Publications by authors named "Shigeki Kushimoto"

181 Publications

Impacts of Natural Environmental Factors and Prevalence of Airway Symptoms on the Local Spread of COVID-19: A Time-Series Analysis in Regional COVID-19 Epidemics.

Tohoku J Exp Med 2021 ;254(2):89-100

Department of Education and Support for Regional Medicine, Tohoku University Hospital.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (N). For the derivatives of the screening test results, data from individuals with a contact history who underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) testing between July 2020 and April 2021 (6,156 participants, including 550 test-positive patients) were used. The value of N correlated with the weekly RT-PCR test-positive rate after close contact, prevalence of cough symptoms in test-positive individuals or in test-negative individuals, lower air temperature, lower air humidity, and higher wind speed. The weekly test-positive rate correlated with lower air humidity and higher wind speed. In cross-correlation analyses, natural environmental factors correlated with the regional epidemic status on a scale of months, whereas the airway symptoms among non-COVID-19 population affected on a scale of weeks. When applying an autoregression model to the serial data of N, large-scale movements of people were suggested to be another factor to influence the local epidemics on a scale of days. In conclusion, the prevalence of cough symptoms in the local population, lower air humidity or higher wind speed, and large-scale movements of people in the locality would jointly influence the local epidemic status of COVID-19.
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http://dx.doi.org/10.1620/tjem.254.89DOI Listing
January 2021

Associations between low body mass index and mortality in patients with sepsis: A retrospective analysis of a cohort study in Japan.

PLoS One 2021 8;16(6):e0252955. Epub 2021 Jun 8.

Department of Emergency and Critical Care Medicine, Tohoku University Hospital, Sendai, Japan.

Background: The distribution of body mass in populations of Western countries differs from that of populations of East Asian countries. In East Asian countries, fewer people have a high body mass index than those in Western countries. In Japan, the country with the highest number of older adults worldwide, many people have a low body mass index. Therefore, this study aimed to determine the association between a low body mass index and mortality in patients with sepsis in Japan.

Methods: We conducted this retrospective analysis of 548 patients with severe sepsis from a multicenter prospective observational study. Multivariate logistic regression analyses determined the association between body mass index and 28-day mortality adjusted for age, sex, pre-existing conditions, the occurrence of septic shock, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores. Furthermore, the association between a low body mass index and 28-day mortality was analyzed.

Results: The low body mass index group represented 18.8% of the study population (103/548); the normal body mass index group, 57.3% (314/548); and the high body mass index group, 23.9% (131/548), with the 28-day mortality rates being 21.4% (22/103), 11.2% (35/314), and 14.5% (19/131), respectively. In the low body mass index group, the crude and adjusted odds ratios (95% confidence intervals) for 28-day mortality relative to the non-low body mass index (normal and high body mass index groups combined) group were 2.0 (1.1-3.4) and 2.3 (1.2-4.2), respectively.

Conclusion: A low body mass index was found to be associated with a higher 28-day mortality than the non-low body mass index in patients with sepsis in Japan. Given that older adults often have a low body mass index, these patients should be monitored closely to reduce the occurrence of negative outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186780PMC
June 2021

COVID-19 transmission in group living environments and households.

Sci Rep 2021 06 2;11(1):11616. Epub 2021 Jun 2.

Department of Education and Support for Regional Medicine, Tohoku University Hospital, Seiryo-machi 1-1, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world's largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.
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http://dx.doi.org/10.1038/s41598-021-91220-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172911PMC
June 2021

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.

Sci Rep 2021 May 26;11(1):11031. Epub 2021 May 26.

Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients.
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http://dx.doi.org/10.1038/s41598-021-90492-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154895PMC
May 2021

Intensive care unit model and in-hospital mortality among patients with severe sepsis and septic shock: A secondary analysis of a multicenter prospective observational study.

Medicine (Baltimore) 2021 May;100(21):e26132

Intensive Care Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Hokkaido, Japan.

Abstract: We aimed to determine the association between the intensive care unit (ICU) model and in-hospital mortality of patients with severe sepsis and septic shock.This was a secondary analysis of a multicenter prospective observational study conducted in 59 ICUs in Japan from January 2016 to March 2017. We included adult patients (aged ≥16 years) with severe sepsis and septic shock based on the sepsis-2 criteria who were admitted to an ICU with a 1:2 nurse-to-patient ratio per shift. Patients were categorized into open or closed ICU groups, according to the ICU model. The primary outcome was in-hospital mortality.A total of 1018 patients from 45 ICUs were included in this study. Patients in the closed ICU group had a higher severity score and higher organ failure incidence than those in the open ICU group. The compliance rate for the sepsis care 3-h bundle was higher in the closed ICU group than in the open ICU group. In-hospital mortality was not significantly different between the closed and open ICU groups in a multilevel logistic regression analysis (odds ratio = 0.83, 95% confidence interval; 0.52-1.32, P = .43) and propensity score matching analysis (closed ICU, 21.2%; open ICU, 25.7%, P = .22).In-hospital mortality between the closed and open ICU groups was not significantly different after adjusting for ICU structure and compliance with the sepsis care bundle.
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http://dx.doi.org/10.1097/MD.0000000000026132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154476PMC
May 2021

Incidence and Impact of Dysglycemia in Patients with Sepsis Under Moderate Glycemic Control.

Shock 2021 May 11. Epub 2021 May 11.

Center for General Medicine Education, School of Medicine, Keio University, Japan Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Japan Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Japan Division of Traumatology, Research Institute, National Defense Medical College, Japan Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Japan Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Japan Department of General Medicine, Juntendo University, Japan Health Services Research and Development Center, University of Tsukuba, Japan Emergency and Trauma Center, Kameda Medical Center, Japan Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health, Japan Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Japan Division of Disaster and Emergency Medicine, Department of Surgery Related, Kobe University Graduate School of Medicine, Japan Advanced Critical Care Center, Aichi Medical University Hospital, Japan Advanced Medical Emergency & Critical Care Center, Yamaguchi University Hospital, Japan Emergency & Critical Care Center, Kawasaki Municipal Hospital, Japan Department of Emergency & Critical Care Medicine, School of Medicine, Kurume University, Japan Department of Emergency and Critical Care Medicine, Aizu Chuo Hospital, Japan Department of Emergency Medicine, Trauma and Resuscitation Center, Teikyo University School of Medicine Department of Acute Medicine, Kawasaki Medical School, Japan Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Japan Department of Emergency and Critical Care Medicine Chiba University Graduate School of Medicine, Japan Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Japan (new) Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Japan Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Japan Emergency and Critical Care Medicine, Saga University Hospital, Japan Center Hospital of the National Center for Global Health and Medicine, Japan Department of Emergency and Critical Care Medicine, Nippon Medical School, Japan Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization, Chukyo Hospital, Japan Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Japan.

Abstract: Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. A total of 1,140 patients with severe sepsis, including 259 patients with pre-existing diabetes, were included. Median blood glucose levels were approximately 140 mg/dL at 0 h and 72 h indicating that blood glucose was moderately controlled. The rate of initial and late hyperglycemia was 27.3% and 21.7%, respectively. The rate of early hypoglycemic episodes during the initial 24 h was 13.2%. Glycemic control was accompanied by a higher percentage of initial and late hyperglycemia but not with early hypoglycemic episodes, suggesting that glycemic control was targeted at excess hyperglycemia. In nondiabetic patients, late hyperglycemia (hazard ratio, 95% confidence interval; p-value: 1.816, 1.116-2.955, 0.016) and early hypoglycemic episodes (1.936, 1.180-3.175, 0.009) were positively associated with in-hospital mortality. Further subgroup analysis suggested that late hyperglycemia and early hypoglycemic episodes independently, and probably synergistically, affect the outcomes. In diabetic patients, however, these correlations were not observed. In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.
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http://dx.doi.org/10.1097/SHK.0000000000001794DOI Listing
May 2021

Variability of extracorporeal cardiopulmonary resuscitation practice in patients with out-of-hospital cardiac arrest from the emergency department to intensive care unit in Japan.

Acute Med Surg 2021 Jan-Dec;8(1):e647. Epub 2021 May 1.

Department of Emergency and Critical Care Medicine Keio University School of Medicine Tokyo Japan.

Aim: A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out-of-hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU).

Methods: An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE-J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra-aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded.

Results: We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two-thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume ( for trend <0.001). Intra-aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions.

Conclusions: We described the variability in ECPR practice in patients with OHCA from the ED to the ICU.
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http://dx.doi.org/10.1002/ams2.647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088390PMC
May 2021

Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis.

World J Emerg Surg 2021 Apr 29;16(1):19. Epub 2021 Apr 29.

Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes.

Methods: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models.

Results: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay.

Conclusions: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED.

Trial Registration: UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.
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http://dx.doi.org/10.1186/s13017-021-00363-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082221PMC
April 2021

Endothelial Glycocalyx Disorders May Be Associated With Extended Inflammation During Endotoxemia in a Diabetic Mouse Model.

Front Cell Dev Biol 2021 1;9:623582. Epub 2021 Apr 1.

Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.

In diabetes mellitus (DM) patients, the morbidity of infectious disease is increased, and these infections can easily progress from local to systemic infection. Sepsis is a characteristic of organ failure related to microcirculation disorders resulting from endothelial cell injury, whose most frequent comorbidity in patients is DM. The aim of the present study was to evaluate the influence of infection on DM-induced microvascular damage on inflammation and pulmonary endothelial structure using an experimental endotoxemia model. Lipopolysaccharide (LPS; 15 mg/kg) was injected intraperitoneally into 10-week-old male C57BLKS/J Iar (db/db) mice and into C57BLKS/J Iarm / + (db/ +) mice, which served as the littermate non-diabetic control. At 48 h after LPS administration, the survival rate of db/db mice (0%, 0/10) was markedly lower ( < 0.05) than that of the db/ + mice (75%, 18/24), whereas the survival rate was 100% in both groups 24 h after LPS administration. In control mice, CD11b-positive cells increased at 6 h after LPS administration; by comparison, the number of CD11b-positive cells increased gradually in db/db mice until 12 h after LPS injection. In the control group, the number of Iba-1-positive cells did not significantly increase before and at 6, 12, and 24 h after LPS injection. Conversely, Iba-1-positive cells continued to increase until 24 h after LPS administration, and this increase was significantly greater than that in the control mice. Expression of , , and related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection. In conclusion, in db/db mice, the endothelial glycocalyx is already injured before LPS administration, and migration of inflammatory cells is both delayed and expanded. This extended inflammation may be involved in endothelial glycocalyx damage due to the attenuation of endothelial glycocalyx synthesis.
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http://dx.doi.org/10.3389/fcell.2021.623582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047120PMC
April 2021

Effect of age on dexmedetomidine treatment for ventilated patients with sepsis: a analysis of the DESIRE trial.

Acute Med Surg 2021 Jan-Dec;8(1):e644. Epub 2021 Apr 9.

Osaka Prefectural Nakakawachi Emergency and Critical Care Center Higashiosaka Japan.

Aim: There are no definitive data to determine whether age influences the effects of dexmedetomidine (DEX) treatment. Thus, we investigated whether older age was associated with more favorable sedative action by DEX in sepsis patients who required mechanical ventilation.

Methods: This study involved a post-hoc analysis of data from the Dexmedetomidine for Sepsis in the ICU Randomized Evaluation (DESIRE) trial. The patients were categorized based on median age into elderly and younger groups. The two groups were then compared during the first 7 days after ventilation based on proportion of patients with well-controlled sedation (Richmond Agitation-Sedation Scale score between -3 and +1), days free from delirium (based on the Confusion Assessment Method for ICU), and days free from coma (Richmond Agitation-Sedation Scale score between -4 and -5).

Results: One hundred and one patients were assigned to the elderly group and 100 patients were assigned to the younger group. In the elderly group, 50 patients received DEX treatment and 51 patients received non-DEX treatment, with the DEX arm having significantly better-controlled sedation (range, 14-52% versus 16-27%;  = 0.01). In the younger group, 50 patients received DEX treatment and 50 patients received non-DEX treatment, with no significant difference in the proportions of well-controlled sedation (range, 20-64% versus 24-60%;  = 0.73). There were no significant differences in the numbers of days free from delirium or coma between the groups.

Conclusion: In elderly sepsis patients who require ventilation, dexmedetomidine could be more effective than other sedative agents for achieving proper sedation.
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http://dx.doi.org/10.1002/ams2.644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033411PMC
April 2021

Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies.

Crit Care 2021 03 19;25(1):114. Epub 2021 Mar 19.

Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Background: A recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype.

Methods: This was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation.

Results: Four sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: - 17.8% [95% CI - 28.7 to - 6.9%]) and in-hospital (adjusted RD: - 17.7% [95% CI - 27.6 to - 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: - 24.9% [95% CI - 49.1 to - 0.7%]) and in-hospital mortality (RD: - 30.9% [95% CI - 55.3 to - 6.6%]).

Conclusions: We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.
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http://dx.doi.org/10.1186/s13054-021-03541-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978458PMC
March 2021

Quick sequential organ failure assessment versus systemic inflammatory response syndrome criteria for emergency department patients with suspected infection.

Sci Rep 2021 Mar 5;11(1):5347. Epub 2021 Mar 5.

Medical Center for Emergency, Yamagata Prefectural Central Hospital, Yamagata, Japan.

Previous studies have shown inconsistent prognostic accuracy for mortality with both quick sequential organ failure assessment (qSOFA) and the systemic inflammatory response syndrome (SIRS) criteria. We aimed to validate the accuracy of qSOFA and the SIRS criteria for predicting in-hospital mortality in patients with suspected infection in the emergency department. A prospective study was conducted including participants with suspected infection who were hospitalised or died in 34 emergency departments in Japan. Prognostic accuracy of qSOFA and SIRS criteria for in-hospital mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Of the 1060 participants, 402 (37.9%) and 915 (86.3%) had qSOFA ≥ 2 and SIRS criteria ≥ 2 (given thresholds), respectively, and there were 157 (14.8%) in-hospital deaths. Greater accuracy for in-hospital mortality was shown with qSOFA than with the SIRS criteria (AUROC: 0.64 versus 0.52, difference + 0.13, 95% CI [+ 0.07, + 0.18]). Sensitivity and specificity for predicting in-hospital mortality at the given thresholds were 0.55 and 0.65 based on qSOFA and 0.88 and 0.14 based on SIRS criteria, respectively. To predict in-hospital mortality in patients visiting to the emergency department with suspected infection, qSOFA was demonstrated to be modestly more accurate than the SIRS criteria albeit insufficiently sensitive.Clinical Trial Registration: The study was pre-registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000027258).
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http://dx.doi.org/10.1038/s41598-021-84743-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935946PMC
March 2021

Predictors of severe sepsis-related in-hospital mortality based on a multicenter cohort study: The Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study.

Medicine (Baltimore) 2021 Feb;100(8):e24844

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine.

Abstract: This study aimed to identify prognostic factors for severe sepsis-related in-hospital mortality using the structural equation model (SEM) analysis with statistical causality. Sepsis data from the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study (FORECAST), a multicenter cohort study, was used. Forty seven observed variables from the database were used to construct 4 latent variables. SEM analysis was performed on these latent variables to analyze the statistical causality among these data. This study evaluated whether the variables had an effect on in-hospital mortality. Overall, 1148 patients were enrolled. The SEM analysis showed that the 72-hour physical condition was the strongest latent variable affecting mortality, followed by physical condition before treatment. Furthermore, the 72-hour physical condition and the physical condition before treatment strongly influenced the Sequential Organ Failure Assessment (SOFA) score with path coefficients of 0.954 and 0.845, respectively. The SOFA score was the strongest variable that affected mortality after the onset of severe sepsis. The score remains the most robust prognostic factor and can facilitate appropriate policy development on care.
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http://dx.doi.org/10.1097/MD.0000000000024844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909210PMC
February 2021

Predictors of SARS-CoV-2 Positivity Based on RT-PCR Swab Tests at a Drive-Through Outpatient Clinic for COVID-19 Screening in Japan.

Tohoku J Exp Med 2021 02;253(2):101-108

Department of Education and Support for Regional Medicine, Tohoku University Hospital.

In response to the COVID-19 pandemic caused by SARS-CoV-2 in 2020, we conducted drive-through nasopharyngeal swab testing for COVID-19 in Sendai city, Japan, since April 2020. All tested individuals were judged in advance by public health centers for the necessity of undergoing the test with possible contact history and/or symptoms suggestive of COVID-19. In this study, to identify the predictors of SARS-CoV-2 test positivity for more efficient and evidenced selection of suspected individuals, we enrolled 3,540 consecutive individuals, tested in the first 7 months of the testing program, with data regarding to the history of close contact with COVID-19 patients, including those involved in cluster outbreaks. This cohort included 284 foreign students (257 males and 27 females) from a vocational school involved in the largest cluster outbreak in the area. Close contact history was present in 952 (26.9%) of the participants. The reverse transcription-polymerase chain reaction (RT-PCR) test results showed that 164 participants (4.6%) were positive and 3,376 participants (95.4%) were negative for the SARS-CoV-2 nucleocapsid gene (N2). In the univariate and multivariate analyses, history of close contact with COVID-19 patients, higher age, cough symptoms, and non-native ethnicity were predictors for SARS-CoV-2 test positivity. However, the significance of age and foreign nationality disappeared or declined upon excluding the foreign students from the aforementioned largest cluster outbreak. In conclusion, a history of close contact with COVID-19 patients and the presence of cough symptoms are significant predictors of SARS-CoV-2 test positivity.
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http://dx.doi.org/10.1620/tjem.253.101DOI Listing
February 2021

Epidemiological features and outcomes of patients with psoas abscess: A retrospective cohort study.

Ann Med Surg (Lond) 2021 Feb 18;62:114-118. Epub 2021 Jan 18.

Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Background: Psoas abscess (PA) is an uncommon disease. Although PA is associated with significant morbidity and mortality, its epidemiology and clinical characteristics remain unknown. This study aimed to evaluate the epidemiological and clinical features and outcomes of patients with PA in a prefectural-wide study.

Materials And Methods: This was a multicenter retrospective cohort study conducted between 2010 and 2012 in the Miyagi prefecture with a population of 2,344,062 in 2011. Adult patients with PA were enrolled from 71 secondary and tertiary care hospitals.

Results: There were 57 patients with adult PA in the Miyagi prefecture. The median age of the patients was 72 years, and 67% patients were male. Fever and flank pain were the primary symptoms in 82% and 74% of patients, respectively. Ten patients (18%) had septic shock, and the hospital mortality rate was 12%. Secondary PA was present in 72% of cases, and the most common origin was pyogenic spondylitis. Of the patients with secondary PA, 44% had an epidural abscess. The most common pathogens were , and 11% (6 cases) of the cases were caused by methicillin-resistant .

Conclusion: In the Miyagi prefecture of Japan, the estimated prevalence of PA was 1.21/100,000 population years and hospital mortality was 12%. Secondary PA accounted for more than 70% of the cases, and was the most common causative pathogen.
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http://dx.doi.org/10.1016/j.amsu.2021.01.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819806PMC
February 2021

Association between low body mass index and increased 28-day mortality of severe sepsis in Japanese cohorts.

Sci Rep 2021 Jan 15;11(1):1615. Epub 2021 Jan 15.

Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization Chukyo Hospital, Nagoya, Japan.

Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06-3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00-1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.
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http://dx.doi.org/10.1038/s41598-020-80284-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810989PMC
January 2021

Heterotopic ossification in a patient with paroxysmal sympathetic hyperactivity following multiple trauma complicated with vitamin D deficiency: a case report.

Surg Case Rep 2020 Nov 23;6(1):293. Epub 2020 Nov 23.

Department of Emergency and Critical Care Medicine, Tohoku University Hospital Emergency Center, 1-1 Seiryo-cho, Aoba-ku, Sendai-shi, 980-8754, Japan.

Background: Paroxysmal sympathetic hyperactivity (PSH) may occur in patients with traumatic brain injury. Heterotopic ossification (HO) has frequently been observed in patients with PSH and has been found to impair patients' recoveries. However, the pathophysiology of HO in patients with PSH remains unelucidated. Vitamin D deficiency is a common abnormality among critically ill patients and may be associated not only with musculoskeletal complications, but also with high morbidity and mortality. The association between vitamin D deficiency and HO in patients with PSH has not yet been evaluated.

Case Presentation: A 21-year-old man was in a motorcycle accident. The initial diagnosis was diffused axonal injury, thoracic aortic injury, bilateral lung contusion with hemopneumothorax, liver injury, vertebral injury of T5, along with fractures of the right humerus, left patella, bilateral scapula, and a stable pelvic fracture, with an Injury Severity Score of 50. Two weeks after admission, he was diagnosed with PSH. One month after the injury, decreased joint mobility and progressive pain were evident. Computed tomography (CT) showed HO in his humerus, ulna, radius, scapula, ilium, pubis, ischium, knee joint, patella, and tibia, as well as renal calculus. To evaluate metabolic bone abnormalities, we measured levels of 25-OH vitamin D, parathyroid hormone, calcitonin, procollagen type I N-terminal propeptide (a marker of bone formation), and tartrate-resistant acid phosphatase 5b (a marker of bone resorption). This revealed a vitamin D deficiency. Bisphosphonate agents and vitamin D were administered for 1 month. Thereafter, his symptoms, radiographic findings, and laboratory abnormalities improved, and he was transferred to another facility.

Conclusions: HO in patients with PSH, following severe head injury, may be associated with vitamin D deficiency. Medication for vitamin-D-related metabolism abnormalities may represent a novel intervention for HO with PSH.
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http://dx.doi.org/10.1186/s40792-020-01031-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683749PMC
November 2020

Current spectrum of causative pathogens in sepsis: A prospective nationwide cohort study in Japan.

Int J Infect Dis 2021 Feb 19;103:343-351. Epub 2020 Nov 19.

Department of Anesthesiology and Critical Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan; Department of Acute and Critical Care Medicine, Sapporo Tokushukai Hospital, Higashi, Sapporo, Hokkaido, Japan. Electronic address:

Background: There is no one-size-fits-all empiric antimicrobial therapy for sepsis because the pathogens vary according to the site of infection and have changed over time. Therefore, updating knowledge on the spectrum of pathogens is necessary for the rapid administration of appropriate antimicrobials.

Objective: The aim of this study was to elucidate the current spectrum of pathogens and its variation by site of infection in sepsis.

Methods: This was a prospective nationwide cohort study of consecutive adult patients with sepsis in 59 intensive care units in Japan. The spectrum of pathogens was evaluated in all patients and in subgroups by site of infection. Regression analyses were conducted to evaluate the associations between the pathogens and mortality.

Results: The study cohort comprised 1184 patients. The most common pathogen was Escherichia coli (21.5%), followed by Klebsiella pneumoniae (9.0%). However, the pattern varied widely by site of infection; for example, gram-positive bacteria were the dominant pathogen in bone/soft tissue infection (55.7%) and cardiovascular infection (52.6%), but were rarely identified in urinary tract infection (6.4%). In contrast, gram-negative bacteria were the predominant pathogens in abdominal infection (38.4%) and urinary tract infection (72.0%). The highest mortality of 47.5% was observed in patients infected with methicillin-resistant Staphylococcus aureus, which was significantly associated with an increased risk of death (odds ratio 1.88, 95% confidence interval 1.22-2.91).

Conclusions: This study revealed the current spectrum of pathogens and its variation based on the site of infection, which is essential for empiric antimicrobial therapy against sepsis.
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http://dx.doi.org/10.1016/j.ijid.2020.11.168DOI Listing
February 2021

Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study.

BMC Geriatr 2020 11 20;20(1):485. Epub 2020 Nov 20.

Division of Acute and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Background: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs.

Methods: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival.

Results: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group.

Conclusion: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.
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http://dx.doi.org/10.1186/s12877-020-01893-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677099PMC
November 2020

Clinical characteristics and prediction of the asymptomatic phenotype of pneumatosis intestinalis in critically ill patients: a retrospective observational study.

Acute Med Surg 2020 Jan-Dec;7(1):e556. Epub 2020 Sep 15.

Division of Emergency and Critical Care Medicine Tohoku University Graduate School of Medicine Sendai Japan.

Aim: The differences in clinical characteristics between benign asymptomatic and symptomatic pneumatosis intestinalis (PI) remain unknown. This study aimed to reveal the clinical characteristics of PI in critically ill patients.

Methods: This was a retrospective observational study undertaken between 2013 and 2017 in a single facility. Patients with PI were enrolled. Pneumatosis intestinalis was diagnosed using computed tomography, and clinical data were collected. Pathologic PI refers to PI with bowel ischemia. Asymptomatic PI refers to PI with a benign etiology.

Results: There were 17 patients with pathologic PI and 31 with asymptomatic PI. Pathologic PI was detected at day 4 of hospital stay, and asymptomatic PI was detected at day 30 of hospital stay ( < 0.01). The symptoms that were different between pathologic and asymptomatic PI were acute diarrhea (18% and 65%,  = 0.01), C-reactive protein level elevation (9.9 and 2.1 mg/dL,  = 0.01), and systemic inflammatory reaction syndrome (100% and 13%,  < 0.01). Computed tomography findings showed a difference in the occurrence of ascites collection (94% versus 23%,  < 0.01) and PI of the ascending colon (47% versus 80%,  = 0.02). Hospital mortality of pathologic PI was 88%, whereas all patients with benign PI survived. The positive likelihood ratio of acute diarrhea with PI of the ascending colon to diagnose benign PI was 7.33 (1.11-48.5).

Conclusions: Pneumatosis intestinalis of the ascending colon that occurs in the post-intensive care phase with a poor inflammatory reaction, acute diarrhea, and no ascites collection could be benign. In other cases, bowel ischemia should be promptly ruled out.
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http://dx.doi.org/10.1002/ams2.556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507103PMC
September 2020

Restrictive transfusion strategy for critically injured patients (RESTRIC) trial: a study protocol for a cluster-randomised, crossover non-inferiority trial.

BMJ Open 2020 09 6;10(9):e037238. Epub 2020 Sep 6.

Division of Emergency and Critical Care Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.

Introduction: Resuscitation using blood products is critical during the acute postinjury period. However, the optimal target haemoglobin (Hb) levels have not been adequately investigated. With the restrictive transfusion strategy for critically injured patients (RESTRIC) trial, we aim to compare the restrictive and liberal red blood cell (RBC) transfusion strategies.

Methods And Analysis: This is a cluster-randomised, crossover, non-inferiority trial of patients with severe trauma at 22 hospitals that have been randomised in a 1:1 ratio based on the use of a restrictive or liberal transfusion strategy with target Hb levels of 70-90 or 100-120 g/L, respectively, during the first year. Subsequently, after 1-month washout period, another transfusion strategy will be applied for an additional year. RBC transfusion requirements are usually unclear on arrival at the emergency department. Therefore, patients with severe bleeding, which could lead to haemorrhagic shock, will be included in the trial based on the attending physician's judgement. Each RBC transfusion strategy will be applied until 7 days postadmission to the hospital or discharge from the intensive care unit. The outcomes measured will include the 28-day survival rate after arrival at the emergency department (primary), the cumulative amount of blood transfused, event-free days and frequency of transfusion-associated lung injury and organ failure (secondary). Demonstration of the non-inferiority of restrictive transfusion will emphasise its clinical advantages.

Ethics And Dissemination: The trial will be performed according to the Japanese and International Ethical guidelines. It has been approved by the Ethics Committee of each participating hospital and The Japanese Association for the Surgery of Trauma (JAST). Written informed consent will be obtained from all patients or their representatives. The results of the trial will be disseminated to the participating hospitals and board-certified educational institutions of JAST, submitted to peer-reviewed journals for publication, and presented at congresses.

Trial Registration Number: UMIN Clinical Trials Registry; UMIN000034405. Registered 8 October 2018.
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http://dx.doi.org/10.1136/bmjopen-2020-037238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478023PMC
September 2020

Chromobacterium haemolyticum Pneumonia Associated with Near-Drowning and River Water, Japan.

Emerg Infect Dis 2020 09;26(9):2186-2189

We report a severe case of Chromobacterium haemolyticum pneumonia associated with near-drowning and detail the investigation of the pathogen and river water. Our genomic and environmental investigation demonstrated that river water in a temperate region can be a source of C. haemolyticum causing human infections.
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http://dx.doi.org/10.3201/eid2609.190670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454080PMC
September 2020

Epidemiology of sepsis and septic shock in intensive care units between sepsis-2 and sepsis-3 populations: sepsis prognostication in intensive care unit and emergency room (SPICE-ICU).

J Intensive Care 2020 30;8:44. Epub 2020 Jun 30.

Division of Acute and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Background: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions.

Methods: This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient's characteristics and outcomes were described according to whether they met each definition or not.

Results: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition.

Conclusions: Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions.

Trial Registration: UMIN000027452.
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http://dx.doi.org/10.1186/s40560-020-00465-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324770PMC
June 2020

Significance of body temperature in elderly patients with sepsis.

Crit Care 2020 06 30;24(1):387. Epub 2020 Jun 30.

Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization, Chukyo Hospital, Nagoya, Japan.

Background: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis.

Methods: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome).

Results: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05).

Conclusions: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.
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http://dx.doi.org/10.1186/s13054-020-02976-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329464PMC
June 2020

A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood.

Cell Transplant 2020 Jan-Dec;29:963689720923574

Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.
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http://dx.doi.org/10.1177/0963689720923574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586270PMC
June 2020

Clinical characteristics of patients with severe sepsis and septic shock in relation to bacterial virulence of beta-hemolytic and .

Acute Med Surg 2020 Jan-Dec;7(1):e513. Epub 2020 May 31.

Division of Acute and Critical Care Medicine Hokkaido University Graduate School of Medicine Sapporo Japan.

Aim: Combined detailed analysis of patient characteristics and treatment as well as bacterial virulence factors, which all play a central role in the cause of infections leading to severe illness, has not been reported. We aimed to describe the patient characteristics (Charlson comorbidity index [CCI]), treatment (3-h bundle), and outcomes in relation to bacterial virulence of and beta-hemolytic (BHS).

Methods: This sepsis primary study is part of the larger Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study, a multicenter, prospective cohort study. We included patients diagnosed with and BHS sepsis and examined virulence, defining the high-virulence factor as follows: serotype 3, 31, 11A, 35F, and 17F; , ; , III; and , typing pattern . Included patients were divided into high and normal categories based on the virulence factor.

Results: Of 1,184 sepsis patients enrolled in the Japanese Association for Acute Medicine's FORECAST study, 62 were included in the current study (29 cases with sepsis and 33 with BHS). The CCI and completion of a 3-h bundle did not differ between normal and high virulence groups. Risk of 28-day mortality was significantly higher for high-virulence compared to normal-virulence when adjusted for CCI and completion of a 3-h bundle (Cox proportional hazards regression analysis, hazard ratio 3.848; 95% confidence interval, 1.108-13.370;  = 0.034).

Conclusion: The risk of 28-day mortality was significantly higher for patients with high-virulence compared to normal-virulence bacteria.
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http://dx.doi.org/10.1002/ams2.513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262430PMC
May 2020

A multicenter prospective validation study on disseminated intravascular coagulation in trauma-induced coagulopathy.

J Thromb Haemost 2020 09;18(9):2232-2244

Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Trauma-induced coagulopathy (TIC) may progress to disseminated intravascular coagulation (DIC) due to dysregulated inflammatory and coagulofibrinolytic responses to trauma.

Objectives: We explored how DIC and TIC elicit the same coagulofibrinolytic changes which lead to massive transfusion.

Methods: Severely injured trauma patients with an injury severity score ≥ 16 were prospectively included. Platelet counts, global markers of coagulation and fibrinolysis and specific markers of thrombin and plasmin generation, anticoagulation, endothelial injury, and inhibition of fibrinolysis were measured at presentation to the emergency department (0 hour) and 3 hour after arrival. The patients were subdivided into those with and without DIC and those with and without TIC using the 0-hour data. Time courses of specific markers and the frequency of massive transfusion were evaluated. The association of various variables with DIC development was also confirmed.

Results: Two hundred and seventy-six patients were eligible for the analyses. The severity of injury (odds ratio; 1.038, P = .022) and thrombin generation (odds ratio; 1.014, P = .024) were associated with the development of DIC. Both DIC and TIC patients showed increased thrombin generation, insufficient anticoagulation controls, endothelial injury and increased fibrinolysis followed by elevated plasminogen activator inhibitor-1 levels at 0 and 3 hours. The frequency of massive transfusion was higher in both DIC (33.6% vs 7.9%, P < .001) and TIC (50.0% vs 13.3%, P < .001) patients than in those without DIC or TIC, respectively.

Conclusions: Disseminated intravascular coagulation and TIC evoked the same coagulofibrinolytic responses in severely injured trauma patients immediately after trauma and needed massive transfusion.
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http://dx.doi.org/10.1111/jth.14931DOI Listing
September 2020

The SIRS criteria have better performance for predicting infection than qSOFA scores in the emergency department.

Sci Rep 2020 05 15;10(1):8095. Epub 2020 May 15.

Emergency & Critical Care Center, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan.

Systemic inflammatory response syndrome (SIRS) reportedly has a low performance for distinguishing infection from non-infection. We explored the distribution of the patients diagnosed by SIRS (SIRS patients) or a quick sequential organ failure assessment (qSOFA) (qSOFA patients) and confirmed the performance of the both for predicting ultimate infection after hospital admission. We retrospectively analyzed the data from a multicenter prospective study. When emergency physicians suspected infection, SIRS or the qSOFA were applied. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the SIRS and qSOFA for predicting established infection. A total of 1,045 patients were eligible for this study. The SIRS patients accounted for 91.6% of qSOFA patients and they showed a higher rate of final infection than that of non-SIRS patients irrespective of the qSOFA diagnosis. The AUCs for predicting infection with SIRS and a qSOFA were 0.647 and 0.582, respectively. The SIRS significantly predicted an ultimate infection (AUC, 0.675; p = 0.018) in patients who met the SIRS and qSOFA simultaneously. In conclusion, the SIRS patients included almost all qSOFA patients. SIRS showed a better performance for predicting infection for qSOFA in those who met both definitions.
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http://dx.doi.org/10.1038/s41598-020-64314-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228957PMC
May 2020

The significance of disseminated intravascular coagulation on multiple organ dysfunction during the early stage of acute respiratory distress syndrome.

Thromb Res 2020 07 18;191:15-21. Epub 2020 Apr 18.

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Japan.

Background: Multiple organ dysfunction syndrome (MODS) is a predominant cause of death in acute respiratory distress syndrome (ARDS). Disseminated intravascular coagulation (DIC) is recognized as a syndrome that frequently develops MODS. To test the hypothesis that DIC scores are useful for predicting MODS development and that DIC is associated with MODS, we retrospectively analyzed the data of a prospective, multicenter study on ARDS.

Methods: Patients who met the Berlin definition of ARDS were included. DIC scores as well as the disease severity and the development of MODS on the day of the diagnosis of ARDS (day 0) and day 3 were evaluated. The primary and secondary outcomes were the development of MODS and the hospital mortality.

Results: In the 129 eligible patients, the prevalence of DIC was 45.7% (59/129). DIC patients were more seriously ill and exhibited a higher prevalence of MODS on days 0 and 3 than non-DIC patients. The DIC scores on day 0 detected the development of MODS with good area under the receiver operating characteristic curve (0.714, p<.001). DIC on day 0 was significantly associated with MODS on days 0 and 3 (odds ratio 1.53 and 1.34, respectively). Patients with persistent DIC from days 0 to 3 had higher rates of both MODS on day 3 (p=.035) and hospital mortality (p=.031) than the other patients.

Conclusions: DIC scores were able to predict MODS, and DIC was associated with MODS during the early stage of ARDS. Persistent DIC may also have role in this association.
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http://dx.doi.org/10.1016/j.thromres.2020.03.023DOI Listing
July 2020

Identifying Septic Shock Populations Benefitting From Polymyxin B Hemoperfusion: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model.

Shock 2020 11;54(5):667-674

Department of Emergency Medicine, Teikyo University School of Medicine, Tokyo, Japan.

Introduction: Polymyxin B hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that removes circulating endotoxin. However, PMX-HP has seldom achieved expectations in randomized trials targeting nonspecific overall sepsis patients. If used in an optimal population, PMX-HP may be beneficial. This study aimed to identify the optimal population for PMX-HP in patients with septic shock.

Methods: We used a prospective nationwide cohort targeting consecutive adult patients with severe sepsis (Sepsis-2) in 59 intensive care units in Japan. Associations between PMX-HP therapy and in-hospital mortality were assessed using multivariable Cox proportional hazard regression models. To identify best targets for PMX-HP, we developed a non-linear restricted cubic spline model including two-way interaction term (treatment × Acute Physiology and Chronic Health Evaluation [APACHE] II score/Sequential Organ Failure Assessment [SOFA] score) and three-way interaction term (treatment × age × each score).

Results: The final study cohort comprised 741 sepsis patients (92 received PMX-HP, 625 did not). Cox proportional hazards regression model adjusted for the covariates suggested no association between PMX-HP therapy and improved mortality overall. Effect modification of PMX-HP by APACHE II score was statistically significant (P for interaction = 0.189) but non-significant for SOFA score (P for interaction = 0.413). Three-way interaction analysis revealed suppressed risk hazard in the PMX-HP group versus control group only in septic shock patients with high age and in the most severe subset of both scores, whereas increased risk hazard was observed in those with high age but in the lower severity subset of both scores.

Conclusions: Our results suggested that although PMX-HP did not reduce in-hospital mortality among overall septic shock patients, it may benefit a limited population with high age and higher disease severity.
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http://dx.doi.org/10.1097/SHK.0000000000001533DOI Listing
November 2020