Critical care (London, England) · 2025
An international observational study validating gene-expression sepsis immune subgroups.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Antcliffe David B, Peronnet Estelle, Pène Frédéric, Strålin Kristoffer, Brealey David, Blein Sophie, Cleaver Richard, Cronhjort Maria, Diehl Jean-Luc, Voiriot Guillaume, Fleurie Aurore, Lannsjö Claudia, Lukaszewicz Anne-Claire, Mårtensson Johan, Pham Tài, De Prost Nicolas, Ricard Jean-Damien, Singer Mervyn, Terraz Gabriel, Timsit Jean-François, Unge Christian, Vieillard-Baron Antoine, Wahlin Rebecka Rubenson, Llitjos Jean-François, Gordon Anthony C
Аннотация
BACKGROUND: Sepsis gene-expression sub-phenotypes with prognostic and theranostic potential have been discovered. These have been identified retrospectively and have not been translated to methods that could be deployed at the bedside. We aimed to identify subgroups of septic patients at high-risk of poor outcome, using a rapid, multiplex RNA-based test.
METHODS: Adults with sepsis, in the intensive care unit (ICU) were recruited from 17 sites in the United Kingdom, Sweden and France. Blood was collected at days 2-5 (S1), 6-8 (S2) and 13-15 (S3) after ICU admission and analyzed centrally. Patients were assigned into 'high' and 'low' risk groups using two models previously developed for the Immune-Profiling Panel prototype on the bioMérieux FilmArray® system.
RESULTS: 357 patients were recruited (March 2021-November 2022). 69% were male with a median age of 67 years, APACHE II score of 21 and a 30% 90-day mortality rate. The proportions of high-risk patients decreased over the three sampling times (model 1: 53%, 40%, 15% and model 2: 81%, 74%, 37%). In model 1, 90-day mortality was higher in a high-risk group at each time (S1: 35% vs 24%, p = 0.04; S2: 43% vs 20%, p < 0.001; S3: 52% vs 24%, p = 0.007). In model 2, mortality was only significantly different at the second sampling time (S1: 30% vs 27%, p = 0.77; S2: 34% vs 14%, p = 0.002; S3: 35% vs 23%, p = 0.13).
CONCLUSIONS: Gene-expression diagnostics can identify patients with sepsis at high-risk of poor outcomes and could be used to identify patients for precision medicine trials.
REGISTRATION: ISRCTN11364482 Registered 24th September 2020.
METHODS: Adults with sepsis, in the intensive care unit (ICU) were recruited from 17 sites in the United Kingdom, Sweden and France. Blood was collected at days 2-5 (S1), 6-8 (S2) and 13-15 (S3) after ICU admission and analyzed centrally. Patients were assigned into 'high' and 'low' risk groups using two models previously developed for the Immune-Profiling Panel prototype on the bioMérieux FilmArray® system.
RESULTS: 357 patients were recruited (March 2021-November 2022). 69% were male with a median age of 67 years, APACHE II score of 21 and a 30% 90-day mortality rate. The proportions of high-risk patients decreased over the three sampling times (model 1: 53%, 40%, 15% and model 2: 81%, 74%, 37%). In model 1, 90-day mortality was higher in a high-risk group at each time (S1: 35% vs 24%, p = 0.04; S2: 43% vs 20%, p < 0.001; S3: 52% vs 24%, p = 0.007). In model 2, mortality was only significantly different at the second sampling time (S1: 30% vs 27%, p = 0.77; S2: 34% vs 14%, p = 0.002; S3: 35% vs 23%, p = 0.13).
CONCLUSIONS: Gene-expression diagnostics can identify patients with sepsis at high-risk of poor outcomes and could be used to identify patients for precision medicine trials.
REGISTRATION: ISRCTN11364482 Registered 24th September 2020.