Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis

Liu, Yong; Hou, Jun-huan; Chen, Kuijun; Wang, Shunan; Wang, Jianmin

doi:10.1186/s40064-016-3591-5

Cited by 104 publications

(100 citation statements)

References 96 publications

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“…Poor sensitivity often delays diagnosis and treatment, resulting in worse outcomes for patients 4 . A multitude of biomarkers has been proposed to aid the diagnosis of sepsis (reviewed in detail by others 5,6 ). However, none of these is currently in clinical use.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay

et al. 2018

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Current methods for the diagnosis of sepsis have insufficient precision, causing regular misdiagnoses. Microbiological tests can help diagnose sepsis but are usually too slow to have an impact on timely clinical-decision making. Neutrophils have high sensitivity to infections, yet measurements of neutrophil surface markers, genomic changes, and phenotype alterations have had only a marginal effect on sepsis diagnosis. Here, we report a microfluidic assay that measures the spontaneous motility of neutrophils in the context of plasma, in one droplet of blood. We measured the performance of the assay in two independent cohorts of critically ill patients suspected of sepsis. In the first cohort, we developed a machine-learning-based scoring system (sepsis score) that segregated patients with sepsis from those without sepsis. In the second cohort, we validated the sepsis score in a double-blinded, prospective case-control study. For the 42 patients across the two cohorts, the assay identified sepsis patients with 97% sensitivity and 98% specificity. The neutrophil assay could potentially be used to accurately diagnose and monitor sepsis in larger populations of at-risk patients.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay

et al. 2018

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“…Procalcitonin qualifies as both a diagnostic (an infection or sepsis marker) and predictive (a guide to antimicrobial therapy) biomarker. This being said, procalcitonin biomarker performance has been subjected to a large number of meta-analyses [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], suggesting a degree of disquiet regarding the actual level of evidence for procalcitonin utility.We first summarize certain key parameters of procalcitonin performance as a diagnostic biomarker in 6 meta-analyses, conducted between the years of 2004-2015; author sub-group analyses are not considered (Table 1) [11,14,[16][17][18][19]. Where reported, heterogeneity was a marked feature, even when restricted to a more circumscribed population of the "critically ill"; the components of heterogeneity presumably reflecting such factors as different procalcitonin assays and threshold levels, patient subgroups, endpoint prevalence, primary study inclusions and exclusions, and study quality / bias [5].…”

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confidence: 99%

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Procalcitonin as a Biomarker for Infection and Sepsis: Yet Again

Moran¹,

Solomon²

2017

Pulm Crit Care Med

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Biomarkers may be characterized as diagnostic, distinguishing between two states (say, infected or non-infected); prognostic, informing of a likely outcome (say, mortality); or predictive, if a treatment effect is differential between biomarker positivity and negativity [1]. One of the most discussed biomarkers in the infectious diseases and critical care literature is procalcitonin [2][3][4], a polypeptide that serves as the precursor for calcitonin in thyroid gland C cells and is released in response to microbial toxins and pro-inflammatory mediators [5]. Procalcitonin qualifies as both a diagnostic (an infection or sepsis marker) and predictive (a guide to antimicrobial therapy) biomarker. This being said, procalcitonin biomarker performance has been subjected to a large number of meta-analyses [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], suggesting a degree of disquiet regarding the actual level of evidence for procalcitonin utility.We first summarize certain key parameters of procalcitonin performance as a diagnostic biomarker in 6 meta-analyses, conducted between the years of 2004-2015; author sub-group analyses are not considered (Table 1) [11,14,[16][17][18][19]. Where reported, heterogeneity was a marked feature, even when restricted to a more circumscribed population of the "critically ill"; the components of heterogeneity presumably reflecting such factors as different procalcitonin assays and threshold levels, patient subgroups, endpoint prevalence, primary study inclusions and exclusions, and study quality / bias [5]. Analytic methods reflected year of publication, with the earlier studies [16][17][18][19] using the linear regression model of Moses et al, as opposed to the mixed-effects bivariate approach of the two more recent studies [11,14]; a point of importance for Wacker and co-authors [14]. Overall, the diagnostic performance could at best be described as modest, a point conceded by some of the authors [11,16,18] and reiterated by Afshari and Harbath [22], commenting upon the somewhat fulsome conclusions of Wacker et al. [14]. The former noted that the sensitivity of 77% corresponded to 23% of patients not receiving adequate therapy and a specificity of 79% corresponded to 21% being unnecessarily treated (Table 1); similarly, a positive likelihood ratio of 3.67 and a negative likelihood ratio of 0.29, being small and containing no information, were "… of little use for guiding initial treatment decisions", especially in the critically ill with a high pre-test sepsis probability [22]. As diagnostic meta-analyses have had a history of poor reporting [23] compared with meta-analyses reporting treatment effects of randomized controlled trials, the attendant vigorous correspondence [22,[24][25][26][27][28][29] to some of the above meta-analyses is perhaps not surprising.One outstanding feature of these diagnostic meta-analyses was the variable cut-point procalcitonin thresholds used in the primary studies. Again in a response to the meta-analysis of Wacker et al. [14], Ruecker and Sch...

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“…U kombinaciji sa drugim markerima sistemske infekcije(CRP, PCT, engl. soluble triggering receptor expressed on myeloid cells 1, sTREM-1), koristan je u regrutovanju obolelih za prijem u bolnicu, kao i za prijem u jedinice intenzivnog lečenja (JIL) 14 . PSP ima relativno slabusamostalnu sposobnost predikcije bakterijemije i potrebe za hospitalizacijom.…”

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Presepsin u akutnim i hroničnim poremećajima bubrežne funkcije

Gluvić¹,

Mitrović²,

Kulić³

et al. 2017

Materia medica

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1 Odeljenje internističke intenzivne nege, Klinika za internu medicinu, Kliničko bolnički centar Zemun 2 Služba za transfuziologiju, Kliničko bolnički centar Zemun Glikoprotein CD14 je komponenta urođene imunosti. Postoji u dve forme, membranskoj (mCD14) i solubilnoj (sCD14). sCD14 nastaje ili indirektno, od mCD14, ili direktno, sekrecijom iz intraćelijskih vezikula fagocita (pod efektom katepsina D). sCD14 se predominantno sekretuje iz jetre i monocita 1, 2 . mCD14 je eksprimiran na površini makrofagnih, neutrofilnih i dendritičnih ćelija, a prevashodno služi kao specifičnivisokoafinitetni koreceptor za lipopolisaharid (LPS) gram negativnih bakterija. Naime, mCD14 zajedno sa toll-like receptorom 4 (TLR4) i MD-2, služi za prepoznavanje i vezivanje kompleksa LPS/ lipopolisaharidnog vezujućeg proteina bakterija. mCD14 se oslobađa iz kompleksa u cirkulaciju i postaje sCD14, a pod efektom serumskih proteaza nastaje sCD14 podtip (engl. sCD14 subtype, sCD14-ST). sCD14-STje presepsin(PSP) [3][4][5] .Indukcija PSP je brza, te se u cirkulaciji detektuje većnakon 2h od značajnog infektivnog prodora, dok je u slučajevima C-reaktivnog proteina (CRP) i prokalcitonina (PCT) ona značajno sporija (>4-6h za CRP, tj. 8-24h za PCT) [6][7][8] . Nivo PSP korelira sa APACHE II skoromi prognozom odnosno ishodom bolesti 9,10 . Ukupna senzitivnost (Se) od 83%, specifičnost (Sp) od 78% i dijagnostička preciznost od 88%,ukazuje da vrednost izmerenog nivoa PSP omogućava relativno bezbedno razlikovanje nespecifičnog sistemskog inflamatornog odgovora (engl. Systemic Inflammatory Response Syndrome, SIRS) od sepse. Ipak, PSP ne bi trebalo koristiti samostalno za potvrdu ili isključenje septičnog stanja, već u kombinaciji sa drugim biomarkerima sistemske infekcije i isključivo u kliničkom kontekstu 11 . Studije su pokazale da je najsenzitivniji cut-off nivo za razlikovanje bakterijske od nebakterijske sistemske infekcije 600pg/ml, sa Se 79-87% i Sp 61-81%. Senzitivnost dijagnostičke vrednosti PSP očekivano raste sa porastom njegovog nivoa. Visoki nivoi PSP su, pored ostalih, ominozan klinički znak -ukazuju na verovatnu lošu prognozu bolesti 12,13 . U kombinaciji sa drugim markerima sistemske infekcije(CRP, PCT, engl. soluble triggering receptor expressed on myeloid cells 1, sTREM-1), koristan je u regrutovanju obolelih za prijem u bolnicu, kao i za prijem u jedinice intenzivnog lečenja (JIL) 14 . PSP ima relativno slabusamostalnu sposobnost predikcije bakterijemije i potrebe za hospitalizacijom. Pored toga, PSP ne nudi značajnu superiornost u odnosu na druge biomarkere sistemske infekcije, poput CRP i PCT 15,16 . PSP i akutna bubrežna insuficijencija (ABI)PSP (13kDa) se filtruje bubrezima i nivo u krvi značajno zavisi od bubrežne funkcije. Relativno je mali broj studija koje su ispitivale korisnost određivanja PSP kod obolelih od ABI. Nivo PSP je značajno povišen kod septičnih bolesnika bez ABI, kao i obolelih od blažih formi ABI (RI po RIFLE ABI klasifikaciji) u poređenju sa ne-septičnim grupama 17,18 . Nivoi PSP u krvi mogu biti pouzdan indik...

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Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis

Cited by 104 publications

References 96 publications

Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay

Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay

Procalcitonin as a Biomarker for Infection and Sepsis: Yet Again

Presepsin u akutnim i hroničnim poremećajima bubrežne funkcije

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