9 results on '"Engert, Andreas"'
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2. Author Correction: Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
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Sud, Amit, Thomsen, Hauke, Law, Philip J., Försti, Asta, da Silva Filho, Miguel Inacio, Holroyd, Amy, Broderick, Peter, Orlando, Giulia, Lenive, Oleg, Wright, Lauren, Cooke, Rosie, Easton, Douglas, Pharoah, Paul, Dunning, Alison, Peto, Julian, Canzian, Federico, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Pashayan, Nora, Henderson, Brian E., Haiman, Christopher A., Benlloch, Sara, Schumacher, Fredrick R., Olama, Ali Amin Al, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Hoffmann, Per, Nöthen, Markus M., Jöckel, Karl-Heinz, von Strandmann, Elke Pogge, Lightfoot, Tracy, Kane, Eleanor, Roman, Eve, Lake, Annette, Montgomery, Dorothy, Jarrett, Ruth F., Swerdlow, Anthony J., Engert, Andreas, Orr, Nick, Hemminki, Kari, and Houlston, Richard S.
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Science ,Medizin ,MEDLINE ,General Physics and Astronomy ,Genome-wide association study ,Computational biology ,Polymorphism, Single Nucleotide ,Article ,General Biochemistry, Genetics and Molecular Biology ,Disease susceptibility ,immune system diseases ,hemic and lymphatic diseases ,Classical Hodgkin lymphoma ,Humans ,Genetic Predisposition to Disease ,Author Correction ,lcsh:Science ,Alleles ,HLA-DP beta-Chains ,Multidisciplinary ,Published Erratum ,General Chemistry ,Hodgkin Disease ,Spelling ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Key (cryptography) ,lcsh:Q ,Psychology ,Genome-Wide Association Study ,HLA-DRB1 Chains - Abstract
Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10−17), 6q23.3 (rs6928977, P = 4.62 × 10−11), 10p14 (rs3781093, P = 9.49 × 10−13), 13q34 (rs112998813, P = 4.58 × 10−8) and 16p13.13 (rs34972832, P = 2.12 × 10−8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response., Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.
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- 2019
3. Related Party Transactions of Listed Companies in Germany
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Engert, Andreas and Florstedt, Tim
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Rechts|Empirie, Law's|Empirics
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- 2019
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4. Additional file 2: of Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
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Schmidt, Amand, Holmes, Michael, Preiss, David, Swerdlow, Daniel, Denaxas, Spiros, Ghazaleh Fatemifar, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Zammy Fairhurst-Hunter, Hartwig, Fernando, Horta, Bernardo, Hypponen, Elina, Power, Christine, Moldovan, Max, Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Goya Wanamethee, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Andrie Panayiotou, N. Onland-Moret, Schouw, Yvonne, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas, Langenberg, Claudia, Scott, Robert, JianâAn Luan, Bobak, Martin, Malyutina, Sofia, K, Andrzej PajÄ, Ruzena Kubinova, Abdonas Tamosiunas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve, Brilliant, Murray, Kitchner, Terrie, Hakon Hakonarson, Carrell, David, McCarty, Catherine, Kirchner Lester, Larson, Eric, Crosslin, David, Mariza Andrade, Roden, Dan, Denny, Joshua, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, OâDonnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Harst, Pim, M. Said, Eppinga, Ruben, Verweij, Niek, Snieder, Harold, Christen, Tim, D. Mook-Kanamori, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Raha Pazoki, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, DĂśrr, Marcus, Lerch, Markus, VĂślker, Uwe, VĂślzke, Henry, Ward, Joey, Pell, Jill, Meade, Tom, Christophersen, Ingrid, Zee, Anke Maitland-Van Der, Baranova, Ekaterina, Young, Robin, Ford, Ian, Campbell, Archie, Sandosh Padmanabhan, Bots, Michiel, Grobbee, Diederick, Froguel, Philippe, DorothĂŠe Thuillier, Roussel, Ronan, AmĂŠlie Bonnefond, Cariou, Bertrand, Smart, Melissa, Yanchun Bao, Kumari, Meena, Anubha Mahajan, Hopewell, Jemma, Seshadri, Sudha, Dale, Caroline, Costa, Rui, Ridker, Paul, Chasman, Daniel, Reiner, Alex, Ritchie, Marylyn, Lange, Leslie, Cornish, Alex, Dobbins, Sara, Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, BjĂśrn Nilsson, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert, Riyaz Patel, Keating, Brendan, Sattar, Naveed, Houlston, Richard, Casas, Juan, and Aroon Hingorani
- Abstract
Supplemental figures and study acknowledgments. (PDF 154 kb)
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- 2019
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5. Prognostische Faktoren bei der chronisch lymphatischen Leukämie: Was wird berichtet?
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Bauer, Kathrin, Herbst, Christine, Monsef, Ina, Engert, Andreas, and Elter, Thomas
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Hintergrund: Die chronisch lymphatische Leukämie (CLL) ist eine der häufigsten lymphatischen Krebserkrankungen. Ihr klinischer Verlauf ist auch innerhalb einzelner Stadien sehr unterschiedlich. Neuere biologische und insbesondere zytogenetische Faktoren könnten eine genauere Prognose [for full text, please go to the a.m. URL], EbM – ein Gewinn für die Arzt-Patient-Beziehung?; Forum Medizin 21 der Paracelsus Medizinischen Privatuniversität & 11. EbM-Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin
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- 2010
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6. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
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Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, Van Der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian’an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., De Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O’Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-Van Der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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Genetic association studies ,LDL-cholesterol ,Phenome-wide association scan ,Mendelian randomisation ,Coronary artery disease ,3. Good health ,Research Article - Abstract
Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
7. Cardiac toxicities after treatment of primary Hodgkin's lymphoma (HL). Analysis of the LENT-SOMA questionnaire registered in the database of the German Hodgkin Study Group (GHSG)
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Nogova Lucia, Karolin Behringer, Lihovac Anesa, Diehl Volker, Gilman Elena, Engert Andreas, and Seegenschmiedt M. Heinrich
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Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cardiac arrhythmia ,Cell Biology ,Hematology ,medicine.disease ,Hodgkin's lymphoma ,Biochemistry ,Chemotherapy regimen ,Lymphoma ,Radiation therapy ,Clinical trial ,Heart failure ,Internal medicine ,medicine ,business - Abstract
Introduction: As a consequence of the impressive long-term remission rates in Hodgkin’s Lymphoma (HL), the reduction of treatment-related complications is becoming increasingly important. The most important treatment-related toxicities are secondary malignancies, infertility, pulmonary, thyroid and cardiac dysfunction. Here, we report results of the prospectively planned LENT-SOMA questionnaire to determine cardiac toxicities in patients successfully treated for HL. Patients and methods: Between 1998 and 2002, the GHSG conducted the fourth generation of clinical trials for the treatment of early, intermediate and advanced stage HL (HD 10–12) involving a total of approximately 4000 evaluable patients. The LENT-SOMA questionnaire was sent out to the participating centers 2, 5 and 10 years after randomisation of participating patients to evaluate cardiac, pulmonary, and gonadal dysfunction after HL treatment. To focus on cardiac toxicities, questions referred to cardiac risk factors, subjective and objective cardiac dysfunction, cardiac intervention and therapy. Results: Overall, approximately 1.900 (50%) LENT-SOMA questionnaires after 2 years and 10% LENT-SOMA questionnaires after 5 years were identified. Among all documented toxicities, oedema were most frequently reported, followed by arrythmia, cardiac failure, myocardial ischaemia, cardiomegaly, and pericardial dysfunction. The frequency of cardiac dysfunction will be evaluated according to treatment modality (chemotherapy, chemo- and radiotherapy) and it will be analysed with respect to age, gender, and cardiac risk factors. Furthermore, the amount of patients suffering from more cardiac toxicities and the probability of recovery, once a cardiac dysfunction has been detected, will be presented. Conclusion: Cardiac toxicities after HL treatment include oedema, cardiac failure, myocardial ischaemia, cardiomegaly, arrythmia, and pericardial dysfunction. The first analysis of the LENT-SOMA questionnaire focussing on cardiac dysfunction will be presented.
8. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
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Schmidt, Amand F, Holmes, Michael V, Preiss, David, Swerdlow, Daniel I, Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, Van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, Van Der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pająk, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E, Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S, McCarty, Catherine A, Lester, Kirchner H, Larson, Eric B, Crosslin, David R, De Andrade, Mariza, Roden, Dan M, Denny, Joshua C, Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, Van Der Harst, Pim, Said, M Abdullah, Eppinga, Ruben N, Verweij, Niek, Snieder, Harold, Lifelines Cohort Authors, Christen, Tim, Mook-Kanamori, DO, ICBP Consortium, Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M, Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P, Meade, Tom, Christophersen, Ingrid E, Maitland-Van Der Zee, Anke H, Baranova, Ekaterina V, Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L, Grobbee, Diederick E, Froguel, Philippe, Thuillier, Dorothée, Roussel, Ronan, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C, Seshadri, Sudha, METASTROKE Consortium Of The ISGC, Dale, Caroline, Costa, Rui Providencia E, Ridker, Paul M, Chasman, Daniel I, Reiner, Alex P, Ritchie, Marylyn D, Lange, Leslie A, Cornish, Alex J, Dobbins, Sara E, Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Björn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W, Patel, Riyaz S, Keating, Brendan J, Sattar, Naveed, Houlston, Richard, Casas, Juan P, and Hingorani, Aroon D
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Genetic association studies ,Serine Proteinase Inhibitors ,Anticholesteremic Agents ,PCSK9 Inhibitors ,Myocardial Infarction ,Down-Regulation ,Cholesterol, LDL ,Polymorphism, Single Nucleotide ,Risk Assessment ,3. Good health ,Brain Ischemia ,Stroke ,Treatment Outcome ,Risk Factors ,LDL-cholesterol ,Humans ,Phenome-wide association scan ,Proprotein Convertase 9 ,Mendelian randomisation ,Biomarkers ,Dyslipidemias ,Genome-Wide Association Study ,Randomized Controlled Trials as Topic - Abstract
BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
9. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial
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Marek Trneny, John M. Timmerman, Andreas Engert, Azra H. Ligon, Voravit Ratanatharathorn, Graham P. Collins, Stephen M. Ansell, Armando Santoro, Anas Younes, John Kuruvilla, Benedetto Farsaci, Michelle A. Fanale, Margaretha G.M. Roemer, Pier Luigi Zinzani, Margaret A. Shipp, Kerry J. Savage, Philippe Armand, Scott J. Rodig, Kazunobu Kato, Jonathon B. Cohen, Susan M. Parker, Younes, Ana, Santoro, Armando, Shipp, Margaret, Zinzani, PIER LUIGI, Timmerman, John M, Ansell, Stephen, Armand, Philippe, Fanale, Michelle, Ratanatharathorn, Voravit, Kuruvilla, John, Cohen, Jonathon B, Collins, Graham, Savage, Kerry J, Trneny, Marek, Kato, Kazunobu, Farsaci, Benedetto, Parker, Susan M, Rodig, Scott, Roemer, Margaretha G. M, Ligon, Azra H, and Engert, Andreas
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Adult ,Male ,PD-L1 ,medicine.medical_specialty ,Immunoconjugates ,Salvage therapy ,Antineoplastic Agents ,Transplantation, Autologous ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,checkpoint inhibition ,Internal medicine ,PD-1 ,medicine ,Clinical endpoint ,Refractory Hodgkin Lymphoma ,Humans ,Brentuximab vedotin ,Survival rate ,Neoplasm Staging ,Brentuximab Vedotin ,Salvage Therapy ,nivolumab ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Hodgkin Disease ,3. Good health ,Surgery ,Survival Rate ,Transplantation ,Oncology ,030220 oncology & carcinogenesis ,Female ,immunotherapy ,Neoplasm Recurrence, Local ,Nivolumab ,business ,Hodgkin lymphoma ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Summary Background Malignant cells of classical Hodgkin's lymphoma are characterised by genetic alterations at the 9p24.1 locus, leading to overexpression of PD-1 ligands and evasion of immune surveillance. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed and refractory classical Hodgkin's lymphoma, with an acceptable safety profile. We aimed to assess the clinical benefit and safety of nivolumab monotherapy in patients with classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin. Methods In this ongoing, single-arm phase 2 study, adult patients (aged ≥18 years) with recurrent classical Hodgkin's lymphoma who had failed to respond to autologous stem-cell transplantation and had either relapsed after or failed to respond to brentuximab vedotin, and with an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled from 34 hospitals and academic centres across Europe and North America. Patients were given nivolumab intravenously over 60 min at 3 mg/kg every 2 weeks until progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response following a prespecified minimum follow-up period of 6 months, assessed by an independent radiological review committee (IRRC). All patients who received at least one dose of nivolumab were included in the primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02181738. Findings Among 80 treated patients recruited between Aug 26, 2014, and Feb 20, 2015, the median number of previous therapies was four (IQR 4–7). At a median follow-up of 8·9 months (IQR 7·8–9·9), 53 (66·3%, 95% CI 54·8–76·4) of 80 patients achieved an IRRC-assessed objective response. The most common drug-related adverse events (those that occurred in ≥15% of patients) included fatigue (20 [25%] patients), infusion-related reaction (16 [20%]), and rash (13 [16%]). The most common drug-related grade 3 or 4 adverse events were neutropenia (four [5%] patients) and increased lipase concentrations (four [5%]). The most common serious adverse event (any grade) was pyrexia (three [4%] patients). Three patients died during the study; none of these deaths were judged to be treatment related. Interpretation Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin. Therefore, nivolumab might be a new treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Funding Bristol-Myers Squibb.
- Published
- 2016
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