Yuichiro Sakamoto

Relationship between effect of polymyxin B-immobilized fiber and high-mobility group box-1 protein in septic shock patients.

Direct hemoperfusion (DHP) using a polymyxin B (PMX)-immobilized fiber column has been used for treatment of endotoxemia-induced septic shock in Japan since 1994 and is now an accepted therapy for reducing serum endotoxin levels. Although a reduction in inflammatory cytokines has been reported, the detailed mechanism of DHP-PMX is not known. We investigated the high-mobility group box-1 (HMGB-1) level in septic shock patients treated with DHP-PMX. Subjects (n = 20) were separated into two group: those whose systolic blood pressure increased to more than 30 mm Hg immediately after DHP-PMX (effective [E] group: nine cases) and those whose systolic blood pressure did not increase to more than 30 mm Hg (noneffective [N-E] group: 11 cases). The interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were measured in each group. The Pao2/Fio2 ratio and the Sepsis-Related Organ Failure Assessment (SOFA) score were also evaluated. Pretreatment interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were similar in the E and N-E groups, but mortality rate was significantly higher in the N-E group. Furthermore, posttreatment SOFA score was significantly lower in the E group. In the E group, only the HMGB-1 levels improved significantly after DHP-PMX. Present data suggest that the circulation dynamics of septic shock patients can be improved by reducing HMGB-1 levels by using DHP-PMX.

IL-8 in Cerebrospinal Fluid from Children with Acute Encephalopathy is Higher than in that from Children with Febrile Seizure

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)‐1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon‐γ, tumour necrosis factor‐α, granulocyte colony‐stimulating factor, granulocyte monocyte colony‐stimulating factor, monocyte chemoattractant protein‐1 and macrophage inflammatory protein‐1β were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL‐8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL‐8 in CSF was also higher than serum IL‐8, suggesting that increased IL‐8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL‐8 in CSF in encephalopathy may protect against severe brain damage.

IL-17 is elevated in cerebrospinal fluids in bacterial meningitis in children.

Bacterial meningitis has a poor prognosis and neurologic complications. The present study aimed to investigate the cytokine/chemokine network in cerebrospinal fluid (CSF) from children with bacterial meningitis and aseptic meningitis. Interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta, were measured simultaneously in CSF supernatants. We found that, IL-17 was significantly elevated in CSF with bacterial meningitis. We believe that IL-17 plays a key role in neutrophil infiltration into CSF and neuronal protection in bacterial meningitis.

Effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter after polymyxin B-immobilized fiber column therapy of septic shock.

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.

High mobility group box 1 in cerebrospinal fluid from several neurological diseases at early time points.

ABSTRACT The present study aimed to elucidate the possible role of High Mobility Group Box 1 (HMGB1), which is a candidate prognostic marker in diseases that combine inflammation and tissue injury, in acute encephalopathy. HMGB1 in cerebrospinal fluid (CSF) obtained on admission from eight children with acute encephalopathy, and 16 children with febrile seizure, eight children with bacterial/aseptic meningitis, and eight children with fever without neurological symptoms were analyzed using enzyme-linked immunosorbent assay (ELISA). We found no increase in HMGB1 in CSF from acute encephalopathy or in CSF from febrile seizure or fever without neurological complications at early time points, while marked elevation of HMGB1 was seen in CSF from bacterial and aseptic meningitis. In conclusion, HMGB1 is a poor disease marker for acute encephalopathy.

An Effective Support System of Emergency Medical Services With Tablet Computers

Background There were over 5,000,000 ambulance dispatches during 2010 in Japan, and the time for transportation has been increasing, it took over 37 minutes from dispatch to the hospitals. A way to reduce transportation time by ambulance is to shorten the time of searching for an appropriate facility/hospital during the prehospital phase. Although the information system of medical institutions and emergency medical service (EMS) was established in 2003 in Saga Prefecture, Japan, it has not been utilized efficiently. The Saga Prefectural Government renewed the previous system in an effort to make it the real-time support system that can efficiently manage emergency demand and acceptance for the first time in Japan in April 2011. Objective The objective of this study was to evaluate if the new system promotes efficient emergency transportation for critically ill patients and provides valuable epidemiological data. Methods The new system has provided both emergency personnel in the ambulance, or at the scene, and the medical staff in each hospital to be able to share up-to-date information about available hospitals by means of cloud computing. All 55 ambulances in Saga are equipped with tablet computers through third generation/long term evolution networks. When the emergency personnel arrive on the scene and discern the type of patient’s illness, they can search for an appropriate facility/hospital with their tablet computer based on the patient’s symptoms and available medical specialists. Data were collected prospectively over a three-year period from April 1, 2011 to March 31, 2013. Results The transportation time by ambulance in Saga was shortened for the first time since the statistics were first kept in 1999; the mean time was 34.3 minutes in 2010 (based on administrative statistics) and 33.9 minutes (95% CI 33.6-34.1) in 2011. The ratio of transportation to the tertiary care facilities in Saga has decreased by 3.12% from the year before, 32.7% in 2010 (regional average) and 29.58% (9085/30,709) in 2011. The system entry completion rate by the emergency personnel was 100.00% (93,110/93,110) and by the medical staff was 46.11% (14,159/30,709) to 47.57% (14,639/30,772) over a three-year period. Finally, the new system reduced the operational costs by 40,000,000 yen (about

Enhanced expression of cytokines/chemokines in cerebrospinal fluids in mumps meningitis in children

400,000 US dollars) a year. Conclusions The transportation time by ambulance was shorter following the implementation of the tablet computer in the current support system of EMS in Saga Prefecture, Japan. The cloud computing reduced the cost of the EMS system.

Clinical responses and improvement of some laboratory parameters following polymyxin B-immobilized fiber treatment in septic shock.

Background:  The mumps virus is frequently the causative agent in aseptic meningitis and mumps has still prevailed in Japan. We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis‐specific cytokine/chemokine alterations in cerebrospinal fluide (CSF).

Can rotational thromboelastometry predict septic disseminated intravascular coagulation

Direct hemoperfusion using a polymyxin B–immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was first developed in 1994 and has since been used for the treatment of septic shock. Positive clinical data, such as an increase in systolic blood pressure (SBP) and an improved Pao2/Fio2 ratio, have also been reported. We treated 27 septic shock patients using DHP-PMX. The patients were separated into two groups for analysis: those whose Pao2/Fio2 ratio increased after DHP-PMX (9 cases) and those whose Pao2/Fio2 ratio did not increase after DHP-PMX (18 cases). The patients were also separated into two other groups for analysis: those whose SBP increased by more than 30 mm Hg immediately after DHP-PMX (15 cases) and those whose SBP did not increase by more than 30 mm Hg after DHP-PMX (12 cases). The Pao2/Fio2 ratio increased significantly after DHP-PMX in the groups showing improved 2AG and PAI-1 levels (p = 0.0040). The SBP increased significantly in the group showing improved HMGB-1 levels (p < 0.0001). We observed a relationship between hemodynamic improvement and increase of the serum HMGB-1 levels and between improvement of respiratory functions and increase of the serum 2-AG and PAI-1 levels in septic shock patients treated with DHP-PMX.

Exogenously-added copper/zinc superoxide dismutase rescues damage of endothelial cells from lethal irradiation

Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been incorporated into various kinds of postsurgical management. However, the utility of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular coagulation (DIC) has not been investigated. This retrospective study includes 13 sepsis patients who underwent ROTEM in our emergency department in 2013. All patients were divided into two groups on the basis of the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We evaluated the demographics, clinical characteristics, laboratory data, ROTEM test and outcomes for each patient. The correlations between JAAM DIC score and significantly different parameters by univariate analysis and receiver operating characteristic (ROC) analysis were performed to assess the accuracy of the variables. There were seven and six patients in the DIC group and non-DIC group, respectively. The DIC group showed significantly longer prothrombin times, international normalized ratio of prothrombin time and clotting times (CTs) in the EXTEM test, and higher fibrinogen and fibrin degradation products and D-dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798), than the standard coagulation test. These parameters were accurate predictors in the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed by the JAAM DIC score, and strongly associated with severity of DIC.