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1673 citation(s) found for "Høst, Christian".

Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status
Feng, Helian , Gusev, Alexander , Wu, Lang , Abu-Full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L. , Antoniou, Antonis C. , Arason, Aðalgeir , Arndt, Volker , Aronson, Kristan J. , Asseryanis, Ella, Auer, Paul L. , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barrowdale, Daniel , Beckmann, Matthias W. , Bermisheva, Marina , Białkowska, Katarzyna , Bogdanova, Natalia , Bojesen, Stig E. , Bolla, Manjeet K. , Borg, Åke , Brauch, Hiltrud , Brenner, Hermann , Brüning, Thomas , Burwinkel, Barbara , Caldés, Trinidad , Canisius, Sander , Campa, Daniele , Carter, Brian D., Castelao, Jose E. , Chang‐Claude, Jenny , Christiansen, Hans , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Cox, Angela , Daly, Mary B., Leeneer, Kim De , Dörk, Thilo , Dwek, Miriam , Eccles, Diana M., Ejlertsen, Bent , Engel, Christoph , Fasching, Peter A. , Flyger, Henrik, Friedman, Eitan , Frost, Debra, Gabrielson, Marike , Ganz, Patricia A. , Gapstur, Susan M. , García‐Closas, Montserrat , Gaudet, Mia M. , Glendon, Gord , Goldberg, Mark S. , Goldgar, David E., González‐Neira, Anna , Greene, Mark H. , Guénel, Pascal , Haiman, Christopher A. , Hamann, Ute, Hake, Christopher R., He, Wei , Heyworth, Jane , Hogervorst, Frans B.L., Hooning, Maartje J. , Hoover, Robert N. , Hopper, John L. , Huang, Guanmengqian, Hulick, Peter J. , Humphreys, Keith , Imyanitov, Evgeny N., Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Jakimovska, Milena , Jakubowska, Anna , James, Paul A. , Janavicius, Ramunas, Jankowitz, Rachel C. , John, Esther M. , Johnson, Nichola , Jung, Audrey , Kiiski, Johanna I. , Konstantopoulou, Irene , Kristensen, Vessela N. , Laitman, Yael , Lambrechts, Diether , Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne , Lindor, Noralane M. , Lindström, Sara, Lo, Wing‐Yee, Loud, Jennifer T. , Makalic, Enes , Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush , Margolin, Sara , Matricardi, Laura , Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons , Menon, Usha , Michailidou, Kyriaki , Kapoor, Pooja M., Montagna, Marco , Moreno, Fernando , Muranen, Taru , Nathanson, Katherine L. , Nevelsteen, Ines, Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Olsson, Håkan , Osório, Ana , Papp, J., Park‐Simon, Tjoung‐Won , Pedersen, Inge Søkilde , Peixoto, Ana , Peterlongo, Paolo , Peto, Julian , Phillips, Kelly‐Anne , Plaseska‐Karanfilska, Dijana , Poppe, Bruce , Pradhan, Nisha , Prajzendanc, Karolina , Punie, Kevin , Pylkäs, Katri , Rantala, Johanna, Rashid, Muhammad Usman , Rennert, Gad , Romero, Atocha , Saloustros, Emmanouil , Sandler, Dale P. , Santos, Catarina , Sawyer, Elinor J. , Schmutzler, Rita K., Schoemaker, Minouk J. , Scott, Rodney J. , Simard, Jacques , Skytte, Anne‐Bine , Soucy, Penny, Spinelli, John J. , Stone, Jennifer , Tapper, William , Taylor, Jack A. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomassen, Mads , Thöne, Kathrin , Thull, Darcy L. , Tollenaar, Rob A.�E.�M. , Torres, Diana , Vachon, Celine M. , Ouweland, Ans M.W. van den, Vega, Ana , Viel, Alessandra , Vieiro‐Balo, Paula, Wang, Qin , Wappenschmidt, Barbara , Weinberg, Clarice R. , Weitzel, Jeffrey N. , Wendt, Camilla, Winqvist, Robert , Yang, Xiaohong R., Easton, Douglas F. , Chenevix‐Trench, Georgia , Durocher, Francine , Eccles, Diana , Janavičius, Ramūnas , Khaw, Kay‐Tee , Lambrechts, Diether , Lindor, Noralane, Dörk, Thilo , Lambrechts, Diether , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Rennert, Gad , Sandler, Dale P , Teixeira, Manuel R , Eccles, Diana , Menon, Usha , Vega, Ana , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , John, Esther M , Konstantopoulou, Irene , Matricardi, Laura , Olopade, Olufunmilayo I , Arndt, Volker , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Muranen, Taru A , Romero, Atocha , Saloustros, Emmanouil , Torres, Diana , García-Closas, Montserrat , Makalic, Enes , Michailidou, Kyriaki , Bogdanova, Natalia V , Taylor, Jack A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Jung, Audrey Y , Gabrielson, Marike , Stone, Jennifer , Pylkäs, Katri , Rashid, Muhammad U , De Leeneer, Kim , Manoukian, Siranoush , Bojesen, Stig E , Schoemaker, Minouk J , Weinberg, Clarice R , Phillips, Kelly-Anne , Terry, Mary Beth , Brauch, Hiltrud , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Paşaniuc, Bogdan , Long, Jirong , Anton‐Culver, Hoda , Arun, Banu , Balmañà, Judith , Barnes, Daniel R. , Behrens, Sabine , Benı́tez, Javier , Blanco, Ana , Blomqvist, Carl , Boeckx, Bram , Bonanni, Bernardo , Borg, Åke , Briceño, Ignacio , Broeks, Annegien , Cai, Qiuyin , Caligo, Maria A. , Campbell, Ian , Carter, Jonathan , Chanock, Stephen Jacob , Chung, Wendy K. , Clarke, Christine L. , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Couch, Fergus J. , Cross, Simon S. , Cybulski, Cezary , Czene, Kamila , Hoya, Miguel de la , Dennis, Joe , Devilee, Peter , Dı́ez, Orland , Domchek, Susan M. , dos‐Santos‐Silva, Isabel , Dunning, Alison M. , Ellberg, Carolina , Eriksson, Mikael , Fletcher, Olivia , Fostira, Florentia , Fritschi, Lin , Garber, Judy E. , García-Sáenz, José Á. , Giles, Graham G. , Godwin, Andrew K. , Goldgar, David E., Gronwald, Jacek , Hall, Per N , Hollestelle, Antoinette , Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Isaacs, Claudine , Vijai, Joseph , Karlan, Beth Y. , Хуснутдинова, Э. К. , Lázaro, Conxi , Leslie, Goska , Lubiński, Jan , Mannermaa, Arto, Martens, John W.M. , Martı́nez, Marı́a Elena , Meindl, Alfons , Kapoor, Pooja M., Miller, Austin , Moserle, Lidia , Mulligan, Anna Marie , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Parsons, Michael T. , Pharoah, Paul D.P. , Presneau, Nadège , Radice, Paolo , Risch, Harvey A. , Robson, Mark E. , Schmidt, Marjanka K. , Schmidt, Daniel F. , Sharma, Priyanka , Shu, Xiao‐Ou , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Swerdlow, Anthony J. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Truong, Thérèse , Tung, Nadine , Vachon, Celine M. , Asperen, Christi J. van , Rensburg, Elizabeth J. van , Yannoukakos, Drakoulis , Ziogas, Argyrios , Milne, Roger L. , Zheng, Wei , Kraft, Peter , Jiang, Xia

Genetic Epidemiology | March 2, 2020 | Volume: 44 | Issue: 5 | Pages: 442-468

10.1002/gepi.22288 | PMID 32115800 Get It

AbstractPrevious transcriptome‐wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome‐wide association studies (GWAS), but analyses of breast cancer subtype‐specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta‐analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case‐only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS‐significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast‐cancer gene in three of six regions harboring multiple TWAS‐significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
Nasal Valve Insufficiency in Dermatologic Surgery
Barbosa, Naiara S. , Baum, Christian L. , Arpey, Christopher J.

Dermatologic Surgery | February 21, 2020 | Volume: 46 | Issue: 7 | Pages: 904-911

10.1097/dss.0000000000002310 | PMID 32079868 Get It

BACKGROUND Few publications have addressed nasal valve (NV) insufficiency as a complication of Mohs micrographic surgery. OBJECTIVE To comprehensively review the literature and further characterize the causes, prevalence, evaluation, and management of NV insufficiency as it relates to cutaneous oncology. MATERIALS AND METHODS A PubMed search was completed to identify articles related to the NV in the context of Mohs micrographic surgery, cutaneous oncology, and reconstruction. RESULTS Nasal valve insufficiency may occur during tumor removal and/or reconstruction. Defect size larger than 1 cm; location on the ala, sidewall, or alar crease; lack of structural support; and poorly planned flaps are the main risk factors for NV insufficiency. Several surgical techniques have been described to avoid and correct this complication. CONCLUSION Nasal valve insufficiency may be an underrecognized and underreported complication of Mohs micrographic surgery. Nasal valve insufficiency may be identified with relatively simple tests. Knowledge of NV anatomy and preoperative function assessment is essential. Recognition of this potential complication and awareness of its prevention and management may decrease morbidity in patients undergoing cutaneous surgery.
Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of Cohort 6 of the COSMIC-021 Study.
Dorff, Tanya B. , Maughan, Benjamin L. , Kelly, William Kevin, Pagliaro, Lance C. , Srinivas, Sandy, Squillante, Christian, Vaishampayan, Ulka N. , Liu, Yingjie , Curran, Dominic, Pal, Sumanta K. , Vaishampayan, Ulka , Agarwal, Neeraj , Loriot, Yohann , McGregor, Bradley A. , Dreicer, Robert , Curran, Dominic , Choueiri, Toni K.

Journal of Clinical Oncology | February 19, 2020 | Volume: 38 | Issue: 6_suppl | Pages: 139-139

10.1200/jco.2020.38.6_suppl.139 Get It

139 Background: C may enhance response to immune checkpoint inhibitors by promoting an immune-permissive microenvironment. COSMIC-021 (NCT03170960), a multinational phase 1b study, is evaluating the combination of C with A in various solid tumors. We report interim results from Cohort 6 in mCRPC. Methods: Eligible pts were required to have radiographic progression in soft tissue after enzalutamide and/or abiraterone, measurable disease, and an ECOG PS of 0 or 1. Prior chemotherapy for mCSPC was permitted. Pts received C 40 mg PO qd and A 1200 mg IV q3w. CT/MRI scans were performed q6w for 52w and q12w thereafter. Bone scans were performed q12w. The primary endpoint is ORR per RECIST 1.1. Other endpoints include safety, ORR per irRECIST, duration of response (DOR), PFS, and OS. Results: As of Oct 2019, 44 mCRPC pts were enrolled with a median follow-up of 10.6 mo (range 3.4+, 17.9). Median age was 70 y (range 49, 90), 50% had ECOG PS 1, 34% had visceral metastases, and 61% had extrapelvic lymph node metastases. 27% of pts had prior docetaxel and 52% had ≥2 prior novel hormonal therapies. The most common any grade TEAEs were fatigue (57%), nausea (48%), decreased appetite (45%), diarrhea (39%), PPE (32%), and vomiting (32%). One Grade 5 TRAE of dehydration was reported in a 90 y/o. Median duration of treatment was 5.3 mo. The ORR per RECIST 1.1 among all pts was 32% (2 CRs [4.5%] and 12 PRs [27%]); 21 (48%) pts had SD giving a disease control rate of 80% in all pts. One pt with initial PD per RECIST 1.1 had an irPR per irRECIST. ORR per RECIST 1.1 was 33% in 36 pts with high-risk clinical features (visceral and/or extrapelvic lymph node metastases). Median DOR for all pts with response per RECIST 1.1 was 8.3 mo (range 1.38+, 9.76+). In 12 responders with at least 1 post-baseline PSA evaluation, 8 (67%) had a PSA decline ≥50%. Conclusions: The combination of C+A had a tolerable safety profile and demonstrated clinically meaningful activity with durable responses in men with mCRPC. Given the encouraging activity in these pts, especially in those with visceral and/or extra pelvic lymph node metastases, further evaluation of C+A in men with mCRPC is being pursued. Clinical trial information: NCT03170960.
Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies
Munn‐Chernoff, Melissa A. , Chou, Yi‐Ling, Coleman, Jonathan R. I. , Thornton, Laura M. , Walters, Raymond K. , Yılmaz, Zeynep , Baker, Jessica H. , Hübel, Christopher , Medland, Sarah E. , Hinney, Anke , Leppä, Virpi , Mattheisen, Manuel , Ripke, Stephan , Yao, Shuyang , Giusti‐Rodríguez, Paola , Hanscombe, Ken B. , Adan, Roger A.H. , Ando, Tetsuya , Berrettini, Wade H., Boehm, Ilka , Boni, Claudette, Perica, Vesna Boraska , Buehren, Katharina, Burghardt, Roland , Cassina, Matteo , Cichon, Sven , Clementi, Maurizio , Courtet, Philippe, Crowley, James J. , Danner, Unna N. , Davis, Oliver S. P. , Zwaan, Martina de, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dikeos, Dimitris, Dina, Christian , Dmitrzak‐Węglarz, Monika , Docampo, Elisa, Duncan, Laramie E. , Egberts, Karin , Ehrlich, Stefan , Escaramís, Geòrgia, Estivill, Xavier , Farmer, Anne, Favaro, Angela , Fernández‐Aranda, Fernando , Fichter, Manfred M., Fischer, Krista , Föcker, Manuel , Foretová, Lenka , Forstner, Andreas J. , Franklin, Christopher S., Gallinger, Steven , Giegling, Ina , Giuranna, Johanna, Gonidakis, Fragiskos , Gorwood, Philip , Mayora, Monica Gratacos, Guo, Yiran , Håkonarson, Håkon , Hatzikotoulas, Konstantinos , Hebebrand, Johannes , Helder, Sietske G., Herpertz‐Dahlmann, Beate, Herzog, Wolfgang , Huckins, Laura M. , Hudson, James I. , Imgart, Hartmut , Inoko, Hidetoshi , Janout, Vladimí­r , Jiménez‐Múrcia, Susana , Kalsi, Gursharan , Kaminská, Deborah , Karwautz, Andreas , Kas, Martien J. , Keski‐Rahkonen, Anna , Kiezebrink, Kirsty , Kim, Youl‐Ri , Klump, Kelly L. , Knudsen, Gun Peggy , Via, Maria C. La, Hellard, Stéphanie Le , Levitan, Robert D., Lilenfeld, Lisa , Lin, Bochao , Lissowska, Jolanta , Luykx, Jurjen J. , Magistretti, Pierre J. , Maj, Mario , Männik, Katrin , Marsal, Sara , Marshall, Christian R. , McDevitt, Sara , McGuffin, Peter, Meulenbelt, Ingrid, Navratilova, Marie, Ντάλλα, Ιωάννα , O’Toole, Julie K., Padyukov, Leonid , Palotie, Aarno , Pantel, Jacques , Papežová, Hana , Pinto, Dalila , Rabionet, Raquel , Raevuori, Anu , Ramoz, Nicolás , Reichborn‐Kjennerud, Ted , Ricca, Valdo , Ritschel, Franziska , Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip , Scherer, Stephen W. , Schmidt, Ulrike , Schork, Nicholas J. , Schosser, Alexandra , Šlachtová, Lenka , Landt, M , Slopien, Agnieszka, Sorbi, Sandro , Świątkowska, Beata , Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso , Tozzi, Federica, Treasure, Janet , Tziouvas, Konstantinos , Elburg, Annemarie , Furth, Eric F. van , Wagner, Gudrun , Walton, Esther , Widén, Elisabeth , Zerwas, Stephanie , Zipfel, Stephan, Bergen, Andrew W. , Brandt, Harry, Crawford, Steven , Halmi, Katherine A. , Johnson, Craig, Kaplan, Allan S. , Kaye, Walter H. , Mitchell, James E. , Olsen, Catherine M. , Pedersen, Nancy L. , Strober, Michael, Whiteman, David C. , Woodside, D. Blake , Grove, Jakob , Henders, Anjali K. , Larsen, Janne Tidselbak , Petersen, Liselotte , Jordan, Jennifer , Kennedy, Martin A. , Birgegård, Andreas , Landén, Mikael , Polimanti, Renato , McClintick, Jeanette N. , Adkins, Amy , Alıev, Fazil , Bacanu, Silviu‐Alin , Batzler, Anthony , Bertelsen, Sarah , Chen, Li‐Shiun , Degenhardt, Franziska , Docherty, Anna R. , Edwards, Alexis C. , Foo, Jerome C. , Fox, Louis , Frank, Josef , Hack, Laura M. , Hartmann, Annette M. , Hartz, Sarah M. , Hodgkinson, Colin A. , Hottenga, Jouke‐Jan, Konte, Bettina , Lahti, Jari , Lahti‐Pulkkinen, Marius , Ligthart, Lannie , Loukola, Anu , Maher, Brion S. , Mbarek, Hamdi , McIntosh, Andrew M. , McQueen, Matthew B. , Meyers, Jacquelyn L. , Milaneschi, Yuri , Palviainen, Teemu , Ryu, Euijung , Saccone, Nancy L. , Salvatore, Jessica E. , Streit, Fabian , Wang, Jen‐Chyong , Webb, Bradley T. , Wetherill, Leah , Wills, Amanda G. , Zhou, Hang , Boardman, Jason D., Chen, Danfeng , Copeland, William , Culverhouse, Robert , Dahmen, Norbert, Domingue, Benjamin W. , Frye, Mark A. , Gäebel, Wolfgang , Ising, Marcus, Keyes, Margaret A., Kiefer, Falk , Koller, Gabriele , Kuperman, Samuel , Lucae, Susanne , Lynskey, Michael T. , Maier, Wolfgang , Müller‐Myhsok, Bertram , Preuss, Ulrich W. , Räikkönen, Katri , Reynolds, Maureen , Ridinger, Monika , Schuckit, Marc A. , Soyka, Michael , Wodarz, Norbert , Zill, Peter , Adkins, Daniel E. , Bucholz, Kathleen K. , Diazgranados, Nancy , Goate, Alison , Goldman, David , Hancock, Dana B. , Hewitt, John K. , Johnson, Eric O. , Krauter, Kenneth , Lind, Penelope A. , McGue, Matt , MacKillop, James , Madden, Pamela A. F. , Maes, Hermine H. , Magnusson, Patrik K. E. , Nelson, Elliot C. , Nöthen, Markus M. , Penninx, Brenda W.J.H. , Porjesz, Bernice , Rice, John P. , Rose, Richard J. , Shen, Pei‐Hong , Silberg, Judy L. , Tarter, Ralph E. , Vrieze, Scott , Zhao, Hongyu , Neale, Benjamin M. , Wade, Tracey , Sullivan, Patrick F., Kaprio, Jaakko , Breen, Gerome , Hottenga, Jouke‐Jan , Hakonarson, Hakon , Lissowska, Jolanta , Kennedy, Martin A , Ehrlich, Stefan , Hottenga, Jouke-Jan , Walton, Esther , Cichon, Sven , Luykx, Jurjen J , Nöthen, Markus M , Le Hellard, Stephanie , Penninx, Brenda W J H , Medland, Sarah E , Rabionet, Raquel , Estivil, Xavier , Padyukov, Leonid , Świątkowska, Beata , Dina, Christian , Palotie, Aarno V. , Ripke, Stephan , Whiteman, David C , Scherer, Stephen W , Tortorella, Alfonso , Streit, Fabian , Egberts, Karin , Goate, Alison M , Docherty, Anna R , Johnson, Eric O , Coleman, Jonathan Ri , Johnson, Emma C. , Gordon, Scott D. , Watson, Hunna J. , Gaspar, Héléna A. , Bryois, Julien , Alfredsson, Lars , Andreassen, Ole A. , Boehm, Ilka , Cone, Roger D. , Courtet, Philippe , Crow, Scott J. , Dedoussis, George , Dick, Danielle M. , Dikeos, Dimitris , Escaramís, Geòrgia , Esko, Tõnu , Forzan, Monica , Guillaume, Sébastien , Hauser, Joanna , Herms, Stefan , Herpertz-Dahlmann, Beate , Julià, Antonio , Karhunen, Leila J. , Kennedy, James L. , Li, Dong , Mattingsdal, Morten , Metspalu, Andres , Micali, Nadia , Mitchell, Karen S. , Monteleone, Alessio Maria , Monteleone, Palmiero , Nacmias, Benedetta , Ophoff, Roel A. , Ripatti, Samuli , Roberts, Marion , Santonastaso, Paolo , Scherag, André , Seitz, Jochen , Slagboom, P. Eline , Tenconi, Elena , Τσίτσικα, Άρτεμις , Tyszkiewicz‐Nwafor, Marta , Zeggini, Eleftheria , Boden, Joseph M. , Horwood, L. John , Pearson, John F , Werge, Thomas Mears , Parker, Richard , Lichtenstein, Paul , Norring, Claes E. A. , Mortensen, Preben Bo , Biernacka, Joanna M. , Bigdeli, Tim B. , Clarke, Toni‐Kim , Heilmann‐Heimbach, Stefanie , Hoffmann, Per , Lai, Dongbing , Peterson, Roseann Elizabeth , Sanchez-Roige, Sandra , Schwandt, Melanie L. , Sherva, Richard , Strohmaier, Jana , Thomas, Nathaniel , Wedow, Robbee , Boardman, Jason D., Choi, Doo‐Sup , Degenhardt, Louisa J , Hayward, Caroline , Kramer, John R. , Mann, Karl F , Männistö, Satu , Murray, Alison D. , Nurnberger, John I , Scherbaum, Norbert , Treutlein, Jens , Witt, Stephanie H. , Boomsma, Dorret I , Bierut, Laura Jean , Brown, Sandra A. , Costello, E. Jane , Wit, Harriet de , Eriksson, Johan G. , Farrer, Lindsay A. , Foroud, Tatiana , Gillespie, Nathan A. , Grucza, Richard A. , Harris, Kathleen Mullan , HESSELBROCK, VICTOR M. , Hopfer, Christian Jean , Iacono, William G. , Karpyak, Victor M. , Kendler, Kenneth S. , Kranzler, Henry R. , Palmer, Abraham A. , Rietschel, Marcella , Riley, Brien P. , Stallings, Michael C. , Vanyukov, Michael M. , Wall, Tamara L. , Whitfield, John B. , Heath, Andrew C. , Montgomery, Grant W. , Martin, Nicholas G. , Gelernter, Joel E. , Edenberg, Howard J , Bulik, Cynthia Marie , Agrawal, Arpana , Webb, Bradley T.

Addiction Biology | February 17, 2020 | Volume: 26 | Issue: 1 | Pages: No page available

10.1111/adb.12880 | PMID 32064741 Get It

Abstract Eating disorders and substance use disorders frequently co‐occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [ r g ], twin‐based = 0.23‐0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome‐wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance‐use‐related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism‐based genetic correlations between eating disorder‐ and substance‐use‐related phenotypes. Significant positive genetic associations emerged between AUD and AN ( r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN ( r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating ( r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating ( r gs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co‐varying for major depressive disorder loci. The patterns of association between eating disorder‐ and substance‐use‐related phenotypes highlights the potentially complex and substance‐specific relationships among these behaviors.
Heart Rate Recovery After Exercise Is Associated With Arrhythmic Events in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Lieve, Krystien V.V. , Dusi, Veronica , Werf, Christian van der , Bos, J. Martijn , Lane, Conor M. , Stokke, Mathis K. , Roston, Thomas M. , Djupsjöbacka, Aurora, Bundgaard, Henning , Rosés‐Noguer, Ferran , Semsarian, Christopher , Robyns, Tomas , Hofman, Nynke , Tanck, Michael W.T. , Berg, Maarten P. van den , Kammeraad, Janneke A.E. , Clur, Sally-Ann B., Sacher, Frédéric , Till, Jan , Skinner, Jonathan R. , Tfelt‐Hansen, Jacob , Horie, Minoru , Swan, Heikki, Roberts, Jason D. , Sanatani, Shubhayan , Haugaa, Kristina H. , Ackerman, Michael J. , Horie, Minoru , Bos, Johan M , Tanck, Michael , Tfelt-Hansen, Jacob , Skinner, Jonathan R , van den Berg, Maarten P , Robyns, Tomas , Haugaa, Kristina , Sanatani, Shubhayan , van der Werf, Christian , Rosés-Noguer, Ferran , Bundgaard, Henning , Lieve, Krystien V , Dusi, Veronica , Wada, Yuko , Denjoy, Isabelle , Krahn, Andrew D. , Clur, Sally‐Ann B. , Probst, Vincent , Leenhardt, Antoine , Schwartz, Peter J. , Semsarian, Christopher

Circulation: Arrhythmia and Electrophysiology | February 16, 2020 | Volume: 13 | Issue: 3 | Pages: No page available

10.1161/circep.119.007471 | PMID 32063070 Get It

Background: Risk stratification in catecholaminergic polymorphic ventricular tachycardia remains ill defined. Heart rate recovery (HRR) immediately after exercise is regulated by autonomic reflexes, particularly vagal tone, and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. Our objective was to evaluate whether HRR after maximal exercise on the exercise stress test (EST) is associated with symptoms and ventricular arrhythmias. Methods: In this retrospective observational study, we included patients ≤65 years of age with an EST without antiarrhythmic drugs who attained at least 80% of their age- and sex-predicted maximal HR. HRR in the recovery phase was calculated as the difference in heart rate (HR) at maximal exercise and at 1 minute in the recovery phase (ΔHRR1′). Results: We included 187 patients (median age, 36 years; 68 [36%] symptomatic before diagnosis). Pre-EST HR and maximal HR were equal among symptomatic and asymptomatic patients. Patients who were symptomatic before diagnosis had a greater ΔHRR1′ after maximal exercise (43 [interquartile range, 25–58] versus 25 [interquartile range, 19–34] beats/min; P <0.001). Corrected for age, sex, and relatedness, patients in the upper tertile for ΔHRR1′ had an odds ratio of 3.4 (95% CI, 1.6–7.4) of being symptomatic before diagnosis ( P <0.001). In addition, ΔHRR1′ was higher in patients with complex ventricular arrhythmias at EST off antiarrhythmic drugs (33 [interquartile range, 22–48] versus 27 [interquartile range, 20–36] beats/min; P =0.01). After diagnosis, patients with a ΔHRR1′ in the upper tertile of its distribution had significantly more arrhythmic events as compared with patients in the other tertiles ( P =0.045). Conclusions: Catecholaminergic polymorphic ventricular tachycardia patients with a larger HRR following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during the first EST off antiarrhythmic drug.
Brentuximab Vedotin and Nivolumab for Relapsed or Refractory Classic Hodgkin Lymphoma: Long-Term Follow-up Results from the Single-Arm Phase 1/2 Study
Moskowitz, Alison J. , Advani, Ranjana H. , Ramchandren, Radhakrishnan , Feldman, Tatyana , LaCasce, Ann S. , Christian, Beth , Ansell, Stephen M. , Moskowitz, Craig H. , Brown, Lisa , Ansari, Sahar , Zak, Daniel E. , Sacchi, Mariana, Manley, Thomas, Herrera, Alex F. , Advani, Ranjana H , Bartlett, Nancy L. , Vose, Julie M. , Taft, David R. , Ansari, Sahar

Blood | February 14, 2020 | Volume: 134 | Issue: Supplement_1 | Pages: 238-238

10.1182/blood-2019-122576 Get It

Introduction Brentuximab vedotin (BV) targets CD30, a receptor expressed on the Reed-Sternberg cells of classic Hodgkin lymphoma (cHL). Nivolumab (Nivo) restores antitumor immunity by blocking the PD-1 receptor on activated T-cells. In this phase 1/2 study, combination treatment (tx) with BV + Nivo demonstrated durable efficacy in patients (pts) with relapsed/refractory (R/R) cHL (Herrera, Blood 2018; NCT02572167). Biomarkers consistent with innate and adaptive immune activation were observed in the peripheral blood of pts treated with the combination regimen. Herein, we associate biomarkers in the peripheral blood with clinical response, and present follow-up results for pts who received BV + Nivo under staggered and concurrent dosing schedules. Methods Enrolled pts had cHL that relapsed or was refractory to frontline chemotherapy. In Parts 1 and 2 (staggered dosing), pts received up to 4 cycles of BV 1.8 mg/kg and Nivo 3.0 mg/kg given on Days 1 and 8 of Cycle 1, respectively, and together on Day 1 of Cycles 2-4. Pts in Part 3 (concurrent dosing) received the same dose of both agents on Day 1 of all 4 cycles. After investigators assessed response (Cheson 2014, with the incorporation of LYRIC [Cheson 2016] for pts in Part 3), pts could undergo ASCT. Results Demographics and baseline characteristics were similar across all treated pts (N=91) in the staggered and concurrent dosing cohorts; median age 34 years (yrs, range; 18-69), 42% with primary refractory disease, and 30% with relapse within 1 yr of frontline therapy. All 91 pts are off-tx and have been observed through the 100-day safety reporting period. A total of 86 pts (92%) completed all 4 cycles of BV + Nivo. Early tx discontinuations were due to; AE (peripheral neuropathy and increased GGT [1 pt each]), progressive disease (PD), investigator decision, and pt decision (1 pt each). Most common AEs prior to ASCT or additional salvage therapy were nausea (52%) and infusion-related reactions (IRRs, 43%). Excluding IRRs, 14% of pts had immune-related AEs requiring tx with systemic steroids, including rash (8%), pneumonitis (4%), and AST increased, diarrhea, and Guillain-Barre syndrome (1% each). The ORR for all-treated pts was 85%, with 67% complete response (CR). A total of 67 pts (74%) underwent ASCT after tx with BV + Nivo. There were 22 pts who received additional salvage therapy after BV + Nivo (7 PD, 6 partial response, 5 stable disease, and 4 CR at EOT), 17 of whom later underwent ASCT. At a median of 22.6 months (range; 1.2, 41.2) from the start of tx, the estimated 2-yr PFS rate in all treated pts was 78%, and for pts who underwent ASCT after tx with BV + Nivo was 91% (Figure 1). At 2 years, the estimated OS rate for all treated pts was 93%. Staggered and concurrent dosing of BV + Nivo resulted in increased levels of activated and dividing CD4+ T cells, activated and dividing CD8+ T cells (concurrent dosing-only), regulatory T cells (Tregs), and circulating plasmablasts in blood. We did not observe any associations between the magnitude of these changes and clinical response. Pts with CR exhibited trends for higher pre-tx blood levels of CD30+ Tregs and CD30+ Th subsets compared to pts without CR, suggesting BV depletion of these populations may have a role in the clinical mode of action of BV + Nivo. Although pre-tx levels of cytotoxic lymphocytes (CTLs) in blood did not differentiate pts with CR from other pts, pts in the lower quartile of pre-tx CTL levels showed significantly shorter PFS than other pts, suggesting a potential association between CTLs and disease control. Changes in blood cytokine and chemokine levels were observed after BV + Nivo, including increased levels of IL-18, IP-10, I-TAC, and sCD30, and decreased levels of TARC, IL-2Ra, and IL-6. Our analyses support strong correlations between pre-tx cytokine/chemokine levels and clinical benefit including trends linking lower pre-tx levels of IL-18, I-TAC, and IL-2RA to achieving CR and longer PFS. Conclusion BV + Nivo, both staggered and current dosing, showed tolerability and high CR rates with durable remissions among pts with R/R cHL. Analysis of blood biomarkers identified trends potentially linking baseline levels of CD30+ immune cells and the baseline pt inflammatory state with the activity of BV + Nivo. Together, these encouraging results support further investigation of BV + Nivo as initial salvage therapy in pts with R/R cHL. Figure 1 Disclosures Moskowitz: Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Merck: Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Incyte: Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding. Advani:Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Forty-Seven: Research Funding; Infinity Pharma: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Merck: Research Funding; Kura: Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agensys: Research Funding; Cell Medica, Ltd: Consultancy; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Millennium: Research Funding; Janssen: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bartlett:Affimed Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Dynavax: Research Funding; Forty-Seven: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medimmune: Research Funding; Merck: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vose:Acerta Pharma: Honoraria, Other: Grants, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Incyte Corporation: Research Funding; Kite Pharma: Honoraria, Other: Grants, Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; AbbVie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Legend Pharmaceuticals: Honoraria. Ramchandren:Genentech: Research Funding; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Pharmacyclics LLC, an Abbvie company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sandoz-Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Feldman:Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding. LaCasce:BMS: Consultancy; Research to Practice: Speakers Bureau; Humanigen: Consultancy; Seattle Genetics: Consultancy, Research Funding. Christian:Bristol-Myers Squibb: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cephalon: Research Funding; Janssen: Research Funding; Immunomedics: Research Funding; Celgene: Research Funding; Acerta: Research Funding; Triphase: Research Funding; Millennium Pharmaceuticals Inc: Research Funding; Merck: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding. Moskowitz:ADC Therapeutics: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Research Funding. Brown:Seattle Genetics, Inc.: Employment, Equity Ownership. Taft:Seattle Genetics, Inc.: Employment, Equity Ownership. Ansari:Seattle Genetics, Inc.: Employment, Equity Ownership. Zak:Seattle Genetics, Inc.: Employment, Equity Ownership. Sacchi:Seattle Genetics, Inc.: Research Funding. Manley:Seattle Genetics: Employment, Equity Ownership. Herrera:Merck: Consultancy, Research Funding; AstraZeneca: Research Funding; Adaptive Biotechnologies: Consultancy; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.
Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment
Goadsby, Peter J. , Lucas, Christian , Bardos, Jennifer, Martinez, James M. , Zhou, Chunmei, Aurora, Sheena K. , Yang, Jyun Yan, Conley, Robert R., Oakes, Tina M. , Goadsby, Peter J , Dodick, David W. , Jensen, Rigmor

Cephalalgia | February 13, 2020 | Volume: 40 | Issue: 9 | Pages: 935-948

10.1177/0333102420905321 | PMID 32050782 Get It

Objective To report efficacy and safety of galcanezumab in adults with chronic cluster headache. Background Galcanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide and inhibits its biological activity. Methods This study comprised a prospective baseline period, a 12-week double-blind, placebo-controlled treatment period, and a 52-week open-label period. Up to six protocol-specified concomitant preventive medications were allowed if patients were on a stable dose for 2 months prior to the prospective baseline period. Patients were randomized 1:1 to monthly subcutaneous galcanezumab (300 mg) or placebo. The primary endpoint was overall mean change from baseline in weekly attack frequency with galcanezumab compared to placebo. Key secondary endpoints were ≥50% response rate and percentage of patients meeting sustained response. Results from the double-blind treatment period are reported. Results A total of 237 patients were randomized and treated (120 placebo; 117 galcanezumab). At baseline, the mean age was 45 years and 63% were using ≥1 preventive drug. The primary endpoint was not met; mean change in weekly attack frequency was −4.6 placebo versus −5.4 galcanezumab ( p = 0.334). Key secondary endpoints also were not met. Injection site-related treatment-emergent adverse events were more common in the galcanezumab than the placebo group, with significantly more injection site erythema. Conclusion Treatment with galcanezumab 300 mg did not achieve its primary and key secondary endpoints. This study underscores the potential distinct biology of cCH as well as the significant unmet need for safe, effective, and well-tolerated preventive treatment. The safety profile of galcanezumab in cCH is consistent with that observed in trials of episodic CH and migraine. Trial registration NCT02438826; https://www.clinicaltrials.gov/ct2/show/NCT02438826 .
Signs of Increased Intrapericardial Pressure on Chest Computed Tomography
Rojas, Carlos, Padilla, Gary, Feldhaus, Jacob M., Rajan, Celin, Shapiro, Brian P. , Mergo, Patricia J. , Livingston, David H. , Bowman, Andrew W.

Journal of Thoracic Imaging | February 7, 2020 | Volume: 35 | Issue: 3 | Pages: 143-152

10.1097/rti.0000000000000475 | PMID 32073542 Get It

We sought to describe incidental imaging features of increased intrapericardial pressure due to pericardial effusion on chest computed tomography (CT) and correlate them with cardiac CT, cardiac magnetic resonance imaging, and echocardiography. It is important for the radiologist to become familiar with imaging findings of increased intrapericardial pressure in the setting of pericardial effusion when identified on chest CT. Recognizing the imaging findings of increased intrapericardial pressure can better guide the care of these patients.
Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis
Atkinson, Stephen R. , Hamesch, Karim , Spivak, Igor , Güldiken, Nurdan , Argemí, Josepmaria , Zoller, Heinz , Cao, Sheng , Mathurin, Philippe , Shah, Vijay H. , Trautwein, Christian, Thursz, Mark , Cabezas, Joaquín , Theurl, Igor , Bataller, Ramon A , Strnad, Pavel

American Journal of Gastroenterology | January 24, 2020 | Volume: 115 | Issue: 3 | Pages: 398-405

10.14309/ajg.0000000000000492 | PMID 31985531 Get It

OBJECTIVES: Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH. METHODS: Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628). RESULTS: Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67–0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61–0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non–transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively). DISCUSSION: In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.
Brush with Death: A Social History of Lead Poisoning. Christian Warren. Baltimore, MD: The Johns Hopkins University Press, 2000, 370 pp., $45.00, hardcover. ISBN 0-8018-6289-2.
Moyer, Thomas P.

Clinical Chemistry | January 24, 2020 | Volume: 48 | Issue: 1 | Pages: 210-210

10.1093/clinchem/48.1.210 Get It