Precision Medicine in Critical Illness: Sepsis and Acute Respiratory Distress Syndrome

Rogers, Angela; Meyer, Nuala J.

doi:10.1007/978-3-030-31507-8_18

Cited by 4 publications

(3 citation statements)

References 155 publications

(156 reference statements)

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“…Выявление генетических биомаркеров дает надежду на создание эффективных методов стратификации, прогнозирования и разработки новых методов лечения ОРДС [39]. Сочетание ОРДС и сепсиса характеризуется значительной летальностью.…”

Section: внедрение принципов пм в медицину критических состоянийunclassified

Personalized Critical Care Medicine (Review)

Голубев

2022

Obŝaâ reanimatologiâ

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Personalized medicine (PM) is a major trend in health care development in the 21st century. This area includes studying risk factors for disease development (prediction), interventions for preventing diseases (prophylaxis), individualization of diagnosis and treatment (personalization), informing the patient on disease prevention and treatment (participation). In the recent years, an intense research to introduce the personalized medicine principles into the management of critically ill patients, has been under way. This includes identification of patient groups based on genomic research, development of diagnostic tests using molecular markers, creation of novel classes of drugs based on individual patient characteristics.The aim of the review is to summarize the available data on the implementation of the principles of PM in the routine practice of critical care institutions.We analyzed more than 300 sources of literature from the Pubmed and Scopus databases, as well as the RSCI database. Eighty five most relevant sources were selected for the review. The paper reports data on the organization and results of implementation of PM principles and advanced technologies, such as Emergency Medicine Sample Bank (EMSB), in the daily activity of clinics providing emergency critical care. The formation of the novel PM concept focused on the treatment of critically ill patients has been discussed. The review contains detailed data on the patterns of development of specific critical illnesses such as acute cerebrovascular events, acute respiratory distress syndrome, traumatic brain injury, shock, myocardial infarction, cardiac rhythm and conduction disturbances. Medication eﬃcacy in view of individual genetic patient characteristics has also been highlighted. No research limitations on the subject were identified.Conclusion. The analysis of literature has demonstrated positive results of implementing PM principles in prevention, diagnosis and treatment of critically ill patients. Creation of Biobanks, development of training programs and regulatory documentation, advancing the scientific research, introduction of new methods of diagnosis and treatment will contribute to the implementation of PM principles in practical healthcare.

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Section: внедрение принципов пм в медицину критических состоянийunclassified

Personalized Critical Care Medicine (Review)

Голубев

2022

Obŝaâ reanimatologiâ

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“…Many experts now believe that the failure is largely due to the heterogeneity of sepsis patients [ 3 ]. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses [ 4 – 6 ]. The hope is to develop targeted therapeutic interventions for sepsis patients based on pathophysiological processes and clinical phenotypes rather than a one-size-fits-all-approach.…”

Section: Introductionmentioning

confidence: 99%

Whole blood transcriptomics identifies subclasses of pediatric septic shock

Yang,

Zinter,

Pellegrini

et al. 2023

Crit Care

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Background Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. Methods The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. Results Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires. Conclusions Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

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“…Many experts now believe that the failure is largely due to the heterogeneity of sepsis patients [3]. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses [4][5][6]. The hope is to develop targeted therapeutic interventions for sepsis patients based on pathophysiological processes and clinical phenotypes rather than a one-size-ts-all-approach.…”

Section: Introductionmentioning

confidence: 99%

Whole Blood Transcriptomics Identifies Subclasses of Pediatric Septic Shock

Yang,

Zinter,

Pellegrini

et al. 2023

Preprint

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Background Sepsis is a highly heterogeneous syndrome, that has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. Methods The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA-sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. Results Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells, and less diverse T-Cell receptor repertoires. Conclusions Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration: This is a secondary analysis of data generated as part of the observational CAF PINT ancillary of the HALF PINT study (NCT01565941). Registered 29 March 2012.

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Precision Medicine in Critical Illness: Sepsis and Acute Respiratory Distress Syndrome

Cited by 4 publications

References 155 publications

Personalized Critical Care Medicine (Review)

Personalized Critical Care Medicine (Review)

Whole blood transcriptomics identifies subclasses of pediatric septic shock

Whole Blood Transcriptomics Identifies Subclasses of Pediatric Septic Shock

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