Point-of-care sensors for the management of sepsis

Reddy, Bobby; Hassan, Umer; Seymour, Christopher W.; Angus, Derek C.; Isbell, T. Scott; White, Karen; Weir, William; Yeh, Leon; Vincent, Andrew; Bashir, Rashid

doi:10.1038/s41551-018-0288-9

Cited by 115 publications

(102 citation statements)

References 45 publications

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“…Multiple groups have developed point-of-care microfluidic devices to investigate potential biomarkers in sepsis diagnosis. C-reactive protein, procalcitonin, interleukin-6, neopterin and many others have been studied extensively but provided limited utility in sepsis severity assessment and outcomes [8][9][10][11][12][13][14] . In a large cohort of patients, using a point-of-care microfluidic device, CD64 surface receptor expression on neutrophils was found to be predictive of patient diagnosis but was of limited use in sepsis severity assessment 9 .…”

Section: Discussionmentioning

confidence: 99%

“…These criteria carry an ~30% misdiagnosis rate 7 and offer little insight into the underlying pathobiology. Multiple point-of-care microfluidic devices have been used to investigate circulating cytokines and other mediators of inflammation as potential biomarkers in sepsis, but no device that reliably predicts severity and outcomes has emerged [8][9][10][11][12][13][14] . Since leukocytes (white blood cells) are sensors for multiple environmental cues and pathogens 4 , their activation and function could prove useful as cellular biomarkers of illness.…”

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confidence: 99%

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Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity

et al. 2019

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Dysregulated leukocyte responses underlie the pathobiology of sepsis, which is a leading cause of death. However, measures of leukocyte function are not routinely available in clinical care. Here we report the development and testing of an inertial microfluidic system for the label-free isolation and downstream functional assessment of leukocytes from 50 μl of peripheral blood. We used the system to assess leukocyte phenotype and function in serial samples from 18 hospitalized patients with sepsis and 10 healthy subjects. The sepsis samples had significantly higher levels of CD16 dim and CD16 − neutrophils and CD16 + 'intermediate' monocytes, as well as significantly lower levels of neutrophil-elastase release, O 2 − production and phagolysosome formation. Repeated sampling of sepsis patients over 7 days showed that leukocyte activation (measured by isodielectric separation) and leukocyte phenotype and function were significantly more predictive of the clinical course than complete-blood-count parameters. We conclude that the serial assessment of leukocyte function in microlitre blood volumes is feasible and that it provides significantly more prognostic information than leukocyte counting.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity

et al. 2019

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“…Evaluation of protein biomarkers is technically easier than evaluating those of transcriptomic nature. Emerging point‐of‐care devices could result in evaluation of these biomarkers in clinical practice as results can be obtained in less than 1 h.…”

Section: Discussionmentioning

confidence: 99%

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients

et al. 2020

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Background: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients.Methods: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals.Results: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11⋅53, 95 per cent c.i. 4⋅15 to 32⋅08; P = 0⋅006) and the best area under the curve (AUC) for detecting sepsis (0⋅86, 95 per cent c.i. 0⋅80 to 0⋅91; P < 0⋅001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8⋅09, 1⋅34 to 48⋅91; P = 0⋅028) and lipocalin 2 (OR 6⋅62, 2⋅47 to 17⋅77; P = 0⋅002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0⋅81, 0⋅73 to 0⋅90; P < 0⋅001). Conclusion: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection. Healthy control Infection Sepsis Septic shockBiomarkers of a,b emergency granulopoiesis and c acute-phase response. Levels of C-reactive protein (CRP) are in mg/l, those of procalcitonin (PCT) are in ng/ml, and those of the remaining biomarkers are copies of cDNA per ng mRNA. MMP, matrix metalloproteinase; LTF, lactoferrin; PRTN, proteinase; LCN, lipocalin, OLFM, olfactomedin; ELANE, elastase, neutrophil expressed; MPO, myeloperoxidase; CTSG, cathepsin G; AZU, azurocidin; BPI, bactericidal/permeability-increasing protein; DEFA, defensin α; CEACAM, carcinoembryonic antigen-related cell adhesion molecule; CD, cluster of differentiation; TCN, transcobalamin; STOM, stomatin; IL1R2, interleukin-1 receptor type 2; CHIT, chitinase. *P ≤ 0⋅050 versus healthy control;†P ≤ 0⋅050 (Kruskal-Wallis test).

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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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Point-of-care sensors for the management of sepsis

Cited by 115 publications

References 45 publications

Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity

Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients

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

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