. M., Li L. -T., She H., Wang J. -S., Gilbert M. A., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., Spinner N. B., Loomes K. M., Piccoli D. A., D'Antiga L., Nicastro E., Sokal A., Demaret T., Ebel N. H., Feinstein J. A., Fawaz R., Nastasio S., Lacaille F., Debray D., Arnell H., Fischler B., Siew S., Stormon M., Karpen S. J., Romero R., Kim K. M., Baek W. Y., Hardikar W., Shankar S., Roberts A. J., Evans H. M., Jensen M. K., Kavan M., Sundaram S. S., Chaidez A., Karthikeyan P., Sanchez M. C., Cavalieri M. L., Verkade H. J., Lee W. S., Squires J. E., Hajinicolaou C., Lertudomphonwanit C., Fischer R. T., Larson-Nath C., Mozer-Glassberg Y., Arikan C., Lin H. C., Bernabeu J. Q., Alam S., Kelly D. A., Carvalho E., Ferreira C. T., Indolfi G., Quiros-Tejeira R. E., Bulut P., Calvo P. L., Anal Z., Valentino P. L., Desai D. M., Eshun J., Rogalidou M., Dezsofi A., Wiecek S., Nebbia G., Pinto R. B., Wolters V. M., Tamara M. L., Zizzo A. N., Garcia J., Schwarz K., Beretta M., Sandahl T. D., Jimenez-Rivera C., Kerkar N., Brecelj J., Mujawar Q., Rock N., Busoms C. M., Karnsakul W., Lurz E., Santos-Silva E., Blondet N., Bujanda L., Shah U., Thompson R. J., Hansen B. E., Kamath B. M., Vandriel, S, Li, L, She, H, Wang, J, Gilbert, M, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, Spinner, N, Loomes, K, Piccoli, D, D'Antiga, L, Nicastro, E, Sokal, A, Demaret, T, Ebel, N, Feinstein, J, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, S, Romero, R, Kim, K, Baek, W, Hardikar, W, Shankar, S, Roberts, A, Evans, H, Jensen, M, Kavan, M, Sundaram, S, Chaidez, A, Karthikeyan, P, Sanchez, M, Cavalieri, M, Verkade, H, Lee, W, Squires, J, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, R, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, H, Bernabeu, J, Alam, S, Kelly, D, Carvalho, E, Ferreira, C, Indolfi, G, Quiros-Tejeira, R, Bulut, P, Calvo, P, Anal, Z, Valentino, P, Desai, D, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, R, Wolters, V, Tamara, M, Zizzo, A, Garcia, J, Schwarz, K, Beretta, M, Sandahl, T, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, C, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, R, Hansen, B, Kamath, B, Vandriel S. M., Li L. -T., She H., Wang J. -S., Gilbert M. A., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., Spinner N. B., Loomes K. M., Piccoli D. A., D'Antiga L., Nicastro E., Sokal A., Demaret T., Ebel N. H., Feinstein J. A., Fawaz R., Nastasio S., Lacaille F., Debray D., Arnell H., Fischler B., Siew S., Stormon M., Karpen S. J., Romero R., Kim K. M., Baek W. Y., Hardikar W., Shankar S., Roberts A. J., Evans H. M., Jensen M. K., Kavan M., Sundaram S. S., Chaidez A., Karthikeyan P., Sanchez M. C., Cavalieri M. L., Verkade H. J., Lee W. S., Squires J. E., Hajinicolaou C., Lertudomphonwanit C., Fischer R. T., Larson-Nath C., Mozer-Glassberg Y., Arikan C., Lin H. C., Bernabeu J. Q., Alam S., Kelly D. A., Carvalho E., Ferreira C. T., Indolfi G., Quiros-Tejeira R. E., Bulut P., Calvo P. L., Anal Z., Valentino P. L., Desai D. M., Eshun J., Rogalidou M., Dezsofi A., Wiecek S., Nebbia G., Pinto R. B., Wolters V. M., Tamara M. L., Zizzo A. N., Garcia J., Schwarz K., Beretta M., Sandahl T. D., Jimenez-Rivera C., Kerkar N., Brecelj J., Mujawar Q., Rock N., Busoms C. M., Karnsakul W., Lurz E., Santos-Silva E., Blondet N., Bujanda L., Shah U., Thompson R. J., Hansen B. E., and Kamath B. M.

Abstract

Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and Results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.

Published
2023

4. Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample

Author

Koch, M, Freitag-Wolf, S, Schlesinger, S, Borggrefe, J, Hov, J R, Jensen, M K, and Pick, J

Subjects
Fatty liver -- Diagnosis -- Development and progression, Metabolites -- Physiological aspects -- Health aspects, Food/cooking/nutrition, Health
Abstract

Background/Objectives: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. Subjects/Methods: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses. Results: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. Conclusions: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies., Author(s): M Koch [sup.1] [sup.2] , S Freitag-Wolf [sup.3] , S Schlesinger [sup.1] , J Borggrefe [sup.4] , J R Hov [sup.5] [sup.6] [sup.7] [sup.8] , M K Jensen [sup.2] [...]

Published
2017
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11. Protein-based HDL subspecies:Rationale and association with cardiovascular disease, diabetes, stroke, and dementia

Author

Sacks, F. M., Furtado, J. D., Jensen, M. K., Sacks, F. M., Furtado, J. D., and Jensen, M. K.

Abstract

HDL-cholesterol is associated with reduced risk of cardiovascular disease, and is used in clinical practice for risk stratification. HDL is composed of many protein-defined subspecies that each comprises just a few percent of the total, some associated with lower and some with higher risk of CVD. HDL that contains apoC3 or apoE are subspecies that have opposing actions on HDL reverse cholesterol transport and opposing associations with risk of future CVD, apoC3 adverse and apoE beneficial. In addition to coronary heart disease, HDL that contains apoC3 is associated with risk of future type 2 diabetes and insulin resistance; ischemic stroke and cerebral infarction; dementia and the deposition of beta-amyloid in the brain. HDL that contains apoE and apoE itself are associated with lower risk of dementia. Other HDL subspecies that contain complement C3, alpha-2 macroglobulin, plasminogen, or haptoglobin are associated with higher future risk of coronary heart disease, whereas others such as HDL that contains apoC1 are associated with lower risk. At this time, these findings provide improved understanding of the multifaceted HDL system to better determine risk and targeting of therapy for the most prevalent chronic lifestyle diseases in our society., HDL-cholesterol is associated with reduced risk of cardiovascular disease, and is used in clinical practice for risk stratification. HDL is composed of many protein-defined subspecies that each comprises just a few percent of the total, some associated with lower and some with higher risk of CVD. HDL that contains apoC3 or apoE are subspecies that have opposing actions on HDL reverse cholesterol transport and opposing associations with risk of future CVD, apoC3 adverse and apoE beneficial. In addition to coronary heart disease, HDL that contains apoC3 is associated with risk of future type 2 diabetes and insulin resistance; ischemic stroke and cerebral infarction; dementia and the deposition of beta-amyloid in the brain. HDL that contains apoE and apoE itself are associated with lower risk of dementia. Other HDL subspecies that contain complement C3, alpha-2 macroglobulin, plasminogen, or haptoglobin are associated with higher future risk of coronary heart disease, whereas others such as HDL that contains apoC1 are associated with lower risk. At this time, these findings provide improved understanding of the multifaceted HDL system to better determine risk and targeting of therapy for the most prevalent chronic lifestyle diseases in our society.

Published
2022

12. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study

Author

Gottlieb, D J, Hek, K, Chen, T-h, Watson, N F, Eiriksdottir, G, Byrne, E M, Cornelis, M, Warby, S C, Bandinelli, S, Cherkas, L, Evans, D S, Grabe, H J, Lahti, J, Li, M, Lehtimäki, T, Lumley, T, Marciante, K D, Pérusse, L, Psaty, B M, Robbins, J, Tranah, G J, Vink, J M, Wilk, J B, Stafford, J M, Bellis, C, Biffar, R, Bouchard, C, Cade, B, Curhan, G C, Eriksson, J G, Ewert, R, Ferrucci, L, Fülöp, T, Gehrman, P R, Goodloe, R, Harris, T B, Heath, A C, Hernandez, D, Hofman, A, Hottenga, J-J, Hunter, D J, Jensen, M K, Johnson, A D, Kähönen, M, Kao, L, Kraft, P, Larkin, E K, Lauderdale, D S, Luik, A I, Medici, M, Montgomery, G W, Palotie, A, Patel, S R, Pistis, G, Porcu, E, Quaye, L, Raitakari, O, Redline, S, Rimm, E B, Rotter, J I, Smith, A V, Spector, T D, Teumer, A, Uitterlinden, A G, Vohl, M-C, Widen, E, Willemsen, G, Young, T, Zhang, X, Liu, Y, Blangero, J, Boomsma, D I, Gudnason, V, Hu, F, Mangino, M, Martin, N G, O'Connor, G T, Stone, K L, Tanaka, T, Viikari, J, Gharib, S A, Punjabi, N M, Räikkönen, K, Völzke, H, Mignot, E, and Tiemeier, H

Published
2015
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14. Relationship of Alcohol Intake and Sex Steroid Concentrations in Blood in Pre- and Post-Menopausal Women: The European Prospective Investigation into Cancer and Nutrition

Author

Rinaldi, S., Peeters, P. H. M., Bezemer, I. D., Dossus, L., Biessy, C., Sacerdote, C., Berrino, F., Panico, S., Palli, D., Tumino, R., Khaw, K. T., Bingham, S., Allen, N. E., Key, T., Jensen, M. K., Overvad, K., Olsen, A., Tjonneland, A., Amiano, P., Ardanaz, E., Agudo, A., Martinez-García, C., Quirós, J. Ramón, Tormo, M. J., Nagel, G., Linseisen, J., Boeing, H., Schulz, M., Grobbee, D. E., Bueno-De-Mesquita, H. B., Koliva, M., Kyriazi, G., Thrichopoulou, A., Boutron-Ruault, M. C., Clavel-Chapelon, F., Ferrari, P., Slimani, N., Saracci, R., Riboli, E., and Kaaks, R.

Published
2006
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18. Alcohol dose in septal ablation for hypertrophic obstructive cardiomyopathy

Author

Veselka, J., Faber, L., Liebregts, M., Cooper, R., Januska, J., Kashtanov, M., Dabrowski, M., Hansen, P. R., Seggewiss, H., Bonaventura, J., Polakova, E., Hansvenclova, E., Bundgaard, H., ten, Berg, J., Stables, R. H., Jarkovsky, J., Jensen, M. K., Veselka, J., Faber, L., Liebregts, M., Cooper, R., Januska, J., Kashtanov, M., Dabrowski, M., Hansen, P. R., Seggewiss, H., Bonaventura, J., Polakova, E., Hansvenclova, E., Bundgaard, H., ten, Berg, J., Stables, R. H., Jarkovsky, J., and Jensen, M. K.

Abstract

Background: The aim of this study was to evaluate short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Current guidelines recommend using 1–3 mL of alcohol administered in the target septal perforator artery, but this recommendation is based more on practical experience of interventionalists rather than on systematic evidence. Methods: We included 1448 patients and used propensity score to match patients who received a low-dose (1.0–1.9 mL) versus a high-dose (2.0–3.8 mL) of alcohol during ASA. Results: The matched cohort analysis comprised 770 patients (n = 385 in both groups). There was a similar occurrence of 30-day post-procedural adverse events (13% vs. 12%; p = 0.59), and similar all-cause mortality rates (0.8% vs. 0.5%; p = 1) in the low-dose group and the high-dose group, respectively. In the long-term follow-up (5.4 ± 4.5 years), a total of 110 (14%) patients died representing 2.58 deaths and 2.64 deaths per 100 patient-years in the low dose and the high dose group (logrank, p = 0.92), respectively. There were no significant differences in the long-term dyspnea and left ventricular outflow gradient between the two groups. Patients treated with a low-dose of alcohol underwent more subsequent septal reduction procedures (logrank, p = 0.04). Conclusions: Matched HOCM patients undergoing ASA with a low-dose (1.0–1.9 mL) or a high-dose (2.0–3.8 mL) of alcohol had similar short- and long-term outcomes. A higher rate of repeated septal reduction procedures was observed in the group treated with a low-dose of alcohol. © 2021 The Authors

Published
2021

21. Alcohol consumption patterns, diet and body weight in 10 European countries

Author

Sieri, S, Krogh, V, Saieva, C, Grobbee, D E, Bergmann, M, Rohrmann, S, Tjønneland, A, Ferrari, P, Chloptsios, Y, Dilis, V, Jenab, M, Linseisen, J, Wallström, P, Johansson, I, Chirlaque, M D, Sanchez, M J, Niravong, M, Clavel-Chapelon, F, Welch, A A, Allen, N E, Bueno-de-Mesquita, H B, van der Schouw, Y T, Sacerdote, C, Panico, S, Parr, C L, Braaten, T, Olsen, A, Jensen, M K, Bingham, S, Riboli, E, and Slimani, N

Published
2009

22. Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition

Author

Cust, A E, Skilton, M R, van Bakel, MME, Halkjær, J, Olsen, A, Agnoli, C, Psaltopoulou, T, Buurma, E, Sonestedt, E, Chirlaque, M D, Rinaldi, S, Tjønneland, A, Jensen, M K, Clavel-Chapelon, F, Boutron-Ruault, M C, Kaaks, R, Nöthlings, U, Chloptsios, Y, Zylis, D, Mattiello, A, Caini, S, Ocké, M C, van der Schouw, Y T, Skeie, G, Parr, C L, Molina-Montes, E, Manjer, J, Johansson, I, McTaggart, A, Key, T J, Bingham, S, Riboli, E, and Slimani, N

Published
2009

23. General and Abdominal Adiposity and Risk of Death in Europe

Author

Pischon, T., Boeing, H., Hoffmann, K., Bergmann, M., Schulze, M. B., Overvad, K., van der Schouw, Y. T., Spencer, E., Moons, K. G.M., Tjønneland, A., Halkjaer, J., Jensen, M. K., Stegger, J., Clavel-Chapelon, F., Boutron-Ruault, M. -C., Chajes, V., Linseisen, J., Kaaks, R., Trichopoulou, A., Trichopoulos, D., Bamia, C., Sieri, S., Palli, D., Tumino, R., Vineis, P., Panico, S., Peeters, P. H.M., May, A. M., Bueno-de-Mesquita, H. B., van Duijnhoven, F. J.B., Hallmans, G., Weinehall, L., Manjer, J., Hedblad, B., Lund, E., Agudo, A., Arriola, L., Barricarte, A., Navarro, C., Martinez, C., Quirós, J. R., Key, T., Bingham, S., Khaw, K. T., Boffetta, P., Jenab, M., Ferrari, P., and Riboli, E.

Published
2008
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25. THE WALK-RUN TRANSITION IS NOT AFFECTED BY ADDED COGNITIVE LOADING

Author

Ernst Albin Hansen, Magnus Kristian Hyttel, Lasse Schrøder Jakobsen, Jensen, M. K., Helena Balle, and Michael Voigt

Abstract

INTRODUCTION:Walk-run transition can be predicted from stride rates (1, 2), based on the assumption that the human acts as a complex system (3), which can be described with Dynamic Systems Theory (4). Besides, two research groups have investigated the hypothesis that added cognitive loading affects the walk-run transition. One of the groups confirmed the hypothesis (5) while the other rejected it (6). To clarify this, we re-tested the hypothesis in the present study.METHODS:Healthy individuals (13 men, 5 women) participated. First, two pressure-sensitive sensors were placed under the insole of the participant’s right shoe at, respectively, a position corresponding to the midpoint of the underside of the heel and at a position corresponding to the midpoint between 1st and 2nd metatarsal heads. The sensors were used for determination of stride characteristics. Then, 10-min warm up was done on a treadmill. For this, the treadmill speed was initially 1 km/h and increased by 1 km/h each min, until the final speed of 10 km/h was completed. After 4 min of rest, the reference walk-run transition test began. For this, the initial treadmill speed was 5 km/h and increased by 0.1 km/h each 10th s, until transition occurred, or a final speed of 9 km/h was reached. This was followed by 4 min of rest. Then, the dual task walk-run transition test began. This test was similar to the reference test. But, in addition to walking, the participant had to perform mental arithmetic, which added cognitive loading. The arithmetic task began with the number 911. From this, 7 were repeatedly subtracted. To increase the cognitive loading, the participant was regularly cheered to perform the arithmetic fast. Data were evaluated with paired samples t-tests. Two subjects were omitted from the evaluation since they did not transit to running in the dual task test.RESULTS:In the reference test, the speed and stride rate at the transition were 7.5±0.5 km/h and 67.0±3.1 strides/min, respectively. In the dual task test, the matching values were 7.6±0.5 km/h and 68.4±3.7 strides/min, respectively. There were no differences between the two types of tests (p>0.05).CONCLUSION:The addition of cognitive loading in a walk-run transition test with monotonous increasing walking speed did not change the speed and stride rate at the transition. We consider this finding to be consistent with the idea that the walking human acts as a self-organized dynamic system, without influence of a central control centre.REFERENCES:1) Hansen et al., Sci Rep, 2017. 2) Hansen et al., Gait Posture, 2018. 3) Soodak & Iberall, Science, 1978. 4) Luenberger, Introduction to dynamics - Theory, models and applications, 1979. 5) Daniels & Newell, Biol Psychol, 2003. 6) Abdolvahab, Atten Percept Psychophys, 2015.

Published
2019

30. Aclarubicin Plus Cytosine Arabinoside Versus Daunorubicin plus Cytosine Arabinoside in De Novo Acute Myelocytic Leukemia: A Danish National Trial

Author

Hansen, O. P., Ellegaard, J., Bastrup-Madsen, P., Brincker, H., Christensen, B. E., Killmann, S. Aa., Lauersen, M. L., Karle, H., Drivsholm, Aa., Jensen, M. K., Laursen, B., Jans, H., Hippe, E., Petersen-Bjergaard, J., Nissen, N., Thorling, K., Jensen, K. B., Hiddemann, W., editor, and Mertelsmann, R., editor

Published
1990
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32. Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children.

Author

Deneau, Mark R., Valentino, Pamela L., Mack, Cara, Alqoaer, Khaled, Amin, Mansi, Amir, Achiya Z., Aumar, Madeleine, Auth, Marcus, Broderick, Annemarie, DiGuglielmo, Matthew, Draijer, Laura G., El-Matary, Wael, Ferrari, Federica, Furuya, Katryn N., Gottrand, Frederic, Gupta, Nitika, Homan, Matjaz, Jensen, M. K., Kamath, Binita M., and Kyung Mo Kim

Published
2020
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34. Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample

Author

Koch, M., Freitag-Wolf, S., Schlesinger, S., Borggrefe, J., Hov, J. R., Jensen, M. K., Pick, J., Markus, M. R. P., Hoepfner, T., Jacobs, G., Siegert, S., Artati, A., Kastenmueller, G., Roemisch-Margl, W., Adamski, J., Illig, T., Nothnagel, M., Karlsen, T. H., Schreiber, S., Franke, A., Krawczak, M., Noethlings, U., Lieb, W., Koch, M., Freitag-Wolf, S., Schlesinger, S., Borggrefe, J., Hov, J. R., Jensen, M. K., Pick, J., Markus, M. R. P., Hoepfner, T., Jacobs, G., Siegert, S., Artati, A., Kastenmueller, G., Roemisch-Margl, W., Adamski, J., Illig, T., Nothnagel, M., Karlsen, T. H., Schreiber, S., Franke, A., Krawczak, M., Noethlings, U., and Lieb, W.

Abstract

BACKGROUND/OBJECTIVES: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. SUBJECTS/METHODS: In a population-based sample (n = 555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection 41 were entered in in silico overrepresentation and pathway analyses. RESULTS: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n = 219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. CONCLUSIONS: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.

Published
2017

35. Mekanisk kredsløbsstøtte ved hjælp af cirkulationspumpe anlagt gennem vena subclavia hos en patient med akut hjertesvigt

Author

Hansen, L. N., Fabrin, A., Jensen, M. K., Schmidt, H., Junker, A., and Jacob Eifer Møller

Subjects
surgical procedures, operative, cardiovascular system
Abstract

A 65-year-old female patient suffered biventricular failure due to severe lymphoid myocarditis. Mechanical circulatory support was established with peripheral arterial-venous extracorporeal membrane oxygenation (AV-ECMO). The left ventricle was relieved by subclavian Impella 5.0. AV-ECMO was weaned with the use of only Impella 5.0 until the 17th day of use, whereupon Impella was phased out. This case report illustrates the use-fulness of combined peripheral VA-ECMO with subclavian Impella 5.0 with the prospect of single use of the subclavian Impella 5.0 until cardiac recovery thereby avoiding central cannulation.

Published
2014

38. A 7-GENE SIGNATURE DEPICTS THE BIOCHEMICAL PROFILE OF EARLY PREFIBROTIC MYELOFIBROSIS

Author

Skov, V., Burton, M., Thomassen, M., Larsen, T. Stauffer, Riley, C. Hasselbalch, Madelung, A. B., Kjaer, L., Bondo, H., Stamp, I., Ehinger, M., Dahl-Sorensen, R., Mortensen, N. B., Nielsen, K., Thiele, J., Jensen, M. K., Bjerrum, O. W., Kruse, T. A., Hasselbalch, H. C., Skov, V., Burton, M., Thomassen, M., Larsen, T. Stauffer, Riley, C. Hasselbalch, Madelung, A. B., Kjaer, L., Bondo, H., Stamp, I., Ehinger, M., Dahl-Sorensen, R., Mortensen, N. B., Nielsen, K., Thiele, J., Jensen, M. K., Bjerrum, O. W., Kruse, T. A., and Hasselbalch, H. C.

Published
2015

42. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study

Author

Gottlieb, D J, primary, Hek, K, additional, Chen, T-h, additional, Watson, N F, additional, Eiriksdottir, G, additional, Byrne, E M, additional, Cornelis, M, additional, Warby, S C, additional, Bandinelli, S, additional, Cherkas, L, additional, Evans, D S, additional, Grabe, H J, additional, Lahti, J, additional, Li, M, additional, Lehtimäki, T, additional, Lumley, T, additional, Marciante, K D, additional, Pérusse, L, additional, Psaty, B M, additional, Robbins, J, additional, Tranah, G J, additional, Vink, J M, additional, Wilk, J B, additional, Stafford, J M, additional, Bellis, C, additional, Biffar, R, additional, Bouchard, C, additional, Cade, B, additional, Curhan, G C, additional, Eriksson, J G, additional, Ewert, R, additional, Ferrucci, L, additional, Fülöp, T, additional, Gehrman, P R, additional, Goodloe, R, additional, Harris, T B, additional, Heath, A C, additional, Hernandez, D, additional, Hofman, A, additional, Hottenga, J-J, additional, Hunter, D J, additional, Jensen, M K, additional, Johnson, A D, additional, Kähönen, M, additional, Kao, L, additional, Kraft, P, additional, Larkin, E K, additional, Lauderdale, D S, additional, Luik, A I, additional, Medici, M, additional, Montgomery, G W, additional, Palotie, A, additional, Patel, S R, additional, Pistis, G, additional, Porcu, E, additional, Quaye, L, additional, Raitakari, O, additional, Redline, S, additional, Rimm, E B, additional, Rotter, J I, additional, Smith, A V, additional, Spector, T D, additional, Teumer, A, additional, Uitterlinden, A G, additional, Vohl, M-C, additional, Widen, E, additional, Willemsen, G, additional, Young, T, additional, Zhang, X, additional, Liu, Y, additional, Blangero, J, additional, Boomsma, D I, additional, Gudnason, V, additional, Hu, F, additional, Mangino, M, additional, Martin, N G, additional, O'Connor, G T, additional, Stone, K L, additional, Tanaka, T, additional, Viikari, J, additional, Gharib, S A, additional, Punjabi, N M, additional, Räikkönen, K, additional, Völzke, H, additional, Mignot, E, additional, and Tiemeier, H, additional

Published
2014
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43. Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition

Author

Cust, A. E. Skilton, M. R. van Bakel, M. M. E. Halkjaer, J. and Olsen, A. Agnoli, C. Psaltopoulou, T. Buurma, E. and Sonestedt, E. Chirlaque, M. D. Rinaldi, S. Tjonneland, A. and Jensen, M. K. Clavel-Chapelon, F. Boutron-Ruault, M. C. and Kaaks, R. Noethlings, U. Chloptsios, Y. Zylis, D. and Mattiello, A. Caini, S. Ocke, M. C. van der Schouw, Y. T. and Skeie, G. Parr, C. L. Molina-Montes, E. Manjer, J. and Johansson, I. McTaggart, A. Key, T. J. Bingham, S. and Riboli, E. Slimani, N.

Abstract

Objective: To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 subjects, aged between 35-74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. Results: Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol. Conclusions: Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease. European Journal of Clinical Nutrition (2009) 63, S37-S60; doi: 10.1038/ejcn.2009.74

Published
2009

44. Alcohol consumption patterns, diet and body weight in 10 European countries

Author

Sieri, S. Krogh, V. Saieva, C. Grobbee, D. E. Bergmann, M. Rohrmann, S. Tjonneland, A. Ferrari, P. Chloptsios, Y. Dilis, V. Jenab, M. Linseisen, J. Wallstrom, P. and Johansson, I. Chirlaque, M. D. Sanchez, M. J. Niravong, M. and Clavel-Chapelon, F. Welch, A. A. Allen, N. E. and Bueno-de-Mesquita, H. B. van der Schouw, Y. T. Sacerdote, C. and Panico, S. Parr, C. L. Braaten, T. Olsen, A. Jensen, M. K. Bingham, S. Riboli, E. Slimani, N.

Subjects
mental disorders
Abstract

Background/objectives: Europe has the highest level of alcohol consumption in the world. As drinking patterns are important determinants of the beneficial and harmful effects of alcohol consumption, we investigated alcohol consumption in relation to nutrient intake, place of consumption, education and body weight in a sample of adults from 10 European countries. Methods: A 24-h dietary recall interview was conducted on 13 025 men and 23 009 women, aged 35-74 years, from 27 centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Means and standard errors of alcohol consumption, adjusted for age, were calculated, stratified by gender and centre. Results: In many centres, higher level drinkers (males consuming 424 g of ethanol/day, equivalent to 42 standard drinks and females consuming 412 g of ethanol/day equivalent to 41 standard drink) obtained more energy from fat and protein and less from sugar than did abstainers. The proportion of energy from starch tended to be higher for male and lower for female higher level drinkers than for abstainers. Female higher level drinkers had a lower body mass index than did abstainers, whereas male higher level drinkers generally weighed more. Male higher level drinkers were less educated than abstainers in Mediterranean countries, but were more educated elsewhere. Female higher level drinkers were usually more educated than were abstainers. Outside the home, consumption (both genders) tended to be at friends’ homes, particularly among men in Northern and Central Europe, and in bars in Spain. Conclusions: This study reveals clear geographical differences in drinking habits across Europe, and shows that the characteristics of different alcohol consumption categories also vary. European Journal of Clinical Nutrition (2009) 63, S81-S100; doi: 10.1038/ejcn.2009.76

Published
2009

45. General and Abdominal Adiposity and Risk of Death in Europe

Author

Pischon, T. Boeing, H. Hoffmann, K. Bergmann, M. and Schulze, M. B. Overvad, K. van der Schouw, Y. T. Spencer, E. and Moons, K. G. M. Tjonneland, A. Halkjaer, J. Jensen, M. K. Stegger, J. Clavel-Chapelon, F. Boutron-Ruault, M. -C. and Chajes, V. Linseisen, J. Kaaks, R. Trichopoulou, A. and Trichopoulos, D. Bamia, C. Sieri, S. Palli, D. Tumino, R. Vineis, P. Panico, S. Peeters, P. H. M. May, A. M. and Bueno-de-Mesquita, H. B. van Duijnhoven, F. J. B. Hallmans, G. Weinehall, L. Manjer, J. Hedblad, B. Lund, E. and Agudo, A. Arriola, L. Barricarte, A. Navarro, C. and Martinez, C. Quiros, J. R. Key, T. Bingham, S. Khaw, K. T. Boffetta, P. Jenab, M. Ferrari, P. Riboli, E.

Subjects
nutritional and metabolic diseases
Abstract

BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P

Published
2008

46. Virus induced gene silencing in pea

Author

Constantin, Gabriela Didina, Grønlund, Mette, Sørensen, J L, Jensen, M K, Mejer, M, Piednoir, E, Krath, B N, MacFarlane, S.A., Nicolaisen, Mogens, Johansen, Ida Elisabeth, and Lund, Ole Søgaard

Published
2005

48. Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies

Author

Qi, Q., primary, Chu, A. Y., additional, Kang, J. H., additional, Huang, J., additional, Rose, L. M., additional, Jensen, M. K., additional, Liang, L., additional, Curhan, G. C., additional, Pasquale, L. R., additional, Wiggs, J. L., additional, De Vivo, I., additional, Chan, A. T., additional, Choi, H. K., additional, Tamimi, R. M., additional, Ridker, P. M., additional, Hunter, D. J., additional, Willett, W. C., additional, Rimm, E. B., additional, Chasman, D. I., additional, Hu, F. B., additional, and Qi, L., additional

Published
2014
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50. General and abdominal adiposity and risk of death in Europe.

Author

Pischon, T, Boeing, H, Hoffmann, K, Bergmann, M, Schulze, M B, Overvad, K, van der Schouw, Y T, Spencer, E, Moons, K G M, Tjønneland, A, Halkjaer, J, Jensen, M K, Stegger, J, Clavel-Chapelon, F, Boutron-Ruault, M-C, Chajes, V, Linseisen, J, Kaaks, R, Trichopoulou, A, Trichopoulos, D, Bamia, C, Sieri, S, Palli, D, Tumino, R, Vineis, P, Panico, S, Peeters, P H M, May, A M, Bueno-de-Mesquita, H B, van Duijnhoven, F J B, Hallmans, Göran, Weinehall, Lars, Manjer, J, Hedblad, B, Lund, E, Agudo, A, Arriola, L, Barricarte, A, Navarro, C, Martinez, C, Quirós, J R, Key, T, Bingham, S, Khaw, K T, Boffetta, P, Jenab, M, Ferrari, P, Riboli, E, Pischon, T, Boeing, H, Hoffmann, K, Bergmann, M, Schulze, M B, Overvad, K, van der Schouw, Y T, Spencer, E, Moons, K G M, Tjønneland, A, Halkjaer, J, Jensen, M K, Stegger, J, Clavel-Chapelon, F, Boutron-Ruault, M-C, Chajes, V, Linseisen, J, Kaaks, R, Trichopoulou, A, Trichopoulos, D, Bamia, C, Sieri, S, Palli, D, Tumino, R, Vineis, P, Panico, S, Peeters, P H M, May, A M, Bueno-de-Mesquita, H B, van Duijnhoven, F J B, Hallmans, Göran, Weinehall, Lars, Manjer, J, Hedblad, B, Lund, E, Agudo, A, Arriola, L, Barricarte, A, Navarro, C, Martinez, C, Quirós, J R, Key, T, Bingham, S, Khaw, K T, Boffetta, P, Jenab, M, Ferrari, P, and Riboli, E

Published
2008

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