研究者詳細 - 佐々木　淳一

論文 - 佐々木　淳一

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Hydrogen gas distribution in organs after inhalation: Real-time monitoring of tissue hydrogen concentration in rat

Yamamoto R., Homma K., Suzuki S., Sano M., Sasaki J.

Scientific Reports （Scientific Reports） 9 （ 1 ） 2019年12月

© 2019, The Author(s). Hydrogen has therapeutic and preventive effects against various diseases. Although animal and clinical studies have reported promising results, hydrogen distribution in organs after administration remains unclear. Herein, the sequential changes in hydrogen concentration in tissues over time were monitored using a highly sensitive glass microsensor and continuous inhalation of 3% hydrogen gas. The hydrogen concentration was measured in the brain, liver, kidney, mesentery fat and thigh muscle of rats. The maximum concentration, time to saturation, and other measurements representing the dynamics of distribution were obtained from the concentration curves, and the results obtained for different organs were compared. The time to saturation was significantly longer (20.2 vs 6.3–9.4 min. P = 0.004 in all cases) and increased more gradually in muscle than in the other organs. The maximum concentration was the highest in liver and the lowest in the kidney (29.0 ± 2.6 vs 18.0 ± 2.2 μmol/L; P = 0.03 in all cases). The concentration varied significantly depending on the organ (P = 0.03). These results provide the fundamentals for elucidating the mechanisms underlying the in vivo favourable effects of hydrogen gas in mammalian systems.

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Epinephrine during resuscitation of traumatic cardiac arrest and increased mortality: A post hoc analysis of prospective observational study

Yamamoto R., Suzuki M., Hayashida K., Yoshizawa J., Sakurai A., Kitamura N., Tagami T., Nakada T., Takeda M., Sasaki J.

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine （Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine） 27 （ 1 ） 2019年08月

© 2019 The Author(s). Background: The beneficial effect of epinephrine during resuscitation from out-of-hospital cardiac arrest (OHCA) has been inconclusive, and potential harm has been suggested, particularly in trauma victims. Although no significant improvement in neurological outcomes has been found among resuscitated patients using epinephrine, including trauma patients, the use of epinephrine is recommended in the Advanced Trauma Life Support protocol. Given that the use of vasopressors was reported to be associated with increased mortality in patients with massive bleeding, the undesirable effects of epinephrine during the resuscitation of traumatic OHCA should be elucidated. We hypothesised that resuscitation with epinephrine would increase mortality in patients with OHCA following trauma. Methods: This study is a post-hoc analysis of a prospective, multicentre, observational study on patients with OHCA between January 2012 and March 2013. We included adult patients with traumatic OHCA who were aged ≥15 years and excluded those with missing survival data. Patient data were divided into epinephrine or no-epinephrine groups based on the use of epinephrine during resuscitation at the hospital. Propensity scores were developed to estimate the probability of being assigned to the epinephrine group using multivariate logistic regression analyses adjusted for known survival predictors. The primary outcome was survival 7 days after injury, which was compared among the two groups after propensity score matching. Results: Of the 1125 adults with traumatic OHCA during the study period, 1030 patients were included in this study. Among them, 822 (79.8%) were resuscitated using epinephrine, and 1.1% (9/822) in the epinephrine group and 5.3% (11/208) in the no-epinephrine group survived 7 days after injury. The use of epinephrine was significantly associated with decreased 7-day survival (odds ratio = 0.20; 95% CI = 0.08-0.48; P < 0.01), and this result was confirmed by propensity score-matching analysis, in which 178 matched pairs were examined (adjusted odds ratio = 0.11; 95% CI = 0.01-0.85; P = 0.02). Conclusions: The relationship between the use of epinephrine during resuscitation and decreased 7-day survival was found in patients with OHCA following trauma, and the propensity score-matched analyses validated the results. Resuscitation without epinephrine in traumatic OHCA should be further studied in a randomised controlled trial.

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Impact of cardiopulmonary resuscitation time on the effectiveness of emergency department thoracotomy after blunt trauma

Yamamoto R., Suzuki M., Nakama R., Kase K., Sekine K., Kurihara T., Sasaki J.

European Journal of Trauma and Emergency Surgery （European Journal of Trauma and Emergency Surgery） 45 （ 4 ） 697 - 704 2019年08月

ISSN 18639933

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Debate remains about the threshold cardiopulmonary resuscitation (CPR) duration associated with futile emergency department thoracotomy (EDT). To validate the CPR duration associated with favorable outcomes, we investigated the relationship between CPR duration and return of spontaneous circulation (ROSC) after EDT in blunt trauma. Methods: A retrospective observational study was conducted at three tertiary centers over the last 7 years. We included bluntly injured adults who were pulseless and required EDT at presentation, but excluded those with devastating head injuries. After multivariate logistic regression identified the CRP duration as an independent predictor of ROSC, receiver operating characteristic curves were used to determine the threshold CPR duration. Patient data were divided into short- and long-duration CPR groups based on this threshold, and we developed a propensity score to estimate assignment to the short-duration CPR group. The ROSC rates were compared between groups after matching. Results: Forty patients were eligible for this study and ROSC was obtained in 12. The CPR duration was independently associated with the achievement of ROSC [odds ratio 1.18; 95% confidence interval (CI) 1.01–1.37, P = 0.04], and the threshold CPR duration was 17 min. Among the 14 patients with a short CPR duration, 13 matched with the patients with a long CPR duration, and a short CPR duration was significantly associated with higher rates of ROSC (odds ratio 8.80; 95% CI 1.35–57.43, P = 0.02). Conclusions: A CPR duration < 17 min is independently associated with higher ROSC rates in patients suffering blunt trauma.

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Nighttime and non-business days are not associated with increased risk of in-hospital mortality in patients with severe sepsis in intensive care units in Japan: The JAAM FORECAST study

Matsumura Y., Nakada T., Abe T., Ogura H., Shiraishi A., Kushimoto S., Saitoh D., Fujishima S., Mayumi T., Shiino Y., Tarui T., Hifumi T., Otomo Y., Okamoto K., Umemura Y., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Yamakawa K., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Fujimi S., Gando S.

Journal of Critical Care （Journal of Critical Care） 52 97 - 102 2019年08月

ISSN 08839441

© 2019 Elsevier Inc. Purpose: Hospital services are reduced during off-hour such as nighttime or weekend. Investigations of the off-hour effect on initial management and outcomes in sepsis are very limited. Thus, we tested the hypothesis that patients who were diagnosed with severe sepsis during the nighttime or on non-business days had altered initial management and clinical outcomes. Materials and methods: Patients with severe sepsis from 59 ICUs between 2016 and 2017 were enrolled. The patients were categorized according to the diagnosis time or day and were then compared. The primary outcome was in-hospital mortality. Results: One thousand one hundred and forty-eight patients were analyzed; 769 daytime patients, vs. 379 nighttime patients, and 791 business day patients vs. 357 non-business day patients. There were no significant differences in in-hospital mortality between either daytime and nighttime (24.4% vs. 21.4%, P =.27; nighttime, adjusted odds ratio [OR]1.17, 95% confidence interval [CI], 0.87–1.59, P =.30)or between business and non-business days (22.9% vs. 24.6%, P =.55; non-business day, adjusted OR 0.85, 95% CI 0.60–1.22, P =.85). Time to antibiotics was significantly shorter in the nighttime (114 vs. 89 min, P =.0055). Conclusions: Nighttime and weekends were not associated with increased in-hospital mortality of severe sepsis.

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In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission

Abe T., Tokuda Y., Shiraishi A., Fujishima S., Mayumi T., Sugiyama T., Deshpande G., Shiino Y., Hifumi T., Otomo Y., Okamoto K., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Hagiwara A., Yamakawa K., Takeyama N., Gando S., Muroya T., Koike K., Anan H., Sugita M., Miki Y., Yamashita H., Kittaka H., Maehara J., Nachi S., Morino K., Hoshino A., Yamaguchi H., Harada M., Ishikura H., Kawakami M., Deguchi Y., Yoshihara H., Hanaki Y., Okada K., Kaneko T., Kiyota K., Shimizu Y.

Critical Care （Critical Care） 23 （ 1 ） 2019年06月

ISSN 13648535

© 2019 The Author(s). Background: Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. Methods: This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. Results: Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). Conclusions: Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

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Role of disseminated intravascular coagulation in severe sepsis

Gando S., Shiraishi A., Yamakawa K., Ogura H., Saitoh D., Fujishima S., Mayumi T., Kushimoto S., Abe T., Shiino Y., Nakada T., Tarui T., Hifumi T., Otomo Y., Okamoto K., Umemura Y., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Fujimi S., Tasaki O., Mizobata Y., Funakoshi H., Okuyama T., Yamashita I., Kanai T., Yamada Y., Aibiki M., Sato K., Yamashita S., Yoshida K., Kasaoka S., Kon A., Rinka H., Kato H., Okudera H., Narimatsu E., Fujiwara T., Sugita M., Shichinohe Y., Nakae H., Iiduka R., Murata Y., Nakamura M., Sato Y., Ishikura H., Myojo Y., Tsujita Y., Kinoshita K., Yamaguchi H., Sakurai T., Miyatake S., Saotome T., Yasuda S., Mizushima Y.

Thrombosis Research （Thrombosis Research） 178 182 - 188 2019年06月

ISSN 00493848

© 2019 Elsevier Ltd Background: Disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome (MODS) plays pivotal roles in severe sepsis. Objectives: We performed a multicenter, prospective data collection study and retrospectively analyzed the data to confirm the role of DIC in severe sepsis. Methods: Eligible patients were ICU patients who met the definitions of severe sepsis, and 1013 patients were included. DIC scores as well as disease severity and the development of MODS on the day of the diagnosis of severe sepsis (day 0) and at day 3 were evaluated. The primary outcome was hospital mortality, and MODS on days 0 and 3 was the secondary outcomes. Results: The overall mortality rate of severe sepsis was 21.5%, and the prevalence of DIC was 50.9% (516/1013). DIC patients were more seriously ill and exhibited a higher prevalence of MODS (32.0% vs. 13.1%) on day 0 and worse mortality rate (24,8% vs. 17.5%) than non-DIC patients. DIC patients also showed a lower survival probability than non-DIC patients (Log rank p = 0.028). Logistic regression analyses after propensity score adjustment for potential confounders confirmed a significant association between DIC and MODS and hospital death in the patients with severe sepsis. The new development of DIC and persistent DIC from days 0 to 3 were associated with a high incidence of MODS and low survival probability. Conclusions: The mortality rate of severe sepsis has been improved; however, DIC is still associated with the poor prognosis of these patients. Evaluating the dynamic changes in the DIC status may improve the prediction capability.

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Variations in infection sites and mortality rates among patients in intensive care units with severe sepsis and septic shock in Japan

Abe T., Ogura H., Kushimoto S., Shiraishi A., Sugiyama T., Deshpande G., Uchida M., Nagata I., Saitoh D., Fujishima S., Mayumi T., Hifumi T., Shiino Y., Nakada T., Tarui T., Otomo Y., Okamoto K., Umemura Y., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Yamakawa K., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Fujimi S., Gando S.

Journal of Intensive Care （Journal of Intensive Care） 7 （ 1 ） 2019年05月

© 2019 The Author(s). Background: Accurate and early identification of infection sites might help to drive crucial decisions regarding the treatment of sepsis. We aimed to determine the clinical and etiological features of infection according to sites among patients with severe sepsis in Japan. Methods: This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICU) and proceeded between January 2016 and March 2017. The study cohort comprised 1184 adults (≥ 16 years) who were admitted to an ICU with severe sepsis and septic shock diagnosed according to the sepsis-2 criteria. Sites of infection diagnosed by physicians in charge at the time of arrival comprised the lung, abdomen, urinary tract, soft tissue, bloodstream, central nervous system (CNS), and undifferentiated infections. The primary outcome was in-hospital mortality. Results: The most common sites of infection were the lungs (31.0%), followed by intra-abdominal sites (26.3%), the urinary tract (18.4%), and soft tissue (10.9%). The characteristics of the patients with severe sepsis across seven major suspected infection sites were heterogeneous. Septic shock was more frequent among patients with intra-abdominal (72.2%) and urinary tract (70.2%) infections than other sites. The in-hospital mortality rate due to severe sepsis and septic shock of a pooled sample was 23.4% (range, 11.9% [urinary tract infection] to 47.6% [CNS infection]). After adjusting for clinical background, sepsis severity, and stratification according to the presence or absence of shock, variations in hospital mortality across seven major sites of infection remained essentially unchanged from those for crude in-hospital mortality; adjusted in-hospital mortality rates ranged from 7.7% (95%CI, - 0.3 to 15.8) for urinary tract infection without shock to 58.3% (95%CI, 21.0-95.7) for CNS infection with shock in a generalized estimating equation model. Intra-abdominal and urinary tract infections were statistically associated with less in-hospital mortality than pneumonia. Infections of the CNS were statistically associated with higher in-hospital mortality rates than pneumonia in a logistic regression model, but not in the generalized estimating equation model. Conclusions: In-hospital mortality and clinical features of patients with severe sepsis and septic shock were heterogeneous according to sites of infection.

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Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study

Kushimoto S., Abe T., Ogura H., Shiraishi A., Saitoh D., Fujishima S., Mayumi T., Hifumi T., Shiino Y., Nakada T., Tarui T., Otomo Y., Okamoto K., Umemura Y., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Yamakawa K., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Fujimi S., Gando S.

Critical care medicine （Critical care medicine） 47 （ 5 ） 691 - 699 2019年05月

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission.None. MEASUREMENTS AND MAIN RESULTS: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134-2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia. CONCLUSIONS: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

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Self-inflicted burn injury is independently associated with increased mortality in a more economically developed country: A propensity score matching analysis

Yamamoto R., Shibusawa T., Kurihara T., Sasaki J.

Journal of Burn Care and Research （Journal of Burn Care and Research） 40 （ 2 ） 228 - 234 2019年02月

ISSN 1559047X

© American Burn Association 2019. All rights reserved. Self-inflicted burn accounts for considerable morbidity and mortality in more economically developed countries, and there is a substantial debate regarding the pathophysiological relevance between self-inflicted burns and unfavorable outcomes. To validate whether self-inflicted injury is an independent predictor of high mortality regardless of the severity of burn, they conducted a retrospective observational study using the Japan Trauma Data Bank, a nationwide database including over 200 major tertiary care centers. Among 2006 patients with burn who had arrived at collaborating centers between 2004 and 2016, they included patients aged ≥15 years, those who did not present with cardiopulmonary arrest upon arrival, and those who had ≥10 percent total body surface area burns. Patients with missing survival data or unknown mechanism of injury were excluded. In total, 1094 patients were eligible, of whom 222 (20.3 percent) had self-inflicted burns. The patients were divided into the self-inflicted and non-self-inflicted groups, and propensity score was calculated using the demographic information of the patients, injury variables, time from injury to hospital arrival, and other survival predictors. Via a propensity score matching, 98 pairs were selected, and the self-inflicted group had a higher mortality than the non-self-inflicted group (43.9 vs 28.6 percent, hazard ratio = 1.77; 95% confidence interval = 1.10-2.86; P =.02). Inverse probability weighting and multivariate logistic regression were performed as sensitivity analyses, and results validated that self-inflicted burn was independently associated with increased in-hospital mortality. Therefore, patients with self-inflicted burns should receive judicious management, regardless of burn injury severity.

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Artificial intelligence to predict needs for urgent revascularization from 12-leads electrocardiography in emergency patients

Goto S., Kimura M., Katsumata Y., Goto S., Kamatani T., Ichihara G., Ko S., Sasaki J., Fukuda K., Sano M.

PLoS ONE （PLoS ONE） 14 （ 1 ） 2019年01月

Copyright: © 2019 Goto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background :Patient with acute coronary syndrome benefits from early revascularization. However, methods for the selection of patients who require urgent revascularization from a variety of patients visiting the emergency room with chest symptoms is not fully established. Electrocardiogram is an easy and rapid procedure, but may contain crucial information not recognized even by well-trained physicians. Objective: To make a prediction model for the needs for urgent revascularization from 12-lead electrocardiogram recorded in the emergency room. Method: We developed an artificial intelligence model enabling the detection of hidden information from a 12-lead electrocardiogram recorded in the emergency room. Electrocardiograms obtained from consecutive patients visiting the emergency room at Keio University Hospital from January 2012 to April 2018 with chest discomfort was collected. These data were splitted into validation and derivation dataset with no duplication in each dataset. The artificial intelligence model was constructed to select patients who require urgent revascularization within 48 hours. The model was trained with the derivation dataset and tested using the validation dataset. Results: Of the consecutive 39,619 patients visiting the emergency room with chest discomfort, 362 underwent urgent revascularization. Of them, 249 were included in the derivation dataset and the remaining 113 were included in validation dataset. For the control, 300 were randomly selected as derivation dataset and another 130 patients were randomly selected for validation dataset from the 39,317 who did not undergo urgent revascularization. On validation, our artificial intelligence model had predictive value of the c-statistics 0.88 (95% CI 0.84-0.93) for detecting patients who required urgent revascularization. Conclusions: Our artificial intelligence model provides information to select patients who need urgent revascularization from only 12-leads electrocardiogram in those visiting the emergency room with chest discomfort.

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Renal function and outcome of out-of-hospital cardiac arrest ― Multicenter prospective study (SOS-KANTO 2012 study) ―

Tamura T., Suzuki M., Hayashida K., Sasaki J., Yonemoto N., Sakurai A., Tahara Y., Nagao K., Yaguchi A., Morimura N.

Circulation Journal （Circulation Journal） 83 （ 1 ） 139 - 146 2019年

ISSN 13469843

© 2019, Japanese Circulation Society. All rights reserved. Background: Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether post-OHCA outcome correlated with renal function early after OHCA. Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45–59 (n=1,311), 30–44 (n=1,441), and <30 mL/min/1.73 m2 (n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54–1.03), 0.42 (95% CI: 0.28–0.62), and 0.43 (95% CI: 0.28–0.68) for eGFR 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52–1.06), 0.40 (95% CI: 0.25–0.64), and 0.48 (95% CI: 0.29–0.81), respectively. Conclusions: An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.

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Prognostic Accuracy of Quick SOFA is different according to the severity of illness in infectious patients

Umemura Y., Ogura H., Gando S., Shiraishi A., Saitoh D., Fujishima S., Mayumi T., Kushimoto S., Abe T., Shiino Y., Nakada T., Tarui T., Hifumi T., Otomo Y., Okamoto K., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Yamakawa K.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 2019年

ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Background: Sepsis-3 proposed the quick Sequential Organ Failure Assessment (qSOFA) to identify sepsis patients likely to have poor outcome. The clinical utility of qSOFA still remains controversial because its predictive accuracy for mortality is quite different across the validation studies. We hypothesized that one of the major causes for these controversial findings was the heterogeneity in severity across the studies, and evaluated the association between severity of illness and the prognostic accuracy of qSOFA. Materials and methods: This was a post hoc analysis of a prospective nationwide cohort of consecutive adult patients with sepsis in 59 intensive care units in Japan. Regression trees analysis for survival was used to classify patients according to severity of illness as determined by SOFA score on registration. We conducted receiver operating characteristic (ROC) analyses and evaluated the differences in the area under the ROC curve (AUROC). As a subgroup analysis, we conducted the above evaluations in emergency department (ED) and non-ED patients separately. Results: We included 1114 patients fulfilling the criteria and classified them into three subsets according to severity. The AUROC for mortality was significantly different according to the severity of illness (p = 0.007), with the highest AUROC being in the low-severity subset (patients with SOFA score ≤ 7). Interestingly, our subgroup analysis revealed that a significant difference in the AUROC of qSOFA was observed only in ED patients. Conclusion: This study suggested that lower severity of illness was associated with the relatively higher prognostic accuracy of qSOFA, especially in ED patients.

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Predictive value of quick surgical airway assessment for trauma (qSAT) score for identifying trauma patients requiring surgical airway in emergency room

Hayashida K., Matsumoto S., Kitano M., Sasaki J.

BMC Emergency Medicine （BMC Emergency Medicine） 18 （ 1 ） 2018年11月

© 2018 The Author(s). Background: A surgical airway is usually unpredictable in trauma patients. The aim of this study was to develop a predictable scoring system to determine the need for a surgical airway by using a database from a large multicenter trauma registry. Methods: We obtained data from the nationwide trauma registry in Japan for adult blunt trauma patients who were intubated in the emergency department. Based on a multivariate logistic regression analysis in the development cohort, the Quick Surgical Airway Assessment for Trauma (qSAT) score was defined to predict the need for a surgical airway. The association of the qSAT with surgical airway was validated in the validation cohort. Results: Between 2004 and 2014, 17,036 trauma patients were eligible. In the development phase (n = 8129), the qSAT score was defined as the sum of the three binary components, including male sex, presence of a facial injury, and presence of a cervical area injury, for a total score ranging from 0 to 3. In the validation cohort (n = 8907), the proportion of patients with a surgical airway markedly increased with increasing qSAT score (0 points, 0.5%; 1 point, 0.9%; 2 points, 3.5%; 3 points, 25.0%; P < 0.001). Multivariate analysis revealed that qSAT score was an independent predictor of surgical airway (adjusted OR, 3.19 per 1 point increase; 95% CI, 2.47-4.12; P < 0.0001). The qSAT score of ≥1 had a had a good sensitivity of 86.8% for predicting the requirement for surgical airway; while qSAT score of 3 had a good specificity of 99.9% in ruling out the need for surgical airway. Conclusions: The qSAT score could be assessed simply using only information present upon hospital arrival to identify patients who may need a surgical airway. The utilize of qSAT score in combination with repeated evaluations on physical finding could improve outcomes in trauma patients.

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Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: The FORECAST study

Abe T., Ogura H., Shiraishi A., Kushimoto S., Saitoh D., Fujishima S., Mayumi T., Shiino Y., Nakada T., Tarui T., Hifumi T., Otomo Y., Okamoto K., Umemura Y., Kotani J., Sakamoto Y., Sasaki J., Shiraishi S., Takuma K., Tsuruta R., Hagiwara A., Yamakawa K., Masuno T., Takeyama N., Yamashita N., Ikeda H., Ueyama M., Fujimi S., Gando S., Tasaki O., Mizobata Y., Funakoshi H., Okuyama T., Yamashita I., Kanai T., Yamada Y., Aibiki M., Sato K., Yamashita S., Yoshida K., Kasaoka S., Kon A., Rinka H., Kato H., Okudera H., Narimatsu E., Fujiwara T., Sugita M., Shichinohe Y., Nakae H., Iiduka R., Nakamura M., Murata Y., Sato Y., Ishikura H., Myojo Y., Tsujita Y., Kinoshita K., Yamaguchi H., Sakurai T., Miyatake S., Saotome T., Yasuda S.

Critical Care （Critical Care） 22 （ 1 ） 2018年11月

ISSN 13648535

© 2018 The Author(s). Background: Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. Methods: This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. Results: In total, 1184 patients (median age 73 years, interquartile range (IQR) 64-81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6-11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21-26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12-46) days. Approximately 37% of the patients were discharged home after recovery. Conclusion: Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. Trial registration: UMIN-CTR, UMIN000019742. Registered on 16 November 2015.

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Quantitative assessment of pupillary light reflex for early prediction of outcomes after out-of-hospital cardiac arrest: A multicentre prospective observational study

Tamura T., Namiki J., Sugawara Y., Sekine K., Yo K., Kanaya T., Yokobori S., Roberts R., Abe T., Yokota H., Sasaki J.

Resuscitation （Resuscitation） 131 108 - 113 2018年10月

ISSN 03009572

© 2018 Elsevier B.V. Aim: To clarify whether quantitative assessment of pupillary light reflexes (PLR) can predict the outcome of post-cardiac arrest (CA) patients during the first 72 h after the return of spontaneous circulation (ROSC). Methods: Fifty adults resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable infrared pupillometry. PLR values for each time point were compared between both survivors and non-survivors, and patients with either favourable (Cerebral Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes. Results: Twenty-three patients survived for 90 days after CA, and 13 patients achieved favourable neurological outcomes. The PLR values of the survivors and patients with favourable neurological outcomes were consistently greater than those of non-survivors (P < 0.001) and those with unfavourable neurological outcomes (P < 0.001), respectively. The change in PLR over time was not statistically different between the outcome groups. The 0-hour PLR best predicted both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA. Conclusions: Quantitatively measured PLR was consistently greater in survivors and patients with favourable neurological outcomes during the 72 h after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential role for prognostication in post-CA patients.

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DECREASE OF PLASMA TRIGLYCERIDE-RICH LIPOPROTEIN REMNANTS BY TREATMENT WITH A DIPEPTIDYL PEPTIDASE-4 INHIBITOR IN DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

佐々木淳一

ATHEROSCLEROSIS SUPPLEMENTS 32 149 - 150 2018年06月

研究論文（学術雑誌）, ISSN 1567-5688

A novel early risk assessment tool for detecting clinical outcomes in patients with heat-related illness (J-ERATO score): Development and validation in independent cohorts in Japan

佐々木淳一

PLoS ONE （PLoS ONE） 13 （ 5 ） 149 - 150 2018年05月

研究論文（学術雑誌）, ISSN 1932-6203

© 2018 Hayashida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background We sought to develop a novel risk assessment tool to predict the clinical outcomes after heat-related illness. Methods Prospective, multicenter observational study. Patients who transferred to emergency hospitals in Japan with heat-related illness were registered. The sample was divided into two parts: 60% to construct the score and 40% to validate it. A binary logistic regression model was used to predict hospital admission as a primary outcome. The resulting model was transformed into a scoring system. Results A total of 3,001 eligible patients were analyzed. There was no difference in variables between development and validation cohorts. Based on the result of a logistic regression model in the development phase (n = 1,805), the J-ERATO score was defined as the sum of the six binary components in the prehospital setting (respiratory rate22 /min, Glasgow coma scale<15, systolic blood pressure100 mmHg, heart rate100 bpm, body temperature38C, and age65 y), for a total score ranging from 0 to 6. In the validation phase (n = 1,196), the score had excellent discrimination (C-statistic 0.84; 95% CI 0.79–0.89, p<0.0001) and calibration (P>0.2 by Hosmer-Lemeshow test). The observed proportion of hospital admission increased with increasing J-ERATO score (score = 0, 5.0%; score = 1, 15.0%; score = 2, 24.6%; score = 3, 38.6%; score = 4, 68.0%; score = 5, 85.2%; score = 6, 96.4%). Multivariate analyses showed that the J-ERATO score was an independent positive predictor of hospital admission (adjusted OR, 2.43; 95% CI, 2.06–2.87; P<0.001), intensive care unit (ICU) admission (3.73; 2.95–4.72; P<0.001) and in-hospital mortality (1.65; 1.18–2.32; P = 0.004). Conclusions The J-ERATO score is simply assessed and can facilitate the identification of patients with higher risk of heat-related hospitalization. This scoring system is also significantly associated with the higher likelihood of ICU admission and in-hospital mortality after heat-related hospitalization.

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Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury

佐々木淳一

Nature Medicine （Nature Medicine） 24 （ 2 ） 232 - + 2018年02月

研究論文（学術雑誌）, ISSN 1078-8956

Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation. The muscle damage most often results from strenuous exercise, muscle hypoxia, medications, or drug abuse and can lead to life-threatening complications, such as acute kidney injury (AKI). Rhabdomyolysis and the AKI complication can also occur during crush syndrome, an emergency condition that commonly occurs in victims of natural disasters, such as earthquakes, and man-made disasters, such as wars and terrorism. Myoglobin released from damaged muscle is believed to trigger renal dysfunction in this form of AKI. Recently, macrophages were implicated in the disease pathogenesis of rhabdomyolysis-induced AKI, but the precise molecular mechanism remains unclear. In the present study, we show that macrophages released extracellular traps (ETs) comprising DNA fibers and granule proteins in a mouse model of rhabdomyolysis. Heme-activated platelets released from necrotic muscle cells during rhabdomyolysis enhanced the production of macrophage extracellular traps (METs) through increasing intracellular reactive oxygen species generation and histone citrullination. Here we report, for the first time to our knowledge, this unanticipated role for METs and platelets as a sensor of myoglobin-derived heme in rhabdomyolysis-induced AKI. This previously unknown mechanism might be targeted for treatment of the disease. Finally, we found a new therapeutic tool for prevention of AKI after rhabdomyolysis, which might rescue some sufferers of this pathology.

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Quantitative assessment of pupillary light reflex for early prediction of outcomes after out-of-hospital cardiac arrest

Tamura Tomoyoshi, Namiki Jun, Sugawara Yoko, Sekine Kazuhiko, Yo Kikuo, Kanaya Takahiro, Yokobori Shoji, Roberts Rachel, Abe Takayuki, Yokota Hiroyuki, Sasaki Junichi

Resuscitation 2018年01月

ISSN 0300-9572

<p>Aim: To clarify whether quantitative assessment of pupillary light reflexes (PLR) can predict the outcome of post-cardiac arrest (CA) patients during the first 72 h after the return of spontaneous circulation (ROSC). Methods: Fifty adults resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable infrared pupillometry. PLR values for each time point were compared between both survivors and non-survivors, and patients with either favourable (Cerebral Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes. Results: Twenty-three patients survived for 90 days after CA, and 13 patients achieved favourable neurological outcomes. The PLR values of the survivors and patients with favourable neurological outcomes were consistently greater than those of non-survivors (P < 0.001) and those with unfavourable neurological outcomes (P < 0.001), respectively. The change in PLR over time was not statistically different between the outcome groups. The 0-hour PLR best predicted both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA. Conclusions: Quantitatively measured PLR was consistently greater in survivors and patients with favourable neurological outcomes during the 72 h after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential role for prognostication in post-CA patients.</p>

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A heart-shaped sleeve simplifies intramedullary tibial nail insertion when using the suprapatellar approach

Tajima K., Shimizu C., Ohno S., Nishida Y., Udagawa K., Sasaki J.

Keio Journal of Medicine （Keio Journal of Medicine） 67 （ 1 ） 10 - 16 2018年01月

ISSN 0022-9717

© 2017 by The Keio Journal of Medicine. The suprapatellar approach for intramedullary tibial nailing has become widely accepted over the past decade. A round sleeve is passed beneath the patella to protect the surface of the patellofemoral joint (PFJ). However, the round sleeve cannot be easily stabilized in the PFJ because it does not conform to the shape of the patellar apex. Consequently, we produced a heart-shaped sleeve to simplify the insertion of the entry sleeve during the suprapatellar approach. Using the new sleeve, the following procedure is used: (1) make a longitudinal 4 cm skin incision proximal to the patella to reach the PFJ, (2) insert the guide pin manually to the ventral edge of the tibial plateau, (3) insert the cannulated trocar along the guide pin, (4) insert the heart-shaped sleeve along the cannulated trocar, (5) remove the cannulated trocar, (6) ream the entry point through the heart-shaped sleeve. Then, continue insertion of the nail in the standard manner. Among 44 patients (29 men, mean age 45.6 years, range 26-87 years) with tibial fractures treated between 2010 and 2015, the first 18 consecutive cases were performed using a round sleeve and the rest were performed using the heart-shaped sleeve. The surgery time until entry reaming commenced was 8.9 min (range 6-12 min) using the round sleeve and 6.2 min (range 3-12 min) using the heart-shaped sleeve (P < 0.05). The heart-shaped sleeve is easily stabilized in the PFJ and greatly simplifies the intramedullary nailing of tibial shaft fractures using the suprapatellar approach.

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