73 research outputs found
Cognition in Sensorimotor Control: Interfacing With the Posterior Parietal Cortex
- Publication venue
- 'Frontiers Media SA'
- Publication date
- 27/02/2019
- Field of study
Millions of people worldwide are afflicted with paralysis from a disruption of neural pathways between the brain and the muscles. Because their cortical architecture is often preserved, these patients are able to plan movements despite an inability to execute them. In such people, brain machine interfaces have great potential to restore lost function through neuroprosthetic devices, circumventing dysfunctional corticospinal circuitry. These devices have typically derived control signals from the motor cortex (M1) which provides information highly correlated with desired movement trajectories. However, sensorimotor control simultaneously engages multiple cognitive processes such as intent, state estimation, decision making, and the integration of multisensory feedback. As such, cortical association regions upstream of M1 such as the posterior parietal cortex (PPC) that are involved in higher order behaviors such as planning and learning, rather than in encoding movement itself, may enable enhanced, cognitive control of neuroprosthetics, termed cognitive neural prosthetics (CNPs). We illustrate in this review, through a small sampling, the cognitive functions encoded in the PPC and discuss their neural representation in the context of their relevance to motor neuroprosthetics. We aim to highlight through examples a role for cortical signals from the PPC in developing CNPs, and to inspire future avenues for exploration in their research and development
Cognition in Sensorimotor Control: Interfacing With the Posterior Parietal Cortex
- Publication venue
- 'Frontiers Media SA'
- Publication date
- 01/02/2019
- Field of study
Millions of people worldwide are afflicted with paralysis from a disruption of neural pathways between the brain and the muscles. Because their cortical architecture is often preserved, these patients are able to plan movements despite an inability to execute them. In such people, brain machine interfaces have great potential to restore lost function through neuroprosthetic devices, circumventing dysfunctional corticospinal circuitry. These devices have typically derived control signals from the motor cortex (M1) which provides information highly correlated with desired movement trajectories. However, sensorimotor control simultaneously engages multiple cognitive processes such as intent, state estimation, decision making, and the integration of multisensory feedback. As such, cortical association regions upstream of M1 such as the posterior parietal cortex (PPC) that are involved in higher order behaviors such as planning and learning, rather than in encoding movement itself, may enable enhanced, cognitive control of neuroprosthetics, termed cognitive neural prosthetics (CNPs). We illustrate in this review, through a small sampling, the cognitive functions encoded in the PPC and discuss their neural representation in the context of their relevance to motor neuroprosthetics. We aim to highlight through examples a role for cortical signals from the PPC in developing CNPs, and to inspire future avenues for exploration in their research and development
Lbx2 regulates formation of myofibrils
- Author
- B Thisse
- BL Martin
- BP Srinivas
- C Birchmeier
- C Neyt
- C Wolff
- CA Davis
- CA Henry
- CA Moore
- CB Kimmel
- CB Kimmel
- CS Blagden
- E Hirsinger
- E Mizuhara
- EN Olson
- ES Weinberg
- F Chen
- F Reifers
- F Stellabotte
- G Peng
- GE Hollway
- H Ochi
- H Ochi
- H Ochi
- Haruki Ochi
- J Garcia-Fernandez
- J Lu
- K Hatta
- K Jagla
- K Wei
- KR Wotton
- M Westerfield
- M Westerfield
- M Westerfield
- MJ Barresi
- MJ Potthoff
- MK Gross
- Monte Westerfield
- N Kahane
- N Kahane
- PW Ingham
- RJ Bryson-Richardson
- S Schulte-Merker
- S Watanabe
- SH Devoto
- SJ Du
- T Jagla
- T Maqbool
- V Sartorelli
- Y Au
- Y Hinits
- Y Nabeshima
- Y Xu
- YL Yan
- Publication venue
- BioMed Central
- Publication date
- 01/02/2009
- Field of study
<p>Abstract</p> <p>Background</p> <p>Skeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils. The <it>Drosophila ladybird homeobox </it>gene (<it>lad</it>) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping. Tetrapods have two homologous genes (<it>Lbx</it>). Lbx1 functions in migration and/or proliferation of hypaxial myoblasts, whereas the function of Lbx2 is poorly understood.</p> <p>Results</p> <p>To elucidate the role of Lbx in vertebrate myogenesis, we examined Lbx function in zebrafish. Zebrafish <it>lbx2 </it>transcripts appear in newly formed paraxial mesoderm and become restricted to adaxial cells, precursors of slow muscle. Slow muscles lose <it>lbx2 </it>expression as they differentiate, while a subset of differentiating fast muscle cells transiently expresses <it>lbx2</it>. Fin and hyoid muscle express <it>lbx2 </it>later. In contrast, <it>lbx1b </it>expression first appears lateral to the somites at late segmentation stages and is later restricted to fin muscle. Morpholino knockdown of Lbx1b and Lbx2 suppresses hypaxial muscle development. Moreover, knockdown of Lbx2 results in malformation of muscle fibers and reduced fusion of fast precursors, although no obvious effects on induction or specification are observed. Expression of myofilament genes, including <it>actin </it>and <it>myosin</it>, requires the engrailed repressor domain of Lbx2.</p> <p>Conclusion</p> <p>Our results elucidate a new function of Lbx2 as a regulator of myofibril formation.</p
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
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- Abdel-Aziz AK
- Abdelfatah S
- Abdellatif M
- Abdoli A
- Abel S
- Abeliovich H
- Abildgaard MH
- Abudu YP
- Acevedo-Arozena A
- Adamopoulos IE
- Adeli K
- Adolph TE
- Adornetto A
- Aflaki E
- Agam G
- Agarwal A
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- Agnello M
- Agostinis P
- Agrewala JN
- Agrotis A
- Aguilar PV
- Ahmad ST
- Ahmed ZM
- Ahumada-Castro U
- Aits S
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- Akoumianaki T
- Akpinar HA
- Al-Abd AM
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- Alaoui-Jamali MA
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- Alcocer-GĂłmez E
- Alessandri C
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- Ălvarez ĂMC
- Ăvalos Y
- Ănal G
- ĂstĂŒn S
- ÄoliÄ M
- ÄokiÄ J
- Ćœerovnik E
- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
- Author
- A. -G. Wu
- A. C. Ma
- A. K. Au
- Abdel-Aziz A. K.
- Abdelfatah S.
- Abdellatif M.
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- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study
- Author
- A Yacoub M.
- A. Adam M.
- A. Nassar M.
- A. Nemer A.
- Aahlin E. K.
- Ab Rahim M. F.
- Abad Gurumeta A.
- Abad-Motos A.
- Abang Jamari D. Z. H.
- Abantanga F.
- Abarca S.
- Abazid E.
- Abbas A.
- Abbas K.
- Abbas M. M.
- Abbasy J.
- Abbosh A.
- Abd B.
- Abd Karim M. F. S.
- Abd Wahab H. H.
- Abdalei A.
- Abdalla Ahmed Elkamel A.
- Abdallah A.
- AbdAllah M. S. M.
- Abdel Malik A. B.
- Abdelhady Mousa H.
- Abdelhady S.
- Abdelhakim A.
- Abdelkader M.
- Abdelkawy S.
- Abdelkhalek M.
- Abdellatif E.
- Abdelmaksoud Tawakel N.
- Abdelmohsen N.
- Abdelmotaleb I.
- Abdelrazek A.
- Abdelsalam I.
- Abdelshakour M.
- Abdelwahed A. M.
- Abdou A.
- Abdou A. O.
- Abdou H.
- Abdul Aziz M. R.
- Abdul Aziz N.
- Abdulgawad Almogy M.
- Abdulla M. A.
- Abdullah M. T.
- Abdullahi L.
- Abdullayev S.
- Abed S.
- Abello D.
- Abiola O.
- Abo mahadi A.
- Abo-khammash A.
- Abou Chaar M. K.
- Abou El. soud M. R.
- Abouelsoad N.
- Abraham J.
- Abreu da Silva A.
- Abu Ahammala A. B.
- Abu Al Amrain M.
- Abu Al-saleem H.
- Abu Alamrain A.
- Abu Alqumboz A.
- Abu Ataya A.
- Abu hallalah M. F. K.
- Abu Jamie N.
- Abu Jayyab I.
- Abu shua'ib R.
- Abu Zainah B.
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- Zupan D.
- Publication venue
- '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
CYP1A2 â a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients
- Author
- A Jemal
- A Markkula
- Andrea Markkula
- AU Buzdar
- B Leyland-Jones
- Carsten Rose
- Christian Ingvar
- CK Osborne
- CK Osborne
- DP Cronin-Fenton
- DW Lum
- E Aklillu
- E BĂ„geman
- G Lunardi
- H Jernström
- H Mouridsen
- H Wang
- Helena Jernström
- HL Blackburn
- IE Smith
- J Kotsopoulos
- J Schneider
- JA Jung
- JK Burmester
- JR Long
- KB Lundin
- L Wang
- LA Li
- LK Kamdem
- LK Kamdem
- LM McShane
- M Fernö
- M Ingelman-Sundberg
- M Kaufmann
- M Simonsson
- M Simonsson
- Maria Simonsson
- N Djordjevic
- N Hou
- O Artigalas
- PA Fasching
- S Helmig
- S Jeong
- SC Sim
- SF Zhou
- Srinivas Veerla
- SW Grimm
- TL Klug
- W Li
- WD Dupont
- WR Miller
- WR Miller
- X Yang
- Y Benjamini
- Y Li
- Y Tsuchiya
- Z Garcia-Casado
- Z Jiang
- Z Jiang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
- Author
- Abassi Yama
- Abelin Jennifer G
- Abolhalaj Milad
- Abraham Tara S
- Adam Ammar
- Adams David
- Adams Homer
- Adams Sarah F
- Adamus Tomasz
- Addepalli Murali
- Addepalli Murali
- Adjei Alex A
- Agapova Larissa
- Agarwala Sanjiv
- Ager Casey
- Aggarwal Charu
- Agnello Giulia
- Agudo Judith
- Aguilar Ethan G
- Aguilera Todd
- Ahamadi Malidi
- Ahn Yong-Oon
- Ahrens Eric T
- Aizer Ayal
- Ajina Reham
- Akerley Wallace
- Al-Muftah Mariam
- Albershardt Tina C
- Albershardt Tina C
- Albrekt Ann-Sofie
- Alekar Shilpa
- Alemany Ramon
- Alemany Ramon
- Alexander Brian
- Allbritton Omaira
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- Alley Evan W
- Allison James
- Allison James
- Allison James
- Alston Tesha
- Alt JĂŒrgen
- Alters Susan
- Amatulli Michael
- Anand Snjezana
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- Anderson Clark
- Anderson Mark
- Andersson Bengt
- Andre Pascale
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- Angiuoli Sam
- Ansari Tameem
- Anthony Scott
- Antonarakis Emmanuel S
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- Wilson James M
- Wilson Nicholas
- Winters Kevin
- Withers Sita
- Wittig Burghardt
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolfreys Alison
- Won Haejung
- Wong Chihunt
- Wong Chihunt
- Wong Deborah J
- Wong Gabriel
- Wong Kenneth R
- Wong Kenneth R
- Wong Michael K
- Wood Laura
- Woodside Darren G
- Workman Creg
- Wu Bill X
- Wu Dongyun
- Wu Jennifer
- Wu Yeting
- Wyant Timothy
- Wythes Martin
- Xi Biao
- Xia Leiming
- Xia Yang
- Xia Yang
- Xiang Bo
- Xiao Christine
- Xiao Hong
- Xiao Zhilan
- Xu Chun-wei
- Xu Chunxiao
- Xu Guifen
- Xu Xiaomei
- Xu Xin
- Xu Ya-Ming
- Xu Yitong
- Yadav Mahesh
- Yagiz Kader
- Yamashiro Darrell J
- Yan Jian
- Yang Chou
- Yang Ning
- Yang Zane
- Yano Hiroshi
- Yao Shiyin
- Ye Yun-bin
- Yin Catherine
- YlösmÀki Erkko
- YlösmÀki Erkko
- Young Gregory
- Young Gregory
- Young Kristina
- Young Rob
- Young Steve W
- Young Steve W
- Youssoufian Hagop
- Yu Huakui
- Yu Ling
- Yu Naichen
- Zafar Sadia
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zappasodi Roberta
- Zappasodi Roberta
- Zauderer Maurice
- Zeh Herbert
- Zelenetz Andrew D
- Zeng Weiping
- Zeng Xue
- Zha Yuanyuan
- Zhang Danhui
- Zhang Jing
- Zhang Ping
- Zhang Qifang
- Zhang Shannon S
- Zhang Theresa
- Zhang Winter
- Zhang Yanping
- Zhao Fei
- Zhao Leyna
- Zhao Xingli
- Zheng Lianxing
- Zheng Wenxin
- Zheng Xianxian
- Zheng Yi
- Zhong Hong
- Zhou Li
- Zhou Xiangjun
- Zippelius Alfred
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zou Jun
- Zuba-Surma Ewa
- Zubkova Olga
- Zureikat Amer
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro CarĂ Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
- Anthony Alpha
- Antoine Marchalot
- Antoine Pierre
- Antoine Studer
- Anumakonda Vikram
- Aparicio Christelle
- Aquino Maia
- Arabi Yaseen M.
- Arachchige Malka
- Aravindan Latha
- Arbane Gill
- Archambault Patrick
- Archer Simon
- Aref Noah
- Arias Ana-Marie
- Arias Sonia
- Arishi Hatim
- Arnold Donald
- Arnold John
- Arnott Andrew
- Arora Anand
- Aryal Diptesh
- Asghar Adeeba
- Asif Namra
- Aspinwall Angelique
- Attokaran Antony
- Attwood Ben
- Au Carly
- Audry Mathilde
- Austin Karen
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- Auvet Adrien
- Avard Bronwyn
- Awan Sidra
- Ayee Robert
- Azaiz Amine
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- Badie Julio
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- Baig Nadia
- Baikady Ravishankar
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- Baillie Kenneth
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- Bakthavatsalam Dhanalakshmi
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- Barbash Ian
- Barber Russell
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- Barker Gareth
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- Barnes Nicky
- Baron Rebecca M.
- Barreau Amelie
- Barreau Amélie
- Bart Robert
- Bartholomew Jazz
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- De Bus Liesbet
- de Courcy-Golder Kim
- de Groot Klaas
- de Jong Menno
- de Jonge Evert
- De Keulenaer Bart
- de la Torre Cisneros Julian
- de Man Angelique
- De Neef Mark
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- del Sorbo Lorenzo
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- Derde Lennie P. G.
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- Deye Nicolas
- de la Fuente Carmen
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- Voiriot Guillaume
- Volkov Lev
- Voza Gennaro
- Vuylsteke Alain
- Wada Asako
- Waddington Natalia
- Wahl Nadine
- Waite Alicia
- Walden Andrew
- Walker Gena
- Walker Rachel
- Walker Susan
- Walsh Joanne
- Walsh Tim
- Walsham James
- Walton Catherine
- Wang Shu
- Ward Geraldine
- Ward Kathryn
- Ward Luke
- Warnapura Loku
- Warnock Majella
- Watchorn Olivia
- Waters Abby
- Waterson Sharon
- Watkins Claire
- Watpool Irene
- Watters Malcolm
- Watts Angela
- Waugh Victoria
- Webb Steve A.
- Weber Lisa
- Webster Denise
- Weerasinghe Thanuja
- Weismann Dirk
- Weiss Daniel
- Weissman Alexandra
- Wells Alan
- Wells Colin
- Wells Karen
- Welters Ingeborg
- West Lauren
- Westlake Samantha
- Wetherill Bill
- Wetzold Richard
- Whileman Amanda
- Whitbread Jennifer
- White Alison
- White Hayden
- White Ian
- White Katie
- Whitehead Christina
- Whitehouse Tony
- Wibrow Bradley
- Wigbers Jeanette
- Wijewardena Gayathri
- Wilby Elizabeth
- Wilcox Elizabeth
- Wilcox Louise
- Wild Helen
- Wild Laura
- Wilding Laura
- Wiles Matt
- Wiley Daisy
- Wilhelmsen Elva
- Wilkinson Dean
- Willams Felicity
- Williams Alexandra
- Williams Angharad
- Williams Anna
- Williams Erin
- Williams Gemma
- Williams Hannah
- Williams Karen
- Williams Marie
- Williams Patricia
- Williams Penny
- Williams Tony
- Williams Virginie
- Williamson Dawn
- Williamson James D
- Willis Joanna
- Willson Jayne
- Wilson Anna
- Wilson Craig
- Wilson Jean
- Wilson Maggie
- Winters James
- Winters Lauren
- Wise Matt
- Wisniewski Mary
- Wittekamp Bastiaan
- Wittenberg Wendy
- Wnuk Chris
- Woelke Amy
- Wong Jenny
- Wong Onyee
- Wood Erica
- Wood Hannah
- Wood Tracy
- Woods Jane
- Woods Lindsey
- Woodward Robert
- Woolett Melissa
- Worner Ruth
- Wren Jess
- Wren Lynn
- Wrey Brown Caroline
- Wright Chris
- Wright Kim
- Wunderley Renee
- Wyatt Rachel
- Wylie Katharine
- Xavier Kugan
- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
- Yates Bryan
- Yates David
- Yealy Donald
- Young Ian
- Young Meredith
- Young Paul
- Youngstein Taryn
- Yu Haili
- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
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