Machine-learning model for predicting oliguria in critically ill patients.

This retrospective cohort study aimed to develop and evaluate a machine-learning algorithm for predicting oliguria, a sign of acute kidney injury (AKI). To this end, electronic health record data from consecutive patients admitted to the intensive care unit (ICU) between 2010 and 2019 were used and oliguria was defined as a urine output of less than 0.5 mL/kg/h. Furthermore, a light-gradient boosting machine was used for model development. Among the 9,241 patients who participated in the study, the proportions of patients with urine output < 0.5 mL/kg/h for 6 h and with AKI during the ICU stay were 27.4% and 30.2%, respectively. The area under the curve (AUC) values provided by the prediction algorithm for the onset of oliguria at 6 h and 72 h using 28 clinically relevant variables were 0.964 (a 95% confidence interval (CI) of 0.963-0.965) and 0.916 (a 95% CI of 0.914-0.918), respectively. The Shapley additive explanation analysis for predicting oliguria at 6 h identified urine values, severity scores, serum creatinine, oxygen partial pressure, fibrinogen/fibrin degradation products, interleukin-6, and peripheral temperature as important variables. Thus, this study demonstrates that a machine-learning algorithm can accurately predict oliguria onset in ICU patients, suggesting the importance of oliguria in the early diagnosis and optimal management of AKI.

Epidemiology of sepsis in a Japanese administrative database.

Sepsis is the leading cause of death worldwide. Considering regional variations in the characteristics of patients with sepsis, a better understanding of the epidemiology in Japan will lead to further development of strategies for the prevention and treatment of sepsis. To investigate the epidemiology of sepsis, we conducted a systematic literature review of PubMed between 2003 and January 2023. Among the 78 studies using a Japanese administrative database, we included 20 that defined patients with sepsis as those with an infection and organ dysfunction. The mortality rate in patients with sepsis has decreased since 2010, reaching 18% in 2017. However, the proportion of inpatients with sepsis is increasing. A study comparing short-course (≤7 days) and long-course (≥8 days) antibiotic administration showed lower 28-day mortality in the short-course group. Six studies on the treatment of patients with septic shock reported that low-dose corticosteroids or polymyxin B hemoperfusion reduced mortality, whereas intravenous immunoglobulins had no such effect. Four studies investigating the effects of treatment in patients with sepsis-associated disseminated intravascular coagulation demonstrated that antithrombin may reduce mortality, whereas recombinant human soluble thrombomodulin does not. A descriptive study of medical costs for patients with sepsis showed that the effective cost per survivor decreased over an 8-year period from 2010 to 2017. Sepsis has a significant impact on public health, and is attracting attention as an ongoing issue. Further research to determine more appropriate prevention methods and treatment for sepsis should be a matter of priority.

Mortality analysis among sepsis patients in and out of intensive care units using the Japanese nationwide medical claims database: a study by the Japan Sepsis Alliance study group.

BACKGROUND: A substantial number of sepsis patients require specialized care, including multidisciplinary care, close monitoring, and artificial organ support in the intensive care unit (ICU). However, the efficacy of ICU management on clinical outcomes remains insufficiently researched. Therefore, we tested the hypothesis that ICU admission would increase the survival rate among sepsis patients. METHODS: We conducted a retrospective study using the nationwide medical claims database of sepsis patients in Japan from 2010 to 2017 with propensity score matching to adjust for baseline imbalances. Patients aged over 20 years, with a combined diagnosis of presumed serious infection and organ failure, were included in this study. The primary outcome studied was the in-hospital mortality among non-ICU and ICU patients. In addition to propensity score matching, we performed a multivariable logistic regression analysis for the primary outcome. As the treatment policy was not extracted from the database, we performed sensitivity analyses to determine mortality differences in adults (20 ≤ age ≤ 64), independent patients, patients without malignant tumors, based on the assumption that treatment intensity is likely to increase in those population. RESULTS: Among 1,167,901 sepsis patients (974,289 in non-ICU and 193,612 in ICU settings), the unadjusted in-hospital mortality was 22.5% among non-ICU patients and 26.2% among ICU patients (3.7% [95% CI 3.5-3.9]). After propensity score matching, the in-hospital mortality was 29.2% among non-ICU patients and 25.8% among ICU patients ([Formula: see text] 3.4% [95% CI [Formula: see text] 3.7 to [Formula: see text] 3.1]). In-hospital mortality with a multivariable regression analysis ([Formula: see text] 5.0% [95% CI [Formula: see text] 5.2 to [Formula: see text] 4.8]) was comparable with the results of the propensity score matching analysis. In the sensitivity analyses, the mortality differences between non-ICU and ICU in adults, independent patients, and patients without malignant tumors were [Formula: see text] 2.7% [95% CI [Formula: see text] 3.3 to [Formula: see text] 2.2], [Formula: see text] 5.8% [95% CI [Formula: see text] 6.4 to [Formula: see text] 5.2], and [Formula: see text] 1.3% [95% CI [Formula: see text] 1.7 to [Formula: see text] 1.0], respectively. CONCLUSIONS: Herein, using the nationwide medical claims database, we demonstrated that ICU admission was potentially associated with decreasing in-hospital mortality among sepsis patients. Further investigations are warranted to validate these results and elucidate the mechanisms favoring ICU management on clinical outcomes.

Temporal trends of medical cost and cost-effectiveness in sepsis patients: a Japanese nationwide medical claims database.

BACKGROUND: Sepsis is the leading cause of death worldwide. Although the mortality of sepsis patients has been decreasing over the past decade, the trend of medical costs and cost-effectiveness for sepsis treatment remains insufficiently determined. METHODS: We conducted a retrospective study using the nationwide medical claims database of sepsis patients in Japan between 2010 and 2017. After selecting sepsis patients with a combined diagnosis of presumed serious infection and organ failure, patients over the age of 20 were included in this study. We investigated the annual trend of medical costs during the study period. The primary outcome was the annual trend of the effective cost per survivor, calculated from the gross medical cost and number of survivors per year. Subsequently, we performed subgroup and multiple regression analyses to evaluate the association between the annual trend and medical costs. RESULTS: Among 50,490,128 adult patients with claims, a total of 1,276,678 patients with sepsis were selected from the database. Yearly gross medical costs to treat sepsis gradually increased over the decade from $3.04 billion in 2010 to $4.38 billion in 2017, whereas the total medical cost per hospitalization declined (rate = - $1075/year, p < 0.0001). While the survival rate of sepsis patients improved during the study period, the effective cost per survivor significantly decreased (rate = - $1806/year [95% CI - $2432 to - $1179], p = 0.001). In the subgroup analysis, the trend of decreasing medical cost per hospitalization remained consistent among the subpopulation of age, sex, and site of infection. After adjusting for age, sex (male), number of chronic diseases, site of infection, intensive care unit (ICU) admission, surgery, and length of hospital stay, the admission year was significantly associated with reduced medical costs. CONCLUSIONS: We demonstrated an improvement in annual cost-effectiveness in patients with sepsis between 2010 and 2017. The annual trend of reduced costs was consistent after adjustment with the confounders altering hospital expenses.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

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.

Risk prediction of biomarkers for early multiple organ dysfunction in critically ill patients.

BACKGROUND: Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA). METHODS: This was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels. RESULTS: Of 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC. CONCLUSIONS: The addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study.

AIM: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. METHODS: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. RESULTS: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. CONCLUSION: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home.

Validation of National Early Warning Score for predicting 30-day mortality after rapid response system activation in Japan.

AIM: Although rapid response systems (RRS) are used to prevent adverse events, Japan reportedly has low activation rates and high mortality rates. The National Early Warning Score (NEWS) could provide a solution, but it has not been validated in Japan. We aimed to validate NEWS for Japanese patients. METHODS: This retrospective observational study included data of 2,255 adult patients from 33 facilities registered in the In-Hospital Emergency Registry in Japan between January 2014 and March 2018. The primary evaluated outcome was mortality rate 30 days after RRS activation. Accuracy of NEWS was analyzed with the correlation coefficient and area under the receiver operating characteristic curve. Prediction weights of NEWS parameters were then analyzed using multiple logistic regression and a machine learning method, classification and regression trees. RESULTS: The correlation coefficient of NEWS for 30-day mortality rate was 0.95 (95% confidence interval [CI], 0.88-0.98) and the area under the receiver operating characteristic curve was 0.668 (95% CI, 0.642-0.693). Sensitivity and specificity values with a cut-off score of 7 were 89.8% and 45.1%, respectively. Regarding prediction values of each parameter, oxygen saturation showed the highest odds ratio of 1.36 (95% CI, 1.25-1.48), followed by altered mental status 1.23 (95% CI, 1.14-1.32), heart rate 1.21 (95% CI, 1.09-1.34), systolic blood pressure 1.12 (95% CI, 1.04-1.22), and respiratory rate 1.03 (95% CI, 1.05-1.26). Body temperature and oxygen supplementation were not significantly associated. Classification and regression trees showed oxygen saturation as the most heavily weighted parameter, followed by altered mental status and respiratory rate. CONCLUSIONS: National Early Warning Score could stratify 30-day mortality risk following RRS activation in Japanese patients.

Accuracy for Mortality Prediction With Additive Biomarkers Including Interleukin-6 in Critically Ill Patients: A Multicenter Prospective Observational Study.

OBJECTIVES: Several inflammation markers have been reported to be associated with unfavorable clinical outcomes in critically ill patients. We aimed to elucidate whether serum interleukin-6 concentration considered with Sequential Organ Failure Assessment score can better predict mortality in critically ill patients. DESIGN: A prospective observational study. SETTING: Five university hospitals in 2016-2018. PATIENTS: Critically ill adult patients who met greater than or equal to two systemic inflammatory response syndrome criteria at admission were included, and those who died or were discharged within 48 hours were excluded. INTERVENTIONS: Inflammatory biomarkers including interleukin (interleukin)-6, -8, and -10; tumor necrosis factor-α; C-reactive protein; and procalcitonin were blindly measured daily for 3 days. Area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score at day 2 according to 28-day mortality was calculated as baseline. Combination models of Sequential Organ Failure Assessment score and additional biomarkers were developed using logistic regression, and area under the receiver operating characteristic curve calculated in each model was compared with the baseline. MEASUREMENTS AND MAIN RESULTS: Among 161 patients included in the study, 18 (11.2%) did not survive at day 28. Univariate analysis for each biomarker identified that the interleukin-6 (days 1-3), interleukin-8 (days 0-3), and interleukin-10 (days 1-3) were higher in nonsurvivors than in survivors. Analyses of 28-day mortality prediction by a single biomarker showed interleukin-6, -8, and -10 at days 1-3 had a significant discrimination power, and the interleukin-6 at day 3 had the highest area under the receiver operating characteristic curve (0.766 [0.656-0.876]). The baseline area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score predicting 28-day mortality was 0.776 (0.672-0.880). The combination model using additional interleukin-6 at day 3 had higher area under the receiver operating characteristic curve than baseline (area under the receiver operating characteristic curve = 0.844, area under the receiver operating characteristic curve improvement = 0.068 [0.002-0.133]), whereas other biomarkers did not improve accuracy in predicting 28-day mortality. CONCLUSIONS: Accuracy for 28-day mortality prediction was improved by adding serum interleukin-6 concentration to Sequential Organ Failure Assessment score.

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.

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.

Blood Interleukin-6 Levels Predict Multiple Organ Dysfunction in Critically Ill Patients.

BACKGROUND: Predicting multiple organ dysfunction (MOD) in the late phase of critical illnesses is essential. Cytokines are considered biomarkers that can predict clinical outcomes; however, their predictive value for late-phase MOD is unknown. This study aimed to identify the biomarker with the highest predictive value for late-phase MOD. METHODS: This observational study prospectively evaluated data on adult patients with systemic inflammatory response syndrome, those who presented to the emergency department or were admitted to intensive care units in five tertiary hospitals (n = 174). Seven blood biomarkers levels (interleukin-6 [IL-6], IL-8, IL-10, tumor-necrosis factor-α, white blood cells, C-reactive protein, and procalcitonin) were measured at three timepoints (days 0, 1, and 2). The area under the receiver operating characteristic curve (AUC) was analyzed to evaluate predictive values for MOD (primary outcome, MOD on day 7 [late-phase]; secondary outcome, MOD on day 3 [early-phase]). RESULTS: Of the measured 7 biomarkers, blood IL-6 levels on day 2 had the highest predictive value for MOD on day 7 using single timepoint data (AUC 0.825, 95% confidence interval [CI] 0.754-0.879). Using three timepoint biomarkers, blood IL-6 levels had the highest predictive value of MOD on day 7 (AUC 0.838, 95% CI 0.768-0.890). Blood IL-6 levels using three timepoint biomarkers had also the highest predictive value for MOD on day 3 (AUC 0.836, 95% CI 0.766-0.888). CONCLUSION: Of the measured biomarkers, blood IL-6 levels had the highest predictive value for MOD on days 3 and 7. Blood IL-6 levels predict early- and late-phase MOD in critically ill patients.

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.

First report based on the online registry of a Japanese multicenter rapid response system: a descriptive study of 35 institutions in Japan.

AIM: Although the concept of a rapid response system (RRS) has been gradually accepted in Japan, detailed information on the Japanese RRS is not well known. We provide the first report of the RRS epidemiological situation based on 4 years of RRS online registry data. METHODS: This is a prospective observational study. All patients registered between January 2014 and March 2018 were eligible for this study. Data related to RRS including physiological measurements were recorded. The mortality rates after rapid response team/medical emergency team (RRT/MET) intervention and after 30 days were recorded as outcomes. RESULTS: In total, 6,784 cases were registered at 35 facilities. Cancer (23.1%) was the most common existing comorbidity. Limitation of medical treatment was identified in 12.7% of the cases. The respiratory category was most frequently activated in 41.3% of the cases. Only two institutions had received more than 15 calls per 1,000 admissions. During RRT/MET intervention, death occurred in 3.6% and transfers to intensive care units occurred in 28.2% of the cases. After 30 days, the mortality rate was significantly higher in the night than in the day shift (30.7% versus 20.4%, respectively, P < 0.01). CONCLUSIONS: We report the first epidemiological study of RRS in Japan. Japanese facilities had a very low rate of RRT/MET calls and a higher mortality rate in the night than in the day shift. Further promotion to increase the number of calls and implementation of a 24-h RRT/MET is required.

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study.

BACKGROUND: Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare. METHODS: We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016-March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score. RESULTS: After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22-33)] than in those without ARDS [21 (16-28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06-3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06-0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04-5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05-1.12) for higher compared with lower score]. CONCLUSIONS: Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

Case Report: Sustained mitochondrial damage in cardiomyocytes in patients with severe propofol infusion syndrome.

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) was administered for five days for sedation. On day 13, he had hypotension with abnormal electrocardiogram findings, acute kidney injury, hyperkalemia and severe rhabdomyolysis. Diagnosis and interventions: The patient was transferred to our intensive care unit (ICU) on suspicion of PRIS. Administration of noradrenaline and renal replacement therapy and fasciotomy for compartment syndrome of lower legs due to PRIS-rhabdomyolysis were performed. Outcomes: The patient gradually recovered and was discharged from the ICU on day 30. On day 37, he had repeated sinus bradycardia with pericardial effusion in echocardiography. Cardiac 18F-FDG PET on day 67 demonstrated heterogeneous 18F-FDG uptake in the left ventricle. Electron microscopic investigation of endomyocardial biopsy on day 75 revealed mitochondrial myelinization of the cristae, which indicated mitochondrial damage of cardiomyocytes. He was discharged without cardiac abnormality on day 192. Conclusions: Mitochondrial damage in both morphological and functional aspects was observed in the present case. Sustained mitochondrial damage may be a therapeutic target beyond the initial therapy of discontinuing propofol administration.

Trends in sepsis care in Japan: comparison of two sepsis cohort studies conducted by the Japanese Association for Acute Medicine.

Our analysis showed that improved compliance with sepsis bundles was associated with lower in-hospital mortality over a 7-year period in Japan, confirming that the SSC has been executed correctly in our country.