Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections

Abstract

These infections are infrequent, but are associated with a significant health burden due to high mortality and risk of severe long-term disability as a consequence of extensive tissue loss or amputations (3)(4)(5). The progression of the disease is rapid, and early identification is therefore pivotal for improving the prognosis of affected patients. Currently, the initial diagnosis of NSTI is challenging due to the often vague symptoms during early stages, a heterogeneous patient group, and lack of specific diagnostic tools (6), which lead to misdiagnoses of NSTI in many cases (7). Still, doctors are advised that in case of NSTI suspicion, patients should be referred to surgical evaluation immediately (8). Previous efforts to improve the diagnosis of NSTIs led to the proposal of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) CONCLUSIONS. This study identifies predictive biomarkers for NSTI clinical phenotypes of potential value for diagnostic, prognostic, and therapeutic approaches in NSTIs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01790698.

Circulating protein and lipid markers of early sepsis diagnosis and prognosis: a scoping review

“…Biomarkers are presented in order of their relative abundance in literature.bThese studies focused on a discrete anatomic source of sepsis (e.g. necrotizing soft-tissue infections (NSTI), burns, and trauma [15,39,43,51,71]) and their results should be interpreted with caution as sepsis outcomes vary by the anatomic source of infection [12].…”

“…: plasma neutrophil gelatinase associated lipocalin (pNGAL) [68][69][70], proenkephalin (PenKid) [70,71], Cystatin C [73]), and coagulopathy (e.g. : Ddimer [66,67], thrombomodulin [15,60], Protein C [21,65], tissue factor pathway inhibitor (TFPI) [17,21]). Markers of lung epithelial injury such as the soluble receptor for advanced glycation end products (sRAGE) and surfactant protein D (SP-D) have also been studied, but primarily in the context of systemic inflammation leading to acute respiratory distress syndrome (ARDS) [84] and their relevance in sepsis due to a nonpulmonary source warrants future investigation.…”

“…The relationship between sepsis outcomes and other circulating endothelial-associated proteins (e.g. : vascular endothelial growth factor (VEGF) [43] and its receptor (VEGFR2) [17], heparin-binding protein (HBP) [48,49 ▪ ,50], E-selectin (also known as cluster of differentiation (CD)62E) [15,17], zonula occludens-1 (ZO-1) [42], and vascular cell adhesion molecule 1 (VCAM-1) [46]) is inconsistent (Table 1).…”

“…The immune response is central to pathogen clearance in sepsis and its excess may explain the association between inflammatory markers and sepsis outcomes [11 && ]. For example, increased levels of IL-6, IL-8, IL-10, interferon (IFN)-g, osteopontin, Pentraxin 3 (PTX-3), myeloperoxidase (MPO), FasL, soluble triggering receptor expressed on myeloid cells-1 (sTREM1), soluble TNF receptor 1 (sTNFR1), soluble urokinase plasminogen activator receptor (suPAR), and high mobility group box 1 (HMGB-1), are associated with sepsis severity and/or mortality [15,[17][18][19][20][21]23,[28][29][30][31][32][36][37][38][39]. However, associations between inflammation quantified by other inflammatory markers and outcome are inconsistent (Table 1) [22,30].…”

How to manage skin and soft-tissue infections in the emergency department

“…A recent study identified 36 biomarkers to differentiate between necrotising and non-necrotising infections at the time of their onset; thrombomodulin was a unique biomarker for necrotising SSTI detection [83 ▪ ].…”