COAGULOPATHY PARAMETERS PREDICTIVE OF OUTCOMES IN SEPSIS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME: A SUBANALYSIS OF THE TWO PROSPECTIVE MULTICENTER COHORT STUDIES.

ABSTRACT: Background: Although coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood. Objectives: This study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS. Method: This study enrolled patients with sepsis-derived ARDS from two nationwide multicenter, prospective observational studies. We explored coagulopathy parameters that could predict outcomes in the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) cohort, and the defined coagulopathy criteria were validated in the Sepsis Prognostication in Intensive Care Unit and Emergency Room-Intensive Care Unit (SPICE-ICU) cohort. The correlation between anticoagulant use and outcomes was also evaluated. Results: A total of 181 patients with sepsis-derived ARDS in the FORECAST study and 61 patients in the SPICE-ICU study were included. In a preliminary study, we found the set of prothrombin time-international normalized ratio ≥1.4 and platelet count ≤12 × 10 4 /µL, and thrombocytopenia and elongated prothrombin time (TEP) coagulopathy as the best coagulopathy parameters and used it for further analysis; the odds ratio (OR) of TEP coagulopathy for in-hospital mortality adjusted for confounding was 3.84 (95% confidence interval [CI], 1.66-8.87; P = 0.005). In the validation cohort, the adjusted OR for in-hospital mortality was 32.99 (95% CI, 2.60-418.72; P = 0.002). Although patients without TEP coagulopathy showed significant improvements in oxygenation over the first 4 days, patients with TEP coagulopathy showed no significant improvement (ΔPaO 2 /FiO 2 ratio, 24 ± 20 vs. 90 ± 9; P = 0.026). Furthermore, anticoagulant use was significantly correlated with mortality and oxygenation recovery in patients with TEP coagulopathy but not in patients without TEP coagulopathy. Conclusion: Thrombocytopenia and elongated prothrombin time coagulopathy is closely associated with better outcomes and responses to anticoagulant therapy in sepsis-induced ARDS, and our coagulopathy criteria may be clinically useful.

Severe Hypercalcemia due to Drowning in an Onsen (Hot Spring).

Hypercalcemia is generally caused by primary hyperparathyroidism, malignancies, and drugs. Herein, we report a case of severe hypercalcemia due to drowning in hot springs. A 55-year-old woman was found floating in a public bath at a hotel and was admitted to a nearby hospital. The patient was intubated because of hypoxia and shock, and noradrenaline was titrated. Computed tomography revealed bilateral aspiration pneumonia. Blood tests revealed hypercalcemia (serum total calcium [Ca]: 18.7 mg/dL). Hyperparathyroidism, malignancy, and drug-related factors were ruled out as the causes of hypercalcemia. In addition, the public bath in which the patient drowned contained high concentrations of Ca. We concluded that the reason for hypercalcemia was accidental ingestion of the hot spring water containing a high concentration of Ca through the gastrointestinal tract. In the case of drowning and hypercalcemia, the cause may be clarified by examining the components that were accidentally swallowed.

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score-matched analysis.

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score-matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60-70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50-60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60-70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Hour-1 bundle adherence was associated with reduction of in-hospital mortality among patients with sepsis in Japan.

BACKGROUND: The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients. METHODS: This was a multicenter, prospective, observational study conducted in 17 intensive care units in tertiary hospitals in Japan. We included all adult patients who were diagnosed as having sepsis by Sepsis-3 and admitted to intensive care units from July 2019 to August 2020. Impacts of hour-1 bundle adherence and delay of adherence on risk-adjusted in-hospital mortality were estimated by multivariable logistic regression analyses. RESULTS: The final study cohort included 178 patients with sepsis. Among them, 89 received bundle-adherent care. Completion rates of each component (measure lactate level, obtain blood cultures, administer broad-spectrum antibiotics, administer crystalloid, apply vasopressors) within 1 hour were 98.9%, 86.2%, 51.1%, 94.9%, and 69.1%, respectively. Completion rate of all components within 1 hour was 50%. In-hospital mortality was 18.0% in the patients with and 30.3% in the patients without bundle-adherent care (p = 0.054). The adjusted odds ratio of non-bundle-adherent versus bundle-adherent care for in-hospital mortality was 2.32 (95% CI 1.09-4.95) using propensity scoring. Non-adherence to obtaining blood cultures and administering broad-spectrum antibiotics within 1 hour was related to in-hospital mortality (2.65 [95% CI 1.25-5.62] and 4.81 [95% CI 1.38-16.72], respectively). The adjusted odds ratio for 1-hour delay in achieving hour-1 bundle components for in-hospital mortality was 1.28 (95% CI 1.04-1.57) by logistic regression analysis. CONCLUSION: Completion of the hour-1 bundle was associated with lower in-hospital mortality. Obtaining blood cultures and administering antibiotics within 1 hour may have been the components most contributing to decreased in-hospital mortality.

Pathophysiology of Coagulopathy Induced by Traumatic Brain Injury Is Identical to That of Disseminated Intravascular Coagulation With Hyperfibrinolysis.

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

Quick sequential organ failure assessment score combined with other sepsis-related risk factors to predict in-hospital mortality: Post-hoc analysis of prospective multicenter study data.

This study aimed to assess the value of quick sequential organ failure assessment (qSOFA) combined with other risk factors in predicting in-hospital mortality in patients presenting to the emergency department with suspected infection. This post-hoc analysis of a prospective multicenter study dataset included 34 emergency departments across Japan (December 2017 to February 2018). We included adult patients (age ≥16 years) who presented to the emergency department with suspected infection. qSOFA was calculated and recorded by senior emergency physicians when they suspected an infection. Different types of sepsis-related risk factors (demographic, functional, and laboratory values) were chosen from prior studies. A logistic regression model was used to assess the predictive value of qSOFA for in-hospital mortality in models based on the following combination of predictors: 1) qSOFA-Only; 2) qSOFA+Age; 3) qSOFA+Clinical Frailty Scale (CFS); 4) qSOFA+Charlson Comorbidity Index (CCI); 5) qSOFA+lactate levels; 6) qSOFA+Age+CCI+CFS+lactate levels. We calculated the area under the receiver operating characteristic curve (AUC) and other key clinical statistics at Youden's index, where the sum of sensitivity and specificity is maximized. Following prior literature, an AUC >0.9 was deemed to indicate high accuracy; 0.7-0.9, moderate accuracy; 0.5-0.7, low accuracy; and 0.5, a chance result. Of the 951 patients included in the analysis, 151 (15.9%) died during hospitalization. The AUC for predicting in-hospital mortality was 0.627 (95% confidence interval [CI]: 0.580-0.673) for the qSOFA-Only model. Addition of other variables only marginally improved the model's AUC; the model that included all potentially relevant variables yielded an AUC of only 0.730 (95% CI: 0.687-0.774). Other key statistic values were similar among all models, with sensitivity and specificity of 0.55-0.65 and 0.60-0.75, respectively. In this post-hoc data analysis from a prospective multicenter study based in Japan, combining qSOFA with other sepsis-related risk factors only marginally improved the model's predictive value.

Association of frailty on treatment outcomes among patients with suspected infection treated at emergency departments.

BACKGROUND: The clinical frailty scale (CFS) score has been validated as a predictor of adverse outcomes in community-dwelling older people. Older people are at a higher risk of sepsis and have a higher mortality rate. However, the association of frailty on outcomes in patients with sepsis has not been completely examined. OBJECTIVE: This study evaluated the association between CFS and outcomes in patients with sepsis. DESIGN: This was a multicenter prospective cohort substudy. SETTINGS AND PARTICIPANTS: The study included 37 emergency departments from across Japan. The patients (age ≥16 years) were included in this study if they had suspected infection at an emergency department during December 2017-February 2018. OUTCOME MEASURE AND ANALYSIS: The primary outcome was 28-day mortality, stratified by the CFS score categories. The secondary outcomes were the duration of hospital stay, number of ICU-free days (ICUFDs) and number of ventilator-free days (VFDs). MAIN RESULTS: A total of 917 patients were included. The median age was 79 years. The CFS score was associated with an increased risk of 28-day mortality and with a higher likelihood of long-term hospital stay and short-term VFDs and ICUFDs. Multivariate logistic regression analysis indicated that the CFS score was a predictor of 28-day mortality [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.11-1.42]. CONCLUSIONS: This study reported that in patients with suspected sepsis in the emergency department, frailty may be associated with poor prognosis and length of hospital stay.

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

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 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.

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

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.

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

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 PaO2 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.

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

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).

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.

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.

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

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.

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

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.

Checklist for infection control in the emergency department.

The risk of encountering human-to-human infections, including emerging infectious diseases, should be adequately and appropriately addressed in the emergency department. However, guidelines based on sufficient evidence on infection control in the emergency department have not been developed anywhere in the world. Each facility examines and implements its own countermeasures. The Japanese Association for Acute Medicine has established the "Committee for Infection Control in the Emergency Department" in cooperation with the Japanese Association for Infectious Diseases, Japanese Society for Infection Prevention and Control, Japanese Society for Emergency Medicine, and Japanese Society for Clinical Microbiology. A joint working group has been established to consider appropriate measures. This group undertook a comprehensive and multifaceted review of infection control measures for emergency outpatients and related matters, and released a checklist for infection control in emergency departments. This checklist has been prepared such that even small emergency departments with few or no emergency physicians can control infection by following the checklist, without committing any major errors. The checklist includes a control system for infection control, education, screening, and vaccination, prompt response to suspected infections, and management of the risk of infection in facilities. In addition, the timing of the check and interval at which the check is carried out are specified as categories. We hope that this checklist will contribute to improving infection control in the emergency department.

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

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.

Significance of body temperature in elderly patients with sepsis.

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.

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).

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.

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

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 Streptococcus pneumoniae and beta-hemolytic Streptococcus (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 S. pneumoniae and BHS sepsis and examined virulence, defining the high-virulence factor as follows: S. pneumoniae serotype 3, 31, 11A, 35F, and 17F; Streptococcus pyogenes, emm 1; Streptococcus agalactiae, III; and Streptococcus dysgalactiae ssp. equisimilis, emm typing pattern stG 6792. 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 S. pneumoniae 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; P = 0.034). CONCLUSION: The risk of 28-day mortality was significantly higher for patients with high-virulence compared to normal-virulence bacteria.