Prognostic and predictive enrichment in sepsis

Stanski, Natalja L.; Wong, Hector R.

doi:10.1038/s41581-019-0199-3

Cited by 194 publications

(157 citation statements)

References 115 publications

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“…Despite the association with adverse outcome, the accuracy of low mHLA-DR expression to predict clinical outcome at the individual patient level was limited in our cohort. That said, considering the amount of literature associating low mHLA-DR and unfavourable outcomes, it remains a valuable marker for enrichment in clinical trials, for example to select a group of patients that may benefit from immunomodulating therapies [25,26]. Nevertheless, in light of the fact that septic shock is a highly complex immunological syndrome, involving multiple immune defects that vary between patients and within patients over time [27], it remains debatable whether a single biomarker will ever be sufficient to gauge a patient's overall immune status.…”

Section: Discussionmentioning

confidence: 99%

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

et al. 2020

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Background: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. Methods: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. Results: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or nonimprovers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). Conclusion: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.

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Section: Discussionmentioning

confidence: 99%

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

et al. 2020

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“…To date, they have not been used as prognostic or predictive tools in contemporary clinical trials. In addition, unidimensional markers (e.g., IL-6, pro-calcitonin) have failed to confer prognostic classification in RCTs evaluating other ICU-related pathologies, such as sepsis or ARDS [63]. There is a pressing need for alternative approaches that can be exploited to better understand and monitor the biological mechanisms related to nutritional risk and metabolic heterogeneity.…”

Section: Systemic Markers Of Inflammationmentioning

confidence: 99%

“…Once reduced to biomarker panels, analytes derived from transcriptomic and epigenomic metadata can be tested in multiplex PCR-based panels [85]. The measurement of whole blood or peripheral blood mononuclear cell mRNA levels can be implemented in the clinical setting and in the context of RCTs [63]. Technologies for the standardized measurement of DNA or RNA are available in clinical laboratories or as point-of-care tests.…”

Section: Assessment Of Mrna Levels and Epigenetic Modificationsmentioning

confidence: 99%

Biomarkers in critical care nutrition

Stoppe

Wendt²,

Mehta

et al. 2020

Crit Care

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The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.

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“…3 The awareness and early recognition of sepsis sources in all clinical practice subsets is the foundation of successful management of sepsis also by bioinformatics and precision medicine. [29][30][31][32][33][34] Increasing bioinformatics literacy by e-learning is a well established strategy. 35 A key point is that the low cost of UltraSound machines makes such investments affordable even in limited-resources settings.…”

Section: Advice and Sustainable Actionsmentioning

confidence: 99%

<p>SEPSIS. Educational and Best Practice Frontiers. Beyond the Boundaries of Fatality, Enhancing Clinical Skills and Precision Medicine</p>

Trovato¹

2020

TCRM

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Dissemination and exploitation of knowledge regarding affordable clinical skills and innovative precision medicine, two current topics in active development in medicine, may contribute to improve also sepsis management. Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is strongly related to all body organs or to systemic diseases and to the quality of the best-practice in use, which is particularly critical in surgical or intervention techniques. Trauma, surgical and mini-invasive procedures, vascular or endoscopic interventions, otolaryngology, obstetrics-gynecological and urological procedures, malnutrition, dental, skin, chronic liver, kidney and respiratory disease are frequently involved. Accordingly, apart from the clinical risk analysis and management of the process of care, the actual factors that may be easily neglected are the techniques used, the personal skills of the health professionals and the quality of the equipment. The quest for biomarkers consistent with the unmet needs of medical doctors and of their patient and the efforts for overcoming bacterial antibiotic resistances are currently the main foci of medical research. In addition, in this regard, research and innovation would benefit from greater knowledge, skills and use of bioinformatics and omics. The caveats related to in-silico approaches must be flagged: algorithms may equally warrant scientific innovations or hide the lack of them; a patient is more than a set of covariates. Epidemiology and prevention includes all the actions suitable for achieving an adequate hygiene and immunization of populations and for safer hospital policies and procedures during Patients' stays. In any subset, the most unresolved critical point in sepsis is a timely diagnosis. This is impaired by low degrees of suspicion for the possibility of emerging sepsis, by the shortage of use of the simplest microbiological testing but, equally or more, by the insufficient diffusion of non-invasive imaging skills suitable to detect and monitor the emerging sites and sources of infection. In primary care, in emergency facilities, in hospital wards and in intensive care units, inclusion of appropriate knowledge, skills, expertise and imaging equipment must be extended as much as possible. The low cost of UltraSound machines and of increasing bioinformatics literacy by e-learning, makes such investments affordable even in limited-resources contexts. Frontier educational and best practice intervention enhancing affordable clinical skills and innovative precision medicine may lead beyond the boundaries of fatal outcomes in sepsis.

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Prognostic and predictive enrichment in sepsis

Cited by 194 publications

References 115 publications

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Biomarkers in critical care nutrition

<p>SEPSIS. Educational and Best Practice Frontiers. Beyond the Boundaries of Fatality, Enhancing Clinical Skills and Precision Medicine</p>

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