Search

Aim: We investigated whether an early‐phase prothrombin time‐international normalized ratio (PT‐INR) is an interventional prognostic indicator for patients with acute liver injury, including acute liver failure. Methods: This was a multicenter retrospective observational study. We included 595 patients with alanine aminotransferase levels ≥300 U/L due to acute liver injury who were admitted to Kagoshima University Hospital or other collaborative investigation organizations between January 1, 2010, and December 31, 2015. Patients with alanine aminotransferase levels ≥300 U/L and no previous liver disease were defined as having an acute liver injury. Acute liver failure was defined by PT‐INR ≥1.5 with or without hepatic encephalopathy in acute liver injury patients. Data were obtained retrospectively from case reports and analyzed. Results: The PT‐INR on day 1 was the most accurate independent prognosis predictor in patients with acute liver injury and acute liver failure. On day 1, the transplant‐free survival rates were significantly lower in patients with PT‐INR ≥1.3. The transplant‐free survival rates were also significantly higher in patients with acute liver injury and acute liver failure, in whom the PT‐INR had recovered from ≥1.3 on day 1 to <1.3 by day 8. Conclusion: Early‐phase changes in the PT‐INR can predict the prognosis of patients with acute liver injury and acute liver failure. Furthermore, PT‐INR ≥1.3 could be an interventional marker, whereas PT‐INR <1.3 after 1 week could reflect prognostic improvement. [ABSTRACT FROM AUTHOR]

Background: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation, which is recovered by the administration of medicine injection. Objective: Sepsis-induced variation and recovery of microcirculation are quantitatively detected using microcirculation images acquired by a non-contact imaging setup, which might assist the clinical diagnosis and therapy of sepsis. Methods: In this study, a non-contact imaging setup was first used to record images of microcirculation on the back of model rats. Specifically, the model rats were divided into three groups: (i) the sham group as a control group; (ii) the cecum ligation and puncture (CLP) group with sepsis; and (iii) the CLP+thrombomodulin (TM) group with sepsis and the application of TM alfa therapy. Furthermore, considering the sparsity of red blood cells (RBCs), the blood velocity is estimated by robust principal component analysis (RPCA) and U-net, and the blood vessel diameter is estimated by the contrast difference between the blood vessel and tissue. Results and Effectiveness: In the experiments, the continuous degradation of the estimated blood velocity and blood vessel diameter in the CLP group and the recovery after degradation of those in the CLP+TM group were quantitatively observed. The variation tendencies of the estimated blood velocity and blood vessel diameter in each group suggested the effects of sepsis and its corresponding therapy. [ABSTRACT FROM AUTHOR]

Background: Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA).Methods: This was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels.Results: Of 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC.Conclusions: The addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction. [ABSTRACT FROM AUTHOR]

Introduction: Resuscitative endovascular balloon occlusion of the aorta (REBOA) increases proximal arterial pressure, but may also induce life-threatening distal ischemia. Partial REBOA (P-REBOA) is thought to mitigate distal ischemia during aortic occlusion. However, feasible indicators of the degree of P-REBOA remain inconsistent. We hypothesised percent balloon volume could be a substitute for pressure measurements of gradients during P- REBOA. This study aimed to compare balloon volume and arterial pressure gradient, and analysed with intra-balloon pressure and balloon shape. Methods: Proximal (carotid) and distal (femoral) arterial pressures were recorded and a 7-Fr REBOA catheter was placed in four swine. Total REBOA was defined as a cessation of distal pulse pressure and maximum balloon volume was documented. The balloon volume was titrated by 20% increments of maximum capacity to adjust the degree of P-REBOA. The distal/proximal arterial pressure gradient and the intra-balloon pressures were also recorded. The changes in shape and the cross-sectional area of the balloon were evaluated with computed tomography (CT) images. Results: The proximal mean arterial pressure (MAP) plateaued after 60% balloon volume; meanwhile, distal pulse pressure was still left. The balloon pressure was traced with proximal MAP before contact with aortic wall. The balloon shape changed unevenly from "cone" to "spindle" shape, although the balloon cross-sectional area of the mid-segment linearly increased. Conclusion: Monitoring distal pressure and titrating percent balloon volume is feasible to manage P-REBOA. In this experiment, 60% balloon volume was enough inflation to elevate central pressure allowing distal perfusion. The intra-balloon pressure was not reliable due to the strong influence of proximal MAP and uneven change of the balloon shape. [ABSTRACT FROM AUTHOR]

Aim: Acute liver failure (ALF) patients with coma need to be revived not only for spontaneous recovery but also as a bridge to liver transplantation. We developed a new high‐volume plasma purification system using an on‐line continuous hemodiafiltration (CHDF) system, and evaluated its safety and efficacy in a multicenter study. Methods: A single arm interventional study using the new apparatus was undertaken in the six major liver centers in Japan. The primary end‐point was the proportion of patients who regained consciousness within 10 days, which was compared with a historical control (47%). Nine ALF patients were enrolled and treated with the new machine. One patient was excluded because of the need for artificial respiration support according to the established protocol. Results: Seven of eight (87.5%) patients regained consciousness during the on‐line CHDF session, with five of those seven waking within 4 days. After waking, one patient spontaneously recovered, three received liver transplantation, two died of liver failure, and one died of another disease. The plasma ammonia levels significantly decreased after the start of on‐line CHDF from 182.5 ± 64.8 μg/dL (mean ± SD) on day 0 to 87.0 ± 38.9 μg/dL on the last day of the session (P < 0.001). Similarly, the plasma glutamine level also significantly decreased from 2069 ± 1234 μmol/L to 628 ± 193 μmol/L. Although seven severe adverse events occurred during on‐line‐CHDF, no causal relationship with liver support was recognized. Conclusions: The newly developed on‐line CHDF system showed high efficacy for regain of consciousness and excellent therapeutic safety for managing ALF. [ABSTRACT FROM AUTHOR]

Introduction: Quality improvement in the administration of extracorporeal cardiopulmonary resuscitation (ECPR) over time and its association with low-flow duration (LFD) and outcomes of cardiac arrest (CA) have been insufficiently investigated. In this study, we hypothesized that quality improvement in efforts to shorten the duration of initiating ECPR had decreased LFD over the last 15 years of experience at an academic tertiary care hospital, which in turn improved the outcomes of in-hospital CA (IHCA). Methods: This was a single-center retrospective observational study of ECPR patients between January 2003 and December 2017. A rapid response system (RRS) and an extracorporeal membrane oxygenation (ECMO) program were initiated in 2011 and 2013. First, the association of LFD per minute with the 90-day mortality and neurological outcome was analyzed using multiple logistic regression analysis. Then, the temporal changes in LFD were investigated. Results: Of 175 study subjects who received ECPR, 117 had IHCA. In the multivariate logistic regression, IHCA patients with shorter LFD experienced significantly increased 90-day survival and favorable neurological outcomes (LFD per minute, 90-day survival: odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94–1.00, P = 0.032; 90-day favorable neurological outcome: OR = 0.97, 95% CI = 0.94–1.00, P = 0.049). In the study period, LFD significantly decreased over time (slope − 5.39 [min/3 years], P < 0.0001). Conclusion: A shorter LFD was associated with increased 90-day survival and favorable neurological outcomes of IHCA patients who received ECPR. The quality improvement in administering ECPR over time, including the RRS program and the ECMO program, appeared to ameliorate clinical outcomes. [ABSTRACT FROM AUTHOR]

A simplified ecosystem model, the Aquatic Tritrophic Ecological Risk Assessment Model (A‐TERAM), for the ecological risk assessment of chemicals is presented. The A‐TERAM comprises a linear grazer food chain with 3 trophic levels (the algae–Daphnia–fish system). The model simulates the seasonal patterns of abundance at each level observed in the field, and it translates the direct toxic effects of chemicals on algae or Daphnia to implications for fish via ecological interactions; thus, the A‐TERAM evaluates ecological risk in terms of the annual population growth rate of fish. The model also incorporates toxicokinetics for fish. The minimum input data required for the A‐TERAM are basic ecotoxicity endpoints (algal growth inhibition median effect concentration [EC50] or no‐observed effect concentration, Daphnia immobility EC50, and fish acute mortality median lethal concentration); however, additional ecotoxicity data (Daphnia reproduction test, fish early life test, and fish reproduction test) are also relevant for improving simulations. Comparisons made across 496 chemicals (255 nonagricultural chemicals and 241 agrochemicals) indicated that the A‐TERAM, in comparison with the conventional predicted‐effect concentration/predicted‐no‐effect concentration method, tended to evaluate higher risk to chemicals that are highly bioaccumulative and toxic to fish by 2 orders of magnitude at the largest but lower or comparable risk to chemicals that are toxic only to algae or Daphnia. Environ Toxicol Chem 2020;39:1086–1100. © 2020 SETAC [ABSTRACT FROM AUTHOR]

The patients with respiratory failure need high tidal volume by mechanical ventilation, which lead to the ventilator-induced lung injury. We developed an extracorporeal lung and renal assist device (ELRAD), comprising acid infusion, membrane lung, continuous hemodiafiltration and alkaline infusion. To evaluate this system, we conducted in vivo studies using experimental swine which were connected to the new system. In vivo experiments consist of four protocols; baseline = hemodiafiltration only (no O2 gas flow to membrane lung); membrane lung = "Baseline" plus O2 gas flow to membrane lung; "Acid infusion" = "Membrane lung" plus continuous acid infusion; ELRAD = "Acid infusion" plus continuous alkaline infusion. We changed the ventilatory rate of the mechanical ventilation to maintain PCO2 at 50–55 mmHg during the four protocols. The results showed that there was statistically no significant difference in the levels of pH, HCO3−, and base excess when each study protocol was initiated. The amount of CO2 eliminated by the membrane lung significantly increased by 1.6 times in the acid infusion protocol and the ELRAD protocol compared to the conventional membrane lung protocol. Minute ventilation in the ELRAD protocol significantly decreased by 0.5 times compared with the hemodiafiltration only protocol (P < 0.0001), the membrane lung (P = 0.0006) and acid infusion protocol (P = 0.0017), respectively. In conclusion, a developed CO2 removal system efficiently removed CO2 at low blood flow and reduced minute ventilation, while maintaining acid–base balance within the normal range. [ABSTRACT FROM AUTHOR]

Acute blood purification therapy is an essential artificial organ in critical care. In the review article, looking back on the history, we describe our present knowledge and techniques of acute blood purification therapy in critical care. The topics include continuous hemodiafiltration (CHDF), online HDF as an artificial liver support, blood purification therapy aiming to remove pathogenic substances of sepsis, a procedure for connecting a CRRT device into an extra-corporeal membrane oxygenation circuit, and replacement fluid for CHDF. We also raise remaining issues and clarify the future direction of acute blood purification therapy in critical care. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2017 (Vol. 46, No. 1, pp. 67–70), with adding some references. [ABSTRACT FROM AUTHOR]

We evaluated the accuracy and precision of a novel non-invasive monitoring device in comparison with conventional monitoring methods used in intensive care units (ICU). The study device was developed to measure blood pressure, pulse rate, respiratory rate, and oxygen saturation, continuously with a single sensor using the photoplethysmographic technique. Patients who were monitored with arterial pressure lines in the ICU were enrolled. Systolic and diastolic blood pressure, pulse rate, respiratory rate, and arterial oxygen saturation were measured continuously for 30 min at 5-min intervals using the conventional methods and the study device. The primary outcome variable was blood pressure. Blood pressure measured by the study device highly correlated with the arterial pressure line values (correlation coefficients > 0.95). Percent errors for systolic, diastolic and mean blood pressures were 2.4% and 6.7% and 6.5%, respectively. Percent errors for pulse rate, respiratory rate and oxygen saturation were 3.4%, 5.6% and 1.4%, respectively. The non-invasive, continuous, multi-parameter monitoring device presented high level of agreement with the invasive arterial blood pressure monitoring, along with sufficient accuracy and precision in the measurements of pulse rate, respiratory rate, and oxygen saturation. [ABSTRACT FROM AUTHOR]

Background: Diffuse axonal injury (DAI) is difficult to identify in the early phase of traumatic brain injury (TBI) using common diagnostic methods. Tau protein is localized specifically in nerve axons. We hypothesized that serum level of tau can be a useful biomarker to diagnose DAI in the early phase of TBI. Methods & results: We measured serum tau levels in 40 TBI patients who were suspected of DAI within 6 hours after TBI to evaluate the accuracy of the tau level as a diagnostic marker for DAI. Diagnosis of DAI was confirmed according to magnetic resonance imaging (MRI) findings. The serum tau level in the DAI group (n = 13) was significantly higher than that in the non-DAI group (n = 27) (DAI vs. non-DAI, 25.3 [0 to 99.1] pg/mL vs. 0 [0 to 44.4] pg/mL, P = 0.03)). A receiver-operating characteristic curve to evaluate the diagnostic ability of serum tau level within 6 hours for DAI showed an area under the curve of 0.690 with 74.1% for sensitivity and 69.2% for specificity. Serum tau level was not significantly higher in unfavorable outcome group (Glasgow Outcome scale [GOS] score = 1–3 at hospital discharge) compared with favorable outcome group (GOS score = 4–5) (P = 0.19). Conclusions: Tau protein may be a useful biomarker for diagnosis of DAI in the early phase of TBI. [ABSTRACT FROM AUTHOR]

Aim: An artificial liver support (ALS) system sustaining patients with acute liver failure (ALF) in good condition until recovery of the native liver or performance of liver transplantation (LT), is essential for the improvement of the poor prognosis of ALF despite the lack of survival benefit. We aimed to investigate the efficacy of various ALS systems for fulminant hepatitis (FH) carried out in our liver unit so far, focusing on the restoration of consciousness from hepatic encephalopathy. Methods: One hundred and ten consecutive adult Japanese patients with FH admitted to Chiba University Hospital (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed. Results: Recovery rate of consciousness improved with the increased dialysate flow rate and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high‐flow CHDF (HFCHDF) (QD = 300 mL/min), 88.6% by HFCHDF (QD = 500 mL/min) (+ sPE), and 92.9% by on‐line HDF (OLHDF) (+ sPE). All patients except one, who could not be fully treated because of circulatory failure, recovered consciousness by OLHDF, including those whose liver function were completely abolished. Superiority of HFCHDF (QD = 500 mL/min) and OLHDF was also shown in patients who died without LT or received LT. Conclusions: More effective ALS should be recognized considering the extremely high recovery rate of consciousness. In particular, OLHDF with predilution reduces the cost of substitution fluid by supplying an unlimited amount of dialysate as substitution fluid prepared using an on‐line system, and simplifies the procedure for the management. [ABSTRACT FROM AUTHOR]

Introduction: Red blood cell (RBC) transfusion is associated with poor clinical outcome in critically ill patients. We investigated the predictive value of biomarkers on intensive care units (ICU) admission for RBC transfusion within 28 days. Methods: Critically ill patients (n = 175) who admitted to our ICU with organ dysfunction and an expected stay of ≥ 48 hours, without hemorrhage, were prospectively studied (derivation cohort, n = 121; validation cohort, n = 54). Serum levels of 12 biomarkers (hemoglobin, creatinine, albumin, interleukin-6 [IL-6], erythropoietin, Fe, total iron binding capacity [TIBC], transferrin, ferritin, transferrin saturation, folate, and vitamin B12) were measured upon ICU admission, days 7, 14, 21 and 28. Results: Among the 12 biomarkers measured upon ICU admission, levels of hemoglobin, albumin, IL-6, TIBC, transferrin and ferritin were statistically different between transfusion and non-transfusion group. Of 6 biomarkers, TIBC upon ICU admission had the highest area under the curve value (0.835 [95% confidence interval] = 0.765–0.906) for predicting RBC transfusion (cut-off value = 234.5 μg/dL; sensitivity = 0.906, specificity = 0.632). This result was confirmed in validation cohort, whose sensitivity and specificity were 0.888 and 0.694, respectively. Measurement of these biomarkers every seven days revealed that albumin, TIBC and transferrin were statistically different between groups throughout hospitalization until 28 days. In validation cohort, patients in the transfusion group had significantly higher serum hepcidin levels than those in the non-transfusion group (P = 0.004). In addition, joint analysis across derivation and validation cohorts revealed that the serum IL-6 levels were higher in the transfusion group (P = 0.0014). Conclusion: Decreased TIBC upon ICU admission has high predictive value for RBC transfusion unrelated to hemorrhage within 28 days. [ABSTRACT FROM AUTHOR]

We developed a novel system comprising acid infusion, membrane lung, and a continuous renal replacement therapy console for efficient CO2 removal at a low blood flow. To evaluate the new system, we used an ex vivo experimental model using swine blood. A liter of aliquoted blood adjusted to pH 7.25 and pCO2 65 mm Hg was mixed with acid (0, 10, or 20 mL of lactic or hydrochloric acid [1 mol/L]) and was immediately delivered to the system in a single pass. We collected blood samples at each point of the circuit and calculated the amount of CO2 eliminated by the membrane lung. The new system removed 13.2 ± 0.8, 32.0 ± 2.1, and 51.6 ± 3.7 mL/min of CO2 (with 0, 10, and 20 mEq/L of lactic acid) and 21.2 ± 1.2, 27.3 ± 0.3, and 42.0 ± 1.3 mL/min (with 0, 10, and 20 mEq/L of hydrochloric acid), respectively. The levels of lactate and Cl− ions for acid-base equilibrium were restored after continuous hemodiafiltration. Thus, the amount of CO2 eliminated by the membrane lung was 3.9 times higher with lactic acid and 2.0 times higher with hydrochloric acid compared with non-acid controls. In conclusion, this easy-to-setup CO2 removal system was safe, effective, and removed CO2 at a low blood flow. [ABSTRACT FROM AUTHOR]

Aim There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF. Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro-inflammatory cytokine levels in the early stage of ALF. Methods Ten consecutive adult Japanese patients with fulminant hepatitis in the early stage, three treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group) and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical data on admission were matched between the groups and retrospectively analyzed for serum concentrations of interleukin-6, tumor necrosis factor-α, and interleukin-1β over a 2-week period. Results Mean cytokine levels on admission were not different between the two groups. Tumor necrosis factor-α was significantly reduced on day 7 in patients with CS. Serum levels of pro-inflammatory cytokines tended to be reduced in patients with CS compared to those without during the observation period, although the differences were not significant. Conclusions It might be possible that introduction of CS pulse therapy in the early stage of ALF could reduce levels of pro-inflammatory cytokines, which might inhibit the cascade of progression of ALF. [ABSTRACT FROM AUTHOR]

To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1-3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients. [ABSTRACT FROM AUTHOR]

Background Histological examination is useful for the diagnosis of acute severe (fulminant) autoimmune hepatitis ( AIH), but it is sometimes difficult to perform liver biopsy due to the complicated coagulopathy and ascites. We have shown that heterogeneous hypoattenuation on unenhanced computed tomography ( CT) is a characteristic imaging feature of acute severe (fulminant) AIH. In the present study, we examined the utility of the imaging feature by applying the score to diagnose acute severe (fulminant) AIH. Methods Twenty-three patients with acute severe (fulminant) AIH were analyzed retrospectively. Modified AIH score was created by adding three points to AIH score with/without histological points in case of the presence of heterogeneous hypoattenuation on unenhanced CT. Results Areas of hypoattenuation were present in 15 (65%) patients, all of which were heterogeneous pattern. Five (22%) patients were diagnosed as 'definite' AIH, 16 (69%) as 'probable' and two (9%) as 'non-diagnosis' by the revised original score without histological score. By adding three points, two of 'non-diagnosis' changed to 'probable' AIH, and all patients were diagnosed as AIH. Conclusions Modified AIH score using heterogeneous CT image finding would be beneficial especially for patients in whom histological examinations cannot be performed because of complications. [ABSTRACT FROM AUTHOR]

Introduction: Although recent studies have reported the efficacy of antithrombin (AT) supplementation for sepsis-associated disseminated intravascular coagulation (DIC), the factors that influence AT’s effect have not been sufficiently studied. The purpose of this survey was to identify factors that modulate the effects and the adverse effects of AT. Methods: We performed a multi-institutional survey. The data from 159 patients with septic DIC with AT ≤70% and who had undergone AT supplementation were analyzed. The patients’ demographic characteristics, including the infection site, baseline sepsis-related organ failure assessment (SOFA) score, baseline DIC score, and baseline AT activity, were analyzed in relation to the 28-day mortality. Bleeding-related adverse events were also examined. Results: Overall, 116 patients survived and 43 did not (28-day mortality: 27.0%). A logistic regression analysis revealed that the baseline SOFA score (odds ratio [OR]: 0.816, P = .001), coadministration of recombinant thrombomodulin (rTM; OR: 3.989, P = .006), and respiratory tract infection (OR: 0.129, P = .000) were significantly associated with the survival. Survivors exhibited a higher peak AT activity than nonsurvivors (85.1% vs 65.0%, P = .027). Bleeding events were observed in 4.13% (major bleeding: 1.65%) of the patients, and the coadministration of rTM did not increase the risk of bleeding (with rTM: 4.11% vs without rTM: 4.17%). Heparin was concomitantly used in 22 (18.2%) cases, and its use nonsignificantly increased the bleeding risk (with heparins: 9.09% vs without heparins: 3.03%; P = .224). Conclusion: The coadministration of rTM may improve survival without increasing the risk of bleeding in patients with sepsis-associated DIC treated with AT. [ABSTRACT FROM AUTHOR]

Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with 'immune system process' and 'biological adhesion' functions compared to those of non-sepsis patients ( P < 0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis ( P < 0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis. [ABSTRACT FROM AUTHOR]

Patients receiving extracorporeal membrane oxygenation (ECMO) often require continuous renal replacement therapy (CRRT). The intra-circuit pressure of adult ECMO usually deviates from the physiological range. We investigated the use of CRRT connected to an ECMO circuit with physiological intra-circuit pressures (0-150 mmHg, defined as the 'safety range') using an in vitro experiment involving a water-filled ECMO circuit. The intra-circuit pressure pre-pump, post-pump, and post-oxygenator were measured while varying the height of the pump or ECMO flow. The bypass conduit pressure and distance from the post-oxygenator port were measured to find the 'safety point', where the bypass pressure remained within the safety range. Both drainage and return limbs of the CRRT machine were connected to the safety point and the inlet and outlet pressures of the hemofilter were recorded while varying the ECMO and CRRT flow. The pre-pump pressure only remained within the safety range for heights >75 cm (ECMO flow = 4 L/min) or ECMO flow <3.5 L min (height = 50 cm). The post-pump and post-oxygenator pressure was generally outside of the safety range. The bypass pressure decreased according to the distance from the post-oxygenator port and the safety point was found at 60 or 75 cm (in a 90-cm length conduit) regardless of ECMO flow. The hemofilter inlet and outlet pressures remained within the safety range for all conditions of ECMO and CRRT flow, findings validated in clinical cases. The bypass conduit within an ECMO circuit can be connected to a CRRT machine safely under physiological pressures in adult patients receiving ECMO. [ABSTRACT FROM AUTHOR]

Purpose: The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome. Materials and Methods: We tested for an association of clinical outcomes with timing and location using a university hospital cohort in Japan (n = 328). The primary outcome was short-term serious outcome (unplanned ICU admission after MET activation or death at scene). Results: Patients for whom the MET was activated in the evening or night-time had significantly higher rates of short-term serious outcome than those for whom it was activated during the daytime (vs. evening: adjusted OR = 2. 53, 95% CI = 1.24–5.13, P = 0.010; night-time: adjusted OR = 2.45, 95% CI = 1.09–5.50, P = 0.030). Patients for whom the MET was activated in public space had decreased short-term serious outcome compared to medical spaces (public space: adjusted OR = 0.19, 95% CI = 0.07–0.54, P = 0.0017). Night-time (vs. daytime) and medical space (vs. public space) were significantly associated with higher risks of unexpected cardiac arrest and 28-day mortality. Conclusions: Patients for whom the MET was activated in the evening/night-time, or in medical space, had a higher rate of short-term serious outcomes. Taking measures against these risk factors may improve MET performance. [ABSTRACT FROM AUTHOR]

Background: Corticosteroid (CS) has been introduced in most acute liver failure (ALF) patients for the purpose of suppressing pro‐inflammatory cytokines in Japan where a shortage of donor livers exists, whereas CS use is evaluated to be no benefit in Western countries. In the present study, we aimed to clarify the association between infectious complications and CS use in ALF, and determine when to evaluate treatment response and consider the timing for switching to liver transplantation (LT). Methods: Corticosteroid was administered to patients in the early stage prospectively. Clinical and biochemical features of 110 adult patients were analyzed. Results: Corticosteroids were administered to 78 (71%) patients. The duration between start of CS and onset of infection was 17 ± 10 days. Multivariate analysis revealed that infection was associated with age >50 years (P = 0.034) and T‐BIL >15 mg/dl (P < 0.001), and not with CS use (P = 0.10). Accumulative incidence of infection was not different between patients with and without CS (P = 0.18). Conclusions: Corticosteroid use did not significantly increase the incidence of infection. Two weeks after introduction of CS is a critical point for evaluating treatment response, avoiding infectious complications and switching to LT. Highlight Aiming to clarify the association between infectious complications and corticosteroid use in acute liver failure, Yasui and colleagues showed that corticosteroid use did not significantly increase the incidence of infection and that two weeks after corticosteroid initiation was a critical point for evaluating treatment response and switching to liver transplantation. [ABSTRACT FROM AUTHOR]

We have previously proposed an estimation method of intravascular oxygen saturation $$({\rm SO}_2)$$ from the images obtained by sidestream dark-field (SDF) imaging (we call it SDF oximetry) and we investigated its fundamental characteristics by Monte Carlo simulation. In this paper, we propose a correction method for scattering by the tissue and performed experiments with turbid phantoms as well as Monte Carlo simulation experiments to investigate the influence of the tissue scattering in the SDF imaging. In the estimation method, we used modified extinction coefficients of hemoglobin called average extinction coefficients (AECs) to correct the influence from the bandwidth of the illumination sources, the imaging camera characteristics, and the tissue scattering. We estimate the scattering coefficient of the tissue from the maximum slope of pixel value profile along a line perpendicular to the blood vessel running direction in an SDF image and correct AECs using the scattering coefficient. To evaluate the proposed method, we developed a trial SDF probe to obtain three-band images by switching multicolor light-emitting diodes and obtained the image of turbid phantoms comprised of agar powder, fat emulsion, and bovine blood-filled glass tubes. As a result, we found that the increase of scattering by the phantom body brought about the decrease of the AECs. The experimental results showed that the use of suitable values for AECs led to more accurate $${\rm SO}_2$$ estimation. We also confirmed the validity of the proposed correction method to improve the accuracy of the $${\rm SO}_2$$ estimation. [ABSTRACT FROM AUTHOR]

Background: It is not yet clear whether hemofiltration can reduce blood cytokine levels sufficiently to benefit patients who suffer prolonged cardiac arrest (CA) treated with cardiopulmonary bypass (CPB). We sought to assess effects of high-volume and standard volume continuous veno-venous hemofiltration (CVVH) on blood cytokine levels and survival in a rat model of prolonged CA treated with CPB. Methods: Sprague-Dawley male rats were subjected to 12 min of asphyxia to induce CA. CPB was initiated for resuscitation of animals and maintained for 30 min. Twenty-four rats were randomly assigned into three groups: without CVVH treatment (sham); standard volume CVVH at a filtration rate of 35-45 mL/kg/h; and high-volume hemofiltration (HVHF, 105-135 mL/kg/h). Hemofiltration was started simultaneously with CPB and maintained for 6 h. Plasma TNFα and IL-6 levels were measured at baseline, 0.5, 1, 2, 3, and 6 h after reperfusion. Survival time, neurological deficit score, and hemodynamic status were assessed. Results: All animals survived over 6 h and died within 24 h. There were no significant differences in survival time (log-rank test, sham vs. CVVH; p = 0.49, sham vs. HVHF; p = 0.33) or neurological deficit scores (ANOVA, p = 0.14) between the groups. There were no significant differences in blood cytokine levels between the groups. Mean blood pressure in sham group animals increased to 1.5-fold higher than baseline levels at 30 min. HVHF significantly reduced blood pressure to 0.7-fold of sham group ( p < 0.01). Conclusions: There was no improvement in mortality, neurological dysfunction, TNFα, or IL-6 levels in rats after prolonged CA with CPB on either hemofiltration group when compared to the sham group. [ABSTRACT FROM AUTHOR]

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. Methods: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. Results: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). Conclusions: Two‐week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve. Highlight Fujiwara and colleagues reveal that the critical point for switching to liver transplantation without infectious complications in autoimmune acute liver failure is two weeks after the start of corticosteroid treatment. It is crucial to evaluate corticosteroid efficacy and, if no improvement is seen, to perform liver transplantation by that time. [ABSTRACT FROM AUTHOR]

On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middleagedJapanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF. [ABSTRACT FROM AUTHOR]

Aim The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. Methods We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. Results Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. Conclusion There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies. [ABSTRACT FROM AUTHOR]

Aim Older age has been widely believed to be associated with a poor prognosis of acute liver failure. We aimed to evaluate the impact of older age on outcomes of Japanese patients with severe and fulminant hepatitis in an era of a highly aging society. Methods We investigated 105 consecutive adult patients with fulminant hepatitis ( FH) or severe hepatitis ( SH) admitted to our liver unit between 2000 and 2013, consisting of 14 elderly patients (≥65 years) and 91 younger ones (<65 years). Results In elderly patients, the proportion of women was greater ( P < 0.001), the levels of aspartate aminotransferase and lactate dehydrogenase on admission were lower ( P = 0.011 and P = 0.010, respectively), and the survival rate without liver transplantation was lower ( P = 0.024) than younger ones. Two of seven SH and all seven FH elderly patients died, whereas all 45 SH and 16 of 46 FH younger patients recovered. Seventy-one percent of elderly patients had underlying diseases with medications, and 57% had additional complications after the start of treatment for acute liver failure. Patients aged 70 years or more showed even poorer prognoses than younger ones and those aged 65-69 years ( P = 0.0052 and P = 0.036, respectively). Conclusion Older age was associated with a poor prognosis of patients with SH and FH. One of the reasons other than complications and loss of organ reserve by aging would be that elderly patients consulted us at a more advanced stage of illness than younger ones. [ABSTRACT FROM AUTHOR]

Background: There has existed important differences in the definition of acute liver failure (ALF) between Japanese criteria and those of other countries. The novel diagnostic criteria for ALF in Japanese patients were established by the Intractable Hepato‐Biliary Diseases Study Group of Japan, in order to correspond to those for ALF in Europe and the USA. We prospectively diagnosed our ALF patients based on this novel criteria, and discussed the etiology by a fixed point observation. Methods: We investigated the etiology of 54 adult inpatients and outpatients with ALF between 2010 and 2012. Results: Of 54 patients, 36 were ALF without coma, 17 ALF with coma and one late onset hepatic failure. The etiology was due to viral infections in 38.9%, autoimmune hepatitis in 11.1%, drug‐induced liver injury in 13.0%, etiologies without hepatitis in 29.6% (circulatory disturbance in 18.5%, infiltration of the liver by malignant cells in 7.4%, and metabolic diseases in 3.7%) and indeterminate causes in 7.4%. Conclusions: Circulatory disturbance was the most frequent etiology according to the novel criteria. Indeterminate etiology was less observed in our study than the nation‐wide survey with significance (P = 0.0014). [ABSTRACT FROM AUTHOR]

Background/Aim: We investigated the clinical efficacy of continuous hemodiafiltration (CHDF) with AN69ST hemofilter (AN69ST-CHDF) in patients with septic shock. Materials and Methods: A prospective, multicenter, single-arm study was conducted. Patients with sepsis and shock defined by hyperlactemia were enrolled. The patients were treated with CHDF and in accordance with the Surviving Sepsis Campaign guidelines (SSCG). Results: Thirty-four patients were enrolled. On ICU admission, the mean blood IL-6 level was 44,800 ± 77,700 pg/ml, and the mean blood lactate level was 69.0 ± 49.4 mg/dl. Both the mean blood IL-6 and lactate levels had significantly decreased to normal ranges after 72 h of AN69ST-CHDF. Though the mean APACHE II score was 32.7 ± 9.8, 28-day survival was 73.5%. Conclusion: The current study suggested that adding AN69ST-CHDF to the treatments outlined in the SSCG might lead to good outcomes for patients with septic shock, probably via the removal of cytokines from the bloodstream. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge. Methods: Patients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors). Results: Non-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771–0.890) for PCT, 0.688 (0.566–0.810) for albumin, 0.861 (0.796–0.927) for SOFA score, and increased to 0.913 (0.858–0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis. Conclusions: Serum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction. [ABSTRACT FROM AUTHOR]

Aim Acute liver failure ( ALF) is a worldwide problem despite its rare incidence because of its extremely high mortality. There are no beneficial therapies except for emergency liver transplantation for ALF. However, in Japan where the problem of a shortage of donor livers still remains, therapies other than transplantation must be further investigated for patients with ALF. Our aim was to elucidate the efficacy of high-dose corticosteroid ( CS) in decreasing liver enzyme levels in the early stage of ALF. Methods Thirty-one consecutive Japanese patients with viral ALF in the early stage were prospectively examined for their clinical and biochemical features and treatment responses during 2 weeks after the start of treatment. Nineteen were treated with high-dose methylprednisolone, and 12 having clinical and biochemical backgrounds with no significant difference were treated without CS. Results The aspartate aminotransferase : alanine aminotransferase ratio became lower in patients treated with CS than in controls ( P < 0.05). Fifteen of 19 patients in the CS group and eight of 12 in the control group recovered ( P = 0.36). Hepatitis B viral infection and advanced liver damage at the start of treatment were associated with poor prognosis ( P < 0.05). Complications during the therapy were not greater in the CS group than control ( P = 0.64). Conclusion The introduction of high-dose CS in the early stage of ALF was effective in suppressing the destruction of hepatocytes. CS-treated patients showed slightly higher survival rates and slightly more improved liver regeneration than controls, although the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Background: Treatment with systemic corticosteroids is often used for acute liver failure (ALF), but this has increased the number of profoundly immunocompromised patients and cases of opportunistic infection. Methods: Between January 2007 and December 2012, all patients ( n = 51) referred to the Chiba University Hospital for treatment of ALF were studied. Patients with prothrombin activity of 40 % or less of the standardized values were defined as having ALF. Patient age, sex, cause of ALF, alanine aminotransferase and total bilirubin levels, prothrombin activity and total amount of corticosteroid were analyzed to determine the factors associated with the occurrence of opportunistic infection. Results: Opportunistic infections occurred in 21.6 % ( n = 11) of ALF patients. Thirty-five patients underwent systemic corticosteroid therapy, and 31.4 % of those patients showed opportunistic infections. Cytomegalovirus ( n = 9, 81.8 %) and Pneumocystis jiroveci ( n = 6, 54.5 %) were the microorganisms frequently suspected as the causes of opportunistic infection. In 7 (63.6 %) of the 11 cases of opportunistic infection, 2 or more species of microorganism were detected. Seven patients (63.6 %) with opportunistic infection were cured by treatment. Cox regression analysis for the patients who underwent systemic corticosteroid therapy steroid treatment revealed that age over 52 years (compared to younger patients: odds ratio = 9.62, 95 % confidence interval = 1.22-76.9) was only the predictive factor for the occurrence of opportunistic infection. Conclusion: Opportunistic infections are not rare in ALF patients, and the appropriate diagnosis and treatment of these infections are critical during ALF treatment. [ABSTRACT FROM AUTHOR]

Objective: Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients. Methods: The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes. Results: No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019). Conclusions: The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation. [ABSTRACT FROM AUTHOR]

Background: The gene doublesex (dsx) is known as a key factor regulating genetic sex determination in many organisms. We previously identified two dsx genes (DapmaDsx1 and DapmaDsx2) from a freshwater branchiopod crustacean, Daphnia magna, which are expressed in males but not in females. D. magna produces males by parthenogenesis in response to environmental cues (environmental sex determination) and we showed that DapmaDsx1 expression during embryonic stages is responsible for the male trait development. The D. magna dsx genes are thought to have arisen by a cladoceran-specific duplication; therefore, to investigate evolutionary conservation of sex specific expression of dsx genes and to further assess their functions in the environmental sex determination, we searched for dsx homologs in four closely related cladoceran species. Results: We identified homologs of both dsx genes from, D. pulex, D. galeata, and Ceriodaphnia dubia, yet only a single dsx gene was found from Moina macrocopa. The deduced amino acid sequences of all 9 dsx homologs contained the DM and oligomerization domains, which are characteristic for all arthropod DSX family members. Molecular phylogenetic analysis suggested that the dsx gene duplication likely occurred prior to the divergence of these cladoceran species, because that of the giant tiger prawn Penaeus monodon is rooted ancestrally to both DSX1 and DSX2 of cladocerans. Therefore, this result also suggested that M. macrocopa lost dsx2 gene secondarily. Furthermore, all dsx genes identified in this study showed male-biased expression levels, yet only half of the putative 5' upstream regulatory elements are preserved in D. magna and D. pulex. Conclusions: The all dsx genes of five cladoceran species examined had similar amino acid structure containing highly conserved DM and oligomerization domains, and exhibited sexually dimorphic expression patterns, suggesting that these genes may have similar functions for environmental sex determination in cladocerans. [ABSTRACT FROM AUTHOR]

Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration ( C) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy. [ABSTRACT FROM AUTHOR]

Since the introduction of the new pathophysiological concept of pathogen-associated molecular patterns (PAMPS) and alarmins, endotoxin has been recognized as only one of the PAMPS. It is widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. Many kinds of blood purification modalities have been proposed as a therapeutic tool against sepsis, including high-volume continuous hemofiltration whose efficacy has recently been questioned. We report that continuous hemodiafiltration (CHDF) with a cytokine-adsorbing hemofilter (CAH), such as polymethyl methacrylate hemofilter and AN69ST hemofilter (CAH-CHDF), can remove many kinds of cytokines and has been very effective in the treatment of severe sepsis and septic shock. Based on the understanding of the recent pathophysiology, we suggest that CAH-CHDF is an alternate therapy to direct hemoperfusion with endotoxin-adsorbing column in the treatment of sepsis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]