34 results on '"Kuukasjärvi P"'
Search Results
2. Information Sharing Between Authorities Combating Foreign Labour Exploitation in Finland
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Terhi Kankaanranta, Saana Rikkilä, and Kimmo Kuukasjärvi
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labour exploitation ,information sharing ,cooperation ,education ,Law in general. Comparative and uniform law. Jurisprudence ,K1-7720 - Abstract
Well-functioning information sharing is an essential element for successful cooperation between authorities in public administration, e.g., when authorities attempt to combat foreign labour exploitation. This paper contributes toward existing literature by broadening the understanding about factors that need to be acknowledged when developing information sharing practices between authorities. The purpose of this study was to analyse authorities’ perceptions of possibilities and obstacles to share information with a focus on legislation, IT infrastructure and the set of electronic registers. In this case, the authorities were those whose legal duties include supervision of work-related immigration. In addition to a summary of legislation, empirical data was used. An electronic questionnaire was sent to 14 relevant authorities (62 respondents); 12 authorities responded. Knowledge gaps related to legislation and content of information were found to hamper information sharing between authorities. In addition, IT infrastructure capability and the fragmented nature of data registers, the so-called ‘silo effect’, complicates information distribution. To secure efficient and smooth information sharing, authorities need to know their legal possibilities and their duties to share information, but also understand what information is valuable to other authorities. In addition, IT infrastructure capability needs to be developed further. Finally, increasing knowledge about legal aspects is an important topic in education.
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- 2023
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3. Genome-wide analysis identifies novel susceptibility loci for myocardial infarction
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Hartiala, Jaana A, Han, Yi, Jia, Qiong, Hilser, James R, Huang, Pin, Gukasyan, Janet, Schwartzman, William S, Cai, Zhiheng, Biswas, Subarna, Trégouët, David-Alexandre, Smith, Nicholas L, Consortium, The INVENT, Group, The CHARGE Consortium Hemostasis Working, Consortium, The GENIUS-CHD, Seldin, Marcus, Pan, Calvin, Mehrabian, Margarete, Lusis, Aldons J, Bazeley, Peter, Sun, Yan V, Liu, Chang, Quyyumi, Arshed A, Scholz, Markus, Thiery, Joachim, Delgado, Graciela E, Kleber, Marcus E, März, Winfried, Howe, Laurence J, Asselbergs, Folkert W, van Vugt, Marion, Vlachojannis, Georgios J, Patel, Riyaz S, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Lehtimäki, Terho, Nieminen, Tuomo VM, Kuukasjärvi, Pekka, Laurikka, Jari O, Chang, Xuling, Heng, Chew-Kiat, Jiang, Rong, Kraus, William E, Hauser, Elizabeth R, Ferguson, Jane F, Reilly, Muredach P, Ito, Kaoru, Koyama, Satoshi, Kamatani, Yoichiro, Komuro, Issei, Japan, Biobank, Stolze, Lindsey K, Romanoski, Casey E, Khan, Mohammad Daud, Turner, Adam W, Miller, Clint L, Aherrahrou, Redouane, Civelek, Mete, Ma, Lijiang, Björkegren, Johan LM, Kumar, S Ram, Tang, WH Wilson, Hazen, Stanley L, and Allayee, Hooman
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Cardiovascular ,Heart Disease ,Clinical Research ,Heart Disease - Coronary Heart Disease ,Human Genome ,Genetics ,Aging ,Atherosclerosis ,Aetiology ,2.1 Biological and endogenous factors ,Coronary Artery Disease ,Endothelial Cells ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Japan ,Myocardial Infarction ,Polymorphism ,Single Nucleotide ,Risk Factors ,Myocardial infarction ,Genetic factors ,Genome-wide association study ,Meta-analysis ,SLC44A3 ,INVENT Consortium ,CHARGE Consortium Hemostasis Working Group ,GENIUS-CHD Consortium ,Biobank Japan ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
AimsWhile most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.Methods and resultsWe carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.ConclusionsA large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
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- 2021
4. IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder
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Kuukasjärvi, Anna, Landoni, Juan C., Kaukonen, Jyrki, Juhakoski, Mika, Auranen, Mari, Torkkeli, Tommi, Velagapudi, Vidya, and Suomalainen, Anu
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- 2021
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5. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis
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Schillemans, T., Tragante, V., Maitusong, B., Gigante, B., Cresci, S., Laguzzi, F., Vikström, M., Richards, M., Pilbrow, A., Cameron, V., Foco, L., Doughty, R.N., Kuukasjärvi, P., Allayee, H., Hartiala, J.A., Tang, W.H., Lyytikäinen, L.P., Nikus, K., Laurikka, J.O., Srinivasan, S., Mordi, I.R., Trompet, S., Kraaijeveld, A., Setten, J. van, Gijsberts, C.M., Maitland-van der Zee, A.H., Saely, C.H., Gong, Y., Johnson, J.A., Cooper-DeHoff, R.M., Pepine, C.J., Casu, G., Leiherer, A., Drexel, H., Horne, B.D., Laan, S.W. van der, Marziliano, N., Hazen, S.L., Sinisalo, J., Kähönen, M., Lehtimäki, T., Lang, C.C., Burkhardt, R., Scholz, M., Jukema, J.W., Eriksson, N., Åkerblom, A., James, S., Held, C., Hagström, E., Spertus, J.A., Algra, A., Faire, U. de, Åkesson, A., Asselbergs, F.W., Patel, R.S., Leander, K., Schillemans, T., Tragante, V., Maitusong, B., Gigante, B., Cresci, S., Laguzzi, F., Vikström, M., Richards, M., Pilbrow, A., Cameron, V., Foco, L., Doughty, R.N., Kuukasjärvi, P., Allayee, H., Hartiala, J.A., Tang, W.H., Lyytikäinen, L.P., Nikus, K., Laurikka, J.O., Srinivasan, S., Mordi, I.R., Trompet, S., Kraaijeveld, A., Setten, J. van, Gijsberts, C.M., Maitland-van der Zee, A.H., Saely, C.H., Gong, Y., Johnson, J.A., Cooper-DeHoff, R.M., Pepine, C.J., Casu, G., Leiherer, A., Drexel, H., Horne, B.D., Laan, S.W. van der, Marziliano, N., Hazen, S.L., Sinisalo, J., Kähönen, M., Lehtimäki, T., Lang, C.C., Burkhardt, R., Scholz, M., Jukema, J.W., Eriksson, N., Åkerblom, A., James, S., Held, C., Hagström, E., Spertus, J.A., Algra, A., Faire, U. de, Åkesson, A., Asselbergs, F.W., Patel, R.S., and Leander, K.
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Contains fulltext : 283506.pdf (Publisher’s version ) (Open Access), Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
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- 2022
6. BRCA2 Mutations in 154 Finnish Male Breast Cancer Patients
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Kirsi Syrjäkoski, Tuula Kuukasjärvi, Kati Waltering, Karin Haraldsson, Anssi Auvinen, Åke Borg, Tommi Kainu, Olli-P Kallioniemi, and Pasi A. Koivisto
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BRCA2 ,mutation ,male breast cancer ,population ,penetrance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The etiology and pathogenesis of male breast cancer (MBC) are poorly known. This is due to the fact that the disease is rare, and large-scale genetic epidemiologic studies have been difficult to carry out. Here, we studied the frequency of eight recurrent Finnish BRCA2 founder mutations in a large cohort of 154 MBC patients (65% diagnosed in Finland from 1967 to 1996). Founder mutations were detected in 10 patients (6.5%), eight of whom carried the 9346(-2) A>G mutation. Two novel mutations (4075 delGT and 5808 del5) were discovered in a screening of the entire BRCA2 coding region in 34 samples. However, these mutations were not found in the rest of the 120 patients studied. Patients with positive family history of breast and/or ovarian cancer were often BRCA2 mutation carriers (44%), whereas those with no family history showed a low frequency of involvement (3.6%; P < .0001). Finally, we found only one Finnish MBC patient with 999 dell, the most common founder mutation in Finnish female breast cancer (FBC) patients, and one that explains most of the hereditary FBC and MBC cases in Iceland. The variation in BRCA2 mutation spectrum between Finnish MBC patients and FBC patients in Finland and breast cancer patients in Iceland suggests that modifying genetic and environmental factors may significantly influence the penetrance of MBC and FBC in individuals carrying germline BRCA2 mutations in some populations.
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- 2004
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7. Negative Pressure Wound Therapy: a Systematic Review on Effectiveness and Safety
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Vikatmaa, P., Juutilainen, V., Kuukasjärvi, P., and Malmivaara, A.
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- 2008
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8. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data
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Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., Patel, R.S., Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., and Patel, R.S.
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Contains fulltext : 235380.pdf (Publisher’s version ) (Closed access), BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I(2)=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, card
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- 2020
9. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events
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Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW
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Male ,Myocardial Infarction ,genetic risk factor ,Coronary Artery Disease ,Middle Aged ,Article ,chromosome 9p21 ,Gene Frequency ,Risk Factors ,Case-Control Studies ,Odds Ratio ,Humans ,Female ,Genetic Predisposition to Disease ,cardiovascular diseases ,Chromosomes, Human, Pair 9 ,secondary prevention - Abstract
Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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- 2019
10. Subsequent Event Risk in Individuals With Established Coronary Heart Disease
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Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), Asselbergs, F.W. (Folkert), Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), and Asselbergs, F.W. (Folkert)
- Abstract
BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants a
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- 2019
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11. Association of Factor V Leiden With Subsequent Atherothrombotic Events
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Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo-Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Wilson Tang, W.H., van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R, Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-van der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F.R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L.J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., and Patel, Riyaz S.
- Abstract
Supplemental Digital Content is available in the text.
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- 2020
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12. Sepelvaltimotaudin kajoavan hoidon vaikuttavuus
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Kuukasjärvi, P., Malmivaara, A., Mäkelä, Marja-Leena, Kuukasjärvi, P., Malmivaara, A., and Mäkelä, Marja-Leena
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- 2005
13. Endoskooppisen sympatektomian vaikuttavuus ja turvallisuus. Järjestelmällinen kirjalisuuskatsaus
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Malmivaara, A., Kuukasjärvi, P., Autti-Rämö, I., Kovanen, N., Mäkelä, Marja-Leena, Malmivaara, A., Kuukasjärvi, P., Autti-Rämö, I., Kovanen, N., and Mäkelä, Marja-Leena
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- 2005
14. Response to Letter to the Editor
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Vikatmaa, P., primary, Juutilainen, V., additional, Kuukasjärvi, P., additional, and Malmivaara, A., additional
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- 2009
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15. Negative Pressure Wound Therapy: a Systematic Review on Effectiveness and Safety
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Vikatmaa, P., primary, Juutilainen, V., additional, Kuukasjärvi, P., additional, and Malmivaara, A., additional
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- 2008
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16. The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients.
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Korhonen, T., Kuukasjärvi, T., Huhtala, H., Alarmo, E.-L., Holli, K., Kallioniemi, A., and Pylkkänen, L.
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BREAST cancer treatment ,HISTOLOGY ,BREAST cancer diagnosis ,METASTASIS ,HISTOPATHOLOGY ,REGRESSION analysis - Abstract
Abstract: The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan–Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant. Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up. [Copyright &y& Elsevier]
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- 2013
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17. Bradykinin preconditioning in coronary artery bypass grafting.
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Wei, Minxin, Wang, Xin, Kuukasjärvi, Pekka, Laurikka, Jari, Rinne, Timo, Honkonen, Eva-Liisa, and Tarkka, Matti
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BRADYKININ ,ISCHEMIA ,BLOOD vessels ,HEMODYNAMICS - Abstract
Background: Experimental studies have shown that activation of bradykinin B
2 receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery.Methods: Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 μg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded.Results: Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 ± 7.9 vs 54.4 ± 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 ± 9.5 vs control, 23.6 ± 12.7 U/L; 12 hours, BK, 19.4 ± 12.4 vs control, 28.7 ± 23.8 U/L; 24 hours, BK, 21.5 ± 14.7 vs control, 35.5 ± 28.9 U/L; 48 hours, BK, 14.4 ± 7.5 vs control, 23.5 ± 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 ± 14.4 vs 37.7 ± 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables.Conclusions: Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure. [Copyright &y& Elsevier]- Published
- 2004
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18. Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development
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Alarmo, Emma-Leena, Huhtala, Heini, Korhonen, Tarja, Pylkkänen, Liisa, Holli, Kaija, Kuukasjärvi, Tuula, Parkkila, Seppo, and Kallioniemi, Anne
- Abstract
Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data.
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- 2013
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19. Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms
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Höyssä, Salla, Rontu, Riikka, Kuukasjärvi, Pekka, Mennander, Ari, Laurikka, Jari, Tarkka, Matti, Nikus, Kjell, Islam, Md., Karhunen, Pekka, and Lehtimäki, Terho
- Abstract
Abstract: Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C>A and NFKBIL1-63 T>A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI). The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users. Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.
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- 2006
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20. THE ANTI-INFLAMMATORY EFFECT OF DIAZOXIDE IN CORONARY ARTERY BYPASS GRAFTING
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Wang, Xin, Wei, Minxin, Laurikka, Jari, Kuukasjärvi, Pekka, Rinne, Timo, Honkonen, Eva-Liisa, Nieminen, Riina, Moilanen, Eeva, and Tarkka, Matti
- Abstract
Many therapeutic strategies have been designed to suppress the inflammatory response in patients undergoing coronary artery bypass grafting (CABG). Pharmacological preconditioning with diazoxide is an alternative in effective cardioprotective strategies, but more evidence is required to show its effect on the inflammatory response. Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control and diazoxide (DZX) groups. In the DZX group, 1.5 mg/kg diazoxide was infused intravenously in 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass. In the control group, placebo infusion was given similarly. Blood samples for cytokine measurement were collected from the radial artery and coronary sinus perioperatively, and hemodynamic data were recorded. Thirty-six patients fulfilled the data collection. Cardiac index (CI) increased in both groups over time as compared with baseline. In the DZX group, the increase of CI was greater than that in the control group (P= 0.002). Systemic and coronary sinus plasma levels of IL-6, IL-8, and IL-10 increased significantly after reperfusion in both groups as compared with baseline (P< 0.05). IL-6 and IL-8 both reached the peak value at 6 h after cardiopulmonary bypass. IL-10 reached peak level at 20 min after reperfusion in both groups. There was significantly higher IL-10 in DZX groups (P= 0.015). The ratios of IL-6 to IL-10 and IL-8 to IL-10 were significantly lower in DZX groups than in controls (P= 0.025 and P= 0.041 for each, respectively). Pharmacological preconditioning with DZX in CABG patients shifts the circulating inflammatory cytokine balance toward the anti-inflammatory direction.
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- 2004
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21. Amplification of a 280-Kilobase Core Region at the ERBB2Locus Leads to Activation of Two Hypothetical Proteins in Breast Cancer
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Kauraniemi, Päivikki, Kuukasjärvi, Tuula, Sauter, Guido, and Kallioniemi, Anne
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Amplification of the ERBB2oncogene at 17q12 is clinically the most relevant genetic aberration in breast cancer and several studies have linked ERBB2activation to poor clinical outcome. The development of targeted antibody-based therapy for ERBB2-overexpressing tumors and the possible role of ERBB2as a predictor of chemotherapy treatment response have further emphasized the essential role of ERBB2in breast cancer. Here, we performed a detailed characterization of the molecular events occurring at the ERBB2amplicon in primary breast tumors. Analysis of the amplicon structure in 330 breast tumors by fluorescence in situhybridization to a tissue microarray revealed a 280-kb common region of amplification that contains 10 transcribed sequences, including eight known genes. The expression levels of these 10 transcripts were determined in 36 frozen samples of grade-matched ERBB2-amplified and -nonamplified (as determined by fluorescence in situhybridization) primary breast tumors by using quantitativereal-time reverse transcriptase-polymerase chain reaction. A highly significant association between amplification and expression levels was observed for six of these genes, including ERBB2and two uncharacterized hypothetical proteins, MGC9753and MGC14832. These results support the recent findings on the influence of copy number on gene expression levels and highlight novel genes that might contribute to the clinical behavior of ERBB2-amplified breast tumors.
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- 2003
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22. INFLAMMATORY CYTOKINES AND SOLUBLE RECEPTORS AFTER CORONARY ARTERY BYPASS GRAFTING
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Wei, Minxin, Kuukasjärvi, Pekka, Laurikka, Jari, Pehkonen, Erkki, Kaukinen, Seppo, Laine, Seppo, and Tarkka, Matti
- Abstract
Much interest has been focused on the overexpression of proinflammatory cytokines, but studies on their soluble receptors are rare. For a comprehensive picture of cytokine activation in cardiac surgery, a combination of cytokines and the corresponding soluble receptor concentration should be determined. Blood samples were collected from the radial artery and coronary sinus perioperatively in ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. TNF-α, IL-6, sTNFRI, sTNFRII, and sIL-6R levels in the plasma were determined. Systemic TNFRI, TNFRII and IL-6 increased significantly after reperfusion to the myocardium, while perioperative systemic sIL-6r levels were similar. Arterial and sinus levels of TNFRI, TNFRII and sIL-6r were similar before cardiopulmonary bypass. Five minutes after reperfusion to the myocardium, higher sinus TNFRI and TNFRII and lower sinus sIL-6R levels were observed as compared to the arterial levels. The myocardium release of sTNFRI (r=0.57, P=0.089) and sTNFRII (r=0.64, P=0.047) positively correlated with the change of cardiac index after cardiopulmonary bypass. Myocardium releases sTNFRI and sTNFRII after ischaemic-reperfusion injury, and this may be of benefit to cardiac performance. sIL-6R is constantly being produced in areas other than the myocardium, while sIL-6R levels are reduced by consumption in the myocardium after ischaemic-reperfusion injury.
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- 2001
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23. Predictive value of topoisomerase IIα and other prognostic factors for epirubicin chemotherapy in advanced breast cancer
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Järvinen, TAH, Holli, K, Kuukasjärvi, T, and Isola, JJ
- Abstract
Although cytotoxic chemotherapy is widely used in advanced breast cancer, there are no powerful predictors for the therapy response. Because topoisomerase IIalpha (Topo IIalpha) is the molecular target for the anthracycline class of anti-cancer drugs, we compared the immunocytochemical assay of Topo IIalpha with other biomarkers in the prediction of clinical response to Topo II inhibitor chemotherapy. Fifty-five patients with advanced breast cancer were treated with a single cytotoxic drug, Topo II-inhibitor, epirubicin (30 mg m(-2) weekly up to 1000 mg m(-2)), as first line cytotoxic chemotherapy. Objective response to treatment was analysed according to UICC criteria. The predictive value of Topo IIalpha expression, c-erbB2 oncoprotein, p53 tumour-suppressor protein, oestrogen (ER) and progesterone receptor (PR), S-phase fraction and DNA ploidy were analysed from representative formalin-fixed paraffin-embedded primary tumour samples. The proportion of Topo IIalpha-positive cells (Topo IIalpha index) failed to predict response to epirubicin therapy. Mean Topo IIalpha scores in 29 responding patients were similar when compared with those with no change in disease progression (n = 13) and those with progressive disease (n = 13) (14.9% +/- 11.4% vs 15.5% +/- 7.6% vs 17.3% +/- 13.2%, not significant). Among the other biomarkers tested, overexpression of c-erbB2 oncoprotein and hormone receptor negativity were significantly associated with poor response. Response rate in patients with c-erbB2-overexpressing tumours was 32% compared with 65% in patients with no c-erbB2 overexpression (P = 0.0058). Accordingly, the response rate for ER-positive patients was 67% compared with 26% in ER-negative patients (P = 0.0021). Although both negative ER status and c-erbB2 overexpression are associated with high Topo IIalpha expression in breast cancer, step-wise logistic regression analysis showed that ER and c-erbB2 were associated with therapy response independent of Topo IIalpha expression. Histological grade, p53, DNA-ploidy, tumour proliferation rate (S-phase fraction), stage of the disease at diagnosis, age of the patient, previous anti-oestrogen therapy or site of metastasis did not predict the response to epirubicin therapy. In conclusion, despite extensive in vitro evidence, expression of Topo IIalpha is unlikely to predict the response to Topo II inhibitor chemotherapy in advanced breast cancer. Among the prognostic biomarkers, overexpression of c-erbB2 oncogene and negative ER may have predictive value in epirubicin therapy in patients with advanced breast cancer.
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- 1998
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24. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis
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Tessa Schillemans, Vinicius Tragante, Buamina Maitusong, Bruna Gigante, Sharon Cresci, Federica Laguzzi, Max Vikström, Mark Richards, Anna Pilbrow, Vicky Cameron, Luisa Foco, Robert N. Doughty, Pekka Kuukasjärvi, Hooman Allayee, Jaana A. Hartiala, W. H. Wilson Tang, Leo-Pekka Lyytikäinen, Kjell Nikus, Jari O. Laurikka, Sundararajan Srinivasan, Ify R. Mordi, Stella Trompet, Adriaan Kraaijeveld, Jessica van Setten, Crystel M. Gijsberts, Anke H. Maitland-van der Zee, Christoph H. Saely, Yan Gong, Julie A. Johnson, Rhonda M. Cooper-DeHoff, Carl J. Pepine, Gavino Casu, Andreas Leiherer, Heinz Drexel, Benjamin D. Horne, Sander W. van der Laan, Nicola Marziliano, Stanley L. Hazen, Juha Sinisalo, Mika Kähönen, Terho Lehtimäki, Chim C. Lang, Ralph Burkhardt, Markus Scholz, J. Wouter Jukema, Niclas Eriksson, Axel Åkerblom, Stefan James, Claes Held, Emil Hagström, John A. Spertus, Ale Algra, Ulf de Faire, Agneta Åkesson, Folkert W. Asselbergs, Riyaz S. Patel, and Karin Leander
- Subjects
polymorphisms ,PPARGC1A ,meta-analysis ,SNPs ,coronary heart disease ,cohort studies ,Physiology ,QP1-981 - Abstract
Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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- 2022
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25. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis.
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Schillemans T, Tragante V, Maitusong B, Gigante B, Cresci S, Laguzzi F, Vikström M, Richards M, Pilbrow A, Cameron V, Foco L, Doughty RN, Kuukasjärvi P, Allayee H, Hartiala JA, Tang WHW, Lyytikäinen LP, Nikus K, Laurikka JO, Srinivasan S, Mordi IR, Trompet S, Kraaijeveld A, van Setten J, Gijsberts CM, Maitland-van der Zee AH, Saely CH, Gong Y, Johnson JA, Cooper-DeHoff RM, Pepine CJ, Casu G, Leiherer A, Drexel H, Horne BD, van der Laan SW, Marziliano N, Hazen SL, Sinisalo J, Kähönen M, Lehtimäki T, Lang CC, Burkhardt R, Scholz M, Jukema JW, Eriksson N, Åkerblom A, James S, Held C, Hagström E, Spertus JA, Algra A, de Faire U, Åkesson A, Asselbergs FW, Patel RS, and Leander K
- Abstract
Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants ( n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline., Competing Interests: SL has received Roche funding for unrelated work; SJ has received grants from AstraZeneca, The Medicines Company; CH declares advisory board and speaker’s bureau for AstraZeneca, institutional research grants from Bristol Myers Squibb, Merck &Co, GlaxoSmithKline, Roche Diagnostics, and advisory board for Bayer and Boehringer Ingelheim; EH declares being an expert committee member, lecture fees, and institutional research grant from Sanofi and Amgen, institutional research grants from AstraZeneca and GlaxoSmithKline, as well as an expert committee member and lecture fees for Novo Nordisk and Behringer; BH has an institutional research grant from AstraZeneca for unrelated work and is an advisory board member for Opsis Health and Lab Me Analytics, and Intermountain Healthcare has licensed his intellectual property to CareCentra and Alluceo; NE declares institutional research grants from AstraZeneca and Pfizer. AXA has received institutional research grant and speaker fee from AstraZeneca and an institutional research grant from Roche Diagnostics; AXA has received an institutional research grant and speaker fee from AstraZeneca and an institutional research grant from Roche Diagnostics; BH has an institutional research grant from AstraZeneca for unrelated work and is an advisory board member for Opsis Health and Lab Me Analytics, and Intermountain Healthcare has licensed his intellectual property to CareCentra and Alluceo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schillemans, Tragante, Maitusong, Gigante, Cresci, Laguzzi, Vikström, Richards, Pilbrow, Cameron, Foco, Doughty, Kuukasjärvi, Allayee, Hartiala, Tang, Lyytikäinen, Nikus, Laurikka, Srinivasan, Mordi, Trompet, Kraaijeveld, van Setten, Gijsberts, Maitland-van der Zee, Saely, Gong, Johnson, Cooper-DeHoff, Pepine, Casu, Leiherer, Drexel, Horne, van der Laan, Marziliano, Hazen, Sinisalo, Kähönen, Lehtimäki, Lang, Burkhardt, Scholz, Jukema, Eriksson, Åkerblom, James, Held, Hagström, Spertus, Algra, de Faire, Åkesson, Asselbergs, Patel and Leander.)
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- 2022
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26. Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.
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Orlenko A, Kofink D, Lyytikäinen LP, Nikus K, Mishra P, Kuukasjärvi P, Karhunen PJ, Kähönen M, Laurikka JO, Lehtimäki T, Asselbergs FW, and Moore JH
- Subjects
- Humans, Machine Learning, Metabolome, Metabolomics, Coronary Artery Disease
- Abstract
Motivation: Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES)., Results: We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes., Availability and Implementation: TPOT is freely available via http://epistasislab.github.io/tpot/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)
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- 2020
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27. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.
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Patel RS, Schmidt AF, Tragante V, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Dubé MP, Allayee H, Almgren P, Alver M, Baranova EV, Behlouli H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dufresne L, Eriksson N, Foco L, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Fitzpatrick N, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Bogaty P, de Borst GJ, Brenner H, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Johnson JA, de Jong PA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Pepinski W, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Scholz M, Siegbahn A, Sinisalo J, Smith JG, Spertus JA, Stewart AFR, Szczeklik W, Szpakowicz A, Ten Berg JM, Thanassoulis G, Thiery J, van der Graaf Y, Visseren FLJ, Waltenberger J, Van der Harst P, Tardif JC, Sattar N, Lang CC, Pare G, Brophy JM, Anderson JL, März W, Wallentin L, Cameron VA, Horne BD, Samani NJ, Hingorani AD, and Asselbergs FW
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- Case-Control Studies, Coronary Artery Disease genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Myocardial Infarction genetics, Myocardial Infarction pathology, Odds Ratio, Risk Factors, Chromosomes, Human, Pair 9, Coronary Artery Disease pathology
- Abstract
Background: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk., Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD., Results: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09)., Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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- 2019
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28. Subsequent Event Risk in Individuals With Established Coronary Heart Disease.
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Patel RS, Tragante V, Schmidt AF, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Allayee H, Almgren P, Alver M, Baranova EV, Behloui H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dubé MP, Dufresne L, Eriksson N, Foco L, Scholz M, Gijsberts CM, Glinge C, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kotti S, Kuukasjärvi P, Lee VV, Leiherer A, Lenzini PA, Levin D, Lyytikäinen LP, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, Van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Al Ali L, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Engstrøm T, Fitzpatrick N, Fox K, Gigante B, James S, Lokki ML, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton-Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Boersma EH, Bogaty P, Bots ML, Brenner H, Brugts JJ, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, Danchin N, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Grobbee DE, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Jabbari R, Johnson JA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Niemcunowicz-Janica A, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Siegbahn A, Simon T, Sinisalo J, Smith JG, Spertus JA, Stender S, Stewart AFR, Szczeklik W, Szpakowicz A, Tardif JC, Ten Berg JM, Tfelt-Hansen J, Thanassoulis G, Thiery J, Torp-Pedersen C, van der Graaf Y, Visseren FLJ, Waltenberger J, Weeke PE, Van der Harst P, Lang CC, Sattar N, Cameron VA, Anderson JL, Brophy JM, Pare G, Horne BD, März W, Wallentin L, Samani NJ, Hingorani AD, and Asselbergs FW
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- Adult, Age Factors, Aged, Female, Humans, Male, Middle Aged, Prognosis, Proportional Hazards Models, Risk Factors, Sex Factors, Smoking, Coronary Disease pathology
- Abstract
Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD., Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events., Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints., Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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- 2019
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29. Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients.
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Kettunen J, Ritchie SC, Anufrieva O, Lyytikäinen LP, Hernesniemi J, Karhunen PJ, Kuukasjärvi P, Laurikka J, Kähönen M, Lehtimäki T, Havulinna AS, Salomaa V, Männistö S, Ala-Korpela M, Perola M, Inouye M, and Würtz P
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- Adult, Aged, Biomarkers blood, Disease-Free Survival, Female, Humans, Male, Middle Aged, Risk Factors, Survival Rate, Biobehavioral Sciences, Cardiovascular Diseases blood, Cardiovascular Diseases diagnostic imaging, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnostic imaging, Kidney Diseases blood, Kidney Diseases diagnostic imaging, Magnetic Resonance Angiography
- Abstract
Background: Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker-a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA's morbidity and mortality risk are currently unknown., Methods: We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up., Results: New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45-9.65) and 5.00 (95% CI, 2.38-10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant., Conclusions: GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.
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- 2018
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30. High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis.
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Würtz P, Raiko JR, Magnussen CG, Soininen P, Kangas AJ, Tynkkynen T, Thomson R, Laatikainen R, Savolainen MJ, Laurikka J, Kuukasjärvi P, Tarkka M, Karhunen PJ, Jula A, Viikari JS, Kähönen M, Lehtimäki T, Juonala M, Ala-Korpela M, and Raitakari OT
- Subjects
- Adult, Carotid Intima-Media Thickness, Female, Humans, Magnetic Resonance Spectroscopy, Male, Plaque, Atherosclerotic diagnosis, Predictive Value of Tests, ROC Curve, Risk Assessment, Young Adult, Atherosclerosis diagnosis, Biomarkers metabolism, Lipid Metabolism physiology
- Abstract
Aims: High-throughput metabolite quantification holds promise for cardiovascular risk assessment. Here, we evaluated whether metabolite quantification by nuclear magnetic resonance (NMR) improves prediction of subclinical atherosclerosis in comparison to conventional lipid testing., Methods and Results: Circulating lipids, lipoprotein subclasses, and small molecules were assayed by NMR for 1595 individuals aged 24-39 years from the population-based Cardiovascular Risk in Young Finns Study. Carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, was measured in 2001 and 2007. Baseline conventional risk factors and systemic metabolites were used to predict 6-year incidence of high IMT (≥ 90 th percentile) or plaque. The best prediction of high intima-media thickness was achieved when total and HDL cholesterol were replaced by NMR-determined LDL cholesterol and medium HDL, docosahexaenoic acid, and tyrosine in prediction models with risk factors from the Framingham risk score. The extended prediction model improved risk stratification beyond established risk factors alone; area under the receiver operating characteristic curve 0.764 vs. 0.737, P =0.02, and net reclassification index 17.6%, P =0.0008. Higher docosahexaenoic acid levels were associated with decreased risk for incident high IMT (odds ratio: 0.74; 95% confidence interval: 0.67-0.98; P = 0.007). Tyrosine (1.33; 1.10-1.60; P = 0.003) and glutamine (1.38; 1.13-1.68; P = 0.001) levels were associated with 6-year incident high IMT independent of lipid measures. Furthermore, these amino acids were cross-sectionally associated with carotid IMT and the presence of angiographically ascertained coronary artery disease in independent populations., Conclusion: High-throughput metabolite quantification, with new systemic biomarkers, improved risk stratification for subclinical atherosclerosis in comparison to conventional lipids and could potentially be useful for early cardiovascular risk assessment.
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- 2012
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31. Short stature is associated with coronary heart disease: a systematic review of the literature and a meta-analysis.
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Paajanen TA, Oksala NK, Kuukasjärvi P, and Karhunen PJ
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- Adult, Case-Control Studies, Humans, Randomized Controlled Trials as Topic, Risk Factors, Body Height physiology, Coronary Disease etiology
- Abstract
Aims: The aim of this study was to assess the relationship between short stature and coronary heart disease (CHD) morbidity and mortality., Methods and Results: We performed a systematic search from MEDLINE, PREMEDLINE, and All EBM Reviews as well as from a reference list of relevant articles. We used SPICO (Study design, Patient, Intervention, Control-intervention, Outcome) criteria. The methodological quality of studies was analysed by modified Borghoust criteria. From a total of 1907 articles, we selected 52 studies comprising population-based follow-up studies and patient cohorts followed after a CHD event, as well as case-control studies with height either as a continuous or categorical variable, totalling 3 012 747 individuals. The short ones were below 160.5 cm and tall ones over 173.9 cm on average. Among the shortest height category, the relative risks were 1.35 (95% CI 1.25-1.44) for all-cause mortality, 1.55 (1.37-1.74) for all cardiovascular disease (CVD) mortality, 1.49 (1.33-1.67) for CHD, and 1.52 (1.28-1.81) for myocardial infarction when compared with those within the highest height category. The mean relative risk was 1.46 (1.37-1.55). Short stature was associated with increased cardiovascular morbidity and mortality in both genders., Conclusion: The relationship between short stature and CVD appears to be a real one. On the basis of comparison, adults within the shortest category had an approximately 50% higher risk of CHD morbidity and mortality than tall individuals.
- Published
- 2010
- Full Text
- View/download PDF
32. Continuous pleural lavage may decrease postoperative morbidity in patients undergoing thoracotomy for stage 2 thoracic empyema.
- Author
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Mennander A, Laurikka J, Kuukasjärvi P, and Tarkka M
- Subjects
- Empyema, Pleural microbiology, Female, Humans, Length of Stay, Male, Middle Aged, Pleura, Postoperative Complications microbiology, Recurrence, Reoperation, Therapeutic Irrigation methods, Empyema, Pleural surgery, Postoperative Complications prevention & control, Thoracotomy methods
- Abstract
Objective: To assess the impact of postoperative continuous pleural lavage (PCPL) after thoracotomy for the treatment of stage 2 pleural empyema in relation to postoperative length of stay and morbidity., Methods: Stage 2 pleural empyema was diagnosed with computer tomography. Conservative treatment including antibiotics and pleural aspiration was introduced. 89 patients treated for stage 2 pleural empyema by thoracotomy, pleural discharge evacuation and irrigation after pleural decortication were identified after unsuccessful conservative treatment for 10 days. Whenever pleural discharge remained opaque after operation, PCPL was administered daily through the cranial chest tube and discharge evacuated through the caudal pleural suction (10-15 mmHg) tube. Risk factors related to pleural pus and patient outcome were sought for., Results: Seventy-seven out of 89 patients (86.5%) had clear empyema discharge immediately after pleural decortication and irrigation. Pleural discharge remained opaque despite surgery in 12 out of 89 patients (13.5%) and PCPL was introduced. Presence of a combination of risk factors for pleural empyema, such as dental caries, alcohol abuse or previous inflammatory reaction, was predictive for persistence of opaque pleural discharge after operation (P<0.05). Need for re-thoracotomies (in 11 cases, P=ns) and postoperative deaths (P<0.05) were related with patients who did not have PCPL. The length of the hospital treatment was 20.1+/-3.1 (days+/-SEM) among patients with PCPL and 19.2+/-1.8 without PCPL before possible re-thoracotomy, respectively (P=ns)., Conclusions: Early postoperative (1 day-11 months) mortality was statistically associated with patients having fibrinopurulent empyema but no PCPL. PCPL is a feasible method to clear pleural pus discharge without prolongation of hospitalization and may be recommended after thoracotomy for patients with fibrinopurulent stage 2 empyema.
- Published
- 2005
- Full Text
- View/download PDF
33. Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting.
- Author
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Wang X, Wei M, Kuukasjärvi P, Laurikka J, Järvinen O, Rinne T, Honkonen EL, and Tarkka M
- Subjects
- Aged, Biomarkers blood, Creatine Kinase blood, Creatine Kinase, MB Form, Female, Hemodynamics drug effects, Humans, Isoenzymes blood, Male, Middle Aged, Myocardial Stunning diagnosis, Myocardial Stunning etiology, Postoperative Period, Coronary Artery Bypass adverse effects, Diazoxide therapeutic use, Ischemic Preconditioning, Myocardial methods, Myocardial Stunning prevention & control, Vasodilator Agents therapeutic use
- Abstract
Objective: To investigate whether novel pharmacological preconditioning with diazoxide could protect the myocardial function and decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG)., Methods: Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control group (n=20) and diazoxide (DZX) group (n=20). In the DZX group, 1.5 mg/kg diazoxide was infused intravenously within 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass (CPB). In the control group, a time-matched period of placebo infusion was given. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively., Results: There were no adverse effects related to diazoxide. Cardiac index (CI) increased postoperatively as compared with baseline. In the DZX group, the improvement of CI was better than that in the control group (p=0.001). Left and right ventricular stroke work indexes decreased postoperatively, and recovered much faster in the DZX group (p=0.027 and p=0.049, respectively). There were no statistically significant differences in the other hemodynamic parameters. The creatine kinase cardiac isoenzyme (CK-MB) was highest in both groups on the first postoperative day (control 28.8+/-23.8 and DZX 27.3+/-19.4, N.S.). The cumulative release of CK-MB postoperatively was lower in the DZX patients as compared with the controls, but the difference remained not significant (p=0.09)., Conclusions: Pharmacological preconditioning of the human heart with diazoxide is feasible; it confers additional myocardial protection beyond that provided by the cardioplegia alone by attenuating myocardial stunning after CABG operations.
- Published
- 2003
- Full Text
- View/download PDF
34. Comparison of computed tomography and systematic lymph node dissection in determining TNM and stage in non-small cell lung cancer.
- Author
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Sioris T, Järvenpää R, Kuukasjärvi P, Helin H, Saarelainen S, and Tarkka M
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung surgery, Female, Follow-Up Studies, Humans, Lung Neoplasms surgery, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms diagnostic imaging, Lung Neoplasms pathology, Neoplasm Staging methods, Tomography, X-Ray Computed
- Abstract
Objective: To compare computed tomography (CT)-based clinical TNM and staging to surgical-pathological staging with systematic lymph node dissection in primary non-small cell lung cancer., Methods: The study included 49 non-small cell lung cancer patients that underwent lung resection and systematic lymph node dissection between 1997 and 2001. Preoperative clinical and CT findings were compared with surgical-pathological findings. Lymph nodes with a shortest diameter of over 1 cm on CT were considered abnormal, but did not contraindicate surgery. Patients with CT indicating an invasive T4 tumor, pleural carcinosis, or bulky N2 disease were excluded., Results: Sixty-five percent (32/49) had epidermoid carcinoma, and 25% (12/49) had adenocarcinoma. N2 metastases were found in 12% (6/49). The clinical T category was correct in 71% (35/49), and the N category in 55% (27/49). The sensitivity for detecting N2 disease was 67% (4/6), and the specificity was 81% (35/43). The positive predictive value for N2 disease was 33% (4/12), and the negative predictive value was 95% (35/37). Node-by-node agreement on N2 metastatic location was 17% (1/6). Skip N2 metastases without any N1 involvement were found in 4% (2/49), or 33% (2/6) of all N2 cases. The clinical stage was correct in 45% (22/49), and complete TNM agreement was 37% (18/49)., Conclusions: The clinical TNM and staging based on CT are inaccurate. The sensitivity for detecting N2 disease is poor, especially on node-by node basis. Preoperative exclusion of N2 metastases is quite reliable, but a positive finding should always be verified. Systematic mediastinal lymph node dissection is necessary to detect N2 metastases inaccessible to cervical mediastinoscopy, and skip N2 metastases without N1 involvement.
- Published
- 2003
- Full Text
- View/download PDF
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