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Abstract 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 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.

Objective: Disseminated intravascular coagulation plays a key role in the pathophysiology of sepsis. Thrombomodulin is essential in the protein C system of coagulation cascade, and functional polymorphisms influence the human thrombomodulin gene (THBD). Therefore, we conducted a multicenter study to evaluate the influence of such polymorphisms on the pathophysiology of sepsis.Methods: A collaborative case-control study in the intensive care unit (ICU) of each of five tertiary emergency centers. The study included 259 patients (of whom 125 displayed severe sepsis), who were admitted to the ICU of Chiba University Hospital, Chiba, Japan between October 2001 and September 2008 (discovery cohort) and 793 patients (of whom 271 patients displayed severe sepsis), who were admitted to the five ICUs between October 2008 and September 2012 (multicenter validation cohort). To assess the susceptibility to severe sepsis, we further selected 222 critically ill patients from the validation cohort matched for age, gender, morbidity, and severity with the patients with severe sepsis, but without any evidence of sepsis.Results: We examined whether the eight THBD single nucleotide polymorphisms (SNPs) were associated with susceptibility to and/or mortality of sepsis. Higher mortality on severe sepsis in the discovery and combined cohorts was significantly associated with the CC genotype in a THBD promoter SNP (−1920*C/G; rs2239562) [odds ratio [OR] 2.709 (1.067–6.877), P = 0.033 and OR 1.768 (1.060–2.949), P = 0.028]. Furthermore, rs2239562 SNP was associated with susceptibility to severe sepsis [OR 1.593 (1.086–2.338), P = 0.017].Conclusions: The data demonstrate that rs2239562, the THBD promoter SNP influences both the outcome and susceptibility to severe sepsis.

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) was administered for five days for sedation. On day 13, he had hypotension with abnormal electrocardiogram findings, acute kidney injury, hyperkalemia and severe rhabdomyolysis. Diagnosis and interventions: The patient was transferred to our intensive care unit (ICU) on suspicion of PRIS. Administration of noradrenaline and renal replacement therapy and fasciotomy for compartment syndrome of lower legs due to PRIS-rhabdomyolysis were performed. Outcomes: The patient gradually recovered and was discharged from the ICU on day 30. On day 37, he had repeated sinus bradycardia with pericardial effusion in echocardiography. Cardiac 18F-FDG PET on day 67 demonstrated heterogeneous 18F-FDG uptake in the left ventricle. Electron microscopic investigation of endomyocardial biopsy on day 75 revealed mitochondrial myelinization of the cristae, which indicated mitochondrial damage of cardiomyocytes. He was discharged without cardiac abnormality on day 192. Conclusions: Mitochondrial damage in both morphological and functional aspects was observed in the present case. Sustained mitochondrial damage may be a therapeutic target beyond the initial therapy of discontinuing propofol administration.

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 Background Exacerbated inflammatory response is considered one of the key elements of acute kidney injury (AKI). Interleukin-6 (IL-6) is an inflammatory cytokine that plays important roles in the inflammatory response and may be useful for predicting the clinical outcomes in patients with AKI. However, supporting evidence adapted to the current KDIGO criteria is lacking. Methods AKI patients admitted to the ICU between Jan 2011 and Dec 2015 were retrospectively screened. Patients were assigned to three groups by admission IL-6 tertiles. Associations between IL-6 on ICU admission and in-hospital 90-day mortality, short-term/long-term renal function were analyzed. Results Patients (n = 646) were divided into low (1.5–150.2 pg/mL), middle (152.0–1168 pg/mL), and high (1189-2,346,310 pg/mL) IL-6 on ICU admission groups. Patients in the high IL-6 group had higher in-hospital 90-day mortality (low vs. middle vs. high, P = 0.0050), lower urine output (low vs. middle vs. high, P

Abstract Background For patients treated with extracorporeal membrane oxygenation (ECMO), employing a well-coordinated, multidisciplinary team specializing in ECMO has reportedly been effective in delivering better clinical outcomes. This study aims to assess the impact of establishing such a specialized team for patients treated with ECMO. Method This retrospective cohort study was performed at a tertiary-care hospital in Japan. We reviewed medical records of all consecutive patients treated with ECMO during October 2010–September 2016. The results obtained in pre-ECMO team cases (PRE group; October 2011–September 2012) and post-ECMO team cases (POST group; October 2014–September 2015) were compared. Results The results obtained in pre-ECMO team cases (PRE group; October 2011–September 2012) and post-ECMO team cases (POST group; October 2014–September 2015) were compared. During the study period, 177 patients were treated with ECMO. Before the introduction of ECMO team, an average of 22.7 patients underwent ECMO treatment per year; after establishing ECMO team, this number increased to 36.3 patients per year. ECMO was applied mainly to cardiac arrest patients 52/69 (75%). The PRE (n = 27) and POST (n = 42) groups did not differ with regard to the survival rate to hospital discharge, ECMO duration, ventilator days, and length of hospital stay. However, PaO2 and positive end-expiratory pressure were significantly higher in the POST group at 6 h after ECMO initiation than those in the PRE group [367 (186–490) vs. 239 (113–430) mmHg, p = 0.047 and 8 (5–10) vs. 7 (5–8) cmH2O, p = 0.01, respectively]. In addition, data recording the detailed time points of ECMO initiation was conducted in significantly more cases in the POST group (28/126 (22%) than in the PRE group (6/81 (7%); p = 0.01). Conclusions Following the establishment of an ECMO team, the survival rate of patients treated with ECMO, ECMO duration, and length of hospital stay were not improved. However, the number of ECMO cases increased and the recording of clinical data was improved.

Extracorporeal membrane oxygenation (ECMO) is a treatment that supports heart and lung functions with a circulation circuit external to the body. In ECMO, it is important to monitor blood oxygen saturation (SO2) in the circulation tube. As a means of continuous SO2 measuring, a special connector is inserted into the circuit. However, this method is unsuitable for emergency treatment. Therefore, it is necessary to measure blood SO2 in the tube without the connector. However, this creates problems for SO2 estimation, due to varying blood concentration and flow velocity, hemolysis, and wall thickness of the tube. Therefore, we developed a SO2 estimation method that can calibrate the variation in blood concentration. The method is based on a conversion model between absorbance and SO2 (CAS), which varies depending on the concentration. In this method, the CAS for the SO2 estimation is estimated by CAS corresponding to two blood samples prepared in advance with different concentrations. The experiment for SO2 estimation was conducted with a spectroscope, a halogen light source, and a cut tube. We confirmed that the average error of estimated SO2 against the SO2 values measured by a gas analysis was 3.8% within a blood volume concentration range from 50 to 90%. In future work, to improve the estimation accuracy, we will improve our method by investigating other factors that may affect the accuracy.

Objectives:. Several inflammation markers have been reported to be associated with unfavorable clinical outcomes in critically ill patients. We aimed to elucidate whether serum interleukin-6 concentration considered with Sequential Organ Failure Assessment score can better predict mortality in critically ill patients. Design:. A prospective observational study. Setting:. Five university hospitals in 2016–2018. Patients:. Critically ill adult patients who met greater than or equal to two systemic inflammatory response syndrome criteria at admission were included, and those who died or were discharged within 48 hours were excluded. Interventions:. Inflammatory biomarkers including interleukin (interleukin)–6, -8, and -10; tumor necrosis factor–α; C-reactive protein; and procalcitonin were blindly measured daily for 3 days. Area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score at day 2 according to 28-day mortality was calculated as baseline. Combination models of Sequential Organ Failure Assessment score and additional biomarkers were developed using logistic regression, and area under the receiver operating characteristic curve calculated in each model was compared with the baseline. Measurements and Main Results:. Among 161 patients included in the study, 18 (11.2%) did not survive at day 28. Univariate analysis for each biomarker identified that the interleukin-6 (days 1–3), interleukin-8 (days 0–3), and interleukin-10 (days 1–3) were higher in nonsurvivors than in survivors. Analyses of 28-day mortality prediction by a single biomarker showed interleukin-6, -8, and -10 at days 1–3 had a significant discrimination power, and the interleukin-6 at day 3 had the highest area under the receiver operating characteristic curve (0.766 [0.656–0.876]). The baseline area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score predicting 28-day mortality was 0.776 (0.672–0.880). The combination model using additional interleukin-6 at day 3 had higher area under the receiver operating characteristic curve than baseline (area under the receiver operating characteristic curve = 0.844, area under the receiver operating characteristic curve improvement = 0.068 [0.002–0.133]), whereas other biomarkers did not improve accuracy in predicting 28-day mortality. Conclusions:. Accuracy for 28-day mortality prediction was improved by adding serum interleukin-6 concentration to Sequential Organ Failure Assessment score.

Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury. DAI was induced in animals using the Marmarou model. After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteen rats were employed in the present study and were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury. Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild, P=0.02; mild vs. severe, P=0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.

Abstract Background l-carnitine is essential for lipid metabolism, and lack of l-carnitine intake and loss by treatments lead to carnitine depletion causing muscle weakness, anemia, and immune dysfunction. Carnitine depletion occurs in critically ill patients after long treatments, but its epidemiology or the risk factors remain unclear. This study aims to investigate the prevalence and risk factors of l-carnitine depletion in critically ill patients. Methods Sixty-four patients were enrolled for the study. Total and free l-carnitine concentrations (t- and f-Carnitine) were measured at ICU admission and every 7 days afterward during hospitalization. Acylcarnitine- to f-Carnitine ratio (A/F Carnitine ratio) was analyzed in a subgroup of patients treated with continuous renal replacement therapy (CRRT). Acylcarnitine concentration was calculated as the difference between t- and f-Carnitine concentrations. Results Carnitine deficiency (f-Carnitine

Abstract Background and purpose The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc. This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

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.

IntroductionRed 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.MethodsCritically 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.ResultsAmong 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).ConclusionDecreased TIBC upon ICU admission has high predictive value for RBC transfusion unrelated to hemorrhage within 28 days.

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 middle-aged Japanese 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.

PurposeAlthough vancomycin (VCM) is not absorbed from healthy intestinal mucosa, elevations in the serum VCM concentrations have been reported in some cases. The aims of this study are to evaluate the necessity of therapeutic drug monitoring (TDM) during enteral VCM administration in critically ill patients.Materials and methodsIn this retrospective study, we enrolled 19 patients admitted to our intensive care unit who were treated with enteral VCM from December 2006 to January 2014. Clinical factors were compared between two groups: Group E whose serum concentrations were detectable, and Group N whose concentrations were below the detection limit of the VCM assay.ResultsGroup E comprises 7 patients, and Group N comprises 12 patients. The fasting duration in Group E was significantly longer compared with that in Group N (17 vs. 8 days, p = 0.023). Furthermore, there was a significant correlation between the serum VCM concentrations and the fasting duration (r = 0.79, p

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.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).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.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.

Diel vertical migration (DVM) of larvae of the phantom midge Chaoborus flavicans (Diptera: Chaoboridae) inhabiting a fishless pond and a fish-abundant lake (Lake Nakanuma) was studied in the field and in the laboratory. In the fishless pond, dissolved oxygen concentration and water temperature were homogeneously distributed in the vertical profiles and Chaoborus larvae did not show DVM. In contrast, there was thermal stratification and an anoxic layer in Lake Nakanuma, and 2nd, 3rd and 4th instar Chaoborus larvae exhibited DVM. Fourth instar Chaoborus larvae collected from the two populations were introduced into thermally stratified acrylic tubes containing 'fish water' (water conditioned by fish and containing only the fish 'smell') or control water free of fish smell after a two-day acclimatization, and the larval positions in the tubes were analysed during the day and at night. The two populations of Chaoborus larvae showed different DVM patterns in the control water: the larvae from Lake Nakanuma exhibited DVM, whereas those from the fishless pond did not. Chaoborus larvae from Lake Nakanuma responded to the fish kairomones, exhibiting marked DVM in the fish water, whereas little response to the fish smell was recognized in the larvae from the fishless pond. The presence of a difference in response between the two populations implies that they had genetically different patterns of expression of DVM and thus different behavioural responses to the fish smell. The fish smell tended to cause the Chaoborus larvae in the tubes to increase their depth, during both the day and night. The effects of the fish smell became ambiguous with time, suggesting microbial degradation of the fish kairomones.

Some water fleas Daphnia change their head morphology to reduce predation risk in response to chemical substances (kairomones) released from larvae of the invertebrate predator Chaoborus (Insecta: Diptera). We tested for evidence of the costs associated with elongation of the head spine in Daphnia galeata and the consequences of these costs on the inducibility of head spine elongation in predictable and unpredictable environments. We exposed D. galeata in outdoor experimental ponds to conditions under which predation pressure by Chaoborus larvae and the concentration of kairomones from this predator were controlled for about 70 days. In the laboratory, we then used Daphnia clones collected from the outdoor ponds to investigate the inducibility of head spine formation in response to Chaoborus kairomones. The inducibility of head spine formation increased in D. galeata from the ponds that had contained both predators and kairomones, whereas in water fleas from the ponds containing only kairomones the plasticity (inducibility) of head spine formation decreased compared with that in the control ponds. These results suggest that the production of a defensive head spine, its phenotypic plasticity, or both entail some costs. Contrary to our predictions, exposure to Chaoborus kairomones in the laboratory resulted in head lengths that were not significantly different among any of the clones from the three outdoor treatments. We found no evidence for costs associated with head spine elongation in terms of fecundity, time to maturity, or intrinsic rate of natural population increase. Average within-clone partial correlations calculated for head length and intrinsic rate of natural population increase, corrected for body length, were not significantly negative, indicating no cost of defence. This was probably because food conditions in the laboratory were so good that the costs of defence could not be detected. Furthermore, community-level changes, such as changes in food conditions caused by manipulation of the predation regime in the outdoor ponds, might have worked as selection pressures and confounded the results.

PurposeThe 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.MethodsPatients 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).ResultsNon-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.ConclusionsSerum 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.

ObjectiveAutophagy 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.MethodsThe 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.ResultsNo 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).ConclusionsThe 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.

Acute liver failure (ALF) during pregnancy remains difficult to treat, and despite advances in treatment, liver transplantation must be selected as treatment option in certain cases. We report a 30-year-old woman with ALF of unknown etiology, occurring during the first trimester of pregnancy. Her condition was complicated by consciousness disturbance and coagulopathy due to ALF, but she was successfully treated with living donor liver transplantation 7 days after dilatation and curettage. At 9-month followup, she was in good medical condition. Liver transplantation has been reported as one of the treatment options for ALF during pregnancy with the prognosis varying depending on the trimester, from living donor or deceased donor liver transplantation. Of importance is that clinicians always think of emergent liver transplantation as a therapeutic option in ALF even in the first trimester of pregnancy.

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) was administered for five days for sedation. On day 13, he had hypotension with abnormal electrocardiogram findings, acute kidney injury, hyperkalemia and severe rhabdomyolysis. Diagnosis and interventions: The patient was transferred to our intensive care unit (ICU) on suspicion of PRIS. Administration of noradrenaline and renal replacement therapy and fasciotomy for compartment syndrome of lower legs due to PRIS-rhabdomyolysis were performed. Outcomes: The patient gradually recovered and was discharged from the ICU on day 30. On day 37, he had repeated sinus bradycardia with pericardial effusion in echocardiography. Cardiac 18F-FDG PET on day 67 demonstrated heterogeneous 18F-FDG uptake in the left ventricle. Electron microscopic investigation of endomyocardial biopsy on day 75 revealed mitochondrial myelinization of the cristae, which indicated mitochondrial damage of cardiomyocytes. He was discharged without cardiac abnormality on day 192. Conclusions: Mitochondrial damage in both morphological and functional aspects was observed in the present case. Sustained mitochondrial damage may be a therapeutic target beyond the initial therapy of discontinuing propofol administration.

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) was administered for five days for sedation. On day 13, he had hypotension with abnormal electrocardiogram findings, acute kidney injury, hyperkalemia and severe rhabdomyolysis. Diagnosis and interventions: The patient was transferred to our intensive care unit (ICU) on suspicion of PRIS. Administration of noradrenaline and renal replacement therapy and fasciotomy for compartment syndrome of lower legs due to PRIS-rhabdomyolysis were performed. Outcomes: The patient gradually recovered and was discharged from the ICU on day 30. On day 37, he had repeated sinus bradycardia with pericardial effusion in echocardiography. Cardiac 18F-FDG PET on day 67 demonstrated heterogeneous 18F-FDG uptake in the left ventricle. Electron microscopic investigation of endomyocardial biopsy on day 75 revealed mitochondrial myelinization of the cristae, which indicated mitochondrial damage of cardiomyocytes. He was discharged without cardiac abnormality on day 192. Conclusions: Mitochondrial damage in both morphological and functional aspects was observed in the present case. Sustained mitochondrial damage may be a therapeutic target beyond the initial therapy of discontinuing propofol administration.

Traumatic coronary artery dissection, which is rare in blunt trauma, has high risk of acute myocardial infarction and cardiac arrest. A 44-year-old man who had a traffic accident was transferred to the emergency department with refractory ventricular fibrillation (VF). After conventional cardiopulmonary resuscitation, we introduced extracorporeal cardiopulmonary resuscitation (ECPR) and obtained return of spontaneous circulation with ST-elevation electrocardiogram at V4-6. Subsequent coronary angiography and intravascular ultrasound supported by extracorporeal membrane oxygenation (ECMO) revealed complete occlusions of left anterior descending and left circumflex artery due to dissections. Drug-eluting stents were placed with restorations of TIMI 2 flows. After ICU admission, his left ventricular function gradually recovered; he was successfully weaned from VA-ECMO on day 9. ECPR may be a valuable option to allow time and stable hemodynamic condition to treat the cause of cardiac arrest.