Details of a Researcher - Sasaki, Junichi

Papers - Sasaki, Junichi

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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 ) 2019.12

© 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 ) 2019.08

© 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 2019.08

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 2019.08

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 ) 2019.06

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 2019.06

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 ) 2019.05

© 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 2019.05

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 2019.02

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 ) 2019.01

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

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

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 ) 2018.11

© 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 ) 2018.11

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 2018.10

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

Homma, Koichiro, Yoshizawa, Joe, Sasaki, Junichi, Yoshizawa, Mamoru, Homma, Yasuhiko

ATHEROSCLEROSIS SUPPLEMENTS 32 149 - 150 2018.06

Research paper (scientific journal), 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

Hayashida, Kei, Kondo, Yutaka, Hifumi, Toru, Shimazaki, Junya, Ode, Yasutaka, Shiraishi, Shinichiro, Fukuda, Tatsuma, Sasaki, Junichi, Shimizu, Keiki

PLOS ONE (PLoS ONE) 13 ( 5 ) 149 - 150 2018.05

Research paper (scientific journal), 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

Okubo, Koshu, Kurosawa, Miho, Kamiya, Mako, Urano, Yasuteru, Suzuki, Akari, Yamamoto, Kazuhiko, Hase, Koji, Homma, Koichiro, Sasaki, Junichi, Miyauchi, Hiroaki, Hoshino, Tatsuo, Hayashi, Matsuhiko, Mayadas, Tanya N., Hirahashi, Junichi

NATURE MEDICINE (Nature Medicine) 24 ( 2 ) 232 - + 2018.02

Research paper (scientific journal), 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 2018.01

ISSN 0300-9572

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

Tajima Kosuke, Shimizu Chikako, Ohno Soichiro, Nishida Yusho, Udagawa Kazuhiko, Sasaki Junichi

Keio Journal of Medicine (Keio Journal of Medicine) 67 ( 1 ) 10 - 16 2018.01

ISSN 0022-9717

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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Effect of retroperitoneal pelvic packing on pelvic cavity pressure

Sato Yukio, Sekine Kazuhiko, Shibusawa Takayuki, Tajima Kosuke, Sasaki Junichi, Imanishi Nobuaki, Aiso Sadakazu, Hori Shingo

Orthopedics 40 ( 6 ) e947 - e951 2017.11

ISSN 0147-7447

Limited clinical evidence demonstrates the effectiveness of direct retroperitoneal pelvic packing for hemorrhage control in pelvic fractures due to the difficulty in measuring pressure on the pelvic walls within the pelvic cavity after retroperitoneal pelvic packing. Using a cadaver model, the authors aimed to assess whether retroperitoneal pelvic packing generates pressure that exceeds the venous return and arterial pressure in the pelvis. The pressure on the pelvic wall was measured in 5 fresh Japanese cadavers. Sensors were placed at 4 points on the pelvic wall, and the pressure at each point was measured after the insertion of each of 3 sponges, per the procedure originally described for direct retroperitoneal pelvic packing. In each specimen, the average pressure across all 4 points on the pelvic wall increased with the addition of each sponge, reaching 12.3±4.5 mm Hg when all 3 sponges were inserted. Furthermore, the pressure at the pelvic floor and posterior pelvic brim increased significantly, whereas the pressure at the anterior and middle pelvic brim increased nonsignificantly. The results of this study suggest that retroperitoneal pelvic packing provides pressure on the pelvic wall that exceeds the venous pressure and is thus effective for the control of venous hemorrhage in pelvic fractures. Currently, the recommended procedure combines external fixation for venous bleeding, transcatheter arterial embolization, and pelvic packing; however, the authors' results suggest that pelvic packing alone may be effective for controlling venous hemorrhage in pelvic fracture.

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Early Use of Hydrogen Gas Inhalation Improves Survival in Rats With Lethal Hemorrhagic Shock

Matsuoka, Tadashi, Suzuki, Masaru, Sano, Motoaki, Hayashida, Kei, Tamura, Tomoyoshi, Homma, Koichiro, Fukuda, Keiichi, Sasaki, Junichi

CIRCULATION 136 2017.11

Research paper (scientific journal), ISSN 0009-7322

Association Between Renal Dysfunction and Outcomes in Out-of-Hospital Cardiac Arrest Patients: A Prospective, Multicenter Observational Study (SOS-KANTO 2012 Study)

Tamura, Tomoyoshi, Suzuki, Masaru, Hayashida, Kei, Sasaki, Junichi, Yonemoto, Naohiro, Yaguchi, Arino, Morimura, Naoto, Sakurai, Atsushi

CIRCULATION 136 2017.11

Research paper (scientific journal), ISSN 0009-7322

Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats

Matsuoka, Tadashi, Suzuki, Masaru, Sano, Motoaki, Hayashida, Kei, Tamura, Tomoyoshi, Homma, Koichiro, Fukuda, Keiichi, Sasaki, Junichi

JOURNAL OF TRAUMA AND ACUTE CARE SURGERY 83 ( 3 ) 469 - 475 2017.09

Research paper (scientific journal), ISSN 2163-0755

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Hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion: a retrospective observational multicentre study

Hayakawa, Mineji, Maekawa, Kunihiko, Kushimoto, Shigeki, Kato, Hiroshi, Sasaki, Junichi, Ogura, Hiroshi, Matsuoka, Tetsuya, Uejima, Toshifumi, Morimura, Naoto, Ishikura, Hiroyasu, Hagiwara, Akiyoshi, Takeda, Munekazu, Kaneko, Naoyuki, Saitoh, Daizoh, Kudo, Daisuke, Kanemura, Takashi, Shibusawa, Takayuki, Furugori, Shintaro, Nakamura, Yoshihiko, Shiraishi, Atsushi, Murata, Kiyoshi, Mayama, Gou, Yaguchi, Arino, Kim, Shiei, Takasu, Osamu, Nishiyama, Kazutaka

CRITICAL CARE 21 469 - 475 2017.08

Research paper (scientific journal), ISSN 1466-609X

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The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction - First Pilot Study in Humans -

Katsumata, Yoshinori, Sano, Fumiya, Abe, Takayuki, Tamura, Tomoyoshi, Fujisawa, Taishi, Shiraishi, Yasuyuki, Kohsaka, Shun, Ueda, Ikuko, Homma, Koichiro, Suzuki, Masaru, Okuda, Shigeo, Maekawa, Yuichiro, Kobayashi, Eiji, Hori, Shingo, Sasaki, Junichi, Fukuda, Keiichi, Sano, Motoaki

CIRCULATION JOURNAL 81 ( 7 ) 940 - + 2017.07

Research paper (scientific journal), ISSN 1346-9843

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A Dipeptidyl Peptidase-4 Inhibitor, Teneligliptin, Decreases Plasma Triglyceride-Rich Lipoprotein Remnants in Diabetic Patients with Chronic Kidney Disease Undergoing Hemodialysis

Homma Koichiro, Yoshizawa Joe, Shiina Yutaka, Ozawa Hideki, Igarashi Muneki, Matsuoka Tadashi, Sasaki Junichi, Yoshizawa Mamoru, Homma Yasuhiko

Drugs in R and D 1 - 6 2017.06

ISSN 1174-5886

Objective: A high plasma level of remnant-like particle cholesterol (RLP-C), which is equivalent to triglyceride-rich lipoprotein remnant, is an important coronary risk marker. RLP-C level is high, independent of other plasma lipids, in patients with chronic kidney disease (CKD) undergoing hemodialysis. The effect of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on plasma levels of RLP-C in patients with diabetes mellitus and CKD under hemodialysis was studied. Methods: Teneligliptin 20 mg/day was administered to 15 patients with diabetes and CKD undergoing hemodialysis for 12 weeks. Ten patients with diabetes and CKD undergoing hemodialysis were allocated to the control group. Blood was sampled following a 12-h fast. Fasting plasma glucose (FPG), C-peptide, triglyceride, low-density lipoprotein (LDL)-cholesterol (C), high-density lipoprotein (HDL)-C, RLP-C, apolipoprotein (apo) B, oxidized LDL, lipoprotein lipase, and glycated hemoglobin (HbA1c) were measured. Results: HbA1c decreased in the teneligliptin group but significantly increased in the control group. FPG and RLP-C significantly decreased in the teneligliptin group. Plasma lipoprotein-related parameters except RLP-C were not affected by teneligliptin treatment. Conclusion: Teneligliptin treatment significantly reduced plasma levels of RLP-C, FPG, and HbA1c in patients with diabetes with CKD who are undergoing hemodialysis.

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Effectiveness of early administration of tranexamic acid in patients with severe trauma

Shiraishi A., Kushimoto S., Otomo Y., Matsui H., Hagiwara A., Murata K., Hayakawa M., Maekawa K., Saitoh D., Ogura H., Sasaki J., Shibusawa T., Uejima T., Yaguchi A., Takeda M., Ishikura H., Nakamura Y., Kudo D., Kaneko N., Matsuoka T., Hagiwara Y., Morimura N., Furugori S., Kato H., Kanemura T., Mayama G., Kim S., Takasu O., Nishiyama K.

British Journal of Surgery 104 ( 6 ) 710 - 717 2017.05

ISSN 0007-1323

Background: A reduction in mortality with the early use of tranexamic acid has been demonstrated in severely injured patients who are bleeding. However, the modest treatment effect with no reduction in blood transfusion has raised concerns. The aim of the present study was to estimate the effectiveness of regular use of tranexamic acid in severely injured patients. Methods: This multicentre observational study used retrospectively collected data from consecutive injured patients (Injury Severity Score at least 16) treated in 15 Japanese academic institutions in 2012. A propensity score-matched analysis compared patients who did or did not receive tranexamic acid administration within 3 h of injury. Study outcomes included 28-day all-cause and cause-specific mortality, and need for blood transfusion. Results: Of 796 eligible subjects, 281 were treated with tranexamic acid. Propensity score matching selected a total of 500 matched subjects (250 in each group). Tranexamic acid administration was associated with lower 28-day mortality (10·0 versus 18·4 per cent; difference −8·4 (95 per cent c.i. –14·5 to −2·3) per cent) and lower 28-day mortality from primary brain injury (6·0 versus 13·2 per cent; difference −7·2 (−12·3 to −2·1) per cent). However, there was no significant difference between groups in the need for blood transfusion (33·2 versus 34·8 per cent; difference −1·6 (−9·9 to 6·7) per cent). Conclusion: Early tranexamic acid use was associated with reduced mortality in severely injured patients, in particular those with a primary brain injury.

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Clinical study on levofloxacin injection for surgical infection

Kusachi Shinya, Oe Keiji, Okuda Yasuyuki, Sasaki Junichi, Maetani Iruru, Watanabe Manabu, Takuma Kiyotsugu, Orito Etsuro, Shimizu Junzo

Japanese Journal of Chemotherapy 65 ( 3 ) 445 - 455 2017.05

ISSN 1340-7007

We evaluated the efficacy and safety of levofloxacin (LVFX) injection 500 mg once-daily by intravenous infusion for 3 days to 14 days in patients with the secondary infections of injury, burns, or surgical wounds, acute cholecystitis, or acute cholangitis. The utility of sequential therapies, from LVFX injection to LVFX oral agent, for the treatment of surgical infection was evaluated. Additionally, the drug penetration into gallbladder bile and duct bile after administrating 500 mg of LVFX by injection was determined in patients with biliary tract infections. Clinical efficacy: The clinical efficacy rate at test of cure (primary endpoint) was 90.0% (9/10) in patients with the secondary infections of injury, burns or surgical wounds. All five patients with acute cholecystitis and all three patients with acute cholangitis were evaluated as cured. Microbiological efficacy: The microbiological efficacy rate at test of cure was 90.0% (9/10) in patients with the secondary infections of injury, burns or surgical wounds. Three (out of five) patients with acute cholecystitis and three patients with acute cholangitis were evaluated as demonstrating microbial eradication. Pharmacokinetics: The concentration of LVFX in gallbladder bile and duct bile after administrating LVFX injections was measured in two patients with acute cholecystitis (gallbladder bile) and four patients with acute cholangitis (duct bile). The LVFX concentration in gallbladder bile 3 h after starting infusion in the two patients was 13.9 μg/mL and 24.5 μg/mL, respectively. The gallbladder bile to plasma concentration ratios were 1.78 and 2.16, respectively. The mean value of the LVFX concentration in duct bile 3 h after starting infusion in the four patients was 12.0 jig/mL (range: 9.0 μg/mL-15.6 μg/mL). The mean value of duct bile to plasma concentration ratio was 1.82 (range: 1.37-2.31). Safety: The incidence rates of adverse events (AEs) and adverse drug reactions (ADRs) were 63.6% (14/ 22) and 13.6% (3/22), respectively. The severities of all ADRs were mild, and all patients who had any ADRs recovered. From these results, LVFX injection 500 mg once-daily was shown to be useful for the treatment of the secondary infections of injury, burns, or surgical wounds, acute cholecystitis, and acute cholangitis, and it was demonstrated that there were no significant problems with its safety.

Fibrinogen level on admission is a predictor for massive transfusion in patients with severe blunt trauma: Analyses of a retrospective multicentre observational study

Nakamura, Yoshihiko, Ishikura, Hiroyasu, Kushimoto, Shigeki, Kiyomi, Fumiaki, Kato, Hiroshi, Sasaki, Junichi, Ogura, Hiroshi, Matsuoka, Tetsuya, Uejima, Toshifumi, Morimura, Naoto, Hayakawa, Mineji, Hagiwara, Akiyoshi, Takeda, Munekazu, Kaneko, Naoyuki, Saitoh, Daizoh, Kudo, Daisuke, Maekawa, Kunihiko, Kanemura, Takashi, Shibusawa, Takayuki, Hagihara, Yasushi, Furugori, Shintaro, Shiraishi, Atsushi, Murata, Kiyoshi, Mayama, Gou, Yaguchi, Arino, Kim, Shiei, Takasu, Osamu, Nishiyama, Kazutaka

INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED 48 ( 3 ) 674 - 679 2017.03

Research paper (scientific journal), ISSN 0020-1383

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Effect of Retroperitoneal Pelvic Packing on Pelvic Cavity Pressure: A Cadaveric Study

Sato, Yukio, Sekine, Kazuhiko, Shibusawa, Takayuki, Tajima, Kosuke, Sasaki, Junichi, Imanishi, Nobuaki, Aiso, Sadakazu, Hori, Shingo

ORTHOPEDICS 40 ( 6 ) E947 - E951 2017.01

Research paper (scientific journal), ISSN 0147-7447

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Initial management of trauma patients for urologists

Shibusawa Takayuki, Sasaki Junichi

Japanese Journal of Clinical Urology 71 ( 3 ) 208 - 212 2017

ISSN 0385-2393

The effects of hydrogen gas inhalation on adverse left ventricular remodeling after percutaneous coronary intervention for ST-elevated myocardial infarction

Katsumata Yoshinori, Sano Fumiya, Abe Takayuki, Tamura Tomoyoshi, Fujisawa Taishi, Shiraishi Yasuyuki, Kohsaka Shun, Ueda Ikuko, Homma Koichiro, Suzuki Masaru, Okuda Shigeo, Maekawa Yuichiro, Kobayashi Eiji, Hori Shingo, Sasaki Junichi, Fukuda Keiichi, Sano Motoaki

Circulation Journal 81 ( 7 ) 940 - 947 2017

ISSN 1346-9843

Background: Hydrogen gas inhalation (HI) reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model of acute myocardial infarction (AMI). We designed a prospective, open-label, rater-blinded clinical pilot study in patients experiencing ST-elevated MI (STEMI). Methods and Results: The 20 patients with an initial diagnosis of STEMI were assigned to either an HI group (1.3% H2 with 26% oxygen) or a control group (26% oxygen). There were no HI-related severe adverse events. In the full analysis set, the cardiac salvage index as evaluated using cardiac magnetic resonance imaging at 7 days after primary percutaneous coronary intervention (PCI), showed no significant between-group difference (HI: 50.0±24.3%; control: 60.1±20.1%; P=0.43). However, the improvement from day 7 in the HI group was numerically greater than that in the control group in some of the surrogate outcomes at 6-month follow-up, including the LV stroke volume index (HI: 9.2±7.1 mL/m²; control: -1.4±7.2 mL/m²; P=0.03) and the LV ejection fraction (HI: 11.0%±9.3%; control: 1.7%±8.3%; P=0.11). Conclusions: The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).

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Generation of kidney tubular organoids from human pluripotent stem cells

Yamaguchi, Shintaro, Morizane, Ryuji, Homma, Koichiro, Monkawa, Toshiaki, Suzuki, Sayuri, Fujii, Shizuka, Koda, Muneaki, Hiratsuka, Ken, Yamashita, Maho, Yoshida, Tadashi, Wakino, Shu, Hayashi, Koichi, Sasaki, Junichi, Hori, Shingo, Itoh, Hiroshi

SCIENTIFIC REPORTS 6 674 - 679 2016.12

Research paper (scientific journal), ISSN 2045-2322

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Hydrogen Gas Inhalation Improves Survival in Rats With Lethal Hemorrhagic Shock Resuscitated With Saline

Matsuoka, Tadashi, Suzuki, Masaru, Sano, Motoaki, Hayashida, Kei, Tamura, Tomoyoshi, Fukuda, Keiichi, Sasaki, Junichi

CIRCULATION 134 2016.11

Research paper (scientific journal), ISSN 0009-7322

DAMAGE ASSOCIATED MOLECULAR PATTERNS RELEASING IN A NEW BLUNT LIVER INJURY MODEL IN MICE

Shibusawa, Takayuki, Namiki, Jun, Suzuki, Sayuri, Sasaki, Junichi

SHOCK 46 ( 4 ) 51 - 52 2016.10

Research paper (scientific journal), ISSN 1073-2322

The international activities in Taiwan by the joint burn care assistance team of physicians from Japan medical association and three medical societies

Matsuda Naoyuki, Yamada Sachiko, Hinoshita Takuga, Sasaki Junichi, Ikeda Hiroto, Harunari Nobuyuki, Sakamoto Tetsuya

Japan Medical Association Journal 59 ( 1 ) 12 - 16 2016.07

ISSN 1346-8650

CAN EARLY AGGRESSIVE ADMINISTRATION OF FRESH FROZEN PLASMA IMPROVE OUTCOMES IN PATIENTS WITH SEVERE BLUNT TRAUMA?-A REPORT BY THE JAPANESE ASSOCIATION FOR THE SURGERY OF TRAUMA

Hagiwara, Akiyoshi, Kushimoto, Shigeki, Kato, Hiroshi, Sasaki, Junichi, Ogura, Hiroshi, Matsuoka, Tetsuya, Uejima, Toshifumi, Hayakawa, Mineji, Takeda, Munekazu, Kaneko, Naoyuki, Saitoh, Daizoh, Otomo, Yasuhiro, Yokota, Hiroyuki, Sakamoto, Teruo, Tanaka, Hiroshi, Shiraishi, Atsushi, Morimura, Naoto, Ishikura, Hiroyasu

SHOCK 45 ( 5 ) 495 - 501 2016.05

Research paper (scientific journal), ISSN 1073-2322

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Development of Novel Criteria of the “Lethal Triad” as an Indicator of Decision Making in Current Trauma Care

Endo Akira, Shiraishi Atsushi, Otomo Yasuhiro, Kushimoto Shigeki, Saitoh Daizoh, Hayakawa Mineji, Ogura Hiroshi, Murata Kiyoshi, Hagiwara Akiyoshi, Sasaki Junichi, Matsuoka Tetsuya, Uejima Toshifumi, Morimura Naoto, Ishikura Hiroyasu, Takeda Munekazu, Kaneko Naoyuki, Kato Hiroshi, Kudo Daisuke, Kanemura Takashi, Shibusawa Takayuki, Hagiwara Yasushi, Furugori Shintaro, Nakamura Yoshihiko, Maekawa Kunihiko, Mayama Gou, Yaguchi Arino, Kim Shiei, Takasu Osamu, Nishiyama Kazutaka

Critical Care Medicine 2016.04

ISSN 0090-3493

OBJECTIVES:: To evaluate the utility of the conventional lethal triad in current trauma care practice and to develop novel criteria as indicators of treatment strategy. DESIGN:: Retrospective observational study. SETTINGS:: Fifteen acute critical care medical centers in Japan. PATIENTS:: In total, 796 consecutive trauma patients who were admitted to emergency departments with an injury severity score of greater than or equal to 16 from January 2012 to December 2012. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: All data were retrospectively collected, including laboratory data on arrival. Sensitivities to predict trauma death within 28 days of prothrombin time international normalized ratio greater than 1.50, pH less than 7.2, and body temperature less than 35°C were 15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and base excess (the cutoff values were 88.8 and –3.05 mmol/L). The optimal cutoff value of hypothermia was 36.0°C. The impact of the fibrin/fibrinogen degradation product and base excess abnormality on the outcome were approximately three- and two-folds compared with those of hypothermia. Using these variables, if the patient had a hemostatic disorder alone or a combined disorder with acidosis and hypothermia, the sensitivity and specificity were 80.7% and 66.8%. CONCLUSIONS:: Because of the low sensitivity and high specificity, conventional criteria were unsuitable as prognostic indicators. Our revised criteria are assumed to be useful for predicting trauma death and have the potential to be the objective indicators for activating the damage control strategy in early trauma care.

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HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL A MULTICENTER RETROSPECTIVE STUDY

Hayakawa, Mineji, Maekawa, Kunihiko, Kushimoto, Shigeki, Kato, Hiroshi, Sasaki, Junichi, Ogura, Hiroshi, Matauoka, Tetsuya, Uejima, Toshifumi, Morimura, Naoto, Ishikura, Hiroyasu, Hagiwara, Akiyoshi, Takeda, Munekazu, Kaneko, Naoyuki, Saitoh, Daizoh, Kudo, Daisuke, Kanemura, Takashi, Shibusawa, Takayuki, Furugori, Shintaro, Nakamura, Yoshihiko, Shiraishi, Atsushi, Murata, Kiyoshi, Mayama, Gou, Yaguchi, Arino, Kim, Shiei, Takasu, Osamu, Nishiyama, Kazutaka

SHOCK 45 ( 3 ) 308 - 314 2016.03

Research paper (scientific journal), ISSN 1073-2322

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Prognostic factors of Streptococcus pneumoniae infection in adults

Hifumi Toru, Fujishima Seitaro, Abe Takayuki, Kiriu Nobuaki, Inoue Junichi, Kato Hiroshi, Koido Yuichi, Kawakita Kenya, Kuroda Yasuhiro, Sasaki Junichi, Hori Shingo

American Journal of Emergency Medicine 34 ( 2 ) 202 - 206 2016.02

ISSN 0735-6757

Objectives The mortality of severe sepsis has markedly decreased since the implementation of the Surviving Sepsis Campaign guidelines. The next logical step is to examine the necessity of individualized management guidelines for targeted therapy against specific bacteria. Streptococcus pneumoniae is the leading cause of community-acquired severe sepsis; however, little is known regarding the prognostic factors in adult patients with S pneumoniae sepsis. We aimed to identify prognostic factors in patients with S pneumoniae sepsis and to explore a subgroup of patients at high risk for death with detailed Sequential Organ Failure Assessment (SOFA) score analysis. Methods We retrospectively reviewed the records of patients with S pneumoniae infection treated between 1st January 2006 and 31st July 2012. We identified prognostic factors for 28-day mortality using univariate and multivariate logistic regression models. Results Of 171 patients (median age, 72 years) with S pneumoniae infection who were included in this study, the 28-day mortality was 17% (29/171). The SOFA score (odds ratio, 2.25; 95% confidence interval, 1.60-3.18; P

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Validation of inflationary noninvasive blood pressure monitoring in the emergency room

Sasaki Junichi, Kikuchi Yoshiharu, Usuda Takashi, Hori Shingo

Blood Pressure Monitoring 20 ( 6 ) 325 - 329 2015.11

ISSN 1359-5237

Objective The aim of this study was to compare the values of a noninvasive blood pressure (NIBP) measurement during cuff inflation (inflationary NIBP) and deflationary NIBP measurements and to verify whether inflationary NIBP is equivalent to conventional deflationary NIBP and is acceptable for clinical use in the emergency room (ER). Materials and methods A total of 2981 NIBP data points were collected from 175 patients (age, 56.5± 22.2 years; range, 7-92 years) who had been treated in the resuscitation area of the ER at Keio University Hospital. The data points were obtained using two alternate algorithms with a standard monitor (BSM-6000). One algorithm consisted of continuous inflationary and deflationary measurements in a single cycle (dual algorithm, 1502 data points); this algorithm was used to verify the success rate and the precision of the data. The second algorithm (1479 data points) consisted of only conventional deflationary measurements and was used to verify the duration of the measurement cycle. Results The success rate of the inflationary NIBP (completed using only the inflationary method) was 69.0%. Failures in the inflationary measurements were caused by arrhythmia and/or body motions. The mean difference and SD of the systolic pressure and the diastolic pressure between inflationary NIBP and deflationary NIBP were-0.6± 8.8 and 3.5± 7.5 mmHg, respectively. The confidence intervals were-0.6 (95% confidence interval=-1.1 to-0.1) and 3.5 (95% confidence interval=3.0 to 4.0) mmHg. The coefficients of correlation were 0.96 and 0.93. Inflationary NIBP was capable of determining the NIBP more quickly compared with deflationary NIBP (average of 15.9 vs. 34.2 s; P

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Pharmacokinetics and skin-tissue penetration of daptomycin in rats

Matsumoto Kazuaki, Kitaoka Masashi, Kuroda Yuko, Ikawa Kazuro, Morikawa Norifumi, Sasaki Junichi, Iketani Osamu, Iwata Satoshi, Horino Tetsuya, Hori Seiji, Kizu Junko

Clinical Pharmacology: Advances and Applications 7 79 - 82 2015.05

Background: Daptomycin is recommended for complicated skin and skin-structure infections. However, information on the penetration of daptomycin into skin is limited. Therefore, the aim of this in vivo investigation was to determine the pharmacokinetics and skin penetration of daptomycin in rats. Materials and methods: Concentrations of daptomycin were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was conducted to estimate the rate and extent of daptomycin penetration from the systemic circulation into skin tissue. Since protein binding of daptomycin in rat serum was 89.3%, the free maximum concentration (C<inf>max</inf>) and free area under the curve from time 0 to infinity (AUC<inf>0-∞</inf>) for plasma were calculated as follows: fC<inf>max,plasma</inf> = (1 - 0.893) × C<inf>max,plasma</inf>, fAUC<inf>0-∞</inf>,<inf>plasma</inf> = (1 - 0.893) × AUC<inf>0-∞,plasma</inf>. Results: The following values (mean ± standard deviation) were obtained: 0.06±0 L/h/kg for total clearance (CL<inf>total</inf>), 0.44±0.06 hours for elimination-rate constant, 1.58±0.23 hours for half-life, 0.14±0.02 L/kg for steady-state volume distribution, and 2.28±0.33 hours for mean residence time. Time to C<inf>max</inf> was 3.0 hours for plasma and skin tissue. C<inf>max</inf> and AUC0-∞ for plasma were 175.8±5.1 μg/mL and 811.8±31.9 μg × h/mL, respectively. C<inf>max</inf> and AUC<inf>0-∞</inf> for skin tissue were 19.1±1.7 μg/mL and 113.9±21.8 μg × h/mL, respectively. Furthermore, fCmax and fAUC<inf>0-∞</inf> for plasma were 18.8 μg/mL and 86.9 μg × h/mL, respectively. The degrees of skin-tissue penetration, defined as the C<inf>max</inf>, skin tissue/fC<inf>max</inf>, plasma ratio and<inf>AUC0-∞, skin tissue</inf>/fAUC<inf>0-∞, plasma</inf> ratio, were 1.0 and 1.3, respectively. Conclusion: Daptomycin exhibited good penetration into skin tissue, supporting its use for the treatment of complicated skin and skin-structure infections. However, further studies are needed in infected patients in order to investigate the relationship between the antimicrobial efficacy of daptomycin and its drug concentrations in skin tissues.

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Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents -Special references to bacteria isolated between April 2011 and March 2012-

Shinagawa Nagao, Taniguchi Masaaki, Hirata Koichi, Furuhata Tomohisa, Mizuguchi Tohru, Osanai Hiroyuki, Yanai Yoshiyuki, Hata Fumitake, Kihara Chikasi, Sasaki Kazuaki, Oono Keisuke, Nakamura Masashi, Shibuya Hitoshi, Hasegawa Itaru, Kimura Masami, Watabe Kosho, Hoshikawa Tsuyoshi, Oshima Hideki, Aikawa Naoki, Sasaki Junichi, Suzuki Masaru, Sekine Kazuhiko, Abe Shinya, Takeyama Hiromitsu, Wakasugi Takehiro, Mashita Keiji, Tanaka Moritsugu, Mizuno Akira, Ishikawa Masakazu, Iwai Akihiko, Saito Takaaki, Muramoto Masayuki, Kubo Shoji, Lee Shigeru, Fukuhara Kenichiro, Kobayashi Yasuhito, Yamaue Hiroki, Hirono Seiko, Takesue Yoshio, Fujiwara Toshiyoshi, Shinoura Susumu, Kimura Hideyuki, Iwagaki Hiromi, Tokunaga Naoyuki, Sueda Taijiro, Hiyama Elso, Murakami Yoshiaki, Ohge Hiroki, Uemura Kenichiro, Tsumura Hiroaki, Kanehiro Tetsuya, Takeuchi Hitoshi, Tanakaya Kouji, Iwasaki Mitsuhiro

Japanese Journal of Antibiotics 67 ( 6 ) 339 - 383 2014.12

ISSN 0368-2781

Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 3 1 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coil was the most predominantly isolated from primary infections, followed by Kiebsielia pneumoniae, Pseudomonas aeruginosa and Enterobacter cioacae, in this order, and from surgical site infection, E. coil was most predominantly isolated, followed by F aeruginosa, K. pneumoniae, and E. cioacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggertheiia lenta was the highest from primary infections, followed by Parvimonas micra, Coilinseila aerofaciens, Lactobaciiius acidophilus and Finegoidia magna, and from surgical site infection, E. ienta was most predominantly isolated, followed by F micra and L. acidophiius, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragiiis was the highest from primary infections, followed by Bilophila wadsworthia, Bactero ides thetaiotaomicron, Bacteroides unformis and Bactero ides vuigatus, and from surgical site infection, B. fragiiis was most predominantly isolated, followed by Bactero ides caccae, B. thetaiotaomicron, Bactero ides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycinresistant Enterococcus spp. and multidrug-resistant F aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many ,lJ-lactams.

Practice guidelines for dealing with candida infection in the fields of surgery, emergency and intensive care

Sasaki Junichi

Japanese Journal of Chemotherapy 62 ( 6 ) 663 - 673 2014.11

ISSN 1340-7007

In the fields of surgery, emergency and intensive care, patients with various severe underlying diseases often have severe infections with treatment-resistant bacteria, such as methicillin-resistant Staphylococcus aureus(MRSA) and multi-drug resistant Pseudomonas aeruginosa(MDRP). In such cases, fungal infections, especially Candida infection, which occur during the process of treatment and are possibly attributable to antimicrobial use, emerge as a serious problem. In order to improve the outcomes of Candida infection, it is important to consider targeted treatment for serious complications, such as for lesions of the eye, osteomyelitis, septic embolisms, and deep-seated abscesses, as well as to focus on extraction of high-risk patients based on the guidelines and early diagnosis and treatment Although many guidelines recommend echinocandin drugs as the first-line antifungal drugs in these fields, it is necessary to implement a set of multidisciplinary practice guidelines, which we refer to as antifungal stewardship, in order to properly and effectively use antifungal drugs and succeed in antifungal therapy. For implementation of the guidelines, early-stage administration of antifungal drugs needs to be established in preemptive therapy or empiric treatment the loading doses of antifungal drugs and the drug disposition need to be considered, and treatment based on antifungal heterogeneity, which uses the most suitable antifungal drug in terms of the drug properties and suppression of resistant strains, needs to be provided.

Pharmacokinetics of a polyene antifungal agent, liposomal amphotericin B (L-AMB), in a severely burned patient

Sasaki Junichi, Matsumoto Kana, Fujishima Seitaro, Morita Kunihiko, Hori Shingo

Journal of Chemotherapy 26 ( 5 ) 312 - 314 2014.10

ISSN 1120-009X

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Efficacy of a high FFP:PRBC transfusion ratio on the survival of severely injured patients: a retrospective study in a single tertiary emergency center in Japan

Kudo, Daisuke, Sasaki, Junichi, Akaishi, Satoshi, Yamanouchi, Satoshi, Koakutsu, Tomoaki, Endo, Tomoyuki, Sato, Takeaki, Nomura, Ryosuke, Yuzawa, Hironao, Kobayashi, Michio, Shinozawa, Yotaro, Kushimoto, Shigeki

SURGERY TODAY 44 ( 4 ) 653 - 661 2014.04

Research paper (scientific journal), ISSN 0941-1291

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Validation of inflationary non-invasive blood pressure monitoring in emergency room patients

Sasaki J., Hori S.

Critical Care 2014.03

ISSN 1364-8535

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Efficacy of a high FFP

Kudo Daisuke, Sasaki Junichi, Akaishi Satoshi, Yamanouchi Satoshi, Koakutsu Tomoaki, Endo Tomoyuki, Sato Takeaki, Nomura Ryosuke, Yuzawa Hironao, Kobayashi Michio, Shinozawa Yotaro, Kushimoto Shigeki

Surgery Today 44 ( 4 ) 653 - 661 2014

ISSN 0941-1291

Purpose: Recent studies have shown increased survival benefits when a high fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratio is used during trauma resuscitation. However, some reports have raised questions about the effect of higher FFP:PRBC transfusion ratios. The aim of this study was to examine the efficacy of high FFP:PRBC ratios in injured patients with regard to survival and morbidity in a single tertiary emergency center in Japan. Methods: This study examined severe trauma patients who received 10 or more PRBC units during the first 24 h of admission. We examined the relationship between the FFP:PRBC ratios during the first 6 h and the patient outcome. Results: The severity was similar among all groups. The mortality rate was 44.4 % in the high (>1:1.5), 16.7 % in the middle (1:1.5-1:2) and 33.3 % in the low (<1:2) F:P ratio groups. Only one patient in the high group developed sepsis, and none of the patients developed ARDS. Conclusions: The current results indicate that the FFP:PRBC ratios during the first 6 h after admission might not affect the mortality or morbidity. However, differences between trauma care systems in Japan and other countries, along with other study limitations, necessitate that a subsequent prospective multicenter study be undertaken before any definitive conclusions can be made.

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Penetration of micafungin into the burn eschar in patients with severe burns

Sasaki Junichi, Yamanouchi Satoshi, Sato Yukio, Abe Shinya, Shinozawa Yotaro, Kishino Satoshi, Aikawa Naoki, Hori Shingo

European Journal of Drug Metabolism and Pharmacokinetics 39 ( 2 ) 93 - 97 2014

ISSN 0378-7966

Micafungin (MCFG) concentrations in the plasma and in burn eschar were investigated after daily intravenous infusion (1 h) of MCFG (200 mg) in three patients with severe burns. MCFG treatment was initiated more than 72 h after the burn injuries. The MCFG concentrations in the plasma were determined at the end of the first administration of MCFG, immediately before the second dosing, at the end of the MCFG infusion after at least 4 days from the initial treatment, and immediately before the subsequent dosing using high-performance liquid chromatography. In addition, the trough levels in burn eschar after both the initial administration and repeated administration were measured. The peak and trough levels in the plasma were comparable to or slightly lower than the reported values in healthy volunteers. The mean (range) MCFG concentrations in the burn eschar after initial administration and repeated administration were 1.41 μg/mL (<0.1-3.98 μg/mL) and 6.65 μg/mL (1.10-14.81 μg/mL), respectively. In most cases, the MCFG concentrations in the burn eschar, especially after repeated administration, were higher than the reported MIC ₉₀ of MCFG against the clinically important pathogenic species of Candida and Aspergillus. These results suggest that MCFG is capable of penetrating burn eschar. © 2013 Springer-Verlag.

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Fatal overwhelming postsplenectomy infection caused by Streptococcus pneumoniae in mothers within 1 year after delivery

Hifumi Toru, Fujishima Seitaro, Chang Bin, Sasaki Junichi, Kiriu Nobuaki, Kato Hiroshi, Inoue Junichi, Koido Yuichi

Journal of Infection and Chemotherapy 19 ( 6 ) 1202 - 1205 2013.12

ISSN 1341-321X

Invasive pneumococcal disease (IPD) has a high mortality. Although preventive strategies including vaccination have been established for children, less attention has been devoted to pregnant and postnatal women and to mothers caring for their infants. As a significant number of women have either undergone splenectomy or are in a hyposplenic state and have not received adequate pneumococcal vaccinations, they can potentially develop overwhelming postsplenectomy infections. A 34-year-old woman with an 8-month-old baby, who underwent splenectomy at the age of 10 for benign pancreatic tumor, presented with fever and petechial eruption. Despite extensive treatment, she died 17 h after admission. A 40-year-old woman with a 11-month-old baby, who underwent splenectomy at 2 years of age for hemolytic anemia, was admitted for septic shock and disseminated intravascular coagulation. Despite extensive treatment, she died 2 h after admission. Blood cultures from both women were positive for Streptococcus pneumoniae and neither of them had been vaccinated against the bacterium. IPD rapidly progressed and developed to multiple organ dysfunction syndromes in mothers caring for their infants, particularly those who had undergone splenectomy or were in a hyposplenic state. Thus, routine pneumococcal vaccination is recommended for pregnant women. In addition, we suggest a thorough medical interview and checkup for splenectomy or hyposplenism in prenatal women. © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.

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Micafungin concentrations in the plasma and burn eschar of severely burned patients

Sasaki Junichi, Yamanouchi Satoshi, Kudo Daisuke, Endo Tomoyuki, Nomura Ryosuke, Takuma Kiyotsugu, Kushimoto Shigeki, Shinozawa Yotaro, Kishino Satoshi, Hori Shingo, Aikawa Naoki

Antimicrobial Agents and Chemotherapy 56 ( 2 ) 1113 - 1115 2012.02

ISSN 0066-4804

Micafungin concentrations in plasma and burn eschar after daily intravenous infusion (1 h) of micafungin (200 to 300 mg) were investigated for six patients with severe burns. Micafungin treatment was initiated more than 72 h after the burn injuries. The peak and trough levels in the plasma after the initial administration and repeated administrations for more than 4 days were comparable with or slightly lower than the reported values for healthy volunteers. Micafungin concentrations in the plasma and burn eschar were between 3.6 and >1,000 times higher than the reported MIC₉₀s of micafungin against clinically important Candida and Aspergillus species. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

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Hemodynamic reactions in patients with hemorrhagic shock from blunt trauma after initial fluid therapy

Hagiwara Akiyoshi, Kimura Akio, Kato Hiroshi, Mizushima Yasuaki, Matsuoka Tetsuya, Takeda Munekazu, Uejima Toshifumi, Hagiwara Yusuke, Sakamoto Yuichiro, Kudo Daisuke, Sasaki Junichi

Journal of Trauma - Injury, Infection and Critical Care 69 ( 5 ) 1161 - 1168 2010.11

ISSN 0022-5282

Object: This study sought to define hemorrhagic shock from blood pressure and heart rate and then to provide a treatment policy based on response to initial fluid therapy. Materials: This was a prospective clinical observational study conducted in eight hospitals. Subjects were consecutive patients with trauma who met any of the field triage conditions proposed by the Committee on Trauma of the American College of Surgeons. Initial fluid therapy was performed in patients with suspected hemorrhagic shock. Patients who required blood transfusion ≥4 U within 24 hours or interventions for active bleeding within 24 hours were classified into a "bleeding group" (B). A "nonbleeding group" (non-B) comprised patients who did not require blood transfusion ≥4 U or other interventions within 24 hours. Our committee maintained the database of survey items. Four of the hospitals were selected at random to provide training data and that was used in a recursive partitioning analysis to predict the B group. Data on patients in the other four facilities were used for validation. Results: There were a total of 400 patients studied. The training set consisted of 261 patients, 50 of whom were classified into the B group. A total of 94% patients with hemorrhagic shock suspected clinically, shock index at admission (first SI) ≥0.8, and SI at 1 L of fluid resuscitation (second SI) ≥1.0 were assigned to the B group. The non-B group (92%) were patients those whose first SI was <0.8 and base deficits at admission ≥-1.0. Validation data consisted of 139 patients. The sensitivity, specificity, and accuracy of these data to predict the B group were 71%, 93%, and 89%, respectively. Conclusions: Patients whose first SI was ≥0.8 and second SI ≥1.0 would be diagnosed as "nonresponders" by American College of Surgeons. Patients with first SI <0.8 and base deficits ≥-1.0 will not be candidates for the B group. Copyright © 2010 by Lippincott Williams & Wilkins.

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Experiences in organizing Advanced Burn Life Support (ABLS) provider courses in Japan

Sasaki Junichi, Takuma Kiyotsugu, Oda Jun, Saitoh Daizoh, Takeda Taichi, Tanaka Hideharu, Harunari Nobuyuki, Hojo Nobuko, Matsumura Hajime, Ueyama Masashi, Shinozawa Yotaro

Burns 36 ( 1 ) 65 - 69 2010.02

ISSN 0305-4179

The ABLS course sponsored by the ABA has not yet been made available in Japan, although it is strongly desired. During the 3 years between 2006 and 2008, authorized ABLS provider courses were given once a year in Japan as part of preparations to reach an agreement between the ABA and the JSBI for the continuation of ABLS provider courses in Japan. These courses were provided as one of the programs available at the annual meeting of the JSBI. Nine Japanese registered ABLS instructors (including some candidates) acted as lecturers. Two national faculty members and one course coordinator, acting as ABA observers, participated in the first and second courses. In total, 64 physicians (37 emergency physicians, 20 plastic surgeons, 4 intensivists and 3 general surgeons) attended the courses. Course management and instructor behavior were reviewed by the ABA observers and the 64 physicians in attendance using questionnaires. The ABA observers rated the courses as "outstanding" in every aspect (course faculty, facilities, course organization, course conduct, and adherence to ABLS philosophies). The pre-course planning, course conduct, and course evaluations were professional and adhered to the highest educational standards. However, several areas of the ABLS course content may require revision to accommodate differences in standard medical treatment between the United States and Japan. Two percent of the physicians rated the courses as easy, 59% rated the course as moderate, 22% rated the course as slightly difficult, and 6% rated the course as difficult. The courses were generally evaluated as very good by 28% of the physicians and good by 56%. The major opinion regarding the organization of the course in Japan was that the course should have undergone appropriate curriculum changes to accommodate societal differences (including the translation of the course into Japanese) as well as modifications to the disaster management and patient transport sections. Regarding the organization of future ABLS courses in Japan, the active involvement of the JSBI is inevitable. Several areas of the ABLS course content may need to be revised to accommodate differences in standard medical treatment between the United States and Japan. A joint effort between the ABA and the JSBI regarding appropriate curriculum changes to accommodate societal differences as well as modifications to some sections would increase the applicability of the course in Japan. © 2009 Elsevier Ltd and ISBI.

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In vivo il-18 supplementation ameliorates lethal acute lung injury in burn-primed endotoxemic mice

Sekine Kazuhiko, Fujishima Seitaro, Sasaki Junichi, Ishizaka Akitoshi, Aiso Sadakazu, Aikawa Naoki

Shock 32 ( 5 ) 554 - 562 2009.11

ISSN 1073-2322

Previously, we have found that a prior burn insult induces lethal acute lung injury (ALI) and overproduction of proinflammatory cytokines after LPS challenge in mice. The current study was aimed to determine the role of IL-18 in burn-induced LPS hypersensitivity. Except sham group, mice were subjected to a 15% total body surface area full-thickness burn and either untreated or treated with IL-18 alone, IL-18 + anti-IL-10 antibody or IL-18 + isotype immunoglobulin G. LPS was intravenously administered to all mice on the 11th day, and the mice were killed at the indicated time point, or survival was examined. We additionally examined cytokine production by splenic cells in vitro for the elucidation of immunologic mechanisms. Unexpectedly, the liver IL-18 decreased transiently after burn injury, and in vivo IL-18 supplementation improved survival and ameliorated ALI, as well as reducing the lung contents of all cytokines examined, except IL-10. Neutralization of IL-10 cancelled the protective effect of IL-18. In splenic macrophages obtained from burned mice, the production of macrophage inflammatory protein 2 (MIP-2), TNF-α, and IL-10 was augmented, whereas in vivo IL-18 supplementation decreased MIP-2 production, but increased IL-10 production. Furthermore, a physiological concentration of IL-18 directly attenuated MIP-2 production by splenic cells in vitro. Burn injury induces LPS hypersensitivity through augmented production of proinflammatory cytokines by systemic macrophages. IL-18 supplementation is protective for LPS-induced lethal ALI through the direct anti-inflammatory effect on macrophages as well as by in vivo acceleration of IL-10 production, and could thus be an effective prophylactic strategy against septic complications in critically ill patients. © 2009 by the Shock Society.

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Discussion

Sasaki Junichi, Davis Kimberly A., Meyer Anthony A., Tanaka Hiroshi, Valente Stephanie

Journal of Trauma - Injury, Infection and Critical Care 67 ( 5 ) 973 - 974 2009

ISSN 0022-5282

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Neutrophil elastase and systemic inflammatory response syndrome in the initiation and development of acute lung injury among critically ill patients

Fujishima Seitaro, Morisaki Hiroshi, Ishizaka Akitoshi, Kotake Yoshifumi, Miyaki Masaru, Yoh Kikuo, Sekine Kazuhiko, Sasaki Junichi, Tasaka Sadatomo, Hasegawa Naoki, Kawai Yohko, Takeda Junzo, Aikawa Naoki

Biomedicine and Pharmacotherapy 62 ( 5 ) 333 - 338 2008.06

ISSN 0753-3322

Critically ill patients are commonly associated with systemic inflammatory response syndrome (SIRS) and are at a greater risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Under these conditions, large amounts of various cytokines are produced, which either directly or indirectly induce tissue injury and finally organ dysfunctions, through the activation of neutrophils and as a result of release of cytotoxic molecules, especially neutrophil elastase (NE). In the present study, we determined plasma neutrophil elastase-alpha-1 antitrypsin complex (NE-AT) and elastase digests of cross-linked fibrin (e-XDP) in critically ill patients to elucidate the significance of NE in the initiation and progression of ALI and ARDS in the presence or absence of SIRS. We found significantly increased levels of plasma NE-AT in the patients with ARDS, especially when the definition of SIRS was met. Among ALI/ARDS groups, plasma NE-AT, but not e-XDP, correlated significantly with the decrease in PaO₂/FIO₂ ratio and the duration of ALI/ARDS. Furthermore, NE-AT, but not e-XDP, significantly increased in subgroups whose PaO₂/FIO₂ ratio decreased by more than 20%. Such correlations and differences between the subgroups were not observed in the non-ALI patients. From these results, we speculate that NE-AT, but not e-XDP, may be predictive of progressive lung injury in the early stage of ALI and ARDS. © 2007 Elsevier Masson SAS. All rights reserved.

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The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model

Xie Xiao Qi, Shinozawa Yotaro, Sasaki Junichi, Takuma Kiyotsugu, Akaishi Satoshi, Yamanouchi Satoshi, Endo Tomoyuki, Nomura Ryosuke, Kobayashi Michio, Kudo Daisuke, Hojo Nobuko

Journal of Surgical Research 146 ( 2 ) 298 - 303 2008.05

ISSN 0022-4804

Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis. © 2008 Elsevier Inc. All rights reserved.

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Positioning of steroids in the treatment of infectious diseases

Sasaki Junichi, Shinozawa Yotaro, Fujishima Seitaro, Aikawa Naoki

Nippon rinsho. Japanese journal of clinical medicine 65 Suppl 2 Pt. 1 315 - 319 2007.02

ISSN 0047-1852

Neuroendocrine system response modulates oxidative cellular damage in burn patients

Xie Xiao Qi, Shinozawa Yotaro, Sasaki Junichi, Takuma Kiyotsugu, Akaishi Satoshi, Yamanouchi Satoshi, Endo Tomoyuki, Nomura Ryosuke, Kobayashi Michio, Kudo Daisuke, Hojo Nobuko

Tohoku Journal of Experimental Medicine 211 ( 2 ) 161 - 169 2007.02

ISSN 0040-8727

Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 ± 31.4 years old, and 32.3 ± 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2′-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn. © 2007 Tohoku University Medical Press.

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Computed tomographic and selective laparoscopy in the diagnosis of blunt bowel injury

Mitsuhide Kitano, Junichi Sasaki, Atsushi Nagashima, Masakazu Doi, Shinobu Hayashi, Tomohisa Egawa, Hiroshi Yoshii, Fakhry Samir M., Leppaniemi Ari, McQuay Nathaniel, Wisner David H.

Journal of Trauma - Injury, Infection and Critical Care 58 ( 4 ) 696 - 703 2005.04

ISSN 0022-5282

Background: We prospectively evaluated whether computed tomographic (CT) scanning and selective laparoscopy (LP) for the diagnosis of blunt bowel injury (BBI) could prevent nontherapeutic laparotomy and delayed diagnosis. Methods: Between April 1994 and May 2002, hemodynamically stable patients suspected of having BBI were enrolled in this study. Patients with hemodynamic instability or solid organ injuries with hemoperitoneum were excluded. All patients underwent a physical examination and contrast CT scanning at admission and once again approximately 12 hours (range, 6-24 hours) after admission. LP was performed under general anesthesia in patients who had local peritoneal signs and indirect CT signs (bowel thickening or isolated intraperitoneal fluid) or in whom abdominal pain or tenderness increased or intraperitoneal fluid increased on the repeat CT scan. The indications for a celiotomy were diffuse peritonitis, pneumoperitoneum on the abdominal CT scan, or bowel perforation visible on LP. Results: During the study period, 399 of 1,074 patients admitted for blunt torso injuries were enrolled in this study. Eleven patients underwent emergency celiotomy and 11 underwent LP immediately after admission to the emergency department. One nontherapeutic laparotomy was performed among the patients who underwent celiotomy. The LPs revealed seven bowel perforations and one mesenteric laceration. After a repeat CT scan, three and seven of the patients underwent laparotomy and LP, respectively. Four bowel perforations were found by LP. The remaining 198 patients were treated conservatively, and no complications related to a delayed BBI diagnosis occurred. Conclusion: CT scanning and selective LP can prevent nontherapeutic laparotomy and delayed diagnosis in patients with suspected BBI. Copyright © 2005 by Lippincott Williams & Wilkins, Inc.

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Prior burn insult induces lethal acute lung injury in endotoxemic mice

Sasaki Junichi, Fujishima Seitaro, Iwamura Hiroyuki, Wakitani Korekiyo, Aiso Sadakazu, Aikawa Naoki

American Journal of Physiology - Lung Cellular and Molecular Physiology 284 ( 2 28-2 ) 2003.02

ISSN 1040-0605

Many patients who experience surgical stress, including burn injury, become susceptible to severe sepsis and septic organ dysfunction, which remains the primary contributor to morbidity and mortality in burn patients. In the present study, we developed a murine model of burn-primed sublethal endotoxemia by producing a 15% BSA full-thickness burn on the dorsum of BALB/c mice under ether anesthesia and administering 10 mg/kg of LPS intravenously on day 11 to model endotoxemia. The prior burn injury in this model induced two-peaked production of cytokines, TNF-α, and macrophage inflammatory protein-2 at 2 and 12 h after LPS administration, and it was associated with increased mortality. We also assessed the effect of pharmacological modulation with cytokine synthesis inhibitors prednisolone and JTE-607 and found that pretreatment with them attenuated later cytokine production and decreased mortality after LPS administration. We speculate that the prior burn injury primed the mice for the secondary insult via cytokine production. These results also suggested that an anticytokine strategy might serve as a novel prophylactic therapy for septic organ dysfunction in burn-primed patients.

A case of traumatic shock complicated by methamphetamine intoxication

Horiguchi T., Hori S., Shinozawa Y., Fujishima S., Kimura H., Yokoyama M., Sasaki J., Takatsuki S., Suzuki M., Yamazaki M., Aikawa N.

Intensive Care Medicine 25 ( 7 ) 758 - 760 1999

ISSN 0342-4642

A case of a 38-year-old male with traumatic shock complicated by methamphetamine intoxication is presented. The patient was involved in an assault which resulted in cardiac tamponade and right ventricular outflow laceration. Pericardiocentesis was immediately performed. However, profound metabolic acidosis greatly in excess of that expected from the short duration of the shock was revealed by arterial blood gas analysis. Another cause of the metabolic acidosis was suspected. The patient subsequently admitted to intravenous use of methamphetamine. Following hemodynamic and metabolic stabilization by continuous pericardial drainage and intravenous administration of sodium bicarbonate, the patient underwent cardiac surgery. His postoperative course was uneventful. There is a substantial association between methamphetamine users and traumatic accidents. In such cases, early identification of drug use is important. Marked metabolic acidosis, which conflicts with the diagnosed cause of shock, may be a clinical clue to methamphetamine intoxication.

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Clinical investigation of intravenous ciprofloxacin in severe and/or refractory infections in the surgical and gynecological fields

Aikawa N., Sasaki J., Iwai S., Kunimatsu M., Furuhata H., Watanabe T., Matsuyama H., Sugiyama Y., Shimizu T., Shinagawa N., Mashita K., Manabe T., Ishikawa S., Mizuno A., Iwai A., Matsumoto K., Hori K., Kinoshita H., Kubo S., Tanaka H., Ueda T., Fujimoto M., Nakatani S., Iwasa R., Yamazaki O., Yokoyama T., Kodama T., Miyoshi N., Maruyama Y., Kishi A., Takesawa G., Matsuda S., Okada H., Nakata Y., Okumura J., Obata T., Endo S., Saito K., Takahashi Y., Osakabe Y., Fujii C., Fukuda M.

Japanese Journal of Chemotherapy 45 ( 11 ) 936 - 950 1997

ISSN 1340-7007

A clinical investigation of intravenous ciprofloxacin (CPFX) in the surgical and gynecological fields was conducted in patients with sepsis, peritonitis, biliary tract infections, secondary infections (due to trauma, burns and operative wounds) and gynecological infections, all of which were severe and/or refractory. CPFX was administered intravenously 300 mg twice a day for 3 to 14 days to 87 patients: 4 with sepsis, 22 with peritonitis, 11 with biliary tract infections, 33 with secondary infections, 13 with gynecological infections and 4 with other infections. The clinical efficacy rate was 85.1% (63/74 cases): 100% (2/2 cases) with sepsis, 88.2% (15/17 cases) with peritonitis, 63.6% (7/11 cases) with biliary tract infections, 90.6% (29/32 cases) with secondary infections and 83.3% (10/12 cases) with gynecological infections. The eradication rate of causative organisms was 67.9% (55/81 strains) in terms of bacteriological efficacy. Side effects were noted in 1 case (1.2%) who developed anemia. Abnormal laboratory findings were observed in 18 cases (21.2%) and major findings were increased eosinophil counts and elevated transaminases. The evaluations of overall safety and usefulness were 80.0% (68/85 cases) and 83.8% (62/74 cases), respectively. Therefore, we found that intravenous CPFX is a highly effective drugs for severe and/or refractory surgical infections in the surgical and gynecological fields.

Serum MIP-1α and IL-8 in septic patients

Fujishima S., Sasaki J., Shinozawa Y., Takuma K., Kimura H., Suzuki M., Kanazawa M., Hori S., Aikawa N.

Intensive Care Medicine 22 ( 11 ) 1169 - 1175 1996

ISSN 0342-4642

We studied blood MIP-1α and IL-8 in 38 septic patients and 5 healthy volunteers. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1α was detected in 45% of the patients and IL-8 in 84%. The levels of MIP-1α, but not of IL-8, correlated with CRP, IL-6 and TNFα levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1α levels. In contrast, we found increased levels of serum IL-8 in septic patients with disseminated intravascular coagulation, central nervous system (CNS) dysfunction or renal failure, and the mortality rate was higher in the IL-8-detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05). In conclusion, the production of both MIP-1α and IL-8 was increased and initially detectable levels of circulating IL-8 predicted high mortality in sepsis.

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Fundamental and clinical studies on cefluprenam in the surgical field

Takahashi Takayuki, Mori Toshio, Ishibiki Kyuya, Kurihara Naoto, Aikawa Naoki, Takuma Kiyotsugu, Shinozawa Yotaro, Sasaki Jun ichi, Hori Shingo

Japanese Journal of Chemotherapy 43 152 - 159 1995

ISSN 1340-7007

The pharmacokinetics and clinical studies were undertaken to evaluate the effect of intravenously administered cefluprenam (CFLP) on the surgical infections. 1. Peritoneal exudate was collected for 3 consecutive days through a Foleys balloon catheter inserted to the subphrenic space at the end of surgery. One g of CFLP was administered twice a day to 3 patients after gastrectomy for gastric cancer. CFLP levels in exudate at 1, 2 and 3 postoperative days were 8.0, 11. 1 and 11.1μg/ml in avarage respectively. The relative mean concentration of CFLP was 5.1μg/ml and belonged to the high value group among 30 β-lactams. 2. Concentration of CFLP in choledocus bile was studied on 1 patient of choledocolithiasis after cholecytectomy and T-tube drainage. Bile levels at 1, 2, 4, 6 and 8 hours after CFLP (1.0g) administration were 0.3, 0.3, 1.9, 4.0 and 4.7μg/ml respectively. 3. In the clinical study, 16 patients received intravenous CFLP (1 or 2g), bid for 4 ~ 16 days. Sixteen patients consisted of 2 cholangitis, 2 panperitonitis, 5 localized peritonitis, 3 postoperative wound infection, 1 burn wound infection, 1 ileopsoas abscess, 1 abdominal wall abscess and 1 periproctal abscess. The clinical effects were excellent in 2 cases, good in 12 cases, fair in 1 case and poor in 1 case ; overall clinical response rate in 16 cases was 87.5%. No adverse drug reaction was noted but slight abnormal laboratory finding in S-GPT was recognized in 1 case. These results suggested CFLP may be useful drug to surgical infections including intraperitoneal infections.

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An alternative limb lead system for electrocardiographs in emergency patients

Takuma Kiyotsugu, Hori Shingo, Sasaki Junichi, Shinozawa Yotaro, Yoshikawa Tsutomu, Handa Shunnosuke, Horikawa Muneyuki, Aikawa Naoki

American Journal of Emergency Medicine 13 ( 5 ) 514 - 517 1995

ISSN 0735-6757

It is occasionally difficult to record the standard 12-lead electrocardiograph (ECG) in emergency patients. The aim of this study was to evaluate the influence on electrocardiographic wave form recordings of moving the location of electrodes from the standard limb lead position to the trunk. The participants were 10 normal subjects and 20 patients with heart disease. In the new lead system, the limb electrodes were placed on the anterior acromial region and the anterior superior iliac spine using adhesive electrodes. Conventional 12-lead ECGs were recorded by the standard and the new lead system simultaneously in the supine position. Wave form analysis was done by an automatic analysis program. Motion artifacts in the recordings were less in the new lead system. The R wave amplitude of the new lead system increased in leads II, III and aVF, and decreased in leads I and aVL. However, the amplitudes of each wave obtained by standard electrocardiography and the new lead system correlated well (y = 1.008x + 2.038, r = 0.99, n = 2,880). In 99.6% of all wave forms, the differences in amplitudes were within 5% of the values of standard recordings. The average of differences in the ST-segment was 2.6 ± 11.4 μV. The frontal plane QRS axis obtained by the new lead system showed a vertical shift of 7.8 ± 8.5 degrees (y = 0.94911x + 10.346, r = 0.98, n = 30). The recording errors produced by the new lead system were within the permissible range of variation. The new lead system is a reasonable alternative for recording ECGs if application of the standard lead is difficult in an emergency. © 1995.

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Interleukin 8 in ARDS

Fujishima Seitaro, Sasaki Jun ichi, Shinozawa Yotaro, Takuma Kiyotsugu, Hori Shingo, Aikawa Naoki

The Lancet 342 ( 8865 ) 237 - 238 1993.07

ISSN 0140-6736

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A case of food-dependent exercise-induced anaphylaxis associated with repeated episodes of syncope

Tashiro H., Hori S., Shinozawa Y., Obara K., Fujishima S., Miyata Y., Namiki J., Koizumi J., Sasaki J., Hirata T.

Respiration and Circulation 41 ( 6 ) 587 - 590 1993.06

ISSN 0452-3458

This report describes a patient with food-dependent exercise-induced anaphylaxis (FEA). A 25-year-old female has had three episodes of syncopal attack associated with urticaria in the past two years: the attacks have been developed by exercise after taking meals made of wheat flour. She has an allergic predisposition to metals. No abnormal findings were observed in the routine work up for syncope including, ECG, 24-hour Holter ECG, UCG, tilt table test, and EEG examinations. A provocative test for FEA was performed. It included food (sandwich) intake followed by exercise. The serum histamine concentration was elevated to a three times higher than the control value after the provocation. Accordingly, she was diagnosed as FEA and advised not to take wheat flour prior to physical exercise. No syncopal episode has been observed during the 16 months since the diagnosis.

Experimental and clinical studies on cefclidin in the treatment of burns

Aikawa N., Takuma K., Shinozawa Y., Sasaki J., Hori S., Ishibiki K., Satoh M., Hachiya S.

Chemotherapy 40 ( SUPPL. 4 ) 509 - 515 1992

ISSN 0009-3165

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