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PurposeAmong patients surviving treatment in intensive care units (ICU), some cases exist for which inflammation persisted with prolonged hospital stays, referred as persistent inflammatory, immunosuppressed, catabolic syndrome (PIICS). C reactive protein (CRP) is regarded as the most important marker for PIICS. Nevertheless, the applicable cut-off of CRP for PIICS has never been described in the literature.MethodsData of patients admitted to the ICU/Emergency ward from May 2015 through June 2019 were analyzed retrospectively. Using K-means clustering, a 14-day CRP transition dataset was analyzed and categorized finally into 7 classes: 4 PIICS classes and 3 non-PIICS classes. Outcomes and the other PIICS characteristics were evaluated.ResultsFrom all 5513 admitted patients, this study examined data of 539 patients who had been admitted for more than 14 days, and for whom 14 day CRP transition analysis could be performed. By the CRP transitions of 7 categorized classes, the CRP cut-off for PIICS was regarded as 3.0 mg/dl on day 14. The Barthel Index at discharge, albumin, and total lymphocyte counts on day 14 were significantly lower in PIICS classes than those of non-PIICS classes. Creatinine kinase, antithrombin activity and thrombomodulin on admission were regarded as independent risk factors for PIICS.ConclusionsAmong patients with prolonged hospital stay, the PIICS population had elevated CRP, but lower Barthel Index, albumin, and total lymphocyte counts. The criterion of day 14 CRP for PIICS should be 3.0 mg/dl.

Eleven adults with reverse transcriptase polymerase chain reaction-confirmed SARS-CoV-2 infection were admitted to the intensive care unit (ICU) at The University of Tokyo Hospital between April 6 and April 21, 2020, and treated with nafamostat mesylate in combination with favipiravir. [...]nafamostat mesylate therapy in combination with favipiravir may allow blockade of virus entry and replication, as well as inhibition of pathogenic host response, i.e., hyper-coagulopathy. Mechanical ventilation SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 TMPRSS2: Transmembrane protease serine 2 VV-ECMO: Venovenous extracorporeal membrane oxygenation 1.

Introduction:A large number of visitors to Tokyo during the Tokyo Olympic and Paralympic Games in 2020 resulted in an increase of injury/illness and burden to the routine emergency medical services system. Furthermore, extremely hot and humid weather, terrorism, and outbreaks of infectious diseases are marked risks.Aim:We introduce the present status of an academic consortium (AC2020) to fulfill our mission as academic organizations. The Japanese Association for Acute Medicine (JAAM) and six academic associations have initially established the AC2020 since 2016, which consists of the 23 associations at this time. The role of the AC2020 is to provide knowledgeable evidence, intelligence, and support for constructing response plans for medical problems via the website (http://2020ac.com/).Methods:The joint committee of the AC2020 (JC-AC2020) has been launched to accomplish consortium activities; make statements and recommendations, compile manuals, conduct seminars, and coordinate the training program of on-site medical teams. The JC-AC2020 organizes nine working groups of heat stroke, lightning strike, nursing, athletes, first responders, foreigners, pre and in-hospital response of MCI, and data collection for audit.Results:As of December in 2018, AC2020 has released 30 documents and 10 event-news on the website including seven statements, two recommendations of a prerequisite of the on-site medical team, and two manuals concerning the treatment of gunshot and explosive injuries. Based on some of these statements, the Tokyo government has already enhanced the previous plan.Discussion:The AC2020 will propose the web site as a portal site and platform, disseminate the activities widely to society, and ask for the cooperation of other related organizations and academic societies. The AC2020 will aim to provide the landmark project of mass-gathering medical care in Japan as well as the transition to the Olympic Games in Paris in 2024.

Acute kidney injury (AKI) complicated by acute lung injury has a detrimental effect on mortality among critically ill patients. Recently, a renal ischemia-reperfusion (IR) model suggested the involvement of histones and neutrophil extracellular traps (NETs) in the development of distant lung injury after renal IR. Given that recombinant thrombomodulin (rTM) has anti-inflammatory roles by binding to circulating histones, we aimed to clarify its effect on distant lung injury induced by AKI in a murine bilateral renal IR model. Both pretreatment and delayed treatment with rTM significantly decreased pulmonary myeloperoxidase activity, but they did not affect renal dysfunction at 24 h after renal IR. Additionally, rTM mitigated the renal IR-augmented expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and keratinocyte-derived chemokine), and vascular leakage, as well as the degree of lung damage. Intense histone accumulation and active NET formation occurred in both the kidneys and the lungs; however, rTM significantly decreased the histone and NET accumulation only in the lungs. Administration of rTM may have protective impact on the lungs after renal IR by blocking histone and NET accumulation in the lungs, although no protection was observed in the kidneys. Treatment with rTM may be an adjuvant strategy to attenuate distant lung injury complicating AKI.

BackgroundUnintentional injury remains the leading cause of death among Japanese people younger than 35 years; however, data are limited on the evaluation of characteristics, long-term mortality trend and mortality risk of patients with penetrating injury in Japan. This prevents the development of effective strategies for trauma care in patients with penetrating injury.MethodsThis retrospective cohort study investigated 313 643 patients registered in the Japan Trauma Data Bank (JTDB) dataset between 1 January 2009 and 31 March 2018. The inclusion criteria comprised patients with penetrating injuries transferred from the injury site by emergency vehicles. Moreover, the patients registered in the JTDB dataset were included in this study regardless of age and sex. Outcomes measured were nationwide trends of characteristics, in-hospital mortality and in-hospital mortality risk among Japanese patients with penetrating injury. The mortality risk was analysed by hospital admission year, age, Injury Severity Score (ISS) and emergency procedures.ResultsOverall, 7132 patients were included. Median age significantly increased during the 10-year study periods (from 48 to 54 years, p=0.002). Trends for the mechanism of injury did not change; the leading cause of penetrating injury was stab wounds (SW: 76%–82%). Overall, the in-hospital mortality rate significantly decreased (4.0% to 1.7%, p=0.008). However, no significant improvement was observed in the in-hospital mortality trend in all ISS groups with SW and active bleeding. Patients with active bleeding who underwent urgent transcatheter arterial embolization had significantly lower mortality risk (p=0.043, OR=0.12, 95% CI=0.017 to 0.936). Conversely, the surgical procedure for haemostasis did not improve the mortality risk of patients with SW and active bleeding.ConclusionThe severity-adjusted mortality trend in patients with penetrating injuries did not improve. Moreover, patients with active bleeding who underwent urgent surgical procedure for haemostasis had a higher mortality risk.

Objectives To evaluate the effectiveness of pre-hospital adrenaline (epinephrine) administered by emergency medical services to patients with out of hospital cardiac arrest.Design Controlled propensity matched retrospective cohort study, in which pairs of patients with or without (control) adrenaline were created with a sequential risk set matching based on time dependent propensity score.Setting Japan’s nationwide registry database of patients with out of hospital cardiac arrest registered between January 2007 and December 2010.Participants Among patients aged 15-94 with out of hospital cardiac arrest witnessed by a bystander, we created 1990 pairs of patients with and without adrenaline with an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT.Main outcome measures Overall and neurologically intact survival at one month or at discharge, whichever was earlier.Results After propensity matching, pre-hospital administration of adrenaline by emergency medical services was associated with a higher proportion of overall survival (17.0% v 13.4%; unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72, 1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to 2.37) among those with non-VF/VT.Conclusions Pre-hospital administration of adrenaline by emergency medical services improves the long term outcome in patients with out of hospital cardiac arrest, although the absolute increase of neurologically intact survival was minimal.

Aim To describe the registry design of the Japanese Association for Acute Medicine – out‐of‐hospital cardiac arrest (JAAM‐OHCA) Registry as well as its profile on hospital information, patient and emergency medical service characteristics, and in‐hospital procedures and outcomes among patients with OHCA who were transported to the participating institutions. Methods The special committee aiming to improve the survival after OHCA by providing evidence‐based therapeutic strategies and emergency medical systems from the JAAM has launched a multicenter, prospective registry that enrolled OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department. The primary outcome was a favorable neurological status 1 month after OHCA. Results Between June 2014 and December 2015, a total of 12,024 eligible patients with OHCA were registered in 73 participating institutions. The mean age of the patients was 69.2 years, and 61.0% of them were male. The first documented shockable rhythm on arrival of emergency medical services was 9.0%. After hospital arrival, 9.4% underwent defibrillation, 68.9% tracheal intubation, 3.7% extracorporeal cardiopulmonary resuscitation, 3.0% intra‐aortic balloon pumping, 6.4% coronary angiography, 3.0% percutaneous coronary intervention, 6.4% targeted temperature management, and 81.1% adrenaline administration. The proportion of cerebral performance category 1 or 2 at 1 month after OHCA was 3.9% among adult patients and 5.5% among pediatric patients. Conclusions The special committee of the JAAM launched the JAAM‐OHCA Registry in June 2014 and continuously gathers data on OHCA patients. This registry can provide valuable information to establish appropriate therapeutic strategies for OHCA patients in the near future. The special committee of the JAAM has launched a multicenter, prospective registry (the JAAM‐OHCA Registry) that focused on OHCA patients who were transported by EMS personnel to the participating institutions since June 2014. This report described this registry's profile and briefly presented the characteristics of 12,024 OHCA patients between June 2014 and December 2015.

Objective The aim of this study was an exploratory evaluation of the association between the stressors and stress levels of nurses offering care to critically ill pediatric patients based on their clinical experience and working department in a university hospital. Methods The data were collected in October 2018 by administering a self-reporting questionnaire to 169 nurses. The initial analysis compared the anxiety levels between the nurse groups based on their workspace. The next analysis estimated the correlation between the total nursing care and stress levels related to caring for critically ill pediatric patients. We assessed the stress level using the visual analog scale (VAS) score and the total duration of working in the hospital, emergency department (ED), and pediatric department among the three nurse groups. Results Overall, 149 (88%) nurses responded to our survey. More nurses from the ED group completed the Advanced Life Support course (19% vs. 3% vs. 7%, p=0.032), and the total VAS scores of the ED group were significantly higher than those of the other groups (median: 80 vs. 56 vs. 54, p=0.005). In the ED group, the total VAS scores negatively correlated with the total duration of working in the hospital (r=-0.292, p=0.022), ED (r=-0.266, p=0.037), and pediatric department (r=-0.505, p<0.001). In the pediatric ward group, the total VAS scores negatively correlated with the total duration of working in the hospital(r=-0.322, p=0.014) and pediatric department (r=-0.375, p=0.004). In the ED group, the proportion of patients who had high anxiety levels with a short duration of working in the pediatric department was significantly higher than that of patients with a long duration of working in the pediatric department (51% vs. 11%, p=0.028). Conclusions The ED nurses, especially those with less clinical experience in pediatric care, felt anxious about pediatric emergency care more strongly than those in the other groups, regardless of age and disease. Establishing a pediatric medical care set and conducting off-the-job training might contribute to reducing anxiety related to pediatric emergency care.

Background Continuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients. Methods Patients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman’s rank test. Results Among a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors ( P  = 0.002) and the matched survivors ( P  = 0.004). Conclusions This study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.

Aim This study aimed to experimentally verify the safety and effectiveness of evaporative plus convective cooling used in heat stroke treatment using a doll simulating a patient with heat stroke. Methods Evaporative plus convective cooling was simulated by blowing air through a fan (speed: approximately 1.0 or 2.5 m/s) and using normal (20°C) or slightly warm (40°C) water on a doll whose surface body temperature was set at 40°C. We measured the change in surface body temperature using a surface heater attached to the back of the doll's chest cover and observed aerosol generation (size: ≥5 μm) using a particulate visualization system. Three particle counters were placed to measure the generated particles that were not captured by the particulate visualization system. Results The cooling effect of the 2.5 m/s wind speed was greater than that of the 1.0 m/s wind speed. No particles >0.5 μm were observed, and no aerosol particles were generated. Conclusions Our results thus suggested that wind force has a significant effect, and there was no risk of aerosol‐related viral infection in evaporative plus convective cooling. However, this does not rule out the risk of droplet infection. Heat stroke treatment simulation was conducted using dolls resembling heat stroke patients, and a greater cooling effect was observed with a typical electric fan than with a handheld fan. Because no aerosol was generated from the body surface by evaporation, there was no risk of aerosol‐related viral infection.