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001-es BibID:
BIBFORM107811
035-os BibID:
(Scopus)85160261108 (WoS)000941419200001
Első szerző:
Weiss, Emmanuel
Cím:
Sympathetic nervous activation, mitochondrial dysfunction, and outcome in acutely decompensated cirrhosis : the metabolomic prognostic models (CLIF-C MET) / Emmanuel Weiss, Carlos De La PeNa-Ramirez, Ferran Aguilar, Juan-José Lozano, Cristina Sánchez, Patricia Sierra, Pedro Izquierdo-Bueno, Juan Manuel Diaz, FranCois Fenaille, Florence Castelli, Thierry Gustot, Wim Laleman, Agustín Albillos, Carlo Alessandria, Marco Domenicali, Paolo Caraceni, Salvatore Piano, Faouzi Saliba, Stefan Zeuzem, Alexander Gerbes, Julia Wendom, Christian Jansen, Wenyi Gu, Maria Papp, Rajeshwar P. Mookerjee, Carmine Gambino, Cesar Jiménez, Ilaria Giovo, Giacomo Zaccherini, Manuela Merli, Antonella Putignano, Frank Erhard Uschner, Thomas Berg, Tony Bruns, Christian Trautwein, Alexander Zipprich, Rafael BaNares, José Presa, Joan Genesca, Victor Vargas, Javier Fernández, Mauro Bernardi, Paolo Angeli, Rajiv Jalan, Joan Claria, Christophe Junot, Richard Moreau, Jonel Trebicka, Vicente Arroyo, Canonic And Predict 22 Study Investigators
Dátum:
2023
ISSN:
0017-5749
Megjegyzések:
ABSTRACT BACKGROUND AND AIMS. Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with ACLF, underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS. Two prospective multi-center large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT validation, n=851) were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS. Three prognostic metabolites strongly associated with death were selected to build the models. 4-hydroxy-3-methoxyphenylglycol sulphate is a norepinephrine derivate, which may derive from the brainstem response to systemic inflammation. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulphate, hexanoylcarnitine, bilirubin, INR, and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared to MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.9399, 0.8339 and 0.7912, and 0.9471, 0.8566 and 0.8101, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa after 7, 14 25 and 28 days after admission for prediction of mortality.CONCLUSIONS. Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (e.g., MELDNa), especially in patients with ACLF.
Tárgyszavak:
Orvostudományok
Klinikai orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:
Gut. - 72 : 8 (2023), p. 1581-1591. -
További szerzők:
de la Pena-Ramirez, Carlos
Aguilar, Ferran
Lozano, Juan-José
Sánchez, Cristina
Sierra, Patricia
Izquierdo-Bueno, Pedro
Diaz, Juan Manuel
Fenaille, Francois
Castelli, Florence
Gustot, Thierry
Laleman, Wim
Albillos, Agustin
Alessandria, Carlo
Domenicali, Marco
Caraceni, Paolo
Piano, Salvatore
Saliba, Faouzi
Zeuzem, Stefan
Gerbes, Alexander
Wendom, Julia
Jansen, Christian
Gu, Wenyi
Papp Mária (1975-) (belgyógyász, gasztroenterológus)
Mookerjee, Rajeshwar P.
Gambino, Carmine
Jimenez, Cesar
Giovo, Ilaria
Zaccherini, Giacomo
Merli, Manuela
Putignano, Antonella
Uschner, Frank Erhard
Berg, Thomas
Bruns, Tony
Trautwein, Christian
Zipprich, Alexander
Bañares, Rafael
Presa, José
Genesca, Joan
Vargas, Victor
Fernández, Javier
Bernardi, Mauro
Angeli, Paolo
Jalan, Rajiv
Claria, Joan
Junot, Christophe
Moreau, Richard
Trebica, Jonel
Arroyo, Vicente
CANONIC and PREDICT 22 study investigators
Internet cím:
DOI
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