Diagnostic Accuracy of HMGB-1, sTREM-1, and CD64 as Markers of Sepsis in Patients Recently Admitted to the Emergency Department

Abstract

Objectives: The objectives were to evaluate the diagnostic accuracy for sepsis in an emergency department (ED) population of the cluster of differentiation-64 (CD64) glycoprotein expression on the surface of neutrophils (nCD64), serum levels of soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1), and high-mobility group box-1 protein (HMGB-1).Methods: Patients with any of the following as admission diagnosis were enrolled: 1) suspected infection, 2) fever, 3) delirium, or 4) acute hypotension of unexplained origin within 24 hours of ED presentation. Levels of nCD64, HMGB-1, and s-TREM-1 were measured within the first 24 hours of the first ED evaluation. Baseline clinical data, Sepsis-related Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, daily clinical and microbiologic information, and 28-day mortality rate were collected. Because there is not a definitive criterion standard for sepsis, the authors used expert consensus based on clinical, microbiologic, laboratory, and radiologic data collected for each patient during the first 7 days of hospitalization. This expert consensus defined the primary outcome of sepsis, and the primary data analysis was based in the comparison of sepsis versus nonsepsis patients. The cut points to define sensitivity and specificity values, as well as positive and negative likelihood ratios (LRs) for the markers related to sepsis diagnosis, were determined using receiver operative characteristics (ROC) curves. The patients in this study were a prespecified nested subsample population of a larger study.Results: Of 631 patients included in the study, 66% (95% confidence interval [CI] = 62% to 67%, n = 416) had sepsis according with the expert consensus diagnosis. Among these sepsis patients, SOFA score defined 67% (95% CI = 62% to 71%, n = 277) in severe sepsis and 1% (95% CI = 0.3% to 3%, n = 6) in septic shock. The sensitivities for sepsis diagnosis were CD64, 65.8% (95% CI = 61.1% to 70.3%); HMGB-1, 57.5% (95% CI = 52.7% to 62.3%); and s-TREM-1, 60% (95% CI = 55.2% to 64.7%). The specificities were CD64, 64.6% (95% CI = 57.8% to 70.8%), HMGB-1, 57.8% (95% CI = 51.1% to 64.3%), and s-TREM-1, 59.2% (95% CI = 52.5% to 65.6%). The positive LR (LR+) for CD64 was 1.85 (95% CI = 1.52 to 2.26) and the negative LR (LR-) was 0.52 (95% CI = 0.44 to 0.62]; for HMGB-1 the LR+ was 1.36 (95% CI = 1.14 to 1.63) and LR-was 0.73 (95% CI = 0.62 to 0.86); and for s-TREM-1 the LR+ was 1.47 (95%

Neutrophil CD64 as a sepsis biomarker

“…In ad dition, CD64 was fou nd to be as so cia ted wi th mor tali ty in this stu dy. Ve ry re cen tly Gáme z-Díaz et al pub lis hed the re sul ts of the lar ge st stu dy ever (20). They in ves ti ga ted emer gen cy de par tme nt pa tients wi th sus pec ted in fec tion, fe ver, de li rium or acute hypo ten sion of un clear ori gin.…”

Diagnostična vrednost označevalcev pri sepsi

“…Kot kontrolno skupino za indeks CD 64 na nevtrofilcih smo vzeli še 11 zdravih preiskovancev (55 % moških), starih 32 (29,35) let. Zdravi preiskovanci so bili statistično značilno mlajši.…”

“…Čeprav je nekaj publikacij nakazalo visoko diagnostično vrednost tega indeksa (33,34), pa tega poleg naše tudi števil-ne druge raziskave niso potrdile (35,36). Eden od razlogov, da so nekatere študije potrdile diagnostično vrednost, druge pa ne, je izbira bolnikov -predvsem bolnikov v primerjalnih skupinah (Tabela 5).…”

“…Podoben rezultat je dobila Gamez-Diaz, ki je vključila bolnike na podoben način kot mi, torej prizadete bolnike, ki so potrebovali zdravljenje na intenzivnem oddelku, ter šele med hospitalizacijo postavila diagnozo sepse oziroma druge bolezni (35). Študije, ki so ugotovile dobro diagnostično vrednost indeksa CD64, pa so za kontrolo uporabile zdrave preiskovance ali bolnike po operacijah (22,28,33).…”

“…Več študij (31,35) je ugotovilo, da ima največjo napovedno vrednost pri diagnosticiranju sepse kombinacija večjega števila označevalcev. V naši raziskavi je imelo vsaj en označevalec (CRP, PCT, indeks CD64, koncentracija nevtrofilcev ali koncentracija paličastih nevtrofilcev) nad diskriminativno vrednostjo za ločitev bolnikov s sepso od bolnikov z okužbo brez sepse 62 % bolnikov.…”