Idioma:

Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes

Antcliffe, David Benjamin ; Mi, Yuxin ; Santhakumaran, Shalini ; Burnham, Katie L ; Prevost, A Toby ; Ward, Josie K ; Marshall, Timothy J ; Bradley, Claire ; Al-Beidh, Farah ; Hutton, Paula ; McKechnie, Stuart ; Davenport, Emma E ; Hinds, Charles J ; O'Kane, Cecilia M ; McAuley, Daniel Francis ; Shankar-Hari, Manu ; Gordon, Anthony C ; Knight, Julian C

Thorax, 2024-06, Vol.79 (6), p.515-523 [Periódico revisado por pares]

England: BMJ Publishing Group Ltd and British Thoracic Society

Texto completo disponível

Citações Citado por

Enviar para

Título:
Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes
Autor: Antcliffe, David Benjamin ; Mi, Yuxin ; Santhakumaran, Shalini ; Burnham, Katie L ; Prevost, A Toby ; Ward, Josie K ; Marshall, Timothy J ; Bradley, Claire ; Al-Beidh, Farah ; Hutton, Paula ; McKechnie, Stuart ; Davenport, Emma E ; Hinds, Charles J ; O'Kane, Cecilia M ; McAuley, Daniel Francis ; Shankar-Hari, Manu ; Gordon, Anthony C ; Knight, Julian C
Assuntos: Aged ; Anti-inflammatory agents ; bacterial infection ; Bacterial infections ; Biomarkers ; Biomarkers - blood ; Blood ; Clinical outcomes ; Clinical trials ; Cluster Analysis ; Critical Care ; Cytokines ; Cytokines - blood ; Datasets ; Failure ; Female ; Humans ; Immunotherapy ; Inflammation ; Kidney diseases ; Latent class analysis ; Leukocytes ; Leukocytes - metabolism ; Male ; Middle Aged ; Patient satisfaction ; Patients ; Phenotype ; Plasma ; Proteins ; Regression analysis ; Respiratory distress syndrome ; Respiratory Distress Syndrome - blood ; Respiratory Distress Syndrome - drug therapy ; Respiratory Distress Syndrome - genetics ; respiratory infection ; Sepsis ; Sepsis - blood ; Sepsis - genetics ; Survival analysis ; Transcription factors ; Transcriptome ; Treatment Outcome ; Variables
É parte de: Thorax, 2024-06, Vol.79 (6), p.515-523
Notas: Original research
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Undefined-3
DBA and YM are joint first authors.
MS-H, ACG and JCK are joint senior authors.
Descrição: RationaleHeterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported.ObjectivesWe investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes.MethodsHierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters.Measurements and main resultsWe identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes.ConclusionsThese findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes.Trial registration number ISRCTN20769191, ISRCTN12776039.
Editor: England: BMJ Publishing Group Ltd and British Thoracic Society
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Resultado 1 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes

England: BMJ Publishing Group Ltd and British Thoracic Society

Buscando em bases de dados remotas. Favor aguardar.