Takeshi Ishii

The University of Tokyo, 白山, Tōkyō, Japan

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Publications (64)254.6 Total impact

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    ABSTRACT: Background: Epidemiological studies recently suggested that acute kidney injury (AKI) in ICUs increases the risk of chronic kidney disease (CKD) development and progression. However, whether any AKI biomarker can predict long-term renal outcomes in ICU survivors remains unclear. This study was undertaken to elucidate the role of urinary biomarkers for long-term renal outcome prediction after ICU discharge. Methods: This retrospective observational study examined 495 adult patients who had been admitted to the ICU of the University of Tokyo Hospital. Major adverse kidney events (MAKE): death, incident end-stage renal disease (ESRD), and halving of estimated glomerular filtration rate (eGFR), at hospital discharge and long-term renal outcomes of 30% reduction of eGFR or incident ESRD were evaluated. Results: Among all the enrolled 495 patients, 393 patients were discharged from the hospital without MAKE. Data of eGFR up to two years after ICU discharge were available for 173 patients; 63 patients (36.4%) were positive for long-term renal outcomes. Step-wise logistic regression analysis demonstrated that male sex and urinary neutrophil gelatinase-associated lipocalin (NGAL) measured at ICU admission showed significant associations with long-term renal outcomes. Receiver operating characteristic curve analysis showed the area under the curve of 0.66 (95% confidence interval 0.57-0.74) for prediction of long-term renal outcome by urinary NGAL. Conclusion: Urinary NGAL measured at ICU admission was significantly associated with long-term renal outcomes after hospital discharge in MAKE-free ICU survivors. Urinary NGAL measurements at ICU might be useful to identify a high risk population of kidney disease progression after intensive care.
    No preview · Article · Feb 2016 · Shock
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    ABSTRACT: Purpose We investigated the marital status and the presence or absence of children in survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma and examined the influence of these factors on the quality of life (QOL) of these survivors. Methods Thirty-eight survivors of childhood and AYA high-grade sarcoma (18 males, 20 females) participated in a questionnaire survey on marital status and presence or absence of children, as well as on the health-related QOL (HR-QOL), using the Short Form 36 Health Survey. Diagnoses among these survivors were osteosarcoma (28 participants), Ewing’s sarcoma (4 participants), synovial sarcoma (4 participants) and others (2 participants). Results Of the 18 males who participated in the survey, eight (44.4 %) were married, of whom five (62.5 %) had children. Fifteen (75.0 %) of the 20 females were married, of whom 14 (93.3 %) had children. The proportions of surviving male patients who were married and who had children, respectively, were lower than those of surviving female patients. The proportion of ifosfamide-treated men with children was significantly lower than that of non-ifosfamide-treated men (p = 0.018). With respect to the relationship between marital status and HR-QOL, the scores for the vitality and mental health domains of the SF-36 of survivors who were married were significantly higher than those of unmarried survivors. Conclusions The results of our questionnaire survey reveal that among the male survivors of high-grade sarcoma, the proportions of those who were married and of those with children were lower than those of female survivors, suggesting that strategies providing support for marriage and child-rearing may be necessary for the male survivor group. In the married group, mental QOL was high.
    No preview · Article · Jan 2016 · International Journal of Clinical Oncology
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    ABSTRACT: Objectives: As interactions of each organ system have been conceptually known to play an important role during life-threatening conditions, we quantitatively evaluated the organ system interactions in critically ill patients and examined the difference in the organ system network structure between the survivors and the nonsurvivors. Design: Prospective observational study. Settings: An ICU of a university hospital. Patients: Two hundred and eighty-two patients who were admitted to the ICU. Interventions: Blood samples were obtained at ICU admission. Measurements and main results: We analyzed the associations among nine representative laboratory variables of each organ system using network analysis. We compared the network structure of the variables in the 40 nonsurvivors with that in the 40 survivors. Their baseline characteristics, including the degree of organ dysfunction, were matched using propensity score matching method. Network structure was quantitatively evaluated using edge (significant correlation among variables evaluated by the p value), weight (connective strength of edge evaluated by coefficient), and cluster (group with tight connection evaluated by edge betweenness). The number of edges among the nine variables was significantly fewer for the nonsurvivors than for the severity-matched survivors (3 vs 12; p = 0.035). The mean weight of edges was significantly smaller for the nonsurvivors (0.055 vs 0.119; p = 0.007). The nine laboratory variables for the nonsurvivors were divided into a significantly larger number of clusters (7 vs 2; p = 0.001). Statistical conclusions were preserved with Bonferroni multiple comparison procedure. These findings were consistently observed in comparison of the 40 nonsurvivors with all the survivors. Conclusions: This study, as a preliminary proof-of-concept, quantitatively demonstrated a more disrupted network structure of organ systems in the nonsurvivors compared with that in the survivors. These observations suggest the necessity of assessment for organ system interactions to evaluate critically ill patients.
    No preview · Article · Oct 2015 · Critical care medicine
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    ABSTRACT: Aim: Erythropoietin (EPO) production is stimulated by hypoxia in the kidney. Ischemic injury plays a crucial role in the pathogenesis of acute kidney injury (AKI). However, EPO concentrations in critically ill patients complicated with AKI have not been evaluated sufficiently. This study was conducted to clarify the factors associated with plasma EPO concentrations in AKI. Methods: This study prospectively enrolled 98 critically ill adult patients treated at the adult mixed ICU. Plasma EPO, insulin-like growth factor-binding protein-1 (IGFBP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and urinary N-acetyl-β-D-glucosaminidase (NAG) were measured on ICU admission. Results: AKI occurred in 42 (42.9%) patients. Significantly higher plasma EPO in the AKI group was detected than in the non-AKI group (16.13 [9.87-28.47] mIU/mL versus 27.81 [10.16-106.02] mIU/mL, p < 0.05). Plasma IGFBP-1 in the AKI group was also significantly higher than in the non-AKI group (19,208 [8,820-50,780] pg/mL versus 63,199 [25,289-147,489] pg/mL, p < 0.05). Plasma EPO concentration was negatively correlated with hemoglobin in the non-AKI group with statistical significance, but not in the AKI group. Multiple logistic regression analysis revealed that plasma EPO in the AKI group was associated significantly with plasma IGFBP-1 and complication of diabetes mellitus, but not the hemoglobin concentration, partial pressure of arterial oxygen (PaO2), and IL-6. Conclusions: Not low arterial oxygen tension, hemoglobin concentration, and inflammation evaluated by IL-6 but plasma IGFBP-1 was significantly associated with plasma EPO concentration in AKI, suggesting unknown mechanism related to systemic stress conditions for EPO regulation in AKI. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Nephrology
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    ABSTRACT: We investigated whether surgical rib fixation improved outcomes in patients with traumatic rib fractures. This was a retrospective study using a Japanese administrative claim and discharge database. We included patients with traumatic rib fractures admitted to hospitals where surgical rib fixation was available from July 1 2010, to March 31, 2013. We detected patients who underwent surgical rib fixation within 10 days of hospital admission (surgical group) and those who did not (control group). The main outcome was prolonged mechanical ventilation, defined as that performed for 5 or more days, or death within 28 days. One-to-four propensity score matching was performed between the 2 groups with adjustment for possible confounders. Among 4577 eligible patients, 90 (2.0%) underwent the surgical rib fixation. After the matching, we obtained 84 and 336 patients in the surgical and control groups, respectively. Logistic regression analyses showed that the surgical group was significantly less likely to receive prolonged mechanical ventilation or die within 28 days than the control group (22.6% vs 33.3%; odds ratio, 0.59; 95% confidence interval, 0.36-0.96; P = .034). Surgical rib fixation within 10 days of hospital admission may improve outcomes in patients with traumatic rib fractures. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Aug 2015 · Journal of critical care

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma. This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513). A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS. The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    No preview · Article · Jul 2015 · Cancer
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    ABSTRACT: Distant metastases from osteosarcoma most commonly occur in the lungs. Osteosarcoma can be cured by complete surgical resection of all metastatic lesions if the number is limited (oligo-recurrence: ≤5 metastatic or recurrent lesions with controlled primary lesions). This study aimed to clarify the prognostic factors for osteosarcoma patients with pulmonary metastasis and determine their oligo-recurrence status. Patients with conventional osteosarcoma who underwent definitive surgery for the primary lesion and at least one thoracotomy for pulmonary metastases were recruited to this retrospective study. Clinicopathological information was collected on each thoracotomy from 1976 to 2011, and was then analyzed statistically. We counted the number of resected nodules that were pathologically confirmed as metastatic lesions from osteosarcoma. In total, 151 thoracotomies in 71 patients were analyzed. Forty-seven patients (66 %) underwent up to two thoracotomies, and the maximum number of thoracotomies was six. The median number of resected nodules on each thoracotomy was two, and the median total size of metastatic lesions was 20 mm. Incomplete surgical remission [relative risk (RR) 3.42], a less than 1-year interval from a previous thoracotomy (RR 1.97), more than three resected nodules (RR 2.42); and total size of more than 30 mm for pulmonary metastases (RR 2.19) were independent predictors of increased risk of tumor death by multivariate analysis. We propose that factors contributing to oligo-recurrence of patients with pulmonary metastatic osteosarcoma include complete surgical remission, an interval from a previous thoracotomy, number of resected nodules, and total size of pulmonary metastases.
    No preview · Article · Jun 2015 · Annals of Surgical Oncology
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    ABSTRACT: Epithelioid sarcoma (ES) is an extremely rare soft tissue sarcoma. Recently, the proximal variant has been reported to be a more aggressive subtype; however, as most reports of ES have involved small case series, the actual prognostic implications remain unclear. We investigated the clinicopathological features of patients with ES to identify the prognostic factors that influence survival. We retrospectively analyzed the clinicopathological features of 44 patients with ES who had been treated at our institutions between 1991 and 2011. Among these patients, 26 were diagnosed histologically as having classic-type ES, whereas the remaining 18 had proximal-type ES. Thirty-three of the patients, all without distant metastases, underwent curative surgery, and the remaining 11 with distant metastases (M1) received palliative treatment. The proximal subtype was significantly correlated with a proximal tumor location, distant metastases at presentation, presence of rhabdoid cells, a higher tumor grade, and vascular invasion. The overall survival (OS) rate at 5 years for the 44 patients was 45 %. A superficial tumor location and lymph node metastases (N1) at presentation were independently predictive of local recurrence-free survival (LRFS), and N1 and M1 tumors were independently predictive of distant metastasis-free survival and OS, respectively. The proximal subtype was associated with unfavorable LRFS and OS, although not to a statistically significant degree. Proximal-type ES has significantly more aggressive clinicopathological features than classic-type ES, and lymph node or distant metastasis has the most critical impact on prognosis.
    Full-text · Article · Feb 2015 · Annals of Surgical Oncology
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    ABSTRACT: IntroductionTissue inhibitor of metalloproteinase-2 (TIMP-2) is an emerging acute kidney injury (AKI) biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI.Methods This study prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-ß-D-glucosaminidase (NAG), and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6), and erythropoietin (EPO) were measured on ICU admission. We evaluated these biomarkers¿ capability of detecting AKI and its severity as determined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria and of predicting in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated.ResultsWe found AKI in 42 (42.9%) patients. All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 (27.6%) patients developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with the area under the receiver operating characteristic curve (AUC-ROC) of 0.80 (95% confidence interval 0.66 to 0.90). A total of 41 one (41.8%) cases were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine.Conclusion Urinary TIMP-2 can detect severe AKI with performance equivalent to those of plasma NGAL and urinary NAG with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.
    Preview · Article · Dec 2014 · Critical care (London, England)
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    ABSTRACT: Background and Objectives Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS.Methods We reviewed 89 patients diagnosed with UPS or MFS and underwent initial surgery at our institute between 1994 and 2011. Growth patterns were assessed radiographically on preoperative MRI. Clinicopathological factors were collected and uni- and multivariate analyses were performed for survival.ResultsInfiltrative growth was observed in 21 patients (24%), which correlated with superficial tumors and positive surgical margin. Infiltrative growth correlated with poor disease-specific and distant failure-free survivals relative to non-infiltrative growth. Multivariate analysis confirmed that these factors remained as significant factors. Patients with non-infiltrative tumors resected inadequately exhibited slightly more favorable local control with postoperative radiotherapy, although no clinical benefit was seen for those with infiltrative tumors.Conclusions Infiltrative growth was an adverse prognostic factor for not only local control, but also disease-specific and metastasis-free survival in patients with UPS and MFS. Radiotherapy could not salvage inadequately resected infiltrative tumors. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2014 · Journal of Surgical Oncology

  • No preview · Article · Oct 2014 · Cancer Research
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    ABSTRACT: Objectives: To investigate the performance of acute kidney injury (AKI) biomarkers for mortality prediction. Materials and methods: Cutoff values of urinary L-type fatty acid-binding protein (L-FABP) and N-acetyl-β-d-glucosaminidase (NAG) for AKI diagnosis in ICU were determined in the derivation cohort. The performance of these AKI biomarkers for mortality prediction was evaluated in the validation cohort with stratification of serum-creatinine based AKI diagnosis. Results: Mortality in the AKI patients diagnosed by serum creatinine was increased remarkably when urinary L-FABP and NAG were positive. Conclusions: These AKI biomarkers can specifically detect high-risk patients among creatinine-base diagnosed AKI.
    No preview · Article · Oct 2014 · Biomarkers

  • No preview · Article · Oct 2014 · Cancer Research
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    ABSTRACT: Background: Osteosarcoma as second malignancy of childhood cancers rarely occurs, and its clinical characteristics are unclear. Methods: Patients with osteosarcoma occurring as second malignancy of childhood cancers were retrospectively surveyed. Results: Of 323 patients with osteosarcoma registered in the database, 10 (3.1%) had a past history of childhood cancers. The mean age at the onset of the first childhood cancer was 2.7 years, and the diagnosis of the first childhood cancer was adrenocortical carcinoma, malignant teratoma, ovarian carcinoma, Ewing's sarcoma, and rhabdomyosarcoma in 1 patient each, and retinoblastoma in 5 patients. Osteosarcoma as second malignancy occurred 14.6 years after the first childhood cancer on average. Seven patients were alive and 3 died. In 1 patient, the cause of death was related to a complication of treatment for the first childhood cancer. Except for this patient, 7 (77.8%) of 9 patients survived with no disease (mean follow-up period: 10.9 years). Conclusions: Attention should be paid to complications of treatment for the first childhood cancer in the treatment for osteosarcoma occurring as second malignancy. The prognosis of osteosarcoma as second malignancy of childhood cancers may be more favorable than that of conventional osteosarcoma.
    No preview · Article · Jul 2014 · International Journal of Clinical Oncology
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    ABSTRACT: Background: Perioperative complication of end-organ injury including acute kidney injury (AKI) is a frequent and severe problem for patients undergoing left ventricular assist device (LVAD) implantation. This study evaluated an emerging AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), in a LVAD implantation cohort. Methods and results: Of 31 LVAD implantation patients enrolled to this study, 17 (55%) patients were diagnosed as having AKI. Six AKI patients showed severe AKI requiring renal replacement therapy (RRT). Plasma NGAL values in the AKI-with-RRT group (n=6) were significantly higher than that in other patients, although the AKI-without-RRT (n=11) group showed a similar level of plasma NGAL to that of the non-AKI group (n=14). Multiple logistic regression analysis revealed that plasma NGAL measured at pre-operation and central venous pressure at pre-operation and 12 h after surgery independently discriminated against postoperative RRT requirement. In the AKI-with-RRT group, plasma NGAL decreased before termination of RRT in 4 patients who eventually showed renal recovery, although no decline of plasma NGAL was observed in 2 patients who showed no recovery of renal function. Removal of blood NGAL by continuous hemodiafiltration was shown to be 70-75% lower than that of creatinine. Conclusions: Measurement of perioperative plasma NGAL is useful for predicting severe AKI requiring RRT and renal recovery in patients who have had LVAD implantation surgery. Further investigation is necessary to confirm these findings because this study examined a low number of patients.
    No preview · Article · Jun 2014 · Circulation Journal

  • No preview · Conference Paper · Nov 2013
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    ABSTRACT: Plasma neutrophil gelatinase-associated lipocalin (NGAL) is reportedly useful for post-cardiac surgery acute kidney injury (AKI). Although chronic kidney disease (CKD) is a strong risk factor for AKI development, no clinical evaluation of plasma NGAL has specifically examined AKI occurring in patients with CKD. This study evaluated plasma NGAL in AKI superimposed on CKD after cardiac surgery. This study prospectively evaluated 146 adult patients with scheduled cardiac surgery at 2 general hospitals. Plasma NGAL was measured before surgery, at ICU arrival after surgery (0 hours), and 2, 4, 12, 24, 36, and 60 hours after ICU arrival. Based on the Kidney Disease Improving Global Outcomes (KDIGO) CKD guideline, 72 (49.3%) were diagnosed as having CKD. Of 146 patients, 53 (36.3%) developed AKI after surgery. Multiple logistic regression analysis revealed that preoperative plasma NGAL, estimated glomerular filtration rate (eGFR), and operation time are significantly associated with AKI occurrence after surgery. Plasma NGAL in AKI measured after surgery was significantly higher than in non-AKI irrespective of CKD complication. However, transient decrease of plasma NGAL at 0 to 4 hours was observed especially in AKI superimposed on CKD. Plasma NGAL peaked earlier than serum creatinine and at the same time in mild AKI and AKI superimposed on CKD with increased preoperative plasma NGAL (>300 ng/ml). Although AKI superimposed on CKD showed the highest plasma NGAL levels after surgery, plasma NGAL alone was insufficient to discriminate de novo AKI from CKD without AKI after surgery. Receiver operating characteristics analysis revealed different cutoff values of AKI for CKD and non-CKD patients. Results show the distinct features of plasma NGAL in AKI superimposed on CKD after cardiac surgery: 1) increased preoperative plasma NGAL is an independent risk factor for post-cardiac surgery AKI; 2) plasma NGAL showed an earlier peak than serum creatinine did, indicating that plasma NGAL can predict the recovery of AKI earlier; 3) different cutoff values of post-operative plasma NGAL are necessary to detect AKI superimposed on CKD distinctly from de novo AKI. Further investigation is necessary to confirm these findings because this study examined a small number of patients.
    Full-text · Article · Nov 2013 · Critical care (London, England)
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    ABSTRACT: It is unclear whether the prehospital termination of resuscitation (TOR) rule is applicable in specific situations such as in areas extremely dense with hospitals. The objective of the study is to assess whether the prehospital TOR rule is applicable in the emergency medical services system in Japan, specifically, in an area dense with hospitals in Tokyo. This study was a retrospective, observational analysis of a cohort of adult out-of-hospital cardiopulmonary arrest (OHCA) patients who were transported to the University of Tokyo Hospital from April 1, 2009, to March 31, 2011. During the study period, 189 adult OHCA patients were enrolled. Of the 189 patients, 108 patients met the prehospital TOR rule. The outcomes were significantly worse in the prehospital TOR rule-positive group than in the prehospital TOR-negative group, with 0.9% vs 11.1% of patients, respectively, surviving until discharge (relative risk [RR], 1.11; 95% confidence interval [CI], 1.03-1.21; P = .0020) and 0.0% vs 7.4% of patients, respectively, discharged with a favorable neurologic outcome (RR, 1.08; 95% CI, 1.02-1.15; P = .0040). The prehospital TOR rule had a positive predictive value (PPV) of 99.1% (95% CI, 96.3-99.8) and a specificity of 90.0% (95% CI, 60.5-98.2) for death and a PPV of 100.0% (95% CI, 97.9-100.0) and a specificity of 100.0% (95% CI, 61.7-100.0) for an unfavorable neurologic outcome. This study suggested that the prehospital TOR rule predicted unfavorable outcomes even in an area dense with hospitals in Tokyo and might be helpful for identifying the OHCA patients for whom resuscitation efforts would be fruitless.
    No preview · Article · Oct 2013 · The American journal of emergency medicine

  • No preview · Article · Oct 2013 · Resuscitation

Publication Stats

636 Citations
254.60 Total Impact Points


  • 2007-2015
    • The University of Tokyo
      • • Department of Nephrology and Endocrinology
      • • Department of Infectious Diseases
      白山, Tōkyō, Japan
  • 1999-2015
    • Chiba Cancer Center
      Tiba, Chiba, Japan
  • 2013
    • Tokyo Medical University
      • Department of Emergency and Critical Care Medicine
      Edo, Tōkyō, Japan
  • 2002
    • Sapporo Medical University
      • Division of Orthopaedic Surgery
      Sapporo, Hokkaido, Japan