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Background: Most suicide attempters suffer from psychiatric disorders, which are often comorbid with personality disorders. The effects of intervention on patients who have attempted suicide with comorbid Axis I and II diagnoses have not been fully elucidated. We evaluated whether assertive case management can reduce the repetition of suicidal behaviours in patients who had attempted suicide with comorbid Axis I and II diagnoses., Methods: This study was a secondary analysis of a randomised controlled trial investigating whether assertive case management could reduce the repetition of suicide attempts, compared with enhanced usual care. Subjects were divided into those who had comorbid Axis I and II diagnoses (Axis I + II group), and those who had an Axis I diagnosis without Axis II comorbidity (Axis I group). Outcome measures were compared between patients receiving a case management intervention and patients receiving enhanced usual care, as allocated. The primary outcome measure was the incidence proportion of the first episode of recurrent suicidal behaviour at 6 months after randomisation. We calculated risk ratios (RR) with 95% confidence intervals (CI) at 6 months and 12 months after randomisation of patients in the Axis I and Axis I + II groups., Results: Of 914 enrolled patients, 120 (13.1%) were in the Axis I + II group, and 794 (86.9%) were in the Axis I group. Assertive case management was significantly effective for the Axis I group on the primary outcome at 6 months (risk ratio [RR] 0.51, 95% confidence intervals [CI] 0.31 to 0.84). The RR of the Axis I + II group was 0.44 (95% CI 0.14 to 1.40)., Conclusions: Assertive case management not only had an effect on patients who had attempted suicide with only Axis I disorders but may also have a similar effect on patients with comorbid Axis I and II disorders.

Traumatic brain injury (TBI) is a leading cause of death and disability in trauma patients. Patients with TBI frequently sustain concomitant injuries in extracranial regions. The effect of severe extracranial injury (SEI) on the outcome of TBI is controversial. For 8 years, we retrospectively enrolled 485 patients with the blunt head injury with head abbreviated injury scale (AIS) ≧ 3. SEI was defined as AIS ≧ 3 injuries in the face, chest, abdomen, and pelvis/extremities. Vital signs and coagulation parameter values were also extracted from the database. Total patients were dichotomized into isolated TBI (n = 343) and TBI associated with SEI (n = 142). The differences in severity and outcome between these two groups were analyzed. To assess the relation between outcome and any variables showing significant differences in univariate analysis, we included the parameters in univariable and multivariable logistic regression analyses. Mortality was 17.8% in the isolated TBI group and 21.8% in TBI with SEI group (P = 0.38), but the Glasgow Outcome Scale (GOS) in the TBI with SEI group was unfavorable compared to the isolated TBI group (P = 0.002). Patients with SBP ≦ 90 mmHg were frequent in the TBI with SEI group. Adjusting for age, GCS, and length of hospital stay, SEI was a strong prognostic factor for mortality with adjusted ORs of 2.30. Hypotension and coagulopathy caused by SEI are considerable factors underlying the secondary insults to TBI. It is important to manage not only the brain but the whole body in the treatment of TBI patients with SEI.

OBJECTIVE Although heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities. METHODS They analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis. RESULTS Patients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3-6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate. CONCLUSIONS Despite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.

Hepatic ischaemia-reperfusion (I/R) injury is a serious liver damage that critically influences the clinical outcome of liver surgery or transplantation. Since recent studies indicated the critical involvement of von Willebrand factor (VWF) in reperfusion injuries of brain and myocardium, we hypothesized that VWF-dependent thrombotic or inflammatory responses also play a role in hepatic I/R injury. Using a mouse model of hepatic I/R injury, we explored the functional relevance of the VWF-ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) axis in this pathologic condition. Time-course studies during hepatic I/R revealed significantly lower alanine aminotransferase (ALT) values, as well as greater hepatic blood flow, in VWF gene-deleted (KO) mice in comparison with wild-type (WT) mice. Histological analysis revealed a significantly lesser extent of neutrophil infiltration and hepatocellular necrosis in liver tissues of VWF-KO mice. Human recombinant ADAMTS13 significantly improved the impairment in ALT values and hepatic blood flow and decreased neutrophil infiltration within the liver tissue of WT mice. Real-time intravital imaging successfully visualized significantly reduced leukocyte-vessel wall interactions in I/R liver of VWF-KO mice. Taken together, our results indicate that VWF promotes neutrophil recruitment in ischaemic mouse liver, critically aggravating reperfusion injury, and suggest that functional regulation of VWF by ADAMTS13 represents a promising therapeutic option for hepatic I/R injury., Competing Interests: None., (Schattauer GmbH Stuttgart.)

Objectives: This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)-associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database., Methods: We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge., Results: DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039)., Conclusions: This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aim: Staphylococcus aureus bacteremia causes significant morbidity and mortality and requires specific management to prevent complications. Most studies evaluating quality of care have been carried out in Europe and North America, and accurate epidemiological data are lacking in Asia. We aimed to describe the epidemiology and evaluate the quality of care for S. aureus bacteremia in Japan., Methods: From February 2011 to January 2014, we undertook a multicenter retrospective observational study in 10 departments of emergency and critical care in Japan. We included 118 hospitalized adult patients with S. aureus bacteremia and evaluated three quality-of-care indicators: follow-up blood culture, treatment duration, and echocardiography., Results: The mean age of the patients was 63.5 ± 17.0 years. The major source of bacteremia was pneumonia ( n  = 22, 19%), followed by skin and soft tissue infection ( n  = 18, 15%). Thirty patients (25%) died in the hospital. Follow-up blood culture was performed in 21/112 patients (19%). The duration of antimicrobial treatment was sufficient in 49/87 patients (56%). Echocardiography for patients with clinical indication was undertaken in 39/59 patients (66%). Any of the three indicators were inadequate in 101/118 (86%)., Conclusion: The rate of adequate care for S. aureus bacteremia is low in Japan. The low adherence rate for follow-up blood culture was particularly notable. Staphylococcus aureus bacteremia can be an important target of quality improvement interventions.

Aim: Bystander cardiopulmonary resuscitation (CPR) is essential for improving the outcomes of sudden cardiac arrest patients. It has been reported that dispatch-assisted CPR (DACPR) accounts for more than half of the incidence of CPR undertaken by bystanders. Its quality, however, can be suboptimal. We aimed to measure the quality of DACPR using a simulation study., Methods: We recruited laypersons at a shopping mall and measured the quality of CPR carried out in our simulation. Dispatchers provided instruction in accordance with the standard DACPR protocol in Japan., Results: Twenty-three laypersons (13 with CPR training experience within the past 2 years and 10 with no training experience) participated in this study. The median chest compression rate and depth were 106/min and 33 mm, respectively. The median time interval from placing the 119 call to the start of chest compressions was 119 s. No significant difference was found between the groups with and without training experience. However, subjects with training experience more frequently placed their hands correctly on the manikin (84.6% versus 40.0%; P = 0.026). Twelve participants (52.2%, seven in trained and five in untrained group) interrupted chest compressions for 3-18 s, because dispatchers asked if the patient started breathing or moving., Conclusion: This current simulation study showed that the quality of DACPR carried out by lay rescuers can be less than optimal in terms of depth, hand placement, and minimization of pauses. Further studies are required to explore better DACPR instruction methods to help lay rescuers perform CPR with optimal quality.

Introduction. Vibrio vulnificus ( V. vulnificus ) causes a severe infection that develops in the compromised host. Its pathophysiology is classified into three types: (1) primary septicaemia, (2) gastrointestinal illness pattern and (3) wound infection pattern. Of these, primary septicaemia is critical. V. vulnificus can be classified into three biotypes and two genotypes and its pathogenicity is type-dependent. Case presentation. A 47-year-old man presented to a local hospital with chief complaints of fever, bilateral lower limb pain and diarrhoea. He had no history of foreign travel or known medical problems. He was in septic shock and developed fulminant purpura within 24 h of the onset. High-dose vasopressor and antibiotic administration failed to alter his status and he died 3 days after the onset of symptoms. V. vulnificus was isolated from blood, skin and nasal discharge cultures. Biotype and gene analysis of the microbe isolated identified it as Biotype 3, mainly reported in Israel in wound infections, and Genotype E, implicating an environmental isolate. These typing analyses indicated that the microbe isolated could be classified as a type with low pathogenicity. Conclusion. This case highlighted that Biotype 3 and Genotype E can also cause primary septicaemia. Although the majority of reports on Biotype 3 have been from the Middle East, this experience with the present case provided evidence that the habitat of Biotype 3 V. vulnificus has been extending to East Asia as well.

Background: To investigate variations in emergency medical service (EMS) pre-arrival cardiopulmonary resuscitation (CPR), including both bystander CPR without dispatch assistance and dispatch-assisted CPR (DACPR)., Methods: We carried out an observational study by implementing EMS pre-arrival CPR reports in three fire agencies. We included adult, non-traumatic, and non-EMS witnessed out-of-hospital cardiac arrests. This reporting system comprised the dispatch instruction process and bystander CPR quality based on evaluations by EMS crews who arrived on the scene. Bystander CPR was categorized as "ongoing CPR" if the bystander was performing CPR when the EMS reached the patient's side and "good-quality CPR" if the CPR was performed proficiently. We compared the frequencies of ongoing and good-quality CPR in the bystander CPR already started without dispatch assistance (CPR in progress) group and DACPR group., Results: Of 688 out-of-hospital cardiac arrests, CPR was already started in 150 cases (CPR in progress group). Dispatcher CPR instruction was provided in 368 cases. Among these, callers started chest compressions in 162 cases (DACPR group). Ongoing CPR was performed in 220 cases and was more frequent in the DACPR group (128/162 [79.0%] versus 92/150 [61.3%], P < 0.001). Good-quality CPR was more frequent in the CPR in progress group, but the difference was not statistically significant (36/92 [39.1%] versus 42/128 [29.0%], P = 0.888)., Conclusions: Ongoing CPR and good-quality CPR were not frequent in EMS pre-arrival CPR. Detailed analysis of dispatch instructions and bystander CPR can contribute to improvement in EMS pre-arrival CPR.

The filament perforation model (FPM) in mice is becoming increasingly popular to elucidate the molecular pathogenesis of neuronal injury after subarachnoid hemorrhage (SAH). We evaluated brain MRI in a mouse FPM. A total of 28 male C57Bl/6J mice were used. Seventeen animals underwent SAH induction by FPM. In two animals, transient middle cerebral artery occlusion (MCAo) was induced. Nine mice served as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2(∗)-weighted images (T2*WI) and apparent diffusion coefficient maps were acquired at day 0 and at various time points following SAH (range: day 1-6 after SAH). Cerebral blood flow (CBF) analysis by (14)C-iodoamphetamine ((14)C-IMP) autoradiography was conducted in nine animals. Hemorrhage could be best confirmed using T2*WI. The degree of hemorrhage varied. All animals evaluated for ⩾2days were hydrocephalic, which was best seen on T2WI. T2-hyperintensity of the corpus callosum and external capsule, indicating white matter (WM) injury, was present after SAH. Ventricle and WM injury volumes were statistically significantly higher at day 3 compared to day 0. Territorial ischemia was detectable in MCAo but not in SAH. Markedly hypointense cortical veins were visible in the hyperacute and delayed phase after SAH on T2*WI. The (14)C-IMP analysis indicated decreased CBF after SAH. MRI is feasible and useful in evaluating pathophysiological changes over time. T2*WI seems best for SAH detection and grading. The chronological change of hydrocephalus and WM injury could be analyzed. T2*WI illustrated specific signal changes of cortical veins, possibly caused by increased oxygen extraction fraction due to decreased CBF., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes., Methods: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event., Results: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25])., Conclusion: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Bacterial meningitis is a fatal infectious disease of the central nervous system complicating intravascular involvements. Multiple microbleeds are rarely identified as complications because of the limited detection threshold of conventional imaging modalities. We report the first case of meningococcal meningitis with successful identification of multiple microbleeds in the cerebellum by susceptibility-weighted imaging., Case Presentation: A 19-year-old Japanese female was brought to our emergency department because of fever and coma. A spinal tap was performed and turbid yellow fluid was collected. A diagnosis of bacterial meningitis was established and the patient was admitted to an intensive care unit. Dexamethasone and Antibiotics were administered and Neisseria meningitides was cultured from the spinal fluid. On day 10, postcontrast magnetic resonance imaging identified enhanced subarachnoid space in the cerebellum. Susceptibility-weighted imaging showed spotty low-intensity signals in the cerebellar tissue, indicating microbleeds. The patient made a full recovery from coma and was discharged without neurological sequelae on day 24., Conclusion: Meningococcal meningitis can cause multiple microbleeds in the cerebellum. In this report, we successfully identified microbleeds by susceptibility-weighed imaging. Using this imaging modality, further investigations will clarify its clinical incidence and significance.

Background: We modified the dispatch protocol for cardiopulmonary resuscitation (CPR) using results of a retrospective analysis that identified descriptions by laypersons of possible patterns of agonal respiration. The purpose of this study was to assess the effectiveness of this modified protocol by comparing the frequency of dispatch instructions for CPR and bystander CPR before and after protocol implementation. We also identified descriptions of abnormal breathing patterns among 'Not in cardiac arrest (CA)' unresponsive cases., Methods: This study was conducted prospectively using the population-based registry of out-of-hospital cardiac arrests (OHCAs). For 8 months we implemented this modified protocol in cooperation with 4 fire departments that cover regions with a total population of 840,000., Results: There were 478 and 427 OHCAs before and after implementation, respectively. Among them, 69 and 71 layperson-witnessed OHCAs for pre- and post-implementation, respectively, were analyzed. Dispatchers provided CPR instructions more frequently after protocol implementation than before (55/71 [77.5 %] vs. 41/69 [59.4 %], p < 0.05). Based on breathing patterns described by emergency callers, dispatchers assessed 143 'Not in CA' unresponsive cases and provided CPR instruction for 45 cases. Sensitivity and specificity of this protocol was 93 % and 50 %, respectively., Conclusions: This modified protocol based on abnormal breathing described by laypersons significantly increased CPR instructions. Considering high sensitivity and low specificity for abnormal breathing to identify CA and the low risk of chest compression for 'Not in CA' cases, our study suggested that dispatchers can provide CPR instruction assertively and safely for those unresponsive individuals with various abnormal breathing patterns.

Case: A 69 year-old female with history of schizophrenia was transported to our hospital by ambulance due to coma. On arrival, she was hypotensive and tachycardic with a Glasgow coma scale score of 3 and a rectal core temperature of 40°C. Heatstroke was strongly suspected as the cause of the coma and hypotension. Active external cooling with an electric fan and cooled IV fluid administration were started. Her electrocardiogram (EKG) showed ST elevation in V2-6, II, III and aVF. Echocardiography revealed apical ballooning, which indicated Takotsubo cardiomyopathy. Coronary angiography indicated normal coronary arteries., Outcome: After admission to the intensive care unit, her cardiovascular status gradually improved and she was transferred to the psychiatric ward on day 36., Conclusion: Heatstroke and Takotsubo cardiomyopathy can share the same pathophysiology. Close evaluation of hemodynamic status and myocardial damage is critical for survival.

Background: Current guidelines for cardiopulmonary resuscitation (CPR) emphasise that emergency medical service (EMS) dispatchers should identify sudden cardiac arrest (CA) with abnormal breathing and assist lay rescuers performing CPR. However, lay rescuers description of abnormal breathing may be inconsistent, and it is unclear how EMS dispatchers provide instruction for CPR based on the breathing status of the CA victims described by laypersons., Methods and Results: To investigate the incidence of abnormal breathing and the association between the EMS dispatcher-assisted CPR instruction and layperson CPR, we retrospectively analysed 283 witnessed CA cases whose information regarding breathing status of CA victims was available from population-based prospective cohort data. In 169 cases (59.7%), laypersons described that the CA victims were breathing in various ways, and that the victims were 'not breathing' in 114 cases (40.3%). Victims described as breathing in various ways were provided EMS dispatch-instruction for CPR less frequently than victims described as 'not breathing' (27.8% (47/169) vs 84.2% (96/114); p<0.001). Multivariate logistic regression showed that EMS dispatch-instruction for CPR was associated significantly with layperson CPR (adjusted OR, 11.0; 95% CI, 5.72 to 21.2)., Conclusions: This population-based study indicates that 60% of CA victims showed agonal respiration, which was described as breathing in various ways at the time of EMS call. Although EMS dispatch-instruction was associated significantly with an increase in layperson CPR, abnormal breathing was associated with a much lower rate of CPR instruction and, in turn, was related to a much lower rate of bystander CPR., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Mouse subarachnoid hemorrhage (SAH) models are becoming increasingly important. We aimed to report and discuss the detailed technical-surgical approach and difficulties associated with the circle of Willis perforation (cWp) model, with reference to the existing literature., Methods: First, the cWp model was reproduced using ddY mice following scarification at 0 h, Days 1, 2, and 3 after SAH. Second, C57BL/6 mice were subjected to SAH with histological examination on Days 1, 2, and 3. Sham-operated mice were sacrificed on Day 2. Neurological performance, amount of subarachnoid blood, cerebral vasospasm (CVS), and neuronal injury were assessed. Relevant articles found in the MEDLINE database were reviewed., Results: Induction of SAH was successfully reproduced. The volume of subarachnoid blood decreased with time due to resorption. Neurological performance was worse in SAH compared with sham. Signs of CVS could be confirmed on Days 2 and 3, but not Day 1. The cumulative number of microthrombi was significantly higher on Days 2 and 3, but not Day 1. Apoptotic and degenerative neurons were found in the cortex and hippocampal area. Our review of the literature revealed the cWp model to be the most frequently used. The present findings largely confirmed previously published results. However, detailed technical-surgical description and its discussion were sparse, which we provide here., Conclusions: The current study provides additional useful information characterizing the cWp model. This model may be of first choice at present, as important pathologies can be reproduced and most findings in the literature are based on it.

Aim: To investigate the association between regional brain oxygen saturation (rSO2) at hospital arrival and neurological outcomes at 90 days in patients with out-of-hospital cardiac arrest (OHCA)., Methods: The Japan-Prediction of neurological Outcomes in patients post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after OHCA. We measured rSO2 in OHCA patients immediately after hospital arrival using a near-infrared spectrometer placed on the forehead with non-blinded fashion. The primary endpoint was "neurological outcomes" at 90 days after OHCA., Results: EMS providers are not permitted to terminate CPR in the field in Japan, and so most patients with OHCA who are treated by EMS personnel are transported to emergency hospitals. Among 1017 OHCA patients, 672 patients including 52 comatose patients with pulses detectable (8%) and 620 cardiac arrest patients (92%) at hospital arrival were enrolled prospectively and consecutively. Twenty-nine patients with good neurological outcome had a significantly higher value of rSO2 at hospital arrival than 643 patients with poor neurological outcome (mean [±SD] 55.6±20.8% vs. 19.7±11.0%, p<0.001). Receiver operating curve analysis indicated an optimal rSO2 cutoff point of >42% for predicting good neurological outcome, with sensitivity 0.79 (95% confidence interval [CI], 0.60-0.92), specificity 0.95 (95% CI, 0.93-0.96), positive predictive value, 0.41 (95% CI, 0.28-0.55), negative predictive value, 0.99 (95% CI, 0.98-1.00), and area under the curve 0.90 (95% CI, 0.88-0.92)., Conclusion: The rSO2 at hospital arrival can predict good neurological outcome at 90 days after OHCA., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: Extravascular lung water (EVLW), as measured by the thermodilution method, reflects the extent of pulmonary edema. Currently, there are no clinically effective treatments for preventing increases in pulmonary vascular permeability, a hallmark of lung pathophysiology, in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In this study, we examined the contributions of hemodynamic and osmolarity factors, for which appropriate interventions are expected in critical care, to EVLW in patients with ALI/ARDS., Methods: We performed a subgroup analysis of a multicenter observational study of patients with acute pulmonary edema. Overall, 207 patients with ALI/ARDS were enrolled in the study. Multivariate regression analysis was used to evaluate the associations of hemodynamic and serum osmolarity parameters with the EVLW index (EVLWI; calculated as EVLW/Ideal body weight). We analyzed factors measured on the day of enrollment (day 0), and on days 1 and 2 after enrollment., Results: Multivariate regression analysis showed that global end-diastolic volume index (GEDVI) was significantly associated with EVLWI measured on days 0, 1, and 2 (P = 0.002, P < 0.001, and P = 0.003, respectively), whereas other factors were not significantly associated with EVLWI measured on all 3 days., Conclusions: Among several hemodynamic and serum osmolarity factors that could be targets for appropriate intervention, GEDVI appears to be a key contributor to EVLWI in patients with ALI/ARDS., Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000003627.

Background: Acute respiratory distress syndrome (ARDS) is characterized by the increased pulmonary permeability secondary to diffuse alveolar inflammation and injuries of several origins. Especially, the distinction between a direct (pulmonary injury) and an indirect (extrapulmonary injury) lung injury etiology is gaining more attention as a means of better comprehending the pathophysiology of ARDS. However, there are few reports regarding the quantitative methods distinguishing the degree of pulmonary permeability between ARDS patients due to pulmonary injury and extrapulmonary injury., Methods: A prospective, observational, multi-institutional study was performed in 23 intensive care units of academic tertiary referral hospitals throughout Japan. During a 2-year period, all consecutive ARDS-diagnosed adult patients requiring mechanical ventilation were collected in which three experts retrospectively determined the pathophysiological mechanisms leading to ARDS. Patients were classified into two groups: patients with ARDS triggered by extrapulmonary injury (ARDSexp) and those caused by pulmonary injury (ARDSp). The degree of pulmonary permeability using the transpulmonary thermodilution technique was obtained during the first three intensive care unit (ICU) days., Results: In total, 173 patients were assessed including 56 ARDSexp patients and 117 ARDSp patients. Although the Sequential Organ Failure Assessment (SOFA) score was significantly higher in the ARDSexp group than in the ARDSp group, measurements of the pulmonary vascular permeability index (PVPI) were significantly elevated in the ARDSp group on all days: at day 0 (2.9 ± 1.3 of ARDSexp vs. 3.3 ± 1.3 of ARDSp, p = .008), at day 1 (2.8 ± 1.5 of ARDSexp vs. 3.2 ± 1.2 of ARDSp, p = .01), at day 2 (2.4 ± 1.0 of ARDSexp vs. 2.9 ± 1.3 of ARDSp, p = .01). There were no significant differences in mortality at 28 days, mechanical ventilation days, and hospital length of stay between the two groups., Conclusions: The results of this study suggest the existence of several differences in the increased degree of pulmonary permeability between patients with ARDSexp and ARDSp., Trial Registration: This report is a sub-group analysis of the study registered with UMIN-CTR (IDUMIN000003627).

Unlabelled: The burn severity depends on the wound depth and area affected. Hitherto burn depth has been judged mainly by visual observation, although concerns have been raised about its validity. The regional tissue blood flow (rTBF) measured by laser Doppler imaging (LDI) in damaged tissue correlates with the depth. However, very few reports are available on the significance of the regional tissue oxygen saturation (rSO2) as an indicator of burn depth. We investigated whether rSO2 by Near-infrared spectroscopy (NIRS) in burn injuries correlates with rTBF by LDI, which would facilitate quantification of the severity of the tissue damage., Methods: We measured rTBF and rSO2 in 50 lesions from 14 patients of burn injury within 24 hours after injury. The correlation between rTBF and rSO2 was evaluated by Spearman rank correlation analysis., Results: The rSO2 (%; range, 52-82) by NIRS and the rTBF (perfusion unit; range, 61-704) by LDI in burn lesions were positively correlated (r=0.755, p<0.001). This statistically positive correlation still remained significant (r=0.678, p<0.001) after the rSO2 values were standardized., Conclusion: This study suggests that NIRS determination of rSO2 in burn injuries shows promise as a reliable and quick method to estimate the depth of burn lesion.

Background: In patients with severe sepsis, depression of cardiac performance is common and is often associated with left ventricular (LV) dilatation to maintain stroke volume. Although it is essential to optimize cardiac preload to maintain tissue perfusion in patients with severe sepsis, the optimal preload remains unknown. This study aimed to evaluate the reliability of global end-diastolic volume index (GEDI) as a parameter of cardiac preload in the early phase of severe sepsis., Methods: Ninety-three mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome secondary to sepsis were enrolled for subgroup analysis in a multicenter, prospective, observational study. Patients were divided into two groups-with sepsis-induced myocardial dysfunction (SIMD) and without SIMD (non-SIMD)-according to a threshold LV ejection fraction (LVEF) of 50% on the day of enrollment. Both groups were further subdivided according to a threshold stroke volume variation (SVV) of 13% as a parameter of fluid responsiveness., Results: On the day of enrollment, there was a positive correlation (r = 0.421, p = 0.045) between GEDI and SVV in the SIMD group, whereas this paradoxical correlation was not found in the non-SIMD group and both groups on day 2. To evaluate the relationship between attainment of cardiac preload optimization and GEDI value, GEDI with SVV ≤13% and SVV >13% was compared in both the SIMD and non-SIMD groups. SVV ≤13% implies the attainment of cardiac preload optimization. Among patients with SIMD, GEDI was higher in patients with SVV >13% than in patients with SVV ≤13% on the day of enrollment (872 [785-996] mL/m(2) vs. 640 [597-696] mL/m(2); p < 0.001); this finding differed from the generally recognized relationship between GEDI and SVV. However, GEDI was not significantly different between patients with SVV ≤13% and SVV >13% in the non-SIMD group on the day of enrollment and both groups on day 2., Conclusions: In the early phase of severe sepsis in mechanically ventilated patients, there was no constant relationship between GEDI and fluid reserve responsiveness, irrespective of the presence of SIMD. GEDI should be used as a cardiac preload parameter with awareness of its limitations.

Susceptibility-weighted imaging (SWI) has recently attracted attention for its ability to investigate acute stroke pathophysiology. SWI detects an increased ratio of deoxyhemoglobin to oxyhemoglobin in cerebral venous compartments, which can illustrate cerebral misery perfusion with a compensatory increase of oxygen extraction fraction in the hypoperfused brain. In this study we make the first case report of blunt cervical trauma leading to a stroke, demonstrating the disparity between diffusion-weighted imaging (DWI) and SWI changes, or DWI-SWI mismatch, in the acute ischemic brain. The area of mismatch between a smaller DWI cytotoxic edema and a larger SWI misery perfusion in our patient matured into a complete infarction with time. The DWI-SWI mismatch may signify the presence of an ischemic penumbra, and provide information about viability of the brain tissue at risk of potential infarction if without early reperfusion., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Emphysematous cystitis is a rare form of infection. Well known symptoms are: dysuria, urinary frequency and lower abdominal pain. We experienced a case of emphysematous cystitis presented with atypical peritoneal sign and computed tomography findings of massive intra-peritoneal fluid collection and abnormal gas appearance in pelvic space. Due to its presentation as acute abdomen, patient underwent exploratory laparotomy and the diagnosis of emphysematous cystitis was established. As far as we know, our case is the first report of emphysematous cystitis with intra-peritoneal fluid collection.

Introduction: The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity., Methods: The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe., Results: Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO2/FIO2 ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO2/FIO2 ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO2/FIO2 ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001)., Conclusions: Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability., Trial Registration: UMIN-CTR ID UMIN000003627.

Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) cleaves ultralarge VWF (ULVWF) secreted from endothelium and by which is regulating its physiologic function. An imbalance between ULVWF secretion and ADAMTS13 level occurs in sepsis and may cause multiple organ dysfunction. We evaluated the association between the VWF-propeptide (VWF-pp)/ADAMTS13 ratio and disease severity in patients with severe sepsis or septic shock. In 27 patients with severe sepsis or septic shock and platelet count less than 120,000/μL, we measured plasma VWF, VWF-pp, and ADAMTS13 levels on hospital days 1, 3, 5, and 7. The VWF-pp/ADAMTS13 ratio was increased greater than 12-fold in patients with severe sepsis or septic shock on day 1 and remained markedly high on days 3, 5, and 7 compared with normal control subjects. The VWF-pp/ADAMTS13 ratio significantly correlated with Acute Physiology and Chronic Health Evaluation II score on days 1 and 5; Sepsis-related Organ Failure Assessment score on days 1, 3, and 5; maximum Sepsis-related Organ Failure Assessment score and tumor necrosis factor α level on days 1, 3, 5, and 7; and creatinine level on days 1, 5, and 7. Patients with greater than stage 1 acute kidney injury had significantly higher VWF-pp/ADAMTS13 ratio than patients without acute kidney injury. In summary, the VWF-pp/ADAMTS13 ratio was associated with disease severity in patients with severe sepsis or septic shock and may help identify patients at risk for multiple organ dysfunction by detecting severe imbalance between ULVWF secretion and ADAMTS13 level.

Introduction: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria., Methods: The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy., Results: Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95)., Conclusion: PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates., Trial Registration: UMIN-CTR ID UMIN000003627.

Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia-reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia-reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia-reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia-reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.

Introduction: Susceptibility-weighted image (SWI) is one of the most sensitive methods for detect microbleeding and useful for evaluation of traumatic brain damage. The purpose of this study is to delineate the characteristics and importance of supratentorial deep white matter hemorrhages detected by SWI in cases of traumatic brain damage., Methods: Twenty-one consecutive cases with severe traumatic head injury were included in the current study. MRI examinations were made within 1 month after injury. We evaluated the degree and distribution of the supratentorial hemorrhages on SWI retrospectively. We classified the degree of bleeding into four grades: "small hemorrhage," "single bead-like hemorrhage," "convergent-type hemorrhage," and "massive hemorrhage." We then correlated the degree and distribution of the hemorrhage to clinical outcomes. We also evaluated the apparent diffusion coefficient (ADC) image of lobes with "convergent-type hemorrhage.", Results: Existence of "massive hemorrhage" correlated with a poor outcome, that is, worse than "severely disabled" on the Glasgow Outcome Scale. The number of lobes affected by "convergent-type hemorrhage" also correlated with poor outcome. There were 45 lobes with "convergent-type hemorrhage" and 27 of them showed increased diffusivity on ADC images., Conclusion: Supratentorial massive hemorrhages and supratentorial convergent-type multiple hemorrhages were associated with poor prognosis after traumatic brain injury. The increased diffusivity in lobes with convergent-type hemorrhages may indicate that congestion of the proximal medullary vein may play some role for these hemorrhages.

A 73-year-old man underwent coronary artery bypass grafting, abdominal aortic aneurysm resection, and prosthetic implantation as a single procedure in 2002. His progress was favorable until April 2008, when he was admitted to our hospital with melena. B-mode ultrasonography revealed a 5-mm defect in the abdominal aorta at the graft anastomosis, and an umbilicated lesion was seen projecting between the posterior wall of the third part of the duodenum and the abdominal aorta. A color signal was noticed at this site on color Doppler ultrasonography, leading to the diagnosis of a secondary aortoduodenal fistula (ADF). We resected the inflammatory mass comprising the graft and the third part of the duodenum, and performed prosthetic re-implantation, omentopexy, and duodenojejunostomy. We could not find any previous reports of successful identification of secondary ADF using ultrasonography. When a patient with gastrointestinal hemorrhage following reconstructive aortic surgery is encountered in the emergency department, ultrasonography may be considered to be a useful modality in the diagnosis of secondary ADF.

Introduction: Histopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor outcomes. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis., Case Presentation: A 30-year-old previously healthy Japanese woman who had fever and headache for five days presented with disorganised speech, unusual behavior and delusional thinking. Real-time polymerase chain reaction amplification of herpes simplex virus type 1 in cerebrospinal fluid was positive (38,000 copies/mL) and antivirus treatment was started. During the course of her illness, the level of her consciousness decreased in association with desaturation and tachycardia. Thrombosis of the right pulmonary artery trunk with pulmonary embolism was evident on enhanced chest computed tomography. In addition, cranial computed tomography revealed subarachnoid and intraventricular bleeding. Intravenous heparin (12,000 U/day) was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximum dose of heparin, 20,400 U/day). After the treatments, her Glasgow coma score increased and the thrombosis of the pulmonary artery trunk had disappeared., Conclusions: The present case raises the question of whether anticoagulant treatment is safe in patients with herpes simplex virus encephalitis complicated by subarachnoid bleeding.