Tatsuyori Shozushima

Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome

CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2xa0±xa0121.4xa0pg/ml; local infection, 721.0xa0±xa0611.3xa0pg/ml; systemic inflammatory response syndrome, 333.5xa0±xa0130.6xa0pg/ml; sepsis, 817.9xa0±xa0572.7xa0pg/ml; and severe sepsis, 1,992.9xa0±xa01509.2xa0pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.

Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study

The clinical usefulness of presepsin for discriminating between bacterial and nonbacterial infections (including systemic inflammatory response syndrome) was studied and compared with procalcitonin (PCT) and interleukin-6 (IL-6) in a multicenter prospective study. Suspected sepsis patients (nxa0=xa0207) were enrolled into the study. Presepsin levels in patients with systemic bacterial infection and localized bacterial infection were significantly higher than in those with nonbacterial infections. In addition, presepsin, PCT, and IL-6 levels in patients with bacterial infectious disease were significantly higher than in those with nonbacterial infectious disease (Pxa0<xa00.0001, Pxa0<xa00.0001, and Pxa0<xa00.0001, respectively). The area under the receiver operating characteristic curve was 0.908 for presepsin, 0.905 for PCT, and 0.825 for IL-6 in patients with bacterial infectious disease and those with nonbacterial infectious disease. The cutoff value of presepsin for discrimination of bacterial and nonbacterial infectious diseases was determined to be 600xa0pg/ml, of which the clinical sensitivity and specificity were 87.8xa0% and 81.4xa0%, respectively. Presepsin levels did not differ significantly between patients with gram-positive and gram-negative bacterial infections. The sensitivity of blood culture was 35.4xa0%; that for presepsin was 91.9xa0%. Also there were no significant differences in presepsin levels between the blood culture-positive and -negative groups. Consequently, presepsin is useful for the diagnosis of sepsis, and it is superior to conventional markers and blood culture.

Presepsin as a powerful monitoring tool for the prognosis and treatment of sepsis: A multicenter prospective study

Presepsin is a protein whose levels increase specifically in the blood of patients with sepsis. It is proposed as a diagnostic and prognostic marker for assessing the degree of sepsis severity. The present multicenter prospective study compared the clinical utility of presepsin with other conventional sepsis biomarkers including procalcitonin, interleukin-6, and C-reactive protein for evaluating the severity of sepsis during follow-up. Patients with sepsis (nxa0=xa0103) admitted to the emergency room or intensive care unit were enrolled in this study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic shock. Blood samples were obtained from each patient on admission and after 1, 3, 5, and 7 days. The patients were further divided into the favorable and unfavorable prognosis groups on the basis of several indicators of sepsis severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score). The patients in the favorable prognosis group exhibited significant decreases in all biomarker levels on days 3 and 7 after admission. In the unfavorable prognosis group, only presepsin levels did not decrease significantly during follow-up. The period of antibiotics treatment in the unfavorable prognosis group was significantly longer than those in the favorable prognosis group (Pxa0<xa00.05). The unfavorable prognosis group had significantly higher 28-day mortality than the favorable prognosis group (Pxa0<xa00.05). Therefore, the results suggest that presepsin levels correlated with the severity of sepsis during follow-up in comparison with other conventional sepsis biomarkers.

Significance of Measuring S100A12 and sRAGE in the Serum of Sepsis Patients with Postoperative Acute Lung Injury

Background: There is a report that S100A12 is useful as an early marker of acute lung injury (ALI). The purpose of this study was to determine whether S100A12 or sRAGE is useful as a marker during the development of ALI in postoperative sepsis patients. Methods: The subjects were patients who underwent emergency surgery because of sepsis secondary to perforation of the lower gastrointestinal tract. We conducted a retrospective study comparing 2 groups of patients: a group of 9 patients who developed postoperative ALI, the ALI(+) group, and a group of 8 patients who did not develop postoperative ALI, the ALI(–) group. Their blood S100A12, sRAGE, IFN-γ, WBC count, and CRP values were measured immediately after surgery and on postoperative day 1 (D1). Results: The changes in S100A12 showed significantly higher values immediately postoperatively in the ALI(+) group (p < 0.05). The sRAGE values immediately postoperatively were similar, but on D1, they were significantly higher in the ALI(–) group (p < 0.05). Conclusions: S100A12 increases in the early stage of development of ALI. sRAGE production increases in patients who do not develop ALI.

Risk factors for early re-bleeding and associated hospitalization in patients with colonic diverticular bleeding

The annual incidence of colonic diverticular bleeding is increasing, but treatments are not yet well established. Here we aimed to identify the risk factors for early re‐bleeding and to determine the associated duration of hospitalization.

Effect of linezolid on cytokine production capacity and plasma endotoxin levels in response to lipopolysaccharide stimulation of whole blood

The purpose of this study was to assess lipopolysaccharide (LPS)-stimulated cytokine production in the presence of linezolid (LZD) in comparison with the drug effect on the plasma endotoxin level. Peripheral venous whole-blood samples collected from five healthy subjects were stimulated with 10xa0μg/ml of LPS. LZD was then added to the LPS-stimulated blood samples at concentrations of 0, 2, 4, and 15xa0μg/ml, followed by incubation for 24xa0h at 37°C in a 5% CO2–95% air atmosphere. Supernatants of the resultant cultures were assayed to determine the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, and endotoxin. Significant decreases in the levels of TNF-α and IFN-γ were observed in the LZD 2, 4, and 15xa0μg/ml groups as compared with that in the 0xa0μg/ml group (Dunnett’s procedure; Pxa0<xa00.05). The level of IL-10 tended to increase irrespective of the LZD concentration; however, no significant intergroup differences were observed [analysis of variance (ANOVA); Pxa0=xa00.68]. No significant decrease of the endotoxin level was observed in the LZD 2, 4, or 15xa0μg/ml groups as compared with that in the 0xa0μg/ml group, with no significant intergroup differences (ANOVA; Pxa0=xa00.83). No change in the MCP-1 levels was observed irrespective of the LZD concentration (ANOVA; Pxa0=xa00.82). To conclude: (1) it appears possible that LZD inhibits the production of INF-γ and TNF-α to a limited extent; (2) LZD did not exert any inhibitory effect on endotoxin production by bacteria, while suppressing cytokine production. The results indicate that LZD may have a significant role in saving the lives of patients with sepsis.

Retrospective study on the effect of tight glucose control in postoperative sepsis patients using an artificial pancreas

Tight glucose control (TGC) using a sliding scale based on intermittent blood glucose measurements occasionally can have a fatal outcome as a result of insulin-induced hypoglycemia. The present study was undertaken to examine whether the use of an artificial pancreas to achieve TGC would be possible in postoperative patients with sepsis. The retrospective study was carried out as an exploratory study, focusing on the possibility of precise evaluation of the significance of TGC as a beneficial intervention by serological monitoring of various mediators. TGC was accomplished using an artificial pancreas (STG-22; (Nikkiso, Tokyo, Japan). The patients were divided into two groups: the TGC group (6 patients with sepsis in whom the target blood glucose level set at <150xa0mg/dl was attempted using the artificial pancreas), and the glucose control (GC) group (6 patients with sepsis in whom glucose control was attempted using a sliding scale; target blood glucose level was set at 200xa0mg/dl or lower). The mean blood glucose level was 129.7xa0±xa09.7xa0mg/dl in the TGC group and 200.9xa0±xa014.7xa0mg/dl in the GC group (Pxa0<xa00.01, ANOVA). No hypoglycemia associated with the artificial pancreas was seen in any of the patients. The serum levels of S100A12 and HMGB-1 tended to decrease, and those of sRAGE tended to increase, in the TGC group. Further data collection from a larger number of cases would be expected to allow a precise assessment of TGC as a potentially beneficial intervention in sepsis patients.

Experimental application of a synthetic luminescent substrate assay using endotoxin-specific limulus amebocyte lysate to human blood

A synthetic luminescent substrate method, using a mutant-type luciferase whose luminescence intensity is more than ten times as intense as the wild type, was developed recently. We conducted the first basic studies on clinical application of the novel endotoxin measurement method. We assessed and established measurement conditions, including reagent concentrations and reaction time, so that it would be possible to apply the luminescent synthetic substrate method proposed by Noda et al. to measurements in human blood. When we added lipopolysaccharide (LPS) to water, it was possible to measure LPS at a concentration of 0.1xa0pg/ml, whereas it was possible to measure LPS in tenfold diluted and heated plasma at a concentration of 1xa0pg/ml. When plasma was further diluted, inhibiting activity decreased considerably. Thus, it will be necessary to completely eliminate the inhibitor present in plasma. However, the shortest time after collecting the specimen in which it was possible to make measurements was 30–40xa0min, suggesting that if an assay is established, it will be possible to use the method as a novel blood endotoxin assay.