Early recognition of sepsis-induced coagulopathy using the C2PAC index: a ratio of soluble type C lectin-like receptor 2 (sCLEC-2) level and platelet count.

C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition. The present study examined the relationship between sCLEC-2 level and degree of coagulation disorder in septic patients. Seventy septic patients were divided into the sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n = 44) and non-SID group (n = 26). The sCLEC-2 levels were compared between the two groups. Because we suspected that the sCLEC-2 level was affected by the platelet count, we calculated the sCLEC-2/platelet count ratio (C2PAC index). We further divided septic patients into four groups using the Japanese Association for Acute Medicine (JAAM) DIC scoring system (DIC scores: 0-1, 2-3, 4-5, and 6-8). The C2PAC index was significantly higher in the SID group (2.6 ± 1.7) compared with the non-SID group (1.2 ± 0.5) (P < .001). The C2PAC indexes in the four JAAM DIC score groups were 0.9 ± 0.3, 1.1 ± 0.3, 1.7 ± 0.7, and 3.6 ± 1.0, respectively, and this index increased significantly as the DIC score increased (P < .001). According to the receiver-operating curve analysis, the area under the curve (AUC) and optimal cutoff value for the diagnosis of SID were 0.8051 and 1.4 (sensitivity, 75.0%; specificity, 76.9%), respectively. When the C2PAC index and D-dimer level, one of the main fibrinolytic markers, were selected as predictive markers for SID diagnosis in stepwise multiple logistic regression analysis, it was possible to diagnose SID with a high probability (AUC, 0.9528; sensitivity, 0.9545; specificity, 0.8846). The C2PAC index is a useful predictor of SID progression and diagnosis in septic patients.

Potential survival benefit of polymyxin B hemoperfusion in patients with septic shock: a propensity-matched cohort study.

BACKGROUND: The purpose of this study was to investigate whether polymyxin B hemoperfusion (PMX-HP) improves the survival of patients with septic shock. METHODS: This was a retrospective, multicenter study conducted on patients treated during a 3-year period. We performed propensity-score analyses of the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study database. The study included data on 1723 patients with septic shock aged 16 years or older. Furthermore, we divided patients into to PMX-HP- and non-PMX-HP-treated groups. The primary endpoint was all-cause hospital mortality; secondary endpoints included intensive care unit (ICU) mortality and number of ICU-free days (ICUFDs) in the first 28 days. RESULTS: Of 1,723 eligible patients, 522 had received PMX-HP. Propensity score matching created 262 matched pairs (i.e., 262 patients in each of the non-PMX-HP and PMX-HP groups). The proportion of all-cause hospital mortality was significantly lower in the PMX-HP group than in the non-PMX-HP group (32.8% vs. 41.2%; odds ratio (OR): 0.681; 95% confidence interval (CI): 0.470-0.987; P = 0.042). The number of ICUFD in the first 28 days was significantly higher in the PMX-HP group than in the non-PMX-HP group (18 (0-22) vs. 14 (0-22) days, respectively; P = 0.045). On the other hand, there was no significant difference in ICU mortality between the two groups (21.8% vs. 24.4%; OR: 0.844; CI: 0.548-1.300; P = 0.443). CONCLUSIONS: Our results strongly suggest that PMX-HP reduces all-cause hospital mortality and length of ICU stay in patients with septic shock.

Potential use of procalcitonin as biomarker for bacterial sepsis in patients with or without acute kidney injury.

INTRODUCTION: There are few investigations regarding the relationships between procalcitonin (PCT) and the acute kidney injury (AKI) in the diagnosis of sepsis. The purpose of this study was to clarify the diagnostic accuracy of the use of PCT levels in patients with or without AKI. METHODS: This study was conducted as a single-center retrospective study. We enrolled 393 patients in whom PCT were measured on admission. We grouped the patients into non-AKI and AKI, and those with AKI were classified according to the RIFLE criteria (Risk, Injury, Failure). The patients in each group were further classified into the sepsis and the non-sepsis group. We subsequently investigated the diagnostic accuracy of the PCT for detecting sepsis in these groups. RESULTS: The levels of PCT were significantly higher in the sepsis group than in the non-sepsis group among the non-AKI and each AKI patients (p < 0.0001). The diagnostic accuracy of the PCT for detecting sepsis was determined according to a ROC analysis; AUC value was 0.958 in the non-AKI group, in the Risk, Injury and Failure groups were 0.888 and 0.917, 0.857, respectively. AUC value for non-AKI group was significantly different from that of Failure group (p < 0.05). CONCLUSIONS: In Failure AKI patients, the diagnostic accuracy of the PCT level is significantly lower than non-AKI patients. It is therefore suggested that we should be careful in using PCT value to diagnose sepsis in patients with Failure under RIFLE criteria.

Relationship between serum zinc level and sepsis-induced coagulopathy.

BACKGROUND: We investigated whether a decrease in the serum zinc level (SZL) among patients with sepsis admitted to the intensive care unit (ICU) was related to sepsis-induced coagulopathy. METHODS: All patients (≥20 years) with a diagnosis of sepsis defined by Sepsis-3 criteria, presenting to the ICU between June 2016 and July 2017, were enrolled. Demographic characteristics and the Sequential Organ Failure Assessment (SOFA) and Japanese Association of Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores were recorded. Blood samples were collected upon admission and analyzed for SZL. RESULTS: One hundred patients with sepsis (median age, 70 years) were enrolled. Patients with SOFA scores ≥8 had a significantly lower SZL compared to those with SOFA scores <8 (p < 0.001). The SZL in the DIC group (JAAM DIC score ≥4) was significantly lower than that in the non-DIC group (JAAM DIC score <4) (p < 0.001). Analysis of receiver operating characteristic (ROC) curves for prediction of sepsis-induced DIC based on SZL in patients with sepsis showed a cut-off value of 25 µg/dL for zinc level and a sensitivity of 63% and a specificity of 72% with AUC of 0.7 (p = 0.0065). CONCLUSION: We observed that SZL reflects organ failure, particularly coagulopathy, in patients with sepsis.

Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury.

BACKGROUND: Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI). METHODS: We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis. RESULTS: In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525) and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, p < .001). The optimal cut-off values for diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin. CONCLUSIONS: In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin.

Prognostic factors for candidaemia in intensive care unit patients: a retrospective analysis.

INTRODUCTION: Candidaemia, recognised as a fairly common disease among intensive care unit (ICU) patients, carries a poor prognosis. However, as studies on the prognostic factors associated with candidaemia in ICU patients are limited, this study aimed to establish the best prognostic factor for ICU patients with candidaemia in a tertiary care hospital in Japan. METHODS: We conducted a retrospective cohort study of patients with candidaemia in the emergency ICU at Fukuoka University Hospital, Fukuoka, Japan, from April 2010 to March 2015. Demographic and clinical data was collected from the patients' medical records and laboratory databases. RESULTS: A total of 25 patients were included in the study. However, 18 patients died during hospitalisation, resulting in an in-hospital mortality rate of 72.0%. The variables of Sequential Organ Failure Assessment (SOFA) score and cumulative number of risk factors for invasive candidiasis showed significant differences between patients in the survivor and non-survivor groups (p < 0.05). The areas under the receiver operating characteristic curves for the SOFA score and cumulative number of risk factors for invasive candidiasis were 0.873 (95% confidence interval [CI] 0.72-1.00) and 0.937 (95% CI 0.84-1.00), respectively. CONCLUSION: Our results suggest that the cumulative number of risk factors for invasive candidiasis was the most useful prognostic indicator for candidaemia in ICU patients.

Therapeutic Dose Monitoring for Linezolid in a Patient with MRSA Pneumonia with Bacteremia in Diabetes Insipidus.

INTRODUCTION: Few studies have investigated the effect of increased creatinine clearance (CrCl) on linezolid (LZD) concentration. Herein, we report the pharmacokinetic/pharmacodynamic (PK/PD) profile of LZD used in the management of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia with concomitant bacteremia in a patient with high CrCl caused by diabetes insipidus (DI). CASE REPORT: A 19-year-old man was admitted to the intensive care unit following a traumatic brain injury. After admission, he underwent a craniotomy for the severe brain injury. However, he developed DI after the operation. Despite treatment with vasopressin, his urine output reached 5-6 L/day as a result of the DI, and his CrCl increased to 180-278 mL/min. We were required to administer 6-7 L of fluid a day to compensate for the high urinary fluid output. On day 55, MRSA pneumonia with sepsis was suspected and, consequently, LZD was administrated intravenously (600 mg every 12 h). He was treated with LZD for 14 days. The patient has since successfully recovered from MRSA pneumonia with concomitant bacteremia, and was transferred to the general ward on day 82. Blood LZD levels from days 60-68, which were measured after the patient's transfer to the general ward, showed that the trough levels were lower than the threshold level of detection. The blood 24-h area under the plasma LZD concentration-time curve (AUC)24/minimum inhibitory concentration (MIC) was 69.3. CONCLUSION: In spite of the low level of LZD AUC24/MIC caused by the high CrCl with DI, MRSA pneumonia with concomitant bacteremia was successfully treated with LZD.

Intravenous immunoglobulin improves sepsis-induced coagulopathy: A retrospective, single-center observational study.

INTRODUCTION: Inflammation and coagulation are closely interrelated processes in the pathogenesis of sepsis. This study aimed to determine whether intravenous immunoglobulin (IVIg) could improve the hyperinflammatory state and coagulation/fibrinolysis abnormalities in patients with sepsis. METHODS: Forty-one patients with sepsis were included. Nineteen patients were treated with IVIg (IVIg group; 5.0 g daily for 3 days within 2 days after hospitalization), and 22 patients were not (non-IVIg group). Inflammatory and coagulation/fibrinolysis molecular markers, Japanese Association for Acute Medicine disseminated intravascular coagulation score, and the Sequential Organ Failure Assessment score were evaluated in each group. RESULTS: On admission, patients in the IVIg group had a significantly more severe condition. In the IVIg group, after treatment, C-reactive protein, procalcitonin, and interleukin-6 levels significantly decreased relative to values on admission. Also, compared with admission, the various coagulation/fibrinolysis molecular markers decreased after treatment. Moreover, the Japanese Association for Acute Medicine disseminated intravascular coagulation score and the Sequential Organ Failure Assessment score also significantly decreased after treatment. In contrast, in the non-IVIg group, only interleukin-6 level and thrombin-antithrombin complex levels significantly decreased. The 28-day mortality rate of the IVIg group was approximately one third of the value of the non-IVIg group (IVIg: 5.3% vs non-IVIg: 18.2%). CONCLUSIONS: Intravenous immunoglobulin treatment significantly improved hemostatic abnormalities along with the hyperinflammatory state in patients with sepsis. Accordingly, IVIg treatment should be classified as an adjunctive therapy for patients complicated with sepsis-induced coagulopathy.