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1. Efficacy of early PET-CT directed switch to carboplatin and paclitaxel based definitive chemoradiotherapy in patients with oesophageal cancer who have a poor early response to induction cisplatin and capecitabine in the UK: a multi-centre randomised controlled phase II trialResearch in context

Author

Somnath Mukherjee, Christopher N. Hurt, Richard Adams, Andrew Bateman, Kevin M. Bradley, Sarah Bridges, Stephen Falk, Gareth Griffiths, Sarah Gwynne, Christopher M. Jones, Philip J. Markham, Tim Maughan, Lisette S. Nixon, Ganesh Radhakrishna, Rajarshi Roy, Simon Schoenbuchner, Hamid Sheikh, Emiliano Spezi, Maria Hawkins, and Thomas D.L. Crosby

Subjects
Oesophageal squamous cell carcinoma, Oesophageal adenocarcinoma, Chemoradiotherapy, Medicine (General), R5-920
Abstract

Summary: Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain. Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m2)/capecitabine (625 mg/m2 days 1–21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUVmax) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m2) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.gov NCT02741856. Findings: This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67–3.08; p = 0.35). Interpretation: In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT. Funding: Cancer Research UK.

Published
2023
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2. Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study

Author

Christopher M. Jones, Heather O'Connor, Maria O'Donovan, Daniel Hayward, Adrienn Blasko, Ruth Harman, Shalini Malhotra, Irene Debiram-Beecham, Bincy Alias, Adam Bailey, Andrew Bateman, Tom D.L. Crosby, Stephen Falk, Simon Gollins, Maria A. Hawkins, Sudarshan Kadri, Stephanie Levy, Ganesh Radhakrishna, Rajarshi Roy, Raj Sripadam, Rebecca C. Fitzgerald, and Somnath Mukherjee

Subjects
Oesophageal Cancer, Chemoradiation, Radiation, Surveillance, Cytosponge, Medicine (General), R5-920
Abstract

Summary: Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

Published
2022
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3. A Multi-Centre Randomised Phase II Trial of Early Pet-Ct Directed Switch to Carboplatin and Paclitaxel Based Definitive Chemoradiotherapy in Patients with Oesophageal Cancer Who Have a Poor Early Response to Induction Cisplatin and Capecitabine

Author

Somnath Mukherjee, Christopher Nicholas Hurt, Richard A. Adams, Andrew Bateman, Kevin Bradley, Sarah Bridges, Stephen Falk, Gareth Griffiths, Sarah Gwynne, Christopher Jones, Philip Markham, Tim Maughan, Lisette Nixon, Ganesh Radhakrishna, Rajarshi Roy, Simon Schoenbuchner, Hamid Sheikh, Emiliano Spezi, Maria Hawkins, and Tom Crosby

Published
2023
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4. Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer

Author

Benjamin R. Challoner, Andrew Woolston, David Lau, Marta Buzzetti, Caroline Fong, Louise J. Barber, Gayathri Anandappa, Richard Crux, Ioannis Assiotis, Kerry Fenwick, Ruwaida Begum, Dipa Begum, Tom Lund, Nanna Sivamanoharan, Harold B. Sansano, Melissa Domingo-Arada, Amina Tran, Bryony Eccles, Richard Ellis, Stephen Falk, Mark Hill, Daniel Krell, Nirupa Murugaesu, Luke Nolan, Vanessa Potter, Mark Saunders, Kai-Keen Shiu, Sebastian Guettler, James L. Alexander, Héctor Lázare-Iglesias, James Kinross, Jamie Murphy, Katharina von Loga, David Cunningham, Ian Chau, Naureen Starling, Juan Ruiz-Bañobre, Tony Dhillon, and Marco Gerlinger

Abstract

Mismatch repair deficient colorectal cancers have high mutation loads and many respond to immune checkpoint-inhibitors. We investigated how genetic and immune landscapes co-evolve in these tumors. All cases had high truncal mutation loads. Driver aberrations showed a clear hierarchy despite pervasive intratumor heterogeneity: Those in WNT/βCatenin, mitogen-activated protein kinase and TGFβ receptor family genes were almost always truncal. Immune evasion drivers were predominantly subclonal and showed parallel evolution. Pan-tumor evolution, subclonal evolution, and evolutionary stasis of genetic immune evasion drivers defined three MMRd CRC subtypes with distinct T-cell infiltrates. These immune evasion drivers have been implicated in checkpoint-inhibitor resistance. Clonality and subtype assessments are hence critical for predictive immunotherapy biomarker development. Cancer cell PD-L1 expression was conditional on loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and likely contributes to the high recurrence risk of MMRd CRCs with impaired CDX2 expression.

Published
2022
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5. Neo-AEGIS (Neoadjuvant Trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Final primary outcome analysis

Author

John V. Reynolds, Shaun R. Preston, Brian O'Neill, Maeve Aine Lowery, Lene Baeksgaard, Thomas Crosby, Moya Cunningham, Sinead Cuffe, Gareth Owen Griffiths, Rajarshi Roy, Stephen Falk, George Hanna, Frederick R. Bartlett, Imelda Parker, Alberto Alvarez-Iglesias, Magnus Nilsson, Guillaume Piessen, Signe Risum, Narayanasamy Ravi, and Raymond S. McDermott

Subjects
Cancer Research, Oncology
Abstract

295 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) remains controversial, specifically whether multimodal therapy or perioperative chemotherapy is superior. Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multimodal CROSS regimen (carboplatin/paclitaxel, 41.4Gy radiation therapy) with a modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) regimen (pre-2018) and more latterly the FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin) regimen. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5% for peri-operative chemotherapy. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 34.2 (0.43-111.8) months, there were 186 deaths, 91 CROSS and 95 MAGIC/FLOT arm, with 3-year estimated survival probability of 57% (95% CI 49,64) and 55% (95% CI 47,62), respectively [(HR 1.03 (95%CI. 0.77-1.38))]. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy in the primary outcome of overall survival, notwithstanding greater proxy markers of local tumor response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in clinical decision making in modern practice. Clinical trial information: NCT01726452 . [Table: see text]

Published
2023
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6. P-P46 The use of FDG-PET/CT in the pre-operative staging of pancreatic ductal adenocarcinoma

Author

Rebecca Jordan, Duncan Muir, Stijn van Laarhoven, Stephen Falk, Andrew Strickland, and James Skipworth

Subjects
Surgery
Abstract

Background The NICE Quality Standard for Pancreatic Cancer (December 2018) recommends that ‘adults with localised pancreatic cancer on CT(should) have staging using fluorodeoxyglucose positron emission tomography/CT(FDG-PET/CT) before they have surgery, radiotherapy or systemic therapy’. Such FDG-PET/CT staging aims to provide additional information to conventional cross-sectional imaging, thus presenting the most accurate staging of disease. However, the sensitivity and specificity of FDG-PET/CT to deliver relevant additional clinical information must be balanced with potential delays to treatment, and additional cost associated with its use, in the management of a time-critical pathology. Methods Consecutive pancreatic ductal adenocarcinoma(PDAC) patients deemed resectable on conventional imaging, and therefore referred for FDG-PET/CT assessment, were included for analysis. Data were derived from a single tertiary Hepatopancreaticobiliary(HPB) centre between May 2018 and June 2021. Data were collected and analysed from a combination of prospectively-collated electronic databases and paper patient records. Results Of 89 patients analysed, 55(61.7%) patients were male. Primary pancreatic lesions were PET avid in 81 cases(91%). Median time from request to FDG-PET/CT performance was 11 days(Range 1-35). Additional clinical information from FDG-PET/CT was provided in 61(68.5%) patients. Further investigations to assess FDG-PET/CT findings were arranged in 23 patients(25.8%; including liver MRI and EUS), demonstrating that FDG-PET/CT findings were true-positive in 6(26.1%), false-positive in 15(65.2%) and equivocal in 2(8.7%). There was a median delay of 60.5 days(Range 26 to 256) from FDG-PET/CT to surgery in those undergoing additional investigation. In total, a new diagnosis of metastatic/non-resectable disease was made in 14(15.7%) patients, preventing progression to planned operative intervention. Conclusions FDG-PET/CT provided additional information to conventional imaging that led to cancellation of planned operative resection in 14(15.7%) PDAC patients-8 directly and 6 following further investigation. However, there was a median delay of 11 days to FDG-PET/CT and 60.5 days from FDG-PET/CT to surgery in those undergoing additional investigation. Whilst FDG-PET/CT can lead to avoidance of unnecessary surgical intervention in PDAC patients with unsuspected metastatic/non-resectable disease, it can lead to delay, over-investigation, excess cost and anxiety in resectable patients. HPB units should audit their own findings to assess whether the use of FDG-PET/CT should be considered on a standard or selected basis.

Published
2021
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7. Association of body mass index with outcomes in patients with newly diagnosed atrial fibrillation: GARFIELD-AF

Author

Daniela Poli, Sophie Testa, Corrado Lodigiani, Toon Wei Lim, Kevin Jones, Kangning Chen, Hui Li, Hilary Pinnock, Grzegorz Bilo, Hack-Lyoung Kim, Andrew Murray, Bernard J Gersh, Kurt Huber, Robin Fox, Sarah Davies, James Rogers, Morten Schou, Xin Li, Vira Tseluyko, Sergey Popov, Rajeev Gupta, Grzegorz Opolski, Preeti Pandya, Bronte Ayres, Milan Gupta, Peter Hutchinson, Phil Simmons, Andrew Gallagher, Michel Galinier, Franck Paganelli, Jens Kilian, Adam Blenkhorn, Mohamed Ibrahim, Fernando Lanas, Karen Pieper, Eivind Berge, M Clark, Agneta Andersson, Karim Ladha, Bijoy Sinha, Torstein Hole, Dan Atar, Hywel Jones, R Smith, Andrew Ross, Emmanuel Ellie, Paul Evans, Yong Wang, Hiroshi Ono, Tadashi Nakamura, Paul MacDonald, Stephen Rogers, Igor Sibon, Simon Dobson, David Fitzmaurice, Jiyan Chen, Neil Roberts, Pierre Amarenco, Nigel Hart, Giancarlo Agnelli, Georges Mairesse, Pekka Raatikainen, Oleg Sychov, Yasuyuki Suzuki, Bo Liu, Mathieu Zuber, John French, Yuejin Yang, Myeong-Chan Cho, Julian Thompson, Michael Stokes, John W Eikelboom, Mark Richardson, John Matthews, Will Murdoch, Jean-Philippe Neau, Freek Verheugt, Ajay K Kakkar, Giuseppe Ambrosio, Marcin Gruchała, Keith A A Fox, Sunil Kumar, Ruiping Zhao, Patrick Carroll, Masanori Kaneko, Thanh Phan, Ping Yang, Sung-Won Jang, Claire Jones, Mårten Rosenqvist, Johan Engdahl, Debabrata Roy, John Cairns, Ping Chen, Michael Olsen, Paul Angaran, David Russell, Helena Dominguez, Béla Merkely, Joseph Berlingieri, James Bennett, Hugo ten Cate, Hiroshi Yamaguchi, Masahiro Minamoto, Hiroyuki Oda, Toshihiko Shiraiwa, Jonathan Webster, Yukihiro Koretsune, Kotaro Obunai, R Thompson, Yong Seog Oh, Giuliana Guazzaloca, Giuliana Martini, Marc Bonnefoy, Michael Cox, András Nagy, Kazuki Sato, Richard Davies, Daisuke Ikeda, Susumu Suzuki, Hiroki Teragawa, Koji Matsushita, Ying Guo, Catherine Neden, Mark Pugsley, Simon Cartwright, Polly Jacobs, Xiaoshu Cheng, Daniel Nishijima, Sylvia Haas, Vinay Kumar, Saverio Virdone, Jean-Pierre Bassand, Samuel Z Goldhaber, Shinya Goto, Frank Misselwitz, Alexander G G Turpie, Alison Macleod, Karen Forshaw, Mark Boon, Stephen Miller, Simon Wetherell, Moustafa Moustafa, Gaetano Serviddio, Renato Lopes, Kazuo Takei, Hiroaki Nishioka, Mykola Stanislavchuk, C Ramesh, R Kamath, Stuart J Connolly, Nooshin Bazargani, Kevin Douglas, Werner Hacke, Gloria Kayani, Ali Oto, Hiroshi Watanabe, Walter Hermans, Kazuya Murata, Christian Fielder Camm, Marco Moia, Niraj Sharma, Jaeyoung Kim, Walter Abhayaratna, Andriy Yagensky, Hosen Kiat, Wilhelm Haverkamp, Yang Jiao, Hitoshi Kato, Jindrich Spinar, Daniel Theodoro, Philip Cooke, Paolo Golino, Tetsuro Yoshida, Prakash Chandwani, Christine A'Court, Brian Ramjattan, Torbjørn Øien, Toshiyuki Kobayashi, Richard West, Petr Jansky, Seil Oh, Jan Steffel, Martin van Eickels, Hyung-Wook Park, Nam-Ho Kim, Søren Rasmussen, Kazuo Suzuki, David Colquhoun, Hiroshi Ando, Simon Franklin, Tae-Joon Cha, Sang Cheol Bae, Guosheng Fu, Yoshihiro Saito, Heinz Drexel, Michel Martelet, Joseph Mouallem, Nicolas Delarche, Sylvain Destrac, Neil Macey, Andreas Kopf, Masayuki Nakano, Olga Barbarash, Takeshi Inoue, Taro Minagawa, Weihua Li, John Eikelboom, Hiroshi Kubo, Lars Andersson, D Burns, Andrea Podczeck-Schweighofer, Megumi Okada, Massimo Volpe, Takuma Aoyama, Karsten Mueller, Carlos Astudillo, Hiroshi Takeda, Peter Mayer, Jung Hoon Sung, Dinesh Jain, Jung Han Yoon, Alessandro Capucci, Dongryeol Ryu, Kelvin Wong, Hong Euy Lim, Xiaowei Yan, Yusheng Zhao, Yuehui Yin, YUKIHIRO SETA, Taek Jong Hong, MASAKI SHIMOYAMA, Dayi Hu, Junichi Minami, Yuriy Mostovoy, David Foo, Ramazan Topsakal, Zhi-Cheng Jing, Dipen Shah, Kenichi Yamamoto, David Coulshed, Olivier Piot, Ramón Corbalán, Silva Severi, Waldemar Myszka, Mehmet Birhan Yilmaz, Gi-Byoung Nam, Jun Kim, Harald Darius, Jan-Erik Karlsson, PETER VANDERGOTEN, Nasser Taha, Shuta Toru, Jörn Nielsen, Tsutomu Takagi, Koji Higuchi, Steen Husted, Tomohiro Katsuya, Frank Cools, Iveta Petrova, Songkwan Silaruks, GÜNTER LEHMANN, Frederic Casassus, Bernard Crousillat, Bernard Doucet, Jean-Joseph Muller, Grzegorz Raczak, Kazuyuki Saito, Anders Ostrem, Chi Keong Ching, KUNIHIKO YAMAMOTO, John Camm, Carmine Mazzone, Jaemin Shim, Jadwiga Nessler, Jan Vercammen, Marc Delforge, Chong-Jin Kim, Pierre Nazeyrollas, Louise Lumley, Paul Roome, Helen Stoddart, Mark Rickenbach, Paul Mullen, Noriyuki Nakanishi, Gordon Irvine, Paul Conn, Kurt Lenz, Richard Coates, E Fisher, Warwick Coulson, Jiri Lastuvka, Pablo García Pavía, P Jhittay, Philip Saunders, Peter Bernhardt, Wanwarang Wongcharoen, Kentaro Yamamoto, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Jørn Dalsgaard Nielsen, Hany Ragy, Matyas Keltai, Jitendra Pal Singh Sawhney, Janina Stepinska, Elizaveta Panchenko, Barry Jacobson, Xavier Viñolas, Pantep Angchaisuksiri, Alex Parkhomenko, Huaiqin Zhang, Shiping Cao, Daowen Wang, Guizhou Tao, Yingmin Chen, Shenghu He, Tongguo Wu, Moshui Chen, Longgen Xiong, Praveen Jadhavm, Raghava Sarma, Govind Kulkarni, Rasesh Atulbhai Pothiwala, Mohanan Padinhare Purayil, Kamaldeep Chawla, Veerappa Annasaheb Kothiwale, Bagirath Raghuraman, Vinod Madan Vijan, Jitendra Sawhney, Ganapathi Bantwal, Aziz Khan, Ramdhan Meena, Manojkumar Chopada, Sunitha Abraham, Vikas Bisne, Govindan Vijayaraghavan, Rajashekhar Durgaprasad, Kartikeya Bhargava, Udigala Madappa Nagamalesh, Rajeeve Kumar Rajput, Seishu Kanamori, Koichiro Kumagai, Yosuke Katsuda, Keiki Yoshida, Fumitoshi Toyota, Yuji Mizuno, Ikuo Misumi, Hiroo Noguchi, Shinichi Ando, Tetsuro Suetsugu, Susumu Adachi, Kei Chiba, Hiroaki Norita, Makoto Tsuruta, Takeshi Koyanagi, Takayuki Higashi, Shiro Azakami, Shinichiro Komaki, Kenshi Kumeda, Takashi Murayama, Jun Matsumura, Yurika Oba, Ryuji Sonoda, Kazuo Goto, Kotaro Minoda, Yoshikuni Haraguchi, Hisakazu Suefuji, Hiroo Miyagi, Tsugihiro Nakamura, Hidekazu Nandate, Ryuji Zaitsu, Yoshihisa Fujiura, Akira Yoshimura, Hiroyuki Numata, Jun Ogawa, Yasuyuki Kamogawa, Kinshiro Murakami, Yutaka Wakasa, Masanori Yamasawa, Hiromitsu Maekawa, Sumihisa Abe, Hajime Kihara, Satoru Tsunoda, Katsumi Saito, Hiroki Tachibana, Ichiro Oba, Takashi Kuwahata, Satoshi Higa, Masamichi Gushiken, Takuma Eto, Hidetoshi Chibana, Kazuaki Fujisawa, Yuhei Shiga, Hirokuni Sumi, Toshihisa Nagatomo, Yoshihiko Atsuchi, Toshiro Nagoshi, Kazuhisa Sanno, Fumihiro Hoshino, Naoto Yokota, Masahiro Kameko, Toshifumi Tabuchi, Munesumi Ishizawa, Yoshitake Fujiura, Taku Seto, Tetsu Iwao, Norio Ishioka, Koichi Oshiro, Keizo Tsuchida, Yutaka Hatori, Motoshi Takeuchi, Hiroto Takezawa, Shinjiro Nagano, Masaaki Iwaki, Yuichiro Nakamura, Naomasa Miyamoto, Toshifumi Taguchi, Ko Ashida, Naoto Yoshizawa, Jun Agata, Seishiro Matsukawa, Osamu Arasaki, Shuji Fukuoka, Hirofumi Murakami, Kazuya Mishima, Yoshiki Hata, Ichiro Sakuma, Ichiro Takamura, Mitsuyuki Akutsu, Toshihide Unoki, Yoshinori Go, Makoto Ikemura, Shoji Morii, Shigeru Marusaki, Hideo Doi, Mitsuru Tanaka, Takaaki Kusumoto, Shigeo Kakinoki, Chiga Ogurusu, Masami Nakatsuka, Yutaka Kitami, Yoichi Nakamura, Hiroshi Oda, Rikimaru Oyama, Masato Ageta, Teruaki Mita, Kazuhiko Nagao, Takafumi Mito, Mitsunori Abe, Masako Fujii, Makoto Okawa, Tsuneo Fujito, Toshiya Taniguchi, Tenei Ko, Mizuho Imamaki, Masahiro Akiyama, Takashi Ueda, Hironori Odakura, Masahiko Inagaki, Yoshiki Katsube, Atsuyuki Nakata, Shinobu Tomimoto, Mitsuhiro Shibuya, Kenichiro Ito, Masahiro Matsuta, Motoyuki Ishiguro, Masamichi Wada, Hiroaki Mukawa, Masato Mizuguchi, Fumio Okuda, Teruaki Kimura, Kuniaki Taga, Masaaki Techigawara, Morio Igarashi, Toshihiko Seo, Shinya Hiramitsu, Hiroaki Hosokawa, Mitsumoto Hoshiai, Michitaka Hibino, Koichi Miyagawa, Hideki Horie, Nobuyoshi Sugishita, Yukio Shiga, Akira Soma, Kazuo Neya, Kunio Akahane, Saori Matsui, Hirofumi Kanda, Shiro Nagasaka, Atsushi Taguchi, Akiko Miyashita, Hiroki Sasaguri, Jin Nariyama, Taketo Hatsuno, Takash Iwase, Kazuya Kawai, Tomobumi Kotani, Tsuyoshi Tsuji, Hirosumi Sakai, Kiyoshi Nishino, Kenichi Ikeda, Kazuo Maeda, Tomohiro Shinozuka, Koichi Kawakami, Hiromichi Kitazumi, Mamoru Hamaoka, Jisho Kojima, Akitoshi Sasaki, Yoshihiro Tsuchiya, Tetsuo Betsuyaku, Masaaki Honda, Koichi Hasegawa, Takao Baba, Kazuaki Mineoi, Toshihiko Koeda, Kunihiko Hirasawa, Toshihide Kumazaki, Akira Nakagomi, Eiji Otaki, Takashi Shindo, Hiroyoshi Hirayama, Chikako Sugimoto, Takashi Yamagishi, Ichiro Mizuguchi, Kazunori Sezaki, Isamu Niwa, Ken Takenaka, Osamu Iiji, Koichi Taya, Hitoshi Kitazawa, Samu Ueda, Hirokazu Kakuda, Takuya Ono, Seizo Oriso, Junya Kamata, Toshihiko Nanke, Itaru Maeda, Yoshifusa Matsuura, Yasuyuki Maruyama, Hajime Horie, Tetsutaro Kito, Hiroshi Asano, Masaichi Nakamura, Takashi Washizuka, Tomoki Yoshida, Masato Sawano, Shinichi Arima, Hidekazu Arai, Hisanori Shinohara, Hiroyuki Takai, Nobufusa Furukawa, Akira Ota, Kenji Aoki, Taku Yamamoto, Takeaki Kasai, Shunji Suzuki, Shu Suzuki, Nitaro Shibata, Masayuki Watanabe, Yosuke Nishihata, Toru Arino, Masaki Okuyama, Tetsushi Wakiyama, Tomoko Kato, Yasuo Sasagawa, Takeshi Tana, Yoshihito Hayashi, Shinichi Hirota, Yukihiko Abe, Hirohide Uchiyama, Shuichi Tohyo, Naoto Hanazono, Seiichi Miyajima, Hisashi Shimono, Yasunobu Shozawa, Yawara Niijima, Osamu Murai, Hideko Inaba, Katsumasa Nomura, Masatsugu Nozoe, Toshiyuki Furukawa, Nobuhisa Ito, Shunichi Nagai, Kiyoharu Sato, Shiro Nakahara, Yujin Shimoyama, Naoko Ohara, Teruhiko Kozuka, Hideaki Okita, Masato Endo, Tsutomu Goto, Makoto Hirose, Emiko Nagata, Toshizumi Mori, Shuichi Seki, Katsuhiro Okamoto, Osamu Moriai, Yoko Emura, Tsuyoshi Fukuda, Haruhiko Date, Shuichi Kawakami, Sho Nagai, Yuya Ueyama, Tetsuro Fudo, Mitsuru Imaizumi, Takuo Ogawa, Shunsuke Take, Hideo Ikeda, Norihiko Sakamoto, Kiyomitsu Ikeoka, Nobuo Wakaki, Masatake Abe, Junji Doiuchi, Tetsuya Kira, Masato Tada, Ken Tsuzaki, Naoya Miura, Yasuaki Fujisawa, Wataru Furumoto, Akinori Fujisawa, Ryosai Nakamura, Hiroyasu Komatsu, Rei Fujiki, Shuichi Kawano, Keijiro Nishizawa, Yoji Kato, Junya Azuma, Kiyoshi Yasui, Toshio Amano, Yasuhiro Sekine, Tatsuo Honzawa, Yuichiro Koshibu, Yasuhide Sakamoto, Shingo Miyaguchi, Kojuro Morishita, Yasuko Samejima, Toyoshi Sasaki, Fumiko Iseki, Hiroshi Kano, Yoichi Takagi, Yoko Onuki Pearce, Takayuki Fukui, Toru Nakayama, Hideaki Kanai, Yoshiyuki Kawano, Tetsuji Ino, Hironori Miyoshi, Yasufumi Miyamoto, Masahito Shigekiyo, Shimato Ono, Yutaka Okamoto, Satoshi Ubukata, Kojiro Kodera, Tatsuo Oriuchi, Naoki Matsumoto, Koichi Inagaki, Atsushi Iseki, Tomohiro Yoshida, Toshihiro Goda, Tsukasa Katsuki, Atsushi Sato, Etsuo Mori, Toshio Tsubokura, Hiroshi Shudo, Shunichi Fujimoto, Yoshiyuki Furukawa, Hiroshi Hosokawa, Jun Narumi, Kiichiro Yamamoto, Masaki Owari, Takuya Inakura, Takafumi Anno, Kazuyuki Shirakawa, Tan Yuyang, Hui Nam Park, Woo-Shik Kim, HyeYoung Lee, Dae Hyeok Kim, Dae-Kyeong Kim, Dong Ju Choi, Hui-Kyung Jeon, Dong-Gu Shin, Sang Weon Park, Hoon Ki Park, Sang-Jin Han, Young Keun On, JaeJin Kwak, Seong Hoon Park, Kee-Sik Kim, Byung Chun Jung, Gyo-Seung Hwang, Sakda 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Hana Burianova, Ondrej Jerabek, Jana Pisova, Vratislav Dedek, Michaela Honkova, Petr Podrazil, Petr Reichert, Miroslav Novak, Vaclav Durdil, Katarina Plocova, Ulrik Hintze, Næstved Sygehus, Arne Bremmelgaard, John Markenvard, Jan Børger, Jorgen Solgaard, Ebbe Eriksen, Thomas Løkkegaard, Michael Bruun, Jacob Mertz, Joël Ohayon, Yannick Gottwalles, Philippe Loiselet, Mohamed Bassel Koujan, André Marquand, Jean-Pierre Cebron, Maxime Guenoun, Dominique Guedj-Meynier, A G Lokesh, James Kadouch, Pierre-Yves Fournier, Jean-Pierre Huberman, Nestor Lemaire, Gilles Rodier, Xavier Vandamme, Marie Hélène Mahagne, Antoine Mielot, Jean-Baptiste Churet, Vincent Navarre, Frederic Sellem, Gilles Monniot, Jean-Paul Boyes, Désiré Obadia, Etienne Bearez, Jean Philippe Brugnaux, Alain Fedorowsky, Jean-Baptiste Berneau, Frédéric Chemin, Sebastien Schellong, Georg Koeniger, Uwe Gerbaulet, Bernd-Thomas Kellner, Thomas Schaefer, Jan Purr, Enno Eißfeller, Heinz-Dieter Zauzig, Peter Riegel, Christoph Axthelm, 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Sandor Kancz, Zoltan Laszlo, Zsolt May, Ebrahim Noori, Tamas Habon, Peter Polgar, Gabriella Szalai, Sandor Vangel, Gabriella Engelthaler, Judit Ferenczi, Mihaly Egyutt, Leone Maria Cristina, Eros Tiraferri, Rita Santoro, Teresa Maria Caimi, Maria Tessitori, Roberto Cappelli, Roberto Quintavalla, Franco Cosmi, Raffaele Fanelli, Vincenzo Oriana, Raffaele Reggio, Roberto Santi, Leonardo Pancaldi, Jorge Salerno Uriate, Flavia Lillo, Enrico Maria Pogliani, Michele Accogli, Antonio Mariani, Mauro Feola, Arturo Raisaro, Luciano Fattore, Andrea Mauric, Fabrizio Germini, Luca Tedeschi, Maria Settimi, Sergio Nicoli, Paolo Ricciarini, Antonio Argena, Paolo Ronchini, Claudio Bulla, Filippo Tradati, Maria Grazia Bongiorni, Enrico Salomone, Claudio Tondo, Saverio Iacopino, Andreas Lucassen, Henk Adriaansen, Maarten Bongaerts, Mathijs Pieterse, Johannes Herrman, Pieter Hoogslag, Cees Buiks, Per Anton Sirnes, Erik Gjertsen, Knut Erga, Arne Hallaråker, Gunnar Skjelvan, Beraki Ghezai, Arne Svilaas, Peter Christersson, Svein Høegh Henrichsen, Jan Erik Otterstad, Jan Berg-Johansen, Andrzej Gieroba, Malgorzata Biedrzycka, Michal Ogorek, Beata Wozakowska-Kaplon, Krystyna Loboz-Grudzien, Jerzy Kuzniar, Roman Zaluska, Jaroslaw Hiczkiewicz, Lucyna Swiatkowska-Byczynska, Lech Kucharski, Piotr Minc, Maciej Olszewski, Grzegorz Kania, Malgorzata Krzciuk, Zbigniew Lajkowski, Bozenna Ostrowska-Pomian, Jerzy Lewczuk, Elzbieta Zinka, Agnieszka Karczmarczyk, Malgorzata Chmielnicka-Pruszczynska, Iwona Wozniak-Skowerska, Marek Bronisz, Marcin Ogorek, Grazyna Glanowska, Piotr Ruszkowski, Grzegorz Skonieczny, Ryszard Sciborski, Boguslaw Okopien, Piotr Kukla, Krzysztof Galbas, Krzysztof Cymerman, Jaroslaw Jurowiecki, Pawel Miekus, Stanislaw Mazur, Roman Lysek, Jacek Baszak, Teresa Rusicka-Piekarz, Ewa Domanska, Jozef Lesnik, Gadel Kamalov, Dmitry Belenky, Liudmila Egorova, Alexander Khokhlov, Eduard Yakupov, Dmitry Zateyshchikov, Olga Miller, Evgeniy Mazur, Konstantin Zrazhevskiy, Tatyana Novikova, 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Fikry, Ahmed Mowafy, Azza Katta, Mazen Tawfik, Moustafa Nawar, Mohamed Sobhy, Tarek Khairy, Ahmed Abd El-Aziz, Ashraf Reda, Atef Elbahry, Mohamed Setiha, Magdi Elkhadem, Adel El-Etreby, David Kettles, Junaid Bayat, Heidi Siebert, Adrian Horak, Ynez Kelfkens, Riaz Garda, Thayabran Pillay, Michele Guerra, Hendrik Theron, Rikus Louw, Deon Greyling, Pindile Mntla, Siddique Ismail, Fayzal Ahmed, Johannes Engelbrecht, Shambu Maharajh, Veronica Ueckermann, Ghazi Yousef, Munther AlOmairi, Rajan Maruthanayagam, Rupesh Singh, Ahmed Naguib, Amrish Agrawal, Mukesh Nathani, Adel Wassef, Scott Beach, Peter Duffy, Stephen Falkowski, Kevin Ferrick, Miguel Franco, Annette Quick, Vance Wilson, Mark Alberts, Edwin Blumberg, Roddy Canosa, Ted Gutowski, Rodney Ison, Jorge Garcia, Howard Noveck, Pamela Rama, Rajneesh Reddy, Marcus Williams, Keith Ferdinand, Ihsan Haque, Robert Mendelson, Sridevi Pitta, Charles Treasure, Cas Cader, Walter Pharr, Alisha Oropallo, George Platt, Jaspal Gujral, James Welker, 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Kakkar, A. John Camm, David A. Fitzmaurice, Keith A.A. Fox, Bernard J. Gersh, Samuel Z. Goldhaber, Lorenzo G. Mantovani, Karen S. Pieper, Alexander G.G. Turpie, Freek W.A. Verheugt, Antonio Carlos PereiraBarretto, Stuart J. Connolly, Jean-Yves Le Heuzey, Jitendra Pal SinghSawhney, Carlos JerjesSánchez Díaz, Hugo Ten Cate, Wael Al Mahmeed, Zhiming Yang Li Xue, A.G. Ravi Shankar, Chiei Takanaka Sen Adachi, Rodolfo AndresAhuad Guerrero, Leonel Adalberto Di Paola, DárioCelestino Sobral Filho, Costantino RobertoFrack Costantini, Weimar Kunz SebbaBarrosodeSouzaem, João David deSouzaNeto, José Carlos MouraJorge, Adalberto MenezesLorga Filho, Carlos Henrique DelCarlo, FernandoAugustoAlves da Costa, Gilson Robertode Araújo, Jose FranciscoKerr Saraiva, João CarlosFerreira Braga, Roberto Álvaro RamosFilho, Cláudio MunhozdaFontoura Tavares, CésarCássio Broilo França, Guido BernardoAranha Rosito, João BatistadeMouraXavierMoraes Junior, Roberto Simõesde Almeida, Ney CarterdoCarmo Borges, LuísGustavo Gomes Ferreira, Benjamin AleckJosehStockins Fernandez, CarlosJerjes Sanchez Diaz, Jesus JaimeIllescas Diaz, Maria GuadalupeRamos Zavala, GuillermoAntonio Llamas Esperón, Manuel delosRios Ibarra, LuisRamon Virgen Carrillo, JuanJose Lopez Prieto, Jose LuisLeiva Pons, Carlos GerardoCantu Brito, EduardoJulianJose Roberto ChuquiureValenzuela, Alberto EstebanBazzoni Ruiz, Oscar MartinLopez Ruiz, Jesus DavidMorales Cerda, Axel De Wolf, Carmela Viitanen, Giovanni Di Minno, Raimondo De Cristofaro, Angelo De Blasio, Maria D'Avino, J.H. Ruiter, Coen van Guldener, P.R. Nierop S.H.K., B.E. Groenemeijer, W. Terpstra, L.V.A. Boersma, Wieslaw Supinski Jaroslaw, Roman Libis Vera Eltishcheva, Maria FernandaLopez Fernandez, Luis MiguelRincon Diaz, Luis FernandoIglesias Alonso, Jose RamonGonzalez Juanatey, Joan Bayo iLlibre, Carlos AlexandreAlmeida Fernandez, Juan JoseMontero Alia, Maria AngelsMoleiro Oliva, Maria delMarRodriguez Alvarez, Maria FeArcocha Torres, Miguel AngelPrieto Diaz, Jan Lindén Centrumkliniken, Juerg H. Beer, Colin Bradshaw Cumberlidge, Daniel Jackson Ben Ward, Nick Hargreaves Ben Frankel, William van Gaal, David O'Donnell, Miranda du Preez, Seif Kamal Abou Seif, Mohamed Gamal El Din, Louis van Zyl, Rehana Loghdey Wessel Oosthuysen, Abdullah Al Naeemi, Ehab M. Esheiba, and W. Michael Kutayli

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.Methods GARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI

Published
2022
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