Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS). The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18–90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9–66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17–60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16^BRIGHT CD62L^DIM neutrophils (82.07 x 10⁶/l ± 18.94 control versus 1,092 x 10⁶/l ± 165 trauma, p < 0.0005) and CD14⁺HLA-DR^low/− monocytes (34.96 x 10⁶/l ± 4.48 control versus 95.72 x 10⁶/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function. Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.

Key Points: Soluble GPVI is elevated in patients with thermal injury with sepsis, and sGPVI levels augment severity score prediction of mortality. The GPVI ligand, fibrin, induces GPVI shedding without requirement for platelet activation or signaling

Despite over a decade of research and technological advances, sublingual microcirculatory monitoring has not yet reached clinical utility. Offline analysis is time consuming and occurs away from the patient. A system to assess the microcirculation at the point of care is desirable. We present a novel 5-point grading system (the point of care microcirculation (POEM) scoring system) that can be used at the point of care during non-invasive sublingual microcirculatory monitoring. The POEM score is an ordinal scale from 1 (worst) to 5 (best), based on a composite assessment of flow and heterogeneity of four individual sublingual video-microscopy clips. Thirty-two healthcare professionals were trained in how to assign POEM scores. Following training they assigned scores to five test sequences (each consisting of four video clips). They were blinded to clinical status. Inter-user consistency and agreement were assessed using intra-class correlation coefficient (ICC) analysis. In addition, blinded expert scores for 68 video clips were compared to offline computer analysis using traditional microcirculatory parameters including total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), microcirculatory flow index (MFI) and microcirculatory heterogeneity index (MHI). The time taken to assign each was recorded. Participants showed good inter-rater consistency (ICC 0.83, 95 % CI 0.626, 0.976) and agreement (ICC 0.815, 95 % CI 0.602, 0.974) for assigned POEM scores. Expert scoring of videos correlated with offline values for PVD (R 2 = 0.39; p < 0.05), PPV (R 2 = 0.71; p < 0.001), MFI (R 2 = 0.75; p < 0.001), and MHI (R 2 = 0.68; p < 0.001). POEM scores took less time to assign than conventional offline computer analysis (2 minutes versus 44 minutes). We present for the first time a novel 5-point ordinal scale of microcirculatory flow and heterogeneity that can be used at the point of care. It has minimal inter-user variability amongst healthcare professionals after just 1 hour of training. POEM scores take a short time to assign, and correspond well to traditional offline computer-analyzed parameters.

The mortality caused by sepsis is high following thermal injury. Diagnosis is difficult due to the ongoing systemic inflammatory response. Previous studies suggest that cellular parameters may show promise as diagnostic markers of sepsis. The aim of this study was to evaluate the effect of thermal injury on novel haematological parameters and to study their association with clinical outcomes. Haematological analysis was performed using a Sysmex XN-1000 analyser on blood samples acquired on the day of the thermal injury to 12 months post-injury in 39 patients (15–95% TBSA). Platelet counts had a nadir at day 3 followed by a rebound thrombocytosis at day 21, with nadir values significantly lower in septic patients. Measurements of extended neutrophil parameters (NEUT-Y and NEUT-RI) demonstrated that septic patients had significantly higher levels of neutrophil nucleic acid content. A combination of platelet impedance count (PLT-I) and NEUT-Y at day 3 post-injury exhibited good discriminatory power for the identifying septic patients (AUROC = 0.915, 95% CI [0.827, 1.000]). Importantly, the model had improved performance when adjusted for mortality with an AUROC of 0.974 (0.931, 1.000). A combination of PLT-I and NEUT-Y show potential for the early diagnosis of sepsis post-burn injury. Importantly, these tests can be performed rapidly and require a small volume of whole blood highlighting their potential utility in clinical practice.

Carbapenemase-producing Enterobacteriaceae (CPE) pose a considerable threat to modern medicine. New treatment options and methods to limit spread need to be investigated. Blue light (BL) is intrinsically antimicrobial, and we have previously demonstrated significant antimicrobial effects on biofilms of a panel of isolates, including two CPEs. This study was performed to assess the antibacterial activity of 405 nm BL against a panel of CPE isolates (four encoding bla_NDM, three bla_KPC, two bla_OXA-48, and three encoding both NDM and OXA-48 carbapenemases). In vitro experiments were conducted on 72 h old biofilms of CPEs which were exposed to 60 mW/cm² of BL. Changes to biofilm seeding were assessed by measuring the optical density of treated and untreated biofilms. Twelve bacterial clinical isolates (comprising eight Klebsiella pnemoniae, one K. oxytoca, and three Escherichia coli) were tested. BL was delivered for 5, 15 and 30 min, achieving doses of 162, 54, and 108 J/cm², respectively. All of the CPEs were susceptible to BL treatment, with increasing reductions in seeding with increasing durations of exposure. At 30 min, reductions in biofilm seeding of ≥80% were observed for 11 of the 12 isolates, compared to five of 12 after 15 min. CPE_8180 was less susceptible than the rest, with a maximum reduction in seeding of 66% at 30 min. BL is effective at reducing the seeding of mature CPE biofilms in vitro, and offers great promise as a topical decontamination/treatment agent for both clinical and environmental applications.