9 research outputs found
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
- Author
- Adams J.D. (John D.)
- Agel J. (Julie)
- Ahn H. (Henry)
- Ahn J. (Jaimo)
- Albers G.H.R. (G.H. Robert)
- Alexander D. (David)
- Alosky R. (Rachel)
- Amirault J.D. (J. David)
- Amundsen A. (Asgeir)
- Anand S. (Sanjeev)
- Anderson C.G. (Christopher G.)
- Anderson L.K. (Linda K.)
- Anderson S.A. (Sarah A.)
- Apostle K. (Kelly)
- Archdeacon M. (Michael)
- Arora V. (Vinod)
- Aurang K. (Kamran)
- Avram V. (Victoria)
- Axelrod T. (Terry)
- Baele J. (Joseph)
- Baker J.K. (Janell K.)
- Bannister E.R. (Evan R.)
- Bardana D. (Davide)
- Barden B.B. (Benjamin B.)
- Beckish M.L. (Michael L.)
- Bedi H. (Harvinder)
- Ben Schmidt G. (G.)
- Bhandari M. (Mohit)
- Bhatia M. (Mahesh)
- Bicknell R. (Ryan)
- Biddulph M. (Michael)
- Bielby S.A. (Shea A.)
- Biert J. (Jan)
- Blokhuis T.J. (Taco J.)
- Borch T. (Tor)
- Borsella V. (Vivian)
- Bosma J. (Jan)
- Bosman C.H.R. (Coks H.R.)
- Bowler C. (Carol)
- Boxma H. (Han)
- Boyer D. (Dory)
- Brattgjerd J.E. (Jan Egil)
- Brekke A.C. (Anne Christine)
- Brennan M.L. (Michael L.)
- Breslin M. (Mary)
- Brien H. (Heather)
- Broderick J.S. (J. Scott)
- Brom H.L.F.
- Bronkhorst M.W.G.A. (Maarten)
- Browner K. (Kieran)
- Bruijninckx M.M.M. (Milko)
- Buckingham L. (Lisa)
- Buckley R.E. (Richard E.)
- Bucknill A. (Andrew)
- Buijk S.E. (Steven E.)
- Butler M.S. (Mark S.)
- Bzovsky S. (Sofia)
- Bøe B. (Berthe)
- Caminiti S. (Stephanie)
- Campo M. (Martin)
- Cannada L.K. (Lisa K.)
- Cantu R.V. (Robert V.)
- Carcary K. (Kimberly)
- Carlisle H. (Hope)
- Carr A. (Ashley)
- Cass J.R. (Joseph R.)
- Charlton M. (Michael)
- Cherian J.J. (Joe Joseph)
- Chia A. (Andrew)
- Chuter G. (Graham)
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- Clarke-Jenssen J. (John)
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- De Rooij P.D. (Peter D.)
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- De Vries J.P.P.M. (Jean Paul P.M.)
- De Waal Malefijt M.C. (Maarten C.)
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- Devereaux P.J.
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- Subash ()
- Sullivan R.J. (Raymond J.)
- Sundaresh D.C. (D. C.)
- Swenson T.K. (Teresa K.)
- Swinton M. (Marilyn)
- Swiontkowski M.F. (Marc )
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- Tan E.C.T.H. (Edward C.T.H.)
- Tanksley J.A. (John A.)
- Tanner S.L. (Stephanie L.)
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- Thabane L. (Lehana)
- Theunissen E.B.M. (Evert B.M.)
- Tieszer C. (Christina)
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- Ton L. (Lu)
- Torchia M.E. (Michael E.)
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- Vermeulen E.G.J. (Erik G.J.)
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- Wai E.K. (Eugene K.)
- Walker J.E. (Jane E.)
- Walter S.D. (Stephen D.)
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- Watson D.J. (Dylan J.)
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- Wood G. (Gavin)
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- Zielinski S.M. (Stephanie)
- Zijl J.A.C. (Jacco A.C.)
- Zohman G. (Gary)
- Zomar M. (Mauri)
- Zurcher A.W. (Arthur W.)
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/05/2018
- Field of study
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations
- Author
- Publication venue
- 'American Society for Biochemistry & Molecular Biology (ASBMB)'
- Publication date
- 20/04/2007
- Field of study
10.1074/jbc.M609466200Journal of Biological Chemistry2821612310-12318JBCH
Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases
- Author
- Arrasate
- Bence
- Bennett
- Bowman
- Chung
- Cuervo
- Cummings
- Donald S. Kirkpatrick
- Esther S.P. Wong
- Fortun
- Goldbaum
- Han Seok Ko
- Hara
- Hicke
- Iwata
- Jeanne M.M. Tan
- Juan Troncoso
- Kah-Leong Lim
- Klement
- Komatsu
- Kopito
- Levine
- Lim
- Lim
- Michael K. Lee
- Michelle W.L. Ho
- Miller
- Mukhopadhyay
- Olga Pletnikova
- Peng
- Pickart
- Pickart
- Ross
- Ross
- Rubinsztein
- Sanchez
- Saudou
- Shiam-Peng Tay
- Steven P. Gygi
- Ted M. Dawson
- Valina L. Dawson
- Volles
- Walsh
- Wang
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/02/2008
- Field of study
10.1093/hmg/ddm320Human Molecular Genetics173431-439HMGE
Autophagy-mediated clearance of aggresomes is not a universal phenomenon
- Author
- Ana Maria Cuervo
- Arrasate
- Auluck
- Berger
- Bjorkoy
- Bowman
- Chung
- Corti
- Costa
- Cuervo
- Cuervo
- Cummings
- Esther S.P. Wong
- Finn
- Fortun
- Fuertes
- Garcia-Mata
- Gotz
- Hara
- Hara
- Iwata
- Iwata
- Jeanne M.M. Tan
- Kabeya
- Kah-Leong Lim
- Kamila Hussein
- Kawaguchi
- Klement
- Klionsky
- Komatsu
- Komatsu
- Komatsu
- Kopito
- Liani
- Lim
- Lim
- Martinez-Vicente
- Massey
- Mignot
- Mishra
- Mizushima
- Mortimore
- Nagaoka
- Nobuyuki Nukina
- Olanow
- Opazo
- Pandey
- Pankiv
- Pica
- Ravikumar
- Ravikumar
- Ravikumar
- Ross
- Rott
- Rubinsztein
- Sarkar
- Saudou
- Shin
- Spillantini
- Sugawara
- Tanaka
- Ted M. Dawson
- Valina L. Dawson
- Waelter
- Wakabayashi
- Wang
- Webb
- Wen-E Soong
- Wigley
- Zatloukal
- Publication venue
- Oxford University Press
- Publication date
- 01/08/2008
- Field of study
Aggresomes are juxtanuclear inclusion bodies that have been proposed to act as staging grounds for the disposal of protein aggregates via the autophagic route. To examine whether the composition of an aggresome influences its clearance by autophagy, we ectopically expressed a variety of aggregation-prone proteins in cultured cells to generate aggresomes that differ in their protein content. We found that whereas aggresomes generated in cells expressing mutant huntingtin or mutant tau, or co-expressing synphilin-1 and α-synuclein, are amenable to clearance by autophagy, those produced in AIMP2 (p38)- or mutant desmin-expressing cells are apparently resistant to autophagic clearance. Notably, AIMP2 (p38)- and desmin-positive inclusions fail to recruit key components of the autophagic/lysosomal system. However, by altering the composition of inclusions, ‘autophagy-resistant’ aggresomes could be rendered ‘autophagy-susceptible’. Taken together, our results demonstrate that not all aggresomes are efficiently primed for autophagic clearance and highlight a certain degree of selectivity for the supposedly non-discriminative pathway
Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data
- Author
- Aceituno A
- Acosta I
- Adams A
- Adatia S
- Aerden Leo A.m.
- Aeron-thomas John
- Aggour Mohamed
- Aghaebrahim A
- Agid R
- Aguettaz Pierre
- Ahle Guido
- Aja L
- Akhtar N
- Al Najjar-carpentier Amen-adam
- Al'boutros S
- Al-ajlan F
- Albers Gregory W
- Albers Gregory W.
- Alexandrou M
- Alhazzaa M
- Ali L
- Allen E
- Almekhlafi M
- Alseraya A
- Aly J
- Amar Arun
- Amaro S
- Amato-marzialli B
- Amerson L
- Amiri H
- Andersen G
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- Apoil-brissard Marion
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- Baillot Pierre-alexandre
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- Saqqur M
- Sarma D
- Sarov Mariana
- Sasadeusz K
- Saver Jeffrey L
- Saver Jeffrey L
- Sawyer R
- Schaafsma Jd
- Scheibe Mirek T
- Scherber J
- Schindler K
- Schipperen Stefanie
- Schlamann M
- Schmidt M
- Schneble Hans-martin
- Schonewille Wouter J
- Schreuder Tobien H.c.m.l.
- Schunck Aurélia
- Schwaiger B
- Schwartzman M
- Schwindt B
- Scroop Rebecca
- Sedat Jacques
- Seder D
- Seifert C
- Selchen D
- Sellal François
- Selle C
- Serena J
- Serena J
- Serre Isabelle
- Seró L
- Sevin-allouet Mathieu
- Shah P
- Shah Q
- Shamloul R
- Shamy M
- Shankar J
- Shankar L
- Sharma Gagan
- Sharma M
- Shea K
- Sheth S
- Shine S
- Shuaib A
- Shuaib A
- Sibon Igor
- Siddiqui A
- Siddiqui Adnan H.
- Siddiqui M
- Silver Fl
- Silver Fl
- Silver Gabriel
- Simonsen C
- Simpson Marion
- Singer O
- Singh D
- Sirelkhatim A
- Sirelkhatim A
- Skaletsky M
- Slokkers Ilse
- Smith Craig
- Smith Ee
- Smith Wade
- Smreczak M
- Smyth G
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- Snyder K
- Snyder V
- Soendergaard H
- Sohn S-i
- Sombutmai C
- Song D
- Sonnberger M
- Sourour Nader
- Spears J
- Spencer B
- Spratt Neil
- Sprengers Marieke E.s.
- Staals Julie
- Stadler K
- Stapf Christian
- Star M
- Stark Richard
- Starkman S
- Starr M
- Stavngaard T
- Steffenhagen N
- Steinfort Brendan
- Stewart T
- Stewart T
- Stewart T
- Steyerberg Ewout W.
- Stijnen Theo
- Storey Kelley
- Stotts G
- Stout C
- Streib S
- Struijk Willy
- Stys Pk
- Subramaniam S
- Subramanian Ganesh
- Suissa Laurent
- Summers D
- Swarnkar A
- Swartz R
- Szatmary Zoltan
- Szeder V
- Sørensen K
- Sørensen L
- Tahon Florence
- Takahasi C
- Tampieri D
- Tampieri D
- Taqui A
- Tarabishy A
- Tarpley J
- Tateshima S
- Taudorf S
- Taylor M
- Taylor R
- Teitelbaum J
- Tekle W
- Ter Brugge K
- Thiesing Jt
- Thomalla G
- Thornton J
- Thornton J
- Tielbeek Alexander V.
- Tilikete Caroline
- Tomasello A
- Toth G
- Totoraitis V
- Totoraitis V
- Toulgoat Frederique
- Tournade Alain
- Tournebize Patrice
- Touze Emmanuel
- Trenkler J
- Trivedi A
- Trystram Denis
- Tu Hans
- Tummala R
- Tunguturi A
- Turc Guillaume
- Turjman Francis
- Turjman Francis
- Turk As
- Turner R
- Uchino K
- Urra X
- Urra Xabier
- Utpadel Fischler D
- Van Boxtel Tiemen
- Van Den Berg Jan S.p.
- Van Den Berg Lucie A
- Van Den Berg Lucie A
- Van Den Berg René
- Van Den Berg-vos Renske M.
- Van Der Heijden Esther
- Van Der Lugt Aad
- Van Der Lugt Aad
- Van Dijk Ewoud J.
- Van Dijk Lukas C.
- Van Dijk R
- Van Hasselt Boudewijn A.a.m.
- Van Oostayen Jacques A.
- Van Oostenbrugge Robert J
- Van Oostenbrugge Robert J.
- Van Rooij Willem Jan J.
- Van Vemde Gina
- Van Walderveen Marianne Aa
- Van Zwam Wim H
- Van Zwam Wim H.
- Vandorpe R
- Velasco Stephane
- Venema Esmee
- Veraque Emelda
- Viader Fausto
- Villar C
- Villwock M
- Vincent F
- Vinken Stefan
- Visser Marieke C.
- Vitello Nicolas
- Voguet Charlotte
- Voguet Charlotte
- Von Kummer Ruüdiger
- Von Weitzel Mudersbach P
- Vora N
- Vos Jan Albert
- Vroomen Patrick C.
- Vuillemet Françis
- Vuillier Fabrice
- Wagner A
- Wagner J
- Wagner M
- Wahlgren Nils
- Wakhloo A
- Walsh T
- Wang Adrien
- Wanke I
- Wardlaw Joanna
- Watson Tw
- Watt M
- Watts M
- Weaver M
- Wechsler L
- Wechsler L
- Weill A
- Weill A
- Weimar C
- Weinstein C
- Weisman Dc
- Wermer Marieke Jh
- Weymayr F
- Whaley M
- Whelan R
- White Philip
- White Philip
- Wiegner R
- Wiertlewski Sandrine
- Wiese C
- Wiggam I
- Wijeratne Tissa
- Williams D
- Williams D
- Williams J
- Willinsky Ra
- Willinsky Ra
- Wisco D
- Witteler A
- Wodarg F
- Wolff Valérie
- Wong Andrew
- Wong Jh
- Wong Jh
- Wong Kitty
- Wortmann G
- Wright Mr
- Wright Mr
- Wu Teddy Y
- Wunderlich S
- Yan Bernard
- Yanase L
- Yang V
- Yassi Nawaf
- Yavagal D
- Yavagal Dileep R
- Yavagal Dileep R.
- Yeo Ta
- Yger Marion
- Yoo Albert J
- Yoo J
- You Sj
- Young Dennis
- Yu Y
- Zacharatos H
- Zaidat O
- Zaidi S
- Zavanone Chiara
- Zech M
- Zegarac V
- Zerlauth Jean-baptiste
- Zimmel L
- Zuniga Paolo
- Zurasky J
- Publication venue
- 'Elsevier BV'
- Publication date
- 16/12/2017
- Field of study
Background:
General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.
Methods:
For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.
Findings:
Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low.
Interpretation:
Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons
Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial
- Author
- Adams J.D. (John D.)
- Agel J. (Julie)
- Ahn H. (Henry)
- Ahn J. (Jaimo)
- Albers G.H.R. (G.H. Robert)
- Alexander D. (David)
- Alosky R. (Rachel)
- Amirault J.D. (J. David)
- Amundsen A. (Asgeir)
- Anand S. (Sanjeev)
- Anderson C.G. (Christopher G.)
- Anderson L.K. (Linda K.)
- Anderson S.A. (Sarah A.)
- Apostle K. (Kelly)
- Archdeacon M. (Michael)
- Arora V. (Vinod)
- Aurang K. (Kamran)
- Avram V. (Victoria)
- Axelrod T. (Terry)
- Baele J. (Joseph)
- Baker J.K. (Janell K.)
- Bannister E.R. (Evan R.)
- Bardana D. (Davide)
- Barden B.B. (Benjamin B.)
- Beckish M.L. (Michael L.)
- Bedi H. (Harvinder)
- Bhandari Mohit
- Bhatia M. (Mahesh)
- Bicknell R. (Ryan)
- Biddulph M. (Michael)
- Bielby S.A. (Shea A.)
- Biert Jan
- Blokhuis T.J. (Taco J.)
- Borch T. (Tor)
- Borsella V. (Vivian)
- Bosma J. (Jan)
- Bosman C.H.R. (Coks H.R.)
- Bowler C. (Carol)
- Boxma Han
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- Brennan M.L. (Michael L.)
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- Brien H. (Heather)
- Broderick J.S. (J. Scott)
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- Bruijninckx Milko
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- Subash ()
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- Swiontkowski Marc
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- Tetteroo Geert
- Thabane Lehana
- Theunissen E.B.M. (Evert B.M.)
- Tieszer C. (Christina)
- Tilzey J.F. (John F.)
- Ton L. (Lu)
- Torchia M.E. (Michael E.)
- Tornetta Paul
- Torres E.T. (Erick T.)
- Trask K. (Kelly)
- Trenholm J.A. (J. Andrew)
- Trivedi M. (Mittal)
- Trommer A. (Axel)
- Turckan K. (Kahn)
- Tyagi V. (Vivek)
- Tynan M.C. (Martin C.)
- Ugland S. (Stein)
- Vallier H.A. (Heather A.)
- van der Brand I. (Igor)
- van der Hoeven H. (Henk)
- van Egmond T. (Teun)
- van Gaalen S.M. (Steven M.)
- van Mulken J. (Jeroen)
- van Vugt A.B. (Arie B.)
- van ‘t Riet M. (Martijne)
- Vang S. (Sandy)
- Verhagen R. (Ronald)
- Verhoeven B. (Bart)
- Verhofstad Michiel
- Vermeulen E.G.J. (Erik G.J.)
- Vesterhus E.B. (Elise Berg)
- Vicente M.R. (Milena R.)
- Vis Harm
- Viskontas D. (Darius)
- Visser G.A. (Gijs A.)
- Viveiros Helena
- Vogt M. (Michelle)
- Vries Alexander
- Vries Mark
- Vuylsteke R. (Ronald)
- Wadey V. (Veronica)
- Waes Oscar
- Wai E.K. (Eugene K.)
- Walker J.E. (Jane E.)
- Walter S.D. (Stephen D.)
- Wang O. (Otis)
- Ward A. (Angela)
- Watson D.J. (Dylan J.)
- Watson S.T. (Scott T.)
- Weber T. (Timothy)
- Weening B. (Brad)
- Weinerman S. (Stuart)
- Weingarten P. (Peter)
- Weinrauch P. (Patrick)
- Wessel R.N. (Ronald N.)
- Wessem K.J.P.
- Westberg J.R. (Jerald R.)
- Whatley E. (Erica)
- Whelan D.B. (Daniel B.)
- Wild L.M. (Lisa M.)
- Wille Jan
- Willems Jaap
- Wittich Philippe
- Wong I. (Ivan)
- Wood G. (Gavin)
- Worman R. (Ripley)
- Wright D.M. (David M.)
- Wyrick J. (John)
- Yach J. (Jeff)
- Yadav V. (Vineet)
- Yang S. (Steven)
- Yee A. (Albert)
- Yen D. (David)
- Yu M. (Michelle)
- Zalzal P. (Paul)
- Zamorano D.P. (David P.)
- Zellar A. (Abby)
- Zhou Q. (Qi)
- Zielinski Stephanie
- Zijl J.A.C. (Jacco A.C.)
- Zohman G. (Gary)
- Zomar M. (Mauri)
- Zurcher A.W. (Arthur W.)
- Publication venue
- 'Elsevier BV'
- Publication date
- 15/04/2017
- Field of study
Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdelrazik Marwa
- Abdollahi Hamed
- Abdullah T.
- Abecasis Goncalo
- Abedalthagafi M.
- Abel Lynn
- Abernathy C.
- Abraheem Azmeralde
- Abul-Husn Noura S.
- Acquilini D.
- Adams C.
- Adams Emma L.
- Adams K.
- Adamsara Alireza
- Adanini Olurenke
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal Shruti
- Agüero D.
- Ahmad N.
- Ahmadi Saeideh
- Ahmed A.
- Ahmed Cecilia
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich Alexandra
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z.Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G.M.
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- Aldridge J.
- Aleagha Afshar Etemadi
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- Publication venue
- Publication date
- 01/01/2022
- Field of study
Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data
- Author
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- Laetitia de Villiers
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- Ludo F.M. Beenen
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- Luis Manera
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- Lukas C. van Dijk
- M Alexandrou
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- M Eesa
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- M Ezzeddine
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- M Gomis
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- M Guglielmetti
- M Hamberger
- M Hammer
- M Hammer
- M Hernández-Pérez
- M Hjørringgaard
- M Hogan
- M Holtmannspötter
- M Horton
- M Howk
- M Jiménez
- M Jumaa
- M Kate
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- M Kowarik
- M Lapierre
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- M Maxwell
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- M Muchada
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- M Möhlenbruch
- M Nour
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- M Pham
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- M Reardon
- M Ribó
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- M Salluzzi
- M Salluzzi
- M Salvat-Plana
- M Santos
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- M Saqqur
- M Schlamann
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- M Shamy
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- M Siddiqui
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- M Smreczak
- M Sonnberger
- M Star
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- M Taylor
- M Villwock
- M Wagner
- M Watt
- M Watts
- M Weaver
- M Whaley
- M Zech
- M-J Danch
- MA de Miquel
- Manon Kappelhof
- Marc Bintner
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- Marcia Jeremenko
- Mariana Sarov
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- O Imoukhuede
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- S Adatia
- S Al-Boutros
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- S Arkin
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- S Biethahn
- S Blayney
- S Boned
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- S Crandall
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- S Decesare
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- S Duff
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- S Subramaniam
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- Sabrina Debruxelles
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- Sandrine Deltour
- Sandrine Wiertlewski
- Sanjeev Nayak
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- Serge Bakchine
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- Servane Mouton
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- Skye Coote
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- SR Belagaje
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- Stephen M Davis
- Stephen M Davis
- Susan Day
- Sylvain Lachaud
- Sylvie Godon-Hardy
- Sébastien Richard
- Sébastien Richard
- Séverine Debiais
- T Boeckh-Behrens
- T Coughlan
- T Daly
- T Daly
- T Davis
- T Devlin
- T Devlin
- T Galvin
- T Harbo
- T Hendrickson
- T Hyldal
- T Jeerakathil
- T Kahles
- T Krings
- T Larson
- T Lowenkopf
- T Lynch
- T Marotta
- T Meindl
- T Musuka
- T Nguyen
- T Reiff
- T Roberts
- T Sajobi
- T Sajobi
- T Scheibe-Mirek
- T Stavngaard
- T Stewart
- T Stewart
- T Stewart
- T Walsh
- TA Yeo
- Tae-Hee Cho
- Tanya Frost
- TB Kotylak
- Teddy Y Wu
- TG Jovin
- Thanh Phan
- Theo Stijnen
- Thibaud Lebouvier
- Thierry Moulin
- Thomas J Oxley
- Thomas Liebig
- Thomas Ritzenthaler
- Thomas Ronziere
- Thompson Robinson
- Tiemen van Boxtel
- Timo Krings
- Timothy Ang
- Timothy J Harrington
- Timothy J Kleinig
- Tiphaine Rouaud
- Tissa Wijeratne
- Tobien H.C.M.L. Schreuder
- Tommy Andersson
- Tony Goddard
- TS Field
- Tudor G Jovin
- Tudor G. Jovin
- TW Watson
- U Grzyska
- V Biberacher
- V Chang
- V Costalat
- V Deshmukh
- V Dubuc
- V Kalugdan
- V Nambiar
- V Obach
- V Pandey
- V Patel
- V Reddy
- V Snyder
- V Szeder
- V Totoraitis
- V Totoraitis
- V Yang
- V Zegarac
- VA Coté
- Valérie Domigo
- Valérie Wolff
- Vasdev Ashok
- Vincent Cahagne
- Vincent Costalat
- Vincent Guiraud
- Violaine Rouaud Jaffrenou
- Vitor Mendes Pereira
- VK Reddy
- W Clark
- W Holloway
- W Maloney
- W Montanera
- W Morgan
- W Pfeilschifer
- W Poon
- W Tekle
- Wade Smith
- Werner Hacke
- WF Morrish
- WF Morrish
- Willem Jan J. van Rooij
- Willy Struijk
- Wilma Pellikaan
- Wim H van Zwam
- Wim H. van Zwam
- Winston Chong
- Wintermark
- WJ Hicks
- WJ Montanera
- WJ Montanera
- Wouter J Schonewille
- X Ayrignac
- X Urra
- Xavier Barreau
- Xavier Ducrocq
- Xavier Leclerc
- Y Deschaintre
- Y Li
- Y Yu
- Yannick Bejot
- YD Kim
- Yince Loh
- Yves Chau
- Yves Samson
- Yvo B W E M Roos
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