Editors' ChoiceSepsis

Spooked neutrophils unmask sepsis

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Science Translational Medicine  11 Apr 2018:
Vol. 10, Issue 436, eaat3891
DOI: 10.1126/scitranslmed.aat3891

Abstract

Microfluidic mazes detect sepsis in patients by monitoring neutrophil motility patterns.

There’s a captivating moment in horror films right before the scream. Eyes wide and mouth agape, the victim is struck with a fear that robs them of their ability to act normally. Some frantically scramble to-and-fro while others tense up, paralyzed in horror. A recent report by Ellett et al. uses this horror movie trope to improve sepsis diagnosis by observing the motion of “frightened” neutrophils through blood-filled microscale labyrinths.

Sepsis is a life-threatening condition in which the immune response to infection leads to systemic inflammation and organ failure. A major challenge in diagnosing sepsis is the dearth of specific biomarkers and the fact that symptoms are easily confused with a cold or flu. To overcome this, the team developed a method of interrogating a defining characteristic of sepsis: the impairment of neutrophil migration toward the site of infection. Diluted whole blood from critically ill patients with or without sepsis was dropped onto networks of microfluidic channels that filtered out red blood cells and enabled the movement of neutrophils to be tracked. Machine learning algorithms identified five aberrant migration characteristics that were elevated in septic blood samples: migratory oscillation, pausing events, reverse migration, average migration distance, and number of neutrophils entering the mazes. Patients in a second validation cohort of 10 septic and 9 nonseptic patients were then followed longitudinally and correctly identified as septic or nonseptic with 96% sensitivity and 100% specificity.

To achieve clinical applicability however, the duration of the assay needs to be shortened from the reported 6.5 hours, and larger cohorts that better represent the target clinical population need to be evaluated. Nonetheless, the ability to accurately identify sepsis from a single drop of blood may provide clinicians with a vital head-start in administering life-saving interventions. Perhaps someday the threat of sepsis will be nothing more than a passing nightmare.

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