Involvement of Innate Immune System in the Pathogenesis of Sepsis-Associated Acute Kidney Injury.

Although experimental models have shown that the innate immune system is a main contributor to acute kidney injury (AKI), its involvement in human sepsis-associated AKI (SA-AKI) remains unclear. We retrospectively evaluated 19 patients with SA-AKI who were treated with continuous renal replacement therapy (CRRT). Serum cytokine, complement components, and the proportion and functions of innate immune cells, such as CD56+ T cells, CD56+ natural killer (NK) cells, and monocytes, were analyzed. There were no differences in the proportions of CD56+ T and NK cells between patients with SA-AKI and healthy controls. In patients with SA-AKI, fas ligand (FasL) expression in CD56+ T cells was significantly upregulated, and the proportion of perforin-positive CD56+ T cells tended to be higher than that in healthy controls. The positive rate of both FasL and perforin of CD56+ T cells was significantly higher than that of CD56- T cells, which include cytotoxic T cells. Antigen-presenting capacity and phagocytic activity of monocytes in patients with SA-AKI were significantly decreased compared to those of healthy controls and did not recover soon after the initiation of CRRT. CD56+ T cells are involved in the disease processes of human SA-AKI through effector molecules such as FasL or perforin.

Comparative Evaluation of Endotoxin Activity Level and Various Biomarkers for Infection and Outcome of ICU-Admitted Patients.

Here, we concurrently measured the endotoxin activity (EA) level and levels of multiple biomarkers in patient blood obtained within 24 h after being admitted into the intensive care unit (ICU) and analyzed whether there were links between these markers and their associations with patient conditions and outcomes. The EA levels highly correlated with disease severity and patient survival, and showed a significant positive association with levels of lactate, procalcitonin, presepsin, and interleukin-6. Notably, the EA level was the marker that most highly correlated with the results of blood culture, and the presepsin level was the marker most highly correlated with the survival outcome at 28 days. Thus, the optimal biomarker should be selected based on whether it will be used to discriminate the presence of an infection or to predict survival.

Usefulness of the endotoxin activity assay as a biomarker to assess the severity of endotoxemia in critically ill patients.

The aim of this study was to investigate the prevalence of endotoxemia in critically ill Japanese patients using the endotoxin activity assay, a newly developed rapid assay of endotoxin. The endotoxin levels (EA levels) in the blood of 314 patients admitted to our university hospital's intensive care unit (ICU) were measured within 24 h of admission, and its correlation with disease severity and outcome examined. In addition, the EA levels in 61 samples from healthy volunteers were measured. EA level was 0.39 ± 0.25 (mean ± SD) in patients admitted to the ICU and 0.10 ± 0.09 in healthy controls. There was less overlap of EA level distribution between patients and controls compared with previous reports measuring EA level in mainly Caucasian populations. Our patients' EA levels were significantly correlated with disease severity criteria and 28-d mortality. When EA and procalcitonin levels were used concomitantly, disease severity could be assessed more precisely than when either marker was used alone. These results suggest that EA level is a useful marker for disease severity assessment and outcome prediction in critically ill patients.

Comparison of whole-body cooling and selective head cooling on changes in urinary 8-hydroxy-2-deoxyguanosine levels in patients with global brain ischemia undergoing mild hypothermia therapy.

BACKGROUND: We evaluated changes in the levels of urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) in patients undergoing mild hypothermia therapy and compared 8-OHdG expressions in those receiving whole-body cooling or selective head cooling. MATERIAL/METHODS: The subjects were 15 patients undergoing mild hypothermia therapy following resuscitation after cardiac arrest in our intensive care unit. We divided the patients into 2 groups receiving either whole-body cooling or selective head cooling, according to their circulatory stability. We examined urinary 8-OHdG level for 1 week and neurological outcomes 28 days after admission. RESULTS: We observed significant decreases in urinary 8-OHdG levels on days 6 and 7 compared with that on day 1 in the whole-body cooling group. Furthermore, we noted significantly lower urinary 8-OHdG levels after days 5, 6 and 7 in the whole-body cooling group than in the selective head-cooling group. Neurological outcomes were similar in both groups. CONCLUSIONS: Mild hypothermia therapy with whole-body cooling had a greater effect on the suppression of free radical production than selective head cooling. However, selective head cooling might be an appropriate indication for patients with circulatory instability after resuscitation, because it provides neuroprotection similar to that of whole-body cooling.

HMGB-1 as a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP.

BACKGROUND: High mobility group box 1 (HMGB-1) has recently received attention as a late mediator of lipopolysaccharide-induced shock, and is thought to function as a mediator in such a disorder as multi-organ failure (MOF). In Japan, we have access to an immobilized polymyxin B fiber column using a direct hemoperfusion (PMX-DHP) for patients with septic shock to improve hemodynamics and organ dysfunction. In this study, we looked at HMGB-1 levels in each category based on the sequential organ failure assessment (SOFA) scores to further dissect its importance in specific aspects of organ failure in patients undergoing PMX-DHP. PATIENTS AND METHODS: Sixty patients with septic shock (40 survivors and 20 non-survivors). We analyzed HMGB-1 and IL-6 levels before and after PMX-DHP and defined organ failure as two or more SOFA points. RESULTS: There was a significant positive correlation between SOFA score and HMGB-1 level (P<0.05). The HMGB-1 level before PMX-DHP significantly increased as the number of organ failures increased (P<0.01: comparing 2 versus 5 organ failures). IL-6 levels decreased after PMX-DHP (P<0.05 compared with before PMX-DHP), but HMGB-1 levels remained unchanged. HMGB-1 levels of survivors with organ failure in liver decreased after PMX-DHP, but those of non-survivors significantly increased 24h after PMX-DHP compared with before PMX-DHP (P<0.01). In non-survivors with organ failure in liver, HMGB-1 levels were significantly higher than among survivors 24h after PMX-DHP (P<0.01). CONCLUSIONS: Our results indicate that HMGB-1 is a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP.

Successful management by recombinant activated factor VII in a case of disseminated intravascular coagulopathy caused by obstetric hemorrhage.

Postpartum hemorrhage (PPH) is a life-threatening emergency in obstetrics. Although recombinant activated factor VII (rFVIIa) has become used for the treatment of some cases of massive hemorrhage, its applications in the field of obstetrics are still limited. We describe a case of successful treatment with rFVIIa for PPH due to placenta accreta. The patient was a 33-year-old woman with placental previa. Cesarean section (CS) was performed at gestational week 35. During CS, there was massive hemorrhage due to placenta accreta. After CS, disseminated intravascular coagulopathy and hypovolemic shock were diagnosed. The PPH was not controlled by transfusion therapy. On the fourth day after CS, rFVIIa (90 microg/kg x 2) was given because of the persistent PPH. Bleeding decreased and no further transfusion was required from 2 days after administration. rFVIIa was useful in the treatment of this case of obstetric hemorrhage.