81 research outputs found
Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study
- Author
- Alanko Tuomo
- Antonarakis Emmanuel S.
- Berger Raanan
- Bono Johann Sebastian de
- Drake Charles G.
- Feyerabend Susan
- Fukasawa Satoshi
- Goh Jeffrey
- Gross-Goupil Marine
- Hoimes Christopher J.
- Kim Jeri
- Li Chunde
- Ojamaa Kristiina
- Omlin Aurelius
- Park Se Hoon
- Piulats Josep M.
- Poehlein Christian
- Procopio Giuseppe
- Qiu Ping
- Sezer Ahmet
- Tabata Ken-ichi
- Vaishampayan Ulka
- Wit Ronald de
- Wu Haiyan
- Publication venue
- 'American Society of Clinical Oncology (ASCO)'
- Publication date
- 01/01/2020
- Field of study
PURPOSE: Pembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger mCRPC population. METHODS: The phase II KEYNOTE-199 study included three cohorts of patients with mCRPC treated with docetaxel and one or more targeted endocrine therapies. Cohorts 1 and 2 enrolled patients with RECIST-measurable PD-L1-positive and PD-L1-negative disease, respectively. Cohort 3 enrolled patients with bone-predominant disease, regardless of PD-L1 expression. All patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary end point was objective response rate per RECIST v1.1 assessed by central review in cohorts 1 and 2. Secondary end points included disease control rate, duration of response, overall survival (OS), and safety. RESULTS: Two hundred fifty-eight patients were enrolled: 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Objective response rate was 5% (95% CI, 2% to 11%) in cohort 1 and 3% (95% CI, = 21.8 months) and 10.6 months (range, 4.4 to 16.8 months), respectively. Disease control rate was 10% in cohort 1, 9% in cohort 2, and 22% in cohort 3. Median OS was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. Treatment-related adverse events occurred in 60% of patients, were of grade 3 to 5 severity in 15%, and led to discontinuation of treatment in 5%. CONCLUSION: Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and OS estimates are encouraging
Genome-Wide Analysis of Light- and Temperature-Entrained Circadian Transcripts in Caenorhabditis elegans
- Author
- A Antebi
- A Claridge-Chang
- A Correa
- A Matsumoto
- A Mehra
- A Sehgal
- A Ward
- A. F Robinson
- A. R Frand
- Alexander M. van der Linden
- B Conradt
- B Kloss
- C Coburn
- C. E Boothroyd
- C. H Johnson
- D Alabadi
- D Bell-Pedersen
- D Ramot
- D. H Mitchell
- D. M Berson
- D. S Chelur
- D. S Portman
- E Harms
- E. M Hedgecock
- F Kippert
- G. E Duffield
- G. T van der Horst
- H Tei
- H Wijnen
- H Wijnen
- H. R Ueda
- I Mori
- J Aschoff
- J Cha
- J Liu
- J. D Plautz
- J. M Gray
- J. T Pierce-Shimomura
- J. W Hastings
- Joseph Rodriguez
- K Kiontke
- K. P Keegan
- L. P Shearman
- M Ashburner
- M Chalfie
- M de Bono
- M Gallego
- M Jeon
- M Merrow
- M Nakajima
- M Nowrousian
- M Rosbash
- M. E Hughes
- M. F Ceriani
- M. J McDonald
- M. J McDonald
- M. W Young
- Matthew Beverly
- Michael Rosbash
- N Fielenbach
- N Gekakis
- N Srivastava
- N. A Croll
- N. Y Garceau
- P Ballario
- P Emery
- P. E Hardin
- P. E Hardin
- P. E Hardin
- Piali Sengupta
- R Allada
- R Allada
- R Stanewsky
- R. A Akhtar
- S Hattar
- S Kadener
- S Yu
- S. A Brown
- S. H Simonetta
- S. H Simonetta
- S. H Simonetta
- S. L Edwards
- Sara Wasserman
- Sebastian Kadener
- T Kondo
- T Minamoto
- T Roenneberg
- T Roenneberg
- T Saigusa
- T Yoshii
- Ueli Schibler
- V Prahlad
- W Yu
- X Zheng
- Y Liu
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2010
- Field of study
Transcriptional profiling experiments identify light- and temperature-entrained circadian transcripts in C. elegans
Thrombosis in vasculitis: from pathogenesis to treatment
- Author
- A Arida
- A Ates
- A Gul
- A Maino
- A Palatinus
- AE Berden
- AF Whyte
- Alessia Grassi
- Amedeo Amedei
- Augusto Vaglio
- AW Souza De
- B Al-Ani
- B Engelmann
- B Seriolo
- B Zoller
- C Belizna
- C Belizna
- C Evereklioglu
- C Moosbauer
- C Salvarani
- C Salvarani
- CA Caldas
- CG Kallenberg
- Chiara Della Bella
- Claudia Fiorillo
- CM Weyand
- D Saadoun
- D Saadoun
- D Sen
- Danilo Squatrito
- Domenico Prisco
- E Alpsoy
- E Kural-Seyahi
- E Onur
- E Seyahi
- E Silvestri
- Elena Niccolai
- Elena Silvestri
- F Atzeni
- G Emmi
- G Espinosa
- G Geri
- G Hatemi
- G Tomasson
- Giacomo Emmi
- H Ceyran
- HJ Jong De
- I Alexoudi
- IC Haznedaroglu
- International Team for the Revision of the International Criteria for Behcet's D
- J Cruveilhier
- J Hernandez-Rodriguez
- J Hwang
- J Sanchez-Manubens
- J Schmidt
- J Springer
- JC Chambers
- JC Jennette
- JC Jennette
- JK Sebastian
- JM Ricart
- K Aksu
- K Kambas
- K Ozoran
- KT Calamia
- L Dagna
- L Halbwachs
- L Li
- Lorenzo Emmi
- M Baldini
- M Faurschou
- M Faurschou
- M Haroon
- M Hilhorst
- M Leiba
- M Macey
- M Regina La
- M Regina La
- M Sahin
- M Samson
- M Silingardi
- MA Gonzalez-Gay
- MA Gonzalez-Gay
- MA Gonzalez-Gay
- Mario Milco D’Elios
- Matteo Becatti
- MD Morgan
- MM Boomsma
- MT Inanc
- N Duzgun
- N Lenk
- N Maugeri
- N Pipitone
- O Kose
- P Caramaschi
- P Hewins
- PD Udayakumar
- PM Stassen
- PR Ames
- R Manna
- R Sarica-Kucukoglu
- R Suppiah
- RA Sari
- S Adler
- S Sangaletti
- S Shadmanfar
- S Weidner
- T Sakane
- TN Pitanga
- V Hamuryudan
- VM Martinez-Taboada
- VM Martinez-Taboada
- W Bono
- Wegener’s Granulomatosis Etanercept Trial Research G
- WS Chung
- WS Chung
- Y Allenbach
- Y Hong
- Y Turkoz
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
- Author
- Abbas J
- Abbate A
- Abdullakutty J
- Abhyanakar AD
- Aboyans V
- Abrantes JAM
- Abu-Fadel M
- Acevedo M
- Adamkova V
- Adhyapak S
- Agarwal H
- Aggarwal R
- Aggarwal RK
- Aguirre A
- Ahmed H
- Ahremark U
- Ahuad Guerrero RA
- Aidar Ayoub JC
- Airaksinen JK
- Aitken D
- Akatova E
- Akhter F
- Ako J
- Akright L
- Akyea-Djamson A
- Al Joundi T
- Al-Windy NYY
- Alan D
- Alcocer Gamba MA
- Alexander JH
- Alexander K
- Alexandru TM
- Alings M
- Alonso Martin JJ
- Alvarisqueta AF
- Alves De Lima AE
- Amarasekera S
- Amarasena N
- Amir O
- Amlani M
- Amosova E
- Amuchastegui M
- Andersen K
- Andersen R
- Anderson J
- Ando K
- Angel Hominal M
- Annam S
- Anscombe R
- Apostolovic SR
- Appel K-F
- Arandjelovic A
- Araneda G
- Arango Benecke JL
- Arbel Y
- Arif I
- Armaganijan L
- Arroyo JAC
- Arstall MA
- Asanin MR
- Atar S
- Athyros V
- Auguadro C
- Ayala CAC
- Aylward PE
- Azizad MM
- Bagai A
- Bagriy A
- Bahit MC
- Bai F
- Balaguer Recena J
- Baldari D
- Balinovac J
- Ball E
- Bang LE
- Banuru S
- Barakovic F
- Baranov E
- Baranova E
- Barbarash OL
- Barbato E
- Barna OM
- Barone-Rochette G
- Barr C
- Barrucco R
- Bartels GL
- Bashir R
- Basson MMDV
- Bastos JM
- Bata I
- Batushkin V
- Bayat J
- Bayram Llamas EA
- Bayron C
- Beauloye C
- Bednarski J
- Behrens S
- Belhassane A
- Benedicto A
- Bengus CM
- Benov HO
- Berger R
- Berglund S
- Berk M
- Berland J
- Berli MA
- Berlowitz M
- Berman B
- Bernan A
- Berti S
- Bhagwat A
- Bhagwat R
- Bhansali P
- Bhatt DL
- Binder R
- Birchem J
- Bittner VA
- Blicharski T
- Blok T
- Blumberg EDS
- Boccara F
- Bodanese LC
- Bodi Peris V
- Boecker D
- Bojovski S
- Bokarev I
- Bokern MJJA
- Bonfanti AJC
- Bono JOE
- Bordonava AP
- Borse R
- Bortnick A
- Bos RJ
- Botas Rodriguez J
- Botelho A
- Botelho RV
- Botia DCL
- Bottcher M
- Bourgeois R
- Brabham D
- Braganza D
- Braun-Dullaeus R
- Breedveld RW
- Brennan JM
- Brodison A
- Bronzwaer PNA
- Brueren BRG
- Bruguera Cortada J
- Budaj A
- Bugan V
- Busmane A
- Bustamante Labarta MH
- Busz-Papiez B
- Butler R
- Bystryk L
- Caccavo A
- Caime GD
- Calabro P
- Camprubi Potau M
- Camsari A
- Caraco Y
- Carey C
- Carlson E
- Carnero GS
- Carranza Madrigal J
- Carrillo Calvillo J
- Carroll PA
- Cartasegna LR
- Carter L
- Caruso OC
- Cassimjee S
- Castadot M
- Cavallini C
- Cequier Fillat AR
- Cerqueira MJAG
- Cestari HG
- Cevc M
- Cha J
- Chae I-H
- Chaitman B
- Chalavarya G
- Chaleff F
- Chambilla JMC
- Chandna H
- Chane M
- Chang M
- Chaudhary S
- Chavez V-CER
- Chen D
- Chen J
- Chen Y
- Cheng S-C
- Cheng X
- Chiang C-E
- Chiang C-E
- Chizhov P
- Chopda M
- Chopra VK
- Christenson S
- Chu A
- Chua T
- Chumakova G
- Chumburidze V
- Civeira Murillo F
- Claeys M
- Clemmensen P
- Clerc J
- Cleveland D
- Clifford P
- Clifton S
- Coching RM
- Codutti OR
- Cohen S
- Collins N
- Colombo HR
- Colquhoun D
- Commerford PJ
- Concha YMR
- Conrad G
- Constantine G
- Constantinescu MCA
- Convens C
- Cools F
- Corbett C
- Cornel JH
- Correa Flores RM
- Cosavalente LAC
- Cosin Sales J
- Costa F
- Coste P
- Cottin Y
- Coufal Z
- Coverdale SGM
- Cristian G
- Cruz Fernandez JM
- Cuccia C
- Cui L
- Cyster HP
- Czerski T
- D'Urso M
- Daboul N
- Dagher G
- Dahl C
- Dai K
- Dalby AJ
- Dalby AJ
- Danchin N
- Dandillaya R
- Daniels C
- Das S
- Davidovic G
- Davidsen F
- Davies R
- Davis W
- De Berrazueta Fernandez JR
- De Cesare NB
- De Leo A
- De Luca G
- De Mora Martin M
- De Pellegrin A
- De Salazar DIM
- de Santos MON
- de Silva HA
- de Souza JA
- De Wolf L
- Delarche N
- Deloatch S
- Demirtas M
- Denham D
- Devarapalli SK
- DeVore AD
- Diamantis S
- Diaz Fernandez JF
- Diaz A
- Diaz R
- Dickey S
- Dilic M
- Dimkovic S
- Dimov BI
- Dincic DV
- Ding C
- Dion D
- Dodic S
- Dombrowski K
- Doncovska S
- Dong S
- Dong Y
- Dorobantu M
- Dorsel T
- Dran RD
- Drexel H
- Drzewiecka A
- Ducas J
- Ducrocq G
- Duda N
- Dujardin K
- Dukat A
- Dulak E
- Dupuis R
- Durak-Nalbantic A
- Duronto EA
- Dzupina A
- Dzyak G
- Eagerton D
- Eapen Z
- East C
- Eaton C
- Ebrahim IO
- Edelberg JM
- Edes I
- Egorova L
- Eisenberg S
- Ekanayaka R
- El Shahawy M
- El-Ahdab F
- Elias M
- Eliaschewitz FG
- Elliott J
- Endsley P
- Eppinger A
- Erglis A
- Erglis A
- Ersanli M
- Fadlallah H
- Faes D
- Faggiano P
- Fairlamb J
- Fajardo Campos P
- Falukozy J
- Fang C-Y
- Fang W
- Fanghanel Salmon G
- Farhat N
- Farrar M
- Fausto Ovando SR
- Fazekas F
- Fazlibegovic E
- Feitosa GS
- Fell D
- Feng Y
- Fernandes Manenti ERF
- Fernandez Portales J
- Fernandez AM
- Fernandez M
- Fernando N
- Ferrari E
- Ferratini M
- Ferrolino A
- Filardi PP
- Fischer S
- Fishberg R
- Fisher D
- Fisher N
- Fisher R
- Florenzano F
- Flores E
- Flores REO
- Fong P
- Forgosh L
- Foster M
- Foster R
- Francis A
- Franek E
- Fras Z
- French WJ
- Friedman D
- Frost L
- Fu G
- Fuchs S
- Fuentes Jimenez F
- Fujii K
- Fujimoto K
- Fujinaga H
- Fulop P
- Fulwani MC
- Furukawa Y
- Galski T
- Galvani M
- Gapon L
- Garcia Brasca DF
- Garcia Castillo A
- Garcia Duran RO
- Garcia Lledo JA
- Garcia-Dorado D
- Gardner G
- Garrahy PJ
- Garrido M
- Garza Ruiz JA
- Gavish D
- Ge J
- Gelormini J
- Gerber J
- Gerber R
- Ghitis A
- Ghlonti R
- Gibson P
- Gielen S
- Giesler G
- Gil-Extremera B
- Gilbert JM
- Gillespie E
- Gilmore R
- Gimple L
- Giordano JA
- Giorgeto FE
- Gislason G
- Giuliano ME
- Gniot J
- Goch A
- Goloborodko B
- Gomez Vilamajo OA
- Gonsorcik J
- Gonzales RJV
- Gonzalez Diaz B
- Gonzalez Salas LG
- Gonzalez-Juanatey C
- Gonzalez-Juanatey JR
- Goodman SG
- Goodman SG
- Gordeev I
- Gordienko A
- Gorny J
- Gosselin G
- Gosselink ATM
- Gotcheva NN
- Gotcheva NN
- Govinda RA
- Goyal NK
- Gremmler U
- Grewal JS
- Griffiths H
- Gring C
- Groenemeijer BE
- Groutars RGEJ
- Guardigli G
- Guerrero De Leon M
- Guha S
- Gullestad L
- Guneri S
- Guneri S
- Guo Y
- Gurevich V
- Gusi Tragant G
- Guzman PN
- Haddad T
- Hagstrom E
- Hagstrom E
- Hahalis PIG
- Halabi M
- Halcox J
- Hald F
- Haldis T
- Hall J
- Halvorsen S
- Hameed A
- Haniffa R
- Hanotin C
- Hansen O
- Haraguchi T
- Harding S
- Harkut P
- Harrington RA
- Harris B
- Harris B
- Hart H
- Hata Y
- Hattler B
- Hedman A
- Heidenreich L
- Heinc P
- Heitzer T
- Hemetsberger R
- Henderson D
- Henkin Y
- Herath JI
- Herazo AS
- Hermans K
- Hermans WRM
- Hernandez HAA
- Herrman JPR
- Hersbach FMRJ
- Hess CN
- Higashikata T
- Higuera JD
- Hii CLS
- Hirayama A
- Hirooka K
- Hlatky MA
- Hoag G
- Hodes Z
- Hoffer E
- Hoffman D
- Hong T
- Hoogslag PAM
- Hoppe U
- Horak D
- Horowitz J
- Horvath I
- Horwitz P
- Hove JD
- Hrabar AD
- Hranai M
- Hsieh I-C
- Huang L
- Huang S
- Huang T-Y
- Huang W
- Huber K
- Huidobro L
- Huikuri H
- Hunter J
- Hurtig U
- Hussein O
- Huynh T
- Hwang J-J
- II TC
- III DG
- III KG
- Ilic S
- Ilieva-Pandeva KA
- Ince C
- Iniguez A
- Investigators ODYSSEYOUTCOMES
- Iqbal SMR
- Irimpen A
- Istratoaie O
- Ito K
- Ivanov IG
- Ivanova R
- Ivanovic N
- Iyengar SS
- Izzo M
- Jacoby D
- Jafar Z
- Jaffrani N
- Jain D
- Janik M
- Janosik D
- Jaramillo N
- Jatin FGM
- Jaworska K
- Jayawardena J
- Jensen SA
- Jensen SA
- Jeong MH
- Jeppesen J
- Jeserich M
- Jiang W
- Jintapakorn W
- Johansen PB
- Jonas M
- Jones WS
- Jordan JD
- Jortveit J
- Joshi AB
- Joshi P
- Jovin I
- Jr CE
- Jr HW
- Jr LC
- Jr MJ
- Jr PW
- Jr RW
- Jr SJ
- Jr SJF
- Jr WD
- Jujjuru S
- Jukema JW
- Juonala M
- Jure HO
- Jurgaitiene R
- Kadr H
- Kaewsuwanna P
- Kahali D
- Kaikkonen K
- Kaiser S
- Kalashetti S
- Kalil R
- Kamensky G
- Kamiya H
- Kandasamy B
- Kapin T
- Kaplan R
- Kapp IE
- Karalis I
- Karlsberg R
- Karna S
- Karpenko O
- Karpenko Y
- Karpov Y
- Karpov Y
- Kartalis A
- Kasim S
- Katona A
- Katsuda Y
- Katz A
- Kaucak V
- Kavaliauskiene R
- Kawasaki T
- Ke Y
- Keating F
- Kedev S
- Keen W
- Kehasukcharoen W
- Kelsey SF
- Kerkar P
- Khabeishvili G
- Khaira AS
- Khaisheva L
- Khan A
- Khan A
- Khan M
- Khasanov N
- Khintibidze I
- Khurana S
- Kibarskis A
- Kichukov KN
- Killat H
- Kim C
- Kim HS
- Kim MH
- Kim S-H
- Kimmelstiel C
- Kimura K
- Kimura T
- King M
- Kirma C
- Kishi K
- Kiss RG
- Kiss RG
- Kiviniemi T
- Kjovkaroski A
- Klancke K
- Klantsa A
- Klausen IC
- Kline G
- Klutstein M
- Knickelbine T
- Knowles JW
- Knutson T
- Koba S
- Kobalava Z
- Kobayashi J
- Koike A
- Koldas L
- Kolls BJ
- Kondo NI
- Kong DF
- Kopytsya M
- Koren M
- Kormann A
- Kornder J
- Kornowski R
- Korol M
- Kosinski E
- Kosmachova E
- Kostarska-Srokosz E
- Kostis J
- Kotha P
- Kouz S
- Kovalskyi I
- Kozuma K
- Krasowski W
- Krawczyk J
- Krichmar P
- Kristensen KS
- Kubica J
- Kubilius R
- Kuchar J
- Kuhlman P
- Kultursay H
- Kumar A
- Kumar P
- Kumbla M
- Kumkumian G
- Kuo J-Y
- Kurian J
- Kushnir M
- Kutniy O
- Kyiak Y
- Labroo A
- Lai C
- Lai W-T
- Landzberg J
- Larry J
- Larsen J
- Laucevicius A
- Laufs U
- Laxson D
- Lazov PV
- Leaes PE
- Leclercq F
- Lee K
- Lee K
- Lefevre T
- Leggewie S
- Lehman SJ
- Leimbach W
- Lekakis J
- Leon RPC
- Leonardi S
- Leone A
- Lepage S
- Lepor N
- Leshchuk O
- Lester FM
- Leung R
- Levy T
- Li H
- Li J
- Li X
- Li Y
- Lianopoulos E
- Liberman A
- Liberopoulos E
- Liberopoulos E
- Libov I
- Licciardello G
- Lieber I
- Liem AAH
- Liew HB
- Lillis L
- Lin J
- Lin W
- Lin WH
- Lin X
- Lindsey J
- Linhart A
- Link C
- Lip GYH
- Lipar L
- Lipko JA
- Liu M-E
- Liu S
- Llamas Esperon GA
- Loma-Osorio Rincon P
- Lomakin NV
- Lomholdt JD
- Lominadze Z
- Lopes RD
- Lopes RD
- Lopes RD
- Lopes RD
- Lopez Rosas E
- Lopez RB
- Lopez-Jaramillo P
- Lorenzatti AJ
- Lotan C
- Lottering H
- Lotun K
- Loussararian A
- Love M
- Lozada HJG
- Lozance N
- Lubinski A
- Luciardi HL
- Lui H
- Luis Zamorano J
- Luo Z
- Lupkovics G
- Lupovitch S
- Luquez HA
- Lyamina N
- Lysek R
- M Escudier J
- MacDonald P
- Macdonell A
- Mach F
- Machado L
- Machova V
- Mackinnon IJ
- Mahaffey KW
- Mahajan A
- Mahal S
- Maia LN
- Majercak I
- Makotoko EM
- Malhotra V
- Malik A
- Malozzi C
- Malynovsky Y
- Manakshe GV
- Mannucci JEB
- Mano T
- Manolis A
- Mansourati J
- Marais HJ
- Marcus J
- Marin Neto JA
- Marin F
- Markov DT
- Markov V
- Maron DJ
- Martinez Sanchez CR
- Martins D
- Martsin K
- Marusincova I
- Marx N
- Marx N
- Marx R
- Maskon O
- Matas Pericas L
- Matei AV
- Mathews R
- Mathur A
- Mathur R
- Matiga G
- May O
- May W
- Mayurathan G
- Mazur J
- Mcclure S
- Mcgough M
- Mclaurin B
- Medrano Allende JC
- Mehta RH
- Mehta S
- Meloni C
- Mendis S
- Mendonca C
- Mendoza JLA
- Mentz RJ
- Merkely B
- Michalaros YL
- Michaud N
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- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study
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- A. Adam M.
- A. Nassar M.
- A. Nemer A.
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- 'Elsevier BV'
- Publication date
- 01/01/2022
- Field of study
Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised
The role of BRCA1 and BRCA2 in prostate cancer
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- Yong H
- Yoon JH
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- Zaidman CJ
- Zainea M
- Zaman A
- Zapata G
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- Zeiher AM
- Zeiher AM
- Zhang R
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- Zheng Y
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- Zhu H
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- Zirlik A
- Zizka J
- Zobouyan I
- Zong W
- Zrazhevsky K
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 04/01/2019
- Field of study
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- Author
- A Gordon Robertson
- Abdullah Kahraman
- Abel Gonzalez-Perez
- Adam A Margolin
- Adam Abeshouse
- Adam Grundhoff
- Adam J Struck
- Adam J Struck
- Adam J Wright
- Adam Lambert
- Adam P Butler
- Adam P Butler
- Adel El-Naggar
- Adnan M Nagrial
- Adrian Ally
- Adrian Baez-Ortega
- Adrian Thorogood
- Adriana Salcedo
- Adrienne M Flanagan
- Ake Borg
- Akihiro Fujimoto
- Akihiro Suzuki
- Akinyemi I Ojesina
- Alain Viari
- Alan J Robertson
- Alan P Hoyle
- Alan Thompson
- Alasdair Stenhouse
- Alastair M Thompson
- Aldo Scarpa
- Alessandro Pastore
- Alex Buchanan
- Alex Buchanan
- Alexander Claviez
- Alexander J Lazar
- Alexander Martinez-Fundichely
- Alfonso Muñoz
- Alfonso Valencia
- Aliaksei Z Holik
- Alice Meng
- Alicia L Bruzos
- Allison Creason
- Allison P Heath
- Alvin Wei Tian Ng
- Alvis Brazma
- Amaro Taylor-Weiner
- Amber L Johns
- Amie Radenbaugh
- Amit G Deshwar
- Ana Dueso-Barroso
- Ana Mijalkovic Mijalkovic-Lazic
- Ana Milovanovic
- Ana Milovanovic
- Andre Kahles
- Andrea Haake
- Andrea Holbrook
- Andrea L Richardson
- Andrea Mafficini
- Andrea Ruzzenente
- Andreas Behren
- Andreas Rosenwald
- Andreia V Pinho
- Andrew Berchuck
- Andrew D Cherniack
- Andrew J Dunford
- Andrew J Mungall
- Andrew J Spillane
- Andrew Menzies
- Andrew Menzies
- Andrew P Barbour
- Andrew Tutt
- Andrew V Biankin
- Andrey Korshunov
- Andrés Lanzós
- Andy Cafferkey
- Andy G Lynch
- Angela Chou
- Angela N Brooks
- Angela Tam
- Angelica Ochoa
- Angelika N Christ
- Angelo P Dei Tos
- Anieta M Sieuwerts
- Anil K Sood
- Anita Langerød
- Anja Füllgrabe
- Anke K Bergmann
- Ann-Marie Patch
- Anna deFazio
- Anna Ehinger
- Anna Fitzgerald
- Anne Hamilton
- Anne Vincent-Salomon
- Anne Y Warren
- Anne-Lise Børresen-Dale
- Annegien Broeks
- Anthony DiBiase
- Anthony J Gill
- Anthony Ng
- Anthony R Green
- Antonia L Pritchard
- Antonio Pea
- Antonios Koures
- Aparna Prasad
- Apurva M Hegde
- Aquila Fatima
- Arcadi Navarro
- Arie B Brinkman
- Arif O Harmanci
- Arindam Maitra
- Armando Lopez-Guillermo
- Arndt Borkhardt
- Arnoud Boot
- Asger Hobolth
- Ashley Williams
- Ashton A Connor
- Atul J Butte
- Aurélien Chateigner
- Austin J Hepperla
- Axel Aretz
- Aya Sasaki-Oku
- Ayellet V Segre
- B F Francis Ouellette
- Bailey Matthew H
- Barbara Hutter
- Barbara Hutter
- Barbara Kremeyer
- Bartha M Knoppers
- Beifang Niu
- Beifang Niu
- Beifang Niu
- Benedikt Brors
- Benita Kiat Tee Tan
- Benjamin J Raphael
- Benjamin P Berman
- Benjamin Raeder
- Bernardo Rodriguez-Martin
- Bernhard Radlwimmer
- Bernice H Wong
- Beth Karlan
- Bin Tean Teh
- Bin Zhu
- Birgit Burkhardt
- Bishoy M Faltas
- Bodil Bjerkehagen
- Bogdan Czerniak
- Boris Winterhoff
- Borislav C Rusev
- Bradly G Wouters
- Brandi N Davis-Dusenbery
- Brian Craft
- Brian D O'Connor
- Brian Patrick O'Neill
- Brice Aminou
- Calvin Wing Yiu Chan
- Cameron M Soulette
- Carl Herrmann
- Carl Morrison
- Carlo Gambacorti-Passerini
- Carlos Caldas
- Carlos D Bustamante
- Carlos López-Otín
- Carlota Rubio-Perez
- Carmen Gomez
- Carolien H M van Deurzen
- Carolyn M Hutter
- Carolyn M Hutter
- Carrie Cibulskis
- Caterina Vicentini
- Catherine A Shang
- Catherine D Moser
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- Stephen H Kazakoff
- Stephen J Chanock
- Stephen J Hayes
- Stephen M Cordner
- Stephenie D Prokopec
- Steve Hawkins
- Steve Hoffmann
- Steven A Roberts
- Steven E Schumacher
- Steven Foltz
- Steven G Rozen
- Steven Gallinger
- Steven Hazell
- Steven J M Jones
- Steven J Newhouse
- Steven Van Laere
- Stian Knappskog
- Stuart Edmonds
- Stuart R Jefferys
- Su Pin Choo
- Subhajit Sengupta
- Sue Merson
- Suet-Feung Chin
- Sultan T Al-Sedairy
- Sung-Min Ahn
- Sung-Soo Yoon
- Sunghoon Cho
- Sunil R Lakhani
- Suresh Ramalingam
- Susan Bullman
- Susanna L Cooke
- Sushant Kumar
- Sushant Kumar
- Suyash S Shringarpure
- Syed Haider
- Sylvia Asa
- Søren Brunak
- Takafumi N Yamaguchi
- Takafumi N Yamaguchi
- Takanori Hasegawa
- Takashi Yugawa
- Takashi Yugawa
- Takuji Okusaka
- Tal Shmaya
- Tannistha Nandi
- Taobo Hu
- Taobo Hu
- Tapio Visakorpi
- Tara J Skelly
- Tari A King
- Tatsuhiko Tsunoda
- Tatsuhiro Shibata
- Ted R Hupp
- Tetsuo Ushiku
- Theodorus Van der Kwast
- Thomas E Carey
- Thomas J Hudson
- Thomas J Matthew
- Thomas J Mitchell
- Thorsten Schlomm
- Thorsten Zenz
- Tian Xia
- Tim Dudderidge
- Tim Ley
- Timothy A Beck
- Timothy Defreitas
- Timothy J C Bruxner
- Timothy J Underwood
- Tina Wong
- Tirso Pons
- Tobias Madsen
- Tobias Rausch
- Todd A Johnson
- Todd D Pihl
- Tom Bodenheimer
- Tom Mikkelsen
- Tom Roques
- Tomas J Tanskanen
- Tomas Marques-Bonet
- Tomoko Urushidate
- Torill Sauer
- Toru Nakamura
- Treasa A McPherson
- Troy Shelton
- Tsun-Po Yang
- Ultan McDermott
- Umadevi Veluvolu
- Umut H Toprak
- Valerie Jakrot
- Varsha Tembe
- Vasilisa A Rudneva
- Venkata D Yellapantula
- Venkata D Yellapantula
- Vera B Kaiser
- Veronica Y Sabelnykova
- Victor Reuter
- Vikram Deshpande
- Viktoriya Korchina
- Ville Mustonen
- Vinayak Bhandari
- Vincent Ferretti
- Vincent Huang
- Vincent Huang
- Vincent J Gnanapragasam
- Vincent Khoo
- Vincenzo Corbo
- Vishal S Chandan
- Volker Hovestadt
- W Kimryn Rathmell
- W M Linehan
- Walker Hale
- Wan Choi
- Wanding Zhou
- Wang Liang-Bo
- Weerasinghe Amila
- Wei Jiao
- Wendl Michael C
- Wenyi Wang
- Wenyi Wang
- Wenyi Wang
- Wheeler David A
- William B Isaacs
- William C Faquin
- William Friedman
- William Howat
- William U Meyerson
- Willie Yu
- Winghing Wong
- Wojciech Bazant
- Wolfgang Huber
- Wolfram Klapper
- Xavier Estivill
- Xavier Pivot
- Xiao Xiao
- Xiaobo Li
- Xiaoping Su
- Xiaotong Li
- Xiaotong Yao
- Xing Hua
- Xingmin Liu
- Xinyue Li
- Xiuqing Zhang
- Xiuqing Zheng
- Xose S Puente
- Xuan Le
- Xuanping Zhang
- Xuemei Luo
- Xueqing Zou
- Yan Shi
- Yan Zhang
- Yang Wu
- Yang Yang
- Yann Joly
- Yanxun Xu
- Yao He
- Yasin Senbabaoglu
- Yassen Assenov
- Yasser Riazalhosseini
- Yasuhito Arai
- Yasushi Rino
- Yasushi Totoki
- Yeng Ang
- Yi Huang
- Yi Huang
- Yifei Men
- Yiling Lu
- Yilong Li
- Yingyan Yu
- Yiwen Chen
- Yogesh Kumar
- Yogesh Kumar
- Yoke-Eng Chiew
- Yong Hou
- Yong Zhou
- Yong-Jie Lu
- Yongzhan Nie
- Yosef E Maruvka
- Yosef E Maruvka
- Yoshiiku Kawakami
- Young Seok Ju
- Youngchoon Woo
- Youngil Koh
- Youngwook Kim
- Youyong Lu
- Yu Fan
- Yu Fan
- Yu Fan
- Yu-Jia Shiah
- Yuan Ji
- Yuan Yuan
- Yuichi Shiraishi
- Yulia Newton
- Yulia Rubanova
- Yumeng Wang
- Yupeng Cun
- Yussanne Ma
- Zachary Heins
- Zechen Chong
- Zechen Chong
- Zemin Zhang
- Zhaohong Chen
- Zhenggang Wu
- Zhenggang Wu
- Zhining Wang
- Zhongming Zhao
- Ziao Lin
- Zsofia Kote-Jarai
- Ólafur Andri Stefánsson
- Øystein Garred
- Publication venue
- Nature Communications
- Publication date
- 01/01/2020
- Field of study
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
Prostate Cancer: Evolution or Revolution?
- Publication venue
- 'American Society of Clinical Oncology (ASCO)'
- Publication date
- Field of study
Drug Monographs: Carfilzomib and Pertuzumab
- Author
- Publication venue
- 'Thomas Land Publishers'
- Publication date
- Field of study
- …