☆ 4.8 Article

Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

CANCER RESEARCH (2020)

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Journal

CANCER RESEARCH
Volume 80, Issue 18, Pages 4004-4013

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-20-0447

Keywords

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Categories

Oncology

Funding

  1. Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI, NIH
  2. NCI at the NIH [5R01CA098870, R03 CA123546-02, U10 CA37429, UM1 CA182883]
  3. Ministry of Health of the Czech Republic [NR 9029-4/2006, NR9422-3, MH CZDRO-MMCI 00209805, NR9998-3]
  4. NCI [P50CA062924, R01CA97075, P30 CA006973]
  5. Lustgarten Foundation
  6. Sol Goldman Pancreas Cancer Research Center
  7. NCI, NIH [HHSN261200800001E, RO1 CA154823]
  8. Mayo Clinic SPORE in Pancreatic Cancer [P50 CA102701]
  9. Geoffrey Beene Foundation
  10. Arnold and Arlene Goldstein Family Foundation
  11. Society of MSKCC
  12. National Health and Medical Research Council of Australia (NHMRC) [442302, 1060183]
  13. NIH-NCI [R01CA1009767, R01CA109767-S1, R01CA059706]
  14. Joan Rombauer Pancreatic Cancer Fund
  15. California Department of Public Health as part of the statewide cancer reporting program
  16. NCI's SEER Program [HSN261201000140C]
  17. CDC's National Program of Cancer Registries [U58DP003862-01]
  18. Czech Science Foundation [P301/12/1734]
  19. Internal Grant Agency of the Czech Ministry of Health [IGA NT 13 263]
  20. Baden-Wuurttemberg State Ministry of Research, Science and Arts
  21. Heidelberger EPZ-Pancobank (Heidelberger Stiftung Chirurgie)
  22. Heidelberger EPZ-Pancobank (BMBF) [01GS08114]
  23. 5 x 1000 voluntary contribution of the Italian Government
  24. Italian Ministry of Health [RC1203GA57, RC1303GA53, RC1303GA54, RC1303GA50]
  25. Italian Association for Research on Cancer (AIRC) [12182]
  26. Italian FIMP-Ministry of Health [12 CUP_J33G13000210001]
  27. National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, UK
  28. American Cancer Society
  29. Centers for Disease Control and Prevention's National Program of Cancer Registries
  30. NCI's Surveillance Epidemiology and End Results Program
  31. Maryland Cigarette Restitution Fund
  32. National Program of Cancer Registries of the Centers for Disease Control and Prevention
  33. Australian National Health and Medical Research Council [209057, 396414, 1074383]
  34. Cancer Council Victoria
  35. VicHealth
  36. Instituto de Salud Carlos III-FEDER, Spain
  37. Fondo de Investigaciones Sanitarias (FIS) [PI13/00082, PI15/01573]
  38. Red Tematica de Investigacion Cooperativa en Cancer, Spain [RD12/0036/0050]
  39. European Cooperation in Science and Technology (COST Action) [BM1204: EU_Pancreas]
  40. Ministerio de Ciencia y Tecnologia [CICYT SAF 2000-0097]
  41. Fondo de Investigacion Sanitaria, Madrid, Spain [95/0017]
  42. Generalitat de Catalunya (CIRIT - SGR)
  43. 'Red tematica de investigacion cooperativa de centros en Cancer' [C03/10]
  44. Red tematica de investigacion cooperativa de centros en Epidemiologia y salud publica' [C03/09]
  45. CIBER de Epidemiologia (CIBERESP), Madrid
  46. NIH [CA63464, CA54281, CA098758, CA132839, CA164973, CA-047988, CA-182913, HL-043851, HL-080467, HL-099355, UM1 CA182934, P30 CA016087, P30 ES000260, CA-097193, CA-34944, CA-40360, HL-26490, HL-34595]
  47. NIH grant from the NCI [CA63464, CA54281, CA098758, CA132839, CA164973, UM1 CA167552, UM1 CA186107, P01 CA87969, R01 CA49449]
  48. Hale Center for Pancreatic Cancer Research
  49. United States Department of Defense [CA130288]
  50. Pancreatic Cancer Action Network
  51. Noble Effort Fund
  52. Peter R. Leavitt Family Fund
  53. Wexler Family Fund
  54. Promises for Purple
  55. Broman Family Fund for Pancreatic Cancer Research
  56. Bob Parsons Fellowship
  57. National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]
  58. Common Fund of the Office of the Director of the NIH
  59. NCI
  60. NHGRI
  61. NHLBI
  62. NIDA
  63. NIMH
  64. NINDS
  65. State of Maryland
  66. Italian Ministry of Research [FIRB - RBAP10AHJB]
  67. BMBH (BMBF) [01EY1101]
  68. [P30CA008748]
  69. NATIONAL CANCER INSTITUTE [ZIACP010193] Funding Source: NIH RePORTER

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Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (+/- 500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 x 10(-6), respectively). After excluding the 20 PDAC susceptibility regions (+/- 500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. Significance: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

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Hanif, Sari Hantunen, Jie Hao, Carla Meneses Hardman, Rachakulla Hari Kumar, Tina Harmer Lassen, Javad Harooni, Seyed Mohammad Hashemi-Shahri, Maria Hassapidou, Jun Hata, Teresa Haugsgjerd, Alison J. Hayes, Jiang He, Yuan He, Yuna He, Regina Heidinger-Felso, Margit Heier, Tatjana Hejgaard, Marleen Elisabeth Hendriks, Rafael dos Santos Henrique, Ana Henriques, Leticia Hernandez Cadena, Sauli Herrala, Marianella Herrera-Cuenca, Victor M. Herrera, Isabelle Herter-Aeberli, Karl-Heinz Herzig, Ramin Heshmat, Allan G. Hill, Sai Yin Ho, Suzanne C. Ho, Michael Hobbs, Doroteia A. Hofelmann, Michelle Holdsworth, Reza Homayounfar, Clara Homs, Wilma M. Hopman, Andrea R. V. R. Horimoto, Claudia M. Hormiga, Bernardo L. Horta, Leila Houti, Christina Howitt, Thein Thein Htay, Aung Soe Htet, Maung Maung Than Htike, Yonghua Hu, Jose Maria Huerta, Ilpo Tapani Huhtaniemi, Laetitia Huiart, Constanta Huidumac Petrescu, Martijn Huisman, Abdullatif Husseini, Chinh Nguyen Huu, Inge Huybrechts, Nahla Hwalla, Jolanda Hyska, Licia Iacoviello, Ellina M. Iakupova, Jesus M. Ibarluzea, Mohsen M. Ibrahim, Norazizah Ibrahim Wong, M. Arfan Ikram, Carmen Iniguez, Violeta Iotova, Vilma E. Irazola, Takafumi Ishida, Godsent C. Isiguzo, Muhammad Islam, Sheikh Mohammed Shariful Islam, Duygu Islek, Ivaila Y. Ivanova-Pandourska, Masanori Iwasaki, Tuija Jaaskelainen, Rod T. Jackson, Jeremy M. Jacobs, Michel Jadoul, Tazeen Jafar, Bakary Jallow, Kenneth James, Kazi M. Jamil, Konrad Jamrozik, Anna Jansson, Imre Janszky, Edward Janus, Juel Jarani, Marjo-Riitta Jarvelin, Grazyna Jasienska, Ana Jelakovic, Bojan Jelakovic, Garry Jennings, Chao Qiang Jiang, Ramon O. Jimenez, Karl-Heinz Jockel, Michel Joffres, Jari J. Jokelainen, Jost B. Jonas, Jitendra Jonnagaddala, Torben Jorgensen, Pradeep Joshi, Josipa Josipovic, Farahnaz Joukar, Jacek J. Jozwiak, Debra S. Judge, Anne Juolevi, Gregor Jurak, Iulia Jurca Simina, Vesna Juresa, Rudolf Kaaks, Felix O. Kaducu, Anthony Kafatos, Monika Kaj, Eero O. Kajantie, Natia Kakutia, Daniela Kallayova, Zhanna Kalmatayeva, Ofra Kalter-Leibovici, Yves Kameli, Freja B. Kampmann, Kodanda R. Kanala, Srinivasan Kannan, Efthymios Kapantais, Eva Karaglani, Argyro Karakosta, Line L. Karhus, Khem B. Karki, Philippe B. Katchunga, Marzieh Katibeh, Joanne Katz, Peter T. Katzmarzyk, Jussi Kauhanen, Prabhdeep Kaur, Maryam Kavousi, Gyulli M. Kazakbaeva, Francois F. Kaze, Calvin Ke, Ulrich Keil, Lital Keinan Boker, Sirkka Keinanen-Kiukaanniemi, Roya Kelishadi, Cecily Kelleher, Han C. G. Kemper, Maryam Keramati, Alina Kerimkulova, Mathilde Kersting, Timothy Key, Yousef Saleh Khader, Arsalan Khaledifar, Davood Khalili, Kay-Tee Khaw, Bahareh Kheiri, Motahareh Kheradmand, Alireza Khosravi, Ilse M. S. L. Khouw, Ursula Kiechl-Kohlendorfer, Sophia J. Kiechl, Stefan Kiechl, Japhet Killewo, Hyeon Chang Kim, Jeongseon Kim, Jenny M. Kindblom, Andrew Kingston, Heidi Klakk, Magdalena Klimek, Jeannette Klimont, Jurate Klumbiene, Michael Knoflach, Bhawesh Koirala, Elin Kolle, Patrick Kolsteren, Jurgen Konig, Raija Korpelainen, Paul Korrovits, Magdalena Korzycka, Jelena Kos, Seppo Koskinen, Katsuyasu Kouda, Eva Kovacs, Viktoria Anna Kovacs, Irina Kovalskys, Sudhir Kowlessur, Slawomir Koziel, Jana Kratenova, Wolfgang Kratzer, Vilma Kriaucioniene, Susi Kriemler, Peter Lund Kristensen, Helena Krizan, Maria F. Kroker-Lobos, Steinar Krokstad, Daan Kromhout, Herculina S. Kruger, Ruan Kruger, Lukasz Kryst, Ruzena Kubinova, Renata Kuciene, Urho M. Kujala, Enisa Kujundzic, Zbigniew Kulaga, Mukhtar Kulimbet, R. Krishna Kumar, Marie Kunesova, Pawel Kurjata, Yadlapalli S. Kusuma, Vladimir Kutsenko, Kari Kuulasmaa, Catherine Kyobutungi, Quang Ngoc La, Fatima Zahra Laamiri, Carl Lachat, Karl J. Lackner, Youcef Laid, Lachmie Lall, Tai Hing Lam, Maritza Landaeta Jimenez, Edwige Landais, Vera Lanska, Georg Lappas, Bagher Larijani, Simo Pone Larissa, Tint Swe Latt, Martino Laurenzi, Laura Lauria, Maria Lazo-Porras, Gwenaelle Le Coroller, Khanh Le Nguyen Bao, Agnes Le Port, Tuyen D. Le, Jeannette Lee, Jeonghee Lee, Paul H. Lee, Nils Lehmann, Terho Lehtimaki, Daniel Lemogoum, Branimir Leskosek, Justyna Leszczak, Katja B. Leth-Moller, Gabriel M. Leung, Naomi S. Levitt, Yanping Li, Merike Liivak, Christa L. Lilly, Charlie Lim, Wei-Yen Lim, M. Fernanda Lima-Costa, Hsien-Ho Lin, Xu Lin, Yi-Ting Lin, Lars Lind, Vijaya Lingam, Birgit Linkohr, Allan Linneberg, Lauren Lissner, Mieczyslaw Litwin, Jing Liu, Lijuan Liu, Wei-Cheng Lo, Helle-Mai Loit, Khuong Quynh Long, Guadalupe Longo Abril, Luis Lopes, Marcus V. V. Lopes, Oscar Lopes, Esther Lopez-Garcia, Tania Lopez, Paulo A. Lotufo, Jose Eugenio Lozano, Janice L. Lukrafka, Dalia Luksiene, Annamari Lundqvist, Nuno Lunet, Charles Lunogelo, Michala Lustigova, Edyta Luszczki, Jean-Rene M'Buyamba-Kabangu, Guansheng Ma, Xu Ma, George L. L. Machado-Coelho, Aristides M. Machado-Rodrigues, Enguerran Macia, Luisa M. Macieira, Ahmed A. Madar, Anja L. Madsen, Gladys E. Maestre, Stefania Maggi, Dianna J. Magliano, Sara Magnacca, Emmanuella Magriplis, Gowri Mahasampath, Bernard Maire, Marjeta Majer, Marcia Makdisse, Paivi Maki, Fatemeh Malekzadeh, Reza Malekzadeh, Rahul Malhotra, Kodavanti Mallikharjuna Rao, Sofia K. Malyutina, Lynell V. Maniego, Yannis Manios, Masimango Imani Manix, Jim I. Mann, Fariborz Mansour-Ghanaei, Taru Manyanga, Enzo Manzato, Anie Marcil, Paula Margozzini, Joany Marino, Anastasia Markaki, Oonagh Markey, Eliza Markidou Ioannidou, Pedro Marques-Vidal, Larissa Pruner Marques, Jaume Marrugat, Yves Martin-Prevel, Rosemarie Martin, Reynaldo Martorell, Eva Martos, Katharina Maruszczak, Stefano Marventano, Giovanna Masala, Luis P. 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Ramires, Jacqueline Ramke, Elisabete Ramos, Rafel Ramos, Lekhraj Rampal, Sanjay Rampal, Lalka S. Rangelova, Vayia Rarra, Ramon A. Rascon-Pacheco, Cassiano Ricardo Rech, Josep Redon, Paul Ferdinand M. Reganit, Valeria Regecova, Jane D. P. Renner, Judit A. Repasy, Cezane P. Reuter, Luis Revilla, Abbas Rezaianzadeh, Yeunsook Rho, Lourdes Ribas-Barba, Robespierre Ribeiro, Elio Riboli, Adrian Richter, Fernando Rigo, Attilio Rigotti, Natascia Rinaldo, Tobias F. Rinke de Wit, Ana I. Rito, Raphael M. Ritti-Dias, Juan A. Rivera, Reina G. Roa, Louise Robinson, Cynthia Robitaille, Romana Roccaldo, Daniela Rodrigues, Fernando Rodriguez-Artalejo, Maria del Cristo Rodriguez-Perez, Laura A. Rodriguez-Villamizar, Andrea Y. Rodriguez, Ulla Roggenbuck, Peter Rohloff, Fabian Rohner, Rosalba Rojas-Martinez, Nipa Rojroongwasinkul, Dora Romaguera, Elisabetta L. Romeo, Rafaela V. Rosario, Annika Rosengren, Ian Rouse, Vanessa Rouzier, Joel G. R. Roy, Maira H. Ruano, Adolfo Rubinstein, Frank J. 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Summary: This study used data from 2,325 population-based studies to analyze the height and BMI of children and adolescents aged 5-19 years in urban and rural areas from 1990 to 2020. The results showed that the height advantage of urban residents over rural residents has decreased in most countries, while it has amplified in sub-Saharan Africa. The BMI difference between urban and rural areas is small in most countries, with faster BMI growth in urban areas observed in some regions.

NATURE (2023)

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Article Public, Environmental & Occupational Health

Associations of maternal preterm birth with subsequent risk for type 2 diabetes in women from the women's health initiative

Aaron Holman-Vittone, Brian Monahan, Erin S. LeBlanc, Simin Liu, Rami Nassir, Nazmus Saquib, Peter F. Schnatz, Aladdin H. Shadyab, Rachel Sinkey, Jean Wactawski-Wende, Robert A. Wild, Lisa Chasan-Taber, JoAnn E. Manson, Cassandra N. Spracklen

Summary: Preterm birth is associated with increased risk of developing type 2 diabetes at an earlier age, but not with overall risk of incident type 2 diabetes. The association between preterm birth and type 2 diabetes may exist during early years but wane over time.

JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (2023)

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Article Pediatrics

Epidemiological Analysis of the Emergency Vascular Access in Pediatric Trauma Patients: Single-Center Experience of Intravenous, Intraosseous, Central Venous, and Arterial Line Placements

Manuel Florian Struck, Franziska Rost, Thomas Schwarz, Peter Zimmermann, Manuela Siekmeyer, Daniel Graefe, Sebastian Ebel, Holger Kirsten, Christian Kleber, Martin Lacher, Bernd Donaubauer

Summary: This study analyzed the performance of different vascular access procedures in severely injured pediatric trauma patients from the scene to admission. The results showed that successful IV or IO access was achieved by emergency medical service physicians at the scene, but there were some issues upon ED admission. Mechanical complications were also observed in the OR and ICU. Therefore, special preparedness is necessary in prehospital, ED, ICU, and OR environments.

CHILDREN-BASEL (2023)

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Article Oncology

Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival

Ana Babic, Qiao-Li Wang, Alice A. Lee, Chen Yuan, Nader Rifai, Juhua Luo, Fred K. Tabung, Aladdin H. Shadyab, Jean Wactawski-Wende, Nazmus Saquib, Jihye Kim, Peter Kraft, Howard D. Sesso, Julie E. Buring, Edward L. Giovannucci, JoAnn E. Manson, Meir J. Stampfer, Kimmie Ng, Charles S. Fuchs, Brian M. Wolpin

Summary: The study found that high levels of adiponectin in the prediagnostic period were associated with shorter survival among women with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR were associated with patient survival.

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION (2023)

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Article Environmental Sciences

Supporting legislative action: Urinary levels of phthalates and phenols among influencers in the 'Plastics in the spotlight' advocacy initiative

Jose Pumarega, Oriol Busca, Magda Gasull, Miquel Porta

Summary: This study aimed to raise awareness among the general public in the European Union about the presence of plastic residues in the human body and increase their support for plastic control legislation. Urine samples were collected from 69 volunteers from Spain, Portugal, Latvia, Slovenia, Belgium, and Bulgaria. The study found that phthalates and phenols were found in all samples, with higher concentrations in females. Most concentrations did not exceed reference values. The limitations of the study include the selection of volunteers and limited data on exposure factors.

ENVIRONMENTAL RESEARCH (2023)

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Article Urology & Nephrology

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Fei Chen, Ravi K. Madduri, Alex A. Rodriguez, Burcu F. Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J. Saunders, Suhn K. Rhie, Jeannette T. f Bensen, Sue A. Ingles, Rick A. Kittles, Sara S. Strom, Benjamin A. Rybicki, Barbara Nemesure, William B. Isaacs, Janet L. Stanford, Wei Zheng, Maureen Sanderson, Esther M. John, Jong Y. Park, Jianfeng Xu, Ying Wang, Sonja I. Berndt, Chad D. Huff, Edward D. Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T. Rentsch, Kelly Cho, Benjamin H. Mcmahon, Richard B. Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Dana C. Crawford, Alpa V. Patel, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M. Neslund-Dudas, Mariana C. Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B. Cook, Anand P. Chokkalingam, Ann W. Hsing, Phyllis J. Goodman, Thomas J. Hoffmann, Bettina F. Drake, Jennifer J. Hu, Jacob M. Keaton, Jacklyn N. Hellwege, Peter E. Clark, Mohamed Jalloh, Serigne M. Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O. Idowu, Olufemi Popoola, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E. Mensah, Halimatou Diop, Stephen K. Van Den Eeden, Pascal Blanchet, Jay H. Fowke, Graham Casey, Anselm J. Hennis, Alexander Lubwama, Ian M. Thompson, Robin Leach, Douglas F. Easton, Michael H. Preuss, Ruth J. Loos, Susan M. Gundell, Peggy Wan, James L. Mohler, Elizabeth T. Fontham, Gary J. Smith, Jack A. Taylor, Shiv Srivastava, Rosaline A. Eeles, John D. Carpten, Adam S. Kibel, Luc Multigner, Marie-Elise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A. Klein, Caroline Andrews, Timothy R. Rebbeck, Laurent Brureau, Stefan Ambs, Todd L. Edwards, Stephen Watya, Stephen J. Chanock, John S. Witte, William J. Blot, J. Michael Gaziano, Amy C. Justice, David Conti, Christopher A. Haiman

Summary: In this study, a large-scale genetic analysis was conducted in men of African ancestry, leading to the discovery of nine novel risk variants for prostate cancer (PCa). Furthermore, a multiancestry polygenic risk score was developed to effectively stratify PCa risk and differentiate the risk of aggressive and nonaggressive disease.

EUROPEAN UROLOGY (2023)

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Article Oncology

Prognostic Factors for Postoperative Bleeding Complications and Prolonged Intensive Care after Percutaneous Hepatic Chemosaturation Procedures with Melphalan

Manuel Florian Struck, Robert Werdehausen, Holger Kirsten, Holger Goessmann, Rhea Veelken, Florian van Boemmel, Sebastian Stehr, Timm Denecke, Sebastian Ebel

Summary: This retrospective analysis found that high perioperative infusion volumes and the omission of heparin reversal with protamine were associated with postoperative bleeding complications. High infusion volumes also contributed to a length of stay in the intensive care unit of more than one day. Our findings suggest a restrictive perioperative infusion regime and support the use of postoperative protamine for heparin reversal in chemosaturation procedures.

CANCERS (2023)

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