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OBJECTIVE:. This study aimed to elucidate the association between IV contrast media CT and acute kidney injury (AKI) and in-hospital mortality among patients requiring emergency admission. DESIGN:. In this retrospective observational study, we examined AKI within 48 hours after CT, renal replacement therapy (RRT) dependence at discharge, and in-hospital mortality in patients undergoing contrast-enhanced CT or nonenhanced CT. We performed 1:1 propensity score matching to adjust for confounders in the association between IV contrast media use and outcomes. Subgroup analyses were performed according to age, sex, diagnosis at admission, ICU admission, and preexisting chronic kidney disease (CKD). SETTING AND PATIENTS:. This study used the Medical Data Vision database between 2008 and 2019. This database is Japan’s largest commercially available hospital-based claims database, covering about 45% of acute-care hospitals in Japan, and it also records laboratory results. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The study included 144,149 patients with (49,057) and without (95,092) contrast media exposure, from which 43,367 propensity score-matched pairs were generated. Between the propensity score-matched groups of overall patients, exposure to contrast media showed no significant risk of AKI (4.6% vs. 5.1%; odds ratio [OR], 0.899; 95% CI, 0.845–0.958) or significant risk of RRT dependence (0.6% vs. 0.4%; OR, 1.297; 95% CI, 1.070–1.574) and significant benefit for in-hospital mortality (5.4% vs. 6.5%; OR, 0.821; 95% CI, 0.775–0.869). In subgroup analyses regarding preexisting CKD, exposure to contrast media was a significant risk for AKI in patients with CKD but not in those without CKD. CONCLUSIONS:. In this large-scale observational study, IV contrast media was not associated with an increased risk of AKI but concurrently showed beneficial effects on in-hospital mortality among patients requiring emergency admission.

Background: Recent studies suggested an expected survival benefit associated with anticoagulant therapies for sepsis in patients with disseminated intravascular coagulation (DIC). However, anticoagulant therapies for overt DIC are no longer assumed to regulate pathologic progression as overt DIC is a late-phase coagulation disorder. Therefore, methods for early prediction of sepsis-induced DIC before its progression to an overt stage are strongly required. Objectives: We aimed to develop a prediction model for overt DIC using machine learning. Methods: This retrospective, observational study included adult septic patients without overt DIC. The objective variable was binary classification of whether patients developed overt DIC based on International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. Explanatory variables were the baseline and time series data within 7 days from sepsis diagnosis. Light Gradient Boosted Machine method was used to construct the prediction model. For controls, we assessed sensitivity and specificity of Japanese Association for Acute Medicine DIC criteria and ISTH sepsis-induced coagulopathy criteria for subsequent onset of overt DIC. Results: Among 912 patients with sepsis, 139 patients developed overt DIC within 7 days from diagnosis of sepsis. Sensitivity, specificity, and area under the receiver operating characteristic curve for predicting onset of overt DIC within 7 days were 84.4%, 87.5%, and 0.867 in the test cohort and 95.0%, 75.9%, and 0.851 in the validation cohort, respectively. Sensitivity and specificity by the diagnostic thresholds were 54.7% and 74.9% for Japanese Association for Acute Medicine DIC criteria and 63.3% and 71.9% for ISTH sepsis-induced coagulopathy criteria, respectively. Conclusion: Compared with conventional DIC scoring systems, a machine learning model might exhibit higher prediction accuracy.

Abstract Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the “KAIZEN checklist”, which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models’ AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally.

Background: The effect of hospital spending on the mortality rate of patients with sepsis has not yet been fully elucidated. We hypothesized that hospitals that consume more medical resources would have lower mortality rates among patients with sepsis. Methods: This retrospective study used administrative data from 2010 to 2017. The enrolled hospitals were divided into quartiles based on average daily medical cost per sepsis case. The primary and secondary outcomes were the average in-hospital mortality rate of patients with sepsis and the effective cost per survivor among the enrolled hospitals, respectively. A multiple regression model was used to determine the significance of the differences among hospital categories to adjust for baseline imbalances. Results: Among 997 hospitals enrolled in this study, the crude in-hospital mortality rates were 15.7% and 13.2% in the lowest and highest quartiles of hospital spending, respectively. After adjusting for confounding factors, the highest hospital spending group demonstrated a significantly lower in-hospital mortality rate than the lowest hospital spending group (coefficient = −0.025, 95% confidence interval [CI] −0.034 to −0.015; p

Abstract 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 ( $$-$$ - 3.4% [95% CI $$-$$ - 3.7 to $$-$$ - 3.1]). In-hospital mortality with a multivariable regression analysis ( $$-$$ - 5.0% [95% CI $$-$$ - 5.2 to $$-$$ - 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 $$-$$ - 2.7% [95% CI $$-$$ - 3.3 to $$-$$ - 2.2], $$-$$ - 5.8% [95% CI $$-$$ - 6.4 to $$-$$ - 5.2], and $$-$$ - 1.3% [95% CI $$-$$ - 1.7 to $$-$$ - 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.

Abstract Background Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Abstract 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

Vapor cooling shield is a key technology for long-term cryogenic propellant storage in space. Cooling channels with a triply periodic minimal surface embedded inside are expected to improve its cooling performance. Herein, a cooling channel with a triangle cross-section embedded gyroid structure, a type of the triply periodic minimal surface structure, was additively manufactured. The pressure drop and heat transfer performances of the channel were experimentally measured using liquid nitrogen vapor. Furthermore, in addition to the gyroid-embedded channel, three channels with different cross-sections were fabricated for comparison: circular, triangle, and triangle with a step/groove on the bottom. The gyroid-embedded channel exhibited unique characteristics, with a thermal conductance that was approximately 40% higher than that of the channel with a simple triangle cross-section, but an excessive pressure drop of approximately 50 times higher than that of the other cross-sections. This denotes that strong vortex and turbulence and the flow separation cause excess pressure drop in the gyroidembedded channel. The pressure drop characteristic of the gyroid-embedded channel against the Reynolds number completely differed from that of the other channels, and the pressure drop of the gyroid-embedded channel can be estimated assuming analogy with particle packed beds.

Abstract 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.

Abstract Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human‐soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis‐induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta‐analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis‐induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

Aim The nationwide impact of the coronavirus disease (COVID‐19) pandemic on major trauma in Japan is unknown. The nationwide registry‐based data of the Japanese Trauma Data Bank were analyzed to elucidate the impact of COVID‐19 on the epidemiology, treatment, and outcomes of major trauma patients. Methods Among patients transported directly from the injury site by ambulance with an Injury Severity Score of ≥16, we compared patients managed from April to December in 2019 to those managed from April to December in 2020. Results In total, 9792 patients were included in this study (2019, n = 5194; 2020, n = 4598). There were no significant differences in age or sex, but there were significant differences between 2019 and 2020 in the rates of “self‐injury (suicide)”, “motor vehicle accident”, “fall from height”, “fall down”, and “fall to the ground”, which are factors associated with patient age. Injury severity in 2019 and 2020 did not differ to a statistically significant extent, but the rate of major spinal injury increased. The time of prehospital care significantly increased in 2020 compared to 2019. There was no noticeable change in hospital treatment or in‐hospital mortality between 2019 and 2020. Conclusion This study suggests that the COVID‐19 pandemic might have altered the injuries of major trauma; however, medical services for major trauma were well supplied in Japan in 2020.

Abstract Aim This study aimed to investigate the association of early vasopressor initiation with improved septic shock outcomes. Methods This multicenter observational study was conducted in 17 intensive care units in Japan and included adult patients with sepsis admitted to the intensive care unit from July 2019 to August 2020 and treated with vasopressor therapy. Patients were divided into the early vasopressor group (≤1 h from sepsis recognition) and the delayed vasopressor group (>1 h). The impact of early vasopressor administration on risk‐adjusted in‐hospital mortality was estimated using logistic regression analyses adjusted by an inverse probability of treatment weighting analysis with propensity scoring. Results Among the 97 patients, 67 received vasopressor therapy within 1 h from sepsis recognition and 30 received vasopressor after 1 h. In‐hospital mortality was 32.8% in the early vasopressor group and 26.7% in the delayed vasopressor group (p = 0.543). The adjusted odds ratio for in‐hospital mortality was 0.76 (95% confidence interval 0.17–3.29) when comparing patients in the early vasopressor with those in the delayed vasopressor group. The fit curve from the mixed‐effects model showed a relatively lower trend toward an infusion volume over time in the early vasopressor group than in the delayed vasopressor group. Conclusion Our study did not reach a definitive conclusion for early vasopressor administration. However, early vasopressor administration may help avoid volume overload in the long course of sepsis care.

ABSTRACT: Introduction: The rapid increase of extended-spectrum beta-lactamase (ESBL)-producing pathogens makes it difficult to choose appropriate antimicrobials in patients with Gram-negative bacterial infection. The Cica-beta reagent (Kanto Chemical, Tokyo, Japan) is a chromogenic test that detects ESBLs from bacterial colonies. This study aimed to reveal whether Cica-beta reagent could detect ESBLs directly from urine samples to facilitate rapid diagnosis of antibiotic susceptibility. Methods: A prospective study was conducted from July 2019 to November 2019. Patients in whom urine culture tests were performed were eligible. Each urine sample was centrifuged, and the pellet was mixed with Cica-beta reagent. The test was considered positive when the enzymatic reaction turned from yellow to red or orange. Results: In total, 350 urine samples were analysed. Urinary tract infection (UTI) was diagnosed in 214 patients. ESBL-producing Enterobacterales were isolated from 79 samples. The Cica-beta test showed sensitivity of 79.8% and specificity of 99.3% in patients with Gram-negative bacteriuria. Sensitivity and specificity improved to 90.2% and 100%, respectively, in patients with UTI. Conclusion: The Cica-beta test could be an efficient test for the detection of ESBL-producing pathogens in urine. By providing immediate information about ESBLs, it might be a useful point-of-care test to guide appropriate antimicrobial use in patients with UTI.

Abstract Background Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated. Methods This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the international statistical classification of diseases and related health problems, 10th revision, and records of organ support. The primary outcomes were the annual incidence of sepsis and death in sepsis per 1000 inpatients. The secondary outcomes were in-hospital mortality rate and length of hospital stay in patients with sepsis. Results The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis across inpatients significantly increased (slope = + 0.30%/year, P

Abstract 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.

Objectives: One of the most significant features of poor prognosis in COVID-19 is pulmonary fibrosis. Nintedanib is a new antifibrotic agent that interferes with processes of pulmonary fibrosis. This study aimed to investigate the efficacy and safety of nintedanib in COVID-19. Methods: This was an interventional study in which adult patients with COVID-19 requiring mechanical ventilation were consecutively enrolled. The primary endpoint was 28-day mortality after the initiation of mechanical ventilation. The secondary endpoints were length of mechanical ventilation, volume of lung injury, and the incidence of gastrointestinal adverse events and acute liver failure. Results: Thirty patients with COVID-19 underwent nintedanib therapy. We included 30 patients not receiving nintedanib as the historical control group. There were no significant differences in 28-day mortality between the groups (23.3% vs 20%, P = 0.834). Lengths of mechanical ventilation were significantly shorter in the nintedanib group (P = 0.046). Computed tomography volumetry showed that the percentages of high-attenuation areas were significantly lower in the nintedanib group at liberation from mechanical ventilation (38.7% vs 25.7%, P = 0.027). There were no significant differences in the adverse events. Conclusions: The administration of nintedanib may offer potential benefits for minimizing lung injury in COVID-19.

Abstract 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

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.

Abstract 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

Abstract Background There is a paucity of information for predicting patient outcomes other than the American Association for the Surgery of Trauma (AAST) renal injury scale. The aim of this study was to evaluate the association between the patient characteristics and outcomes of patients with blunt renal trauma using a nationwide database in Japan. Methods We performed a retrospective analysis of the Japan Trauma Data Bank (JTDB) from 2004 to 2018. We identified patients with blunt renal trauma by AIS codes converted to AAST grades. We evaluated trends in patient characteristics and management and assessed factors associated with mortality and nephrectomy using a multivariable logistic regression analysis. Results We identified 3550 patients with blunt renal trauma. Their median age was 43 years and 74.2% were male. Nephrectomy was performed in 3.8%, and the overall mortality rate was 9.5%. We found increasing trends in age and emergency abdominal angiography and decreasing trends in nephrectomy and mortality over the 15-year period. The following factors were associated with mortality: age ≥ 65 years (adjusted OR 3.36); pedestrian accident (adjusted OR 1.94); fall from height (adjusted OR 1.91); shock on arrival (adjusted OR 4.02); concomitant injuries to the head/neck (adjusted OR 3.14), pelvis/lower-extremity (adjusted OR 1.59), liver (adjusted OR 1.68), spleen (adjusted OR 1.45), and gastrointestinal tract (adjusted OR 1.90); AAST grades III–V (adjusted ORs 1.42, 2.16, and 5.55); and emergency abdominal angiography (adjusted OR 0.70). The following factors were associated with nephrectomy: shock on arrival (adjusted OR 1.98), concomitant injuries to the thorax (adjusted OR 0.46) and spleen (adjusted OR 2.07), AAST grades III, IV, and V (adjusted ORs 18.40, 113.89, and 468.17), and emergency abdominal angiography (adjusted OR 0.28). Conclusions We demonstrated that the AAST grade and emergency angiography were associated with mortality and nephrectomy in blunt renal trauma in the Japanese population.

Abstract 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

Abstract 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

Abstract 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.

Aim To clarify the immune cellular changes in critically ill patients recovering from coronavirus disease 2019 (COVID‐19). Methods The immune response of peripheral blood mononuclear cells from patients with severe COVID‐19 in different stages of recovery (3, 6, and 12 months from hospitalization) was evaluated by single‐cell mass cytometry. Immunological changes in patients were compared with those in age‐matched healthy donors. Results Three patients with severe COVID‐19 were compared with four healthy donors. In the patients, there was an increase in the cell density of CD4‐ and CD8‐positive T lymphocytes, and B cells, over the course of the recovery period. CD4‐ and CD8‐positive T lymphocytes expressing T‐bet and granzyme B (Gzm B) in patients were abundant during all recovery periods. The level of regulatory T cells remained high throughout the year. The levels of natural killer (NK) cells in patients were higher than in those in the healthy donors, and the frequency of CD16+ NK cells expressing Gzm B increased throughout the year. Conclusion Patients recovering from severe COVID‐19 showed persistence of cytotoxic lymphocytes, NK cells, and regulatory T cells throughout the posthospitalization year of recovery.

Aim To assess relationships between abdominal angiography and outcomes in adults with blunt liver injuries. Methods A retrospective observational study carried out from January 2004 to December 2018. Adult blunt‐trauma patients with AAST grade Ⅲ–Ⅴ were analyzed with in‐hospital mortality as the primary outcome using propensity‐score‐(PS) matching to seek associations with abdominal angiography findings. Results A total of 1,821 patients were included, of which 854 had available abdominal angiography data (AA+) and 967 did not (AA−). From these, 562 patients were selected from each group by propensity score matching. In‐hospital mortality was found to be lower in the AA+ than in the AA− group (15.1% [87/562] versus 25.4% [143/562]; odds ratio 0.544, 95% confidence interval 0.398–0.739). Conclusion Abdominal angiography is shown to be of benefit for adult patients with blunt liver injury in terms of their lower in‐hospital mortality.

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.

Background: Nutritional status of critically ill patients is an important factor affecting complications and mortality. This study aimed to investigate the impact of three nutritional indices, the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT), on mortality in patients with sepsis in Japan. Methods: This retrospective observational study used the Medical Data Vision database containing data from 42 acute-care hospitals in Japan. We extracted data on baseline characteristics on admission. GNRI, PNI, and CONUT scores on admission were also calculated. To evaluate the significance of these three nutritional indices on mortality, we used logistic regression to fit restricted cubic spline models and constructed Kaplan–Meier survival curves. Results: We identified 32,159 patients with sepsis according to the inclusion criteria. Of them, 1804 patients were treated in intensive care units, and 3461 patients were non-survivors. When the GNRI dropped below 100, the risk of mortality rose sharply, as did that when the PNI dropped below about 40. An increased CONUT score was associated with increased mortality in an apparent linear manner. Conclusion: In sepsis management, GNRI and PNI values may potentially be helpful in identifying patients with a high risk of death.

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.

Disseminated Intravascular Coagulation (DIC) commonly complicates sepsis and considerably worsens mortality. Recent studies suggested that anticoagulant therapies improved mortality only in specific sepsis populations, and key pathologies for selecting optimal targets needed to be identified. Anticoagulant activities were naturally altered with aging. This study aimed to evaluate age-related differences in efficacy of anticoagulant therapies in sepsis. This post hoc analysis of a nationwide multicenter cohort study was conducted in 42 intensive care units in Japan. Adult patients with septic DIC were divided into anticoagulant and control groups. Age-related changes in predicted mortality in both groups were compared using a logistic regression model including 2-way interaction terms. Patients were also stratified into 3 subsets based on age, and propensity score-adjusted Cox regression analyses were conducted to examine survival effect of anticoagulants in each subset. We included 1432 patients with septic DIC; 867 patients received anticoagulants and 565 received none. Age-related change in predicted mortality was significantly different between groups ( P for interaction = 0.013), and the gap between groups was broad in the younger population. Similarly, in Cox regression analyses, anticoagulant therapies were associated with significantly lower mortality in the subsets of age ≤ 60 and 60-79 (hazard ratios = 0.461, 0.617, P = 0.007, 0.005, respectively), whereas there was no difference in survival between the groups in the subsets of age ≥ 80. The efficacy of anticoagulant therapies for septic DIC might be associated with patient age.

Abstract Background Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. Methods This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0–60, 61–120, 121–180, 181–240, 241–360, and 361–1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with “hospital” as the grouping variable. Results Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55–189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48–164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39–180 min)] and longest in patients transferred from wards [120 min (62–226)]. Overall crude mortality was 23.4%, where patients in the 0–60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3–34.1%)], whereas those in the 61–120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5–26.6%)]. Differences in mortality were noted only between the 0–60 min and 61–120 min groups. Conclusions We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Disseminated intravascular coagulation (DIC) is a frequent complication in sepsis. Once patients develop DIC, the mortality rate increases significantly. Moreover, recent studies have suggested that coagulation disorder plays a significant role in the development of organ dysfunction in sepsis. Thus, the early detection of DIC is vital in sepsis care, and the Japanese Association for Acute Medicine established a set of original diagnostic criteria in 2006 (JAAM DIC). Since then, the usefulness of the JAAM DIC has been repeatedly reported, and these criteria have been widely adopted in emergency and critical care settings in Japan. Different criteria have also been released by the International Society on Thrombosis and Haemostasis (ISTH overt‐DIC), and the latter criteria are presently considered to be the international standard. Compared with the JAAM DIC, the ISTH overt‐DIC criteria are stricter and the timing of diagnosis is later. This discrepancy is because of conceptual differences. As many physicians think sepsis‐associated DIC is the target of anticoagulant therapies in Japan, the JAAM DIC criteria were designed to allow the early initiation of treatment. As other countries do not provide DIC‐specific treatments, early diagnosis is not necessary, and this situation has led to a significant gap. However, as overt‐DIC is a late‐phase coagulation disorder, a need for early detection has been advocated, and members of the ISTH have recently proposed the category of sepsis‐induced coagulopathy. In this review, we introduce the strengths and weaknesses of the major criteria including JAAM‐DIC, ISTH overt‐DIC, sepsis‐induced coagulopathy, and Japanese Society on Thrombosis and Haemostasis‐DIC.

Abstract Disseminated intravascular coagulation (DIC) is a common complication in sepsis. Since DIC not only promotes organ dysfunction but also is a strong prognostic factor, its diagnosis at the earliest possible timing is important. Thrombocytopenia is often present in patients with DIC but can also occur in a number of other critical conditions. Of note, many of the rare thrombocytopenic diseases require prompt diagnoses and specific treatments. To differentiate these diseases correctly, the phenotypic expressions must be considered and the different disease pathophysiologies must be understood. There are three major players in the background characteristics of thrombocytopenia: platelets, the coagulation system, and vascular endothelial cells. For example, the activation of coagulation is at the core of the pathogenesis of sepsis-associated DIC, while platelet aggregation is the essential mechanism in thrombotic thrombocytopenic purpura and endothelial damage is the hallmark of hemolytic uremic syndrome. Though each of the three players is important in all thrombocytopenic diseases, one of the three dominant players typically establishes the individual features of each disease. In this review, we introduce the pathogeneses, symptoms, diagnostic measures, and recent therapeutic advances for the major diseases that should be immediately differentiated from DIC in sepsis.

Abstract Background Accurate and early identification of infection sites might help to drive crucial decisions regarding the treatment of sepsis. We aimed to determine the clinical and etiological features of infection according to sites among patients with severe sepsis in Japan. Methods This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICU) and proceeded between January 2016 and March 2017. The study cohort comprised 1184 adults (≥ 16 years) who were admitted to an ICU with severe sepsis and septic shock diagnosed according to the sepsis-2 criteria. Sites of infection diagnosed by physicians in charge at the time of arrival comprised the lung, abdomen, urinary tract, soft tissue, bloodstream, central nervous system (CNS), and undifferentiated infections. The primary outcome was in-hospital mortality. Results The most common sites of infection were the lungs (31.0%), followed by intra-abdominal sites (26.3%), the urinary tract (18.4%), and soft tissue (10.9%). The characteristics of the patients with severe sepsis across seven major suspected infection sites were heterogeneous. Septic shock was more frequent among patients with intra-abdominal (72.2%) and urinary tract (70.2%) infections than other sites. The in-hospital mortality rate due to severe sepsis and septic shock of a pooled sample was 23.4% (range, 11.9% [urinary tract infection] to 47.6% [CNS infection]). After adjusting for clinical background, sepsis severity, and stratification according to the presence or absence of shock, variations in hospital mortality across seven major sites of infection remained essentially unchanged from those for crude in-hospital mortality; adjusted in-hospital mortality rates ranged from 7.7% (95%CI, − 0.3 to 15.8) for urinary tract infection without shock to 58.3% (95%CI, 21.0–95.7) for CNS infection with shock in a generalized estimating equation model. Intra-abdominal and urinary tract infections were statistically associated with less in-hospital mortality than pneumonia. Infections of the CNS were statistically associated with higher in-hospital mortality rates than pneumonia in a logistic regression model, but not in the generalized estimating equation model. Conclusions In-hospital mortality and clinical features of patients with severe sepsis and septic shock were heterogeneous according to sites of infection.

Abstract Background Early and accurate diagnosis of sepsis is challenging. Although procalcitonin and presepsin have been identified as potential biomarkers to differentiate between sepsis and other non-infectious causes of systemic inflammation, the diagnostic accuracy of these biomarkers remains controversial. Herein, we performed a comprehensive meta-analysis to assess the overall diagnostic value of procalcitonin and presepsin for the diagnosis of sepsis. Methods We searched three electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for relevant studies. Two authors independently screened articles on the basis of inclusion and exclusion criteria. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. The quality of evidence for diagnostic accuracy in absolute effects, i.e., the number of true or false positives and true or false negatives, gave a particular pre-test probability. Results We included 19 studies (19 observational studies and no randomized controlled trials) that had enrolled 3012 patients. Analyses of summary receiver operating characteristic curves revealed areas under the receiver operating characteristic curves of 0.84 for procalcitonin and 0.87 for presepsin. The pooled sensitivities and specificities were 0.80 (95% confidence interval 0.75 to 0.84) and 0.75 (95% confidence interval 0.67 to 0.81) for procalcitonin. For presepsin, these values were 0.84 (95% confidence interval 0.80 to 0.88) and 0.73 (95% confidence interval 0.61 to 0.82), respectively. There were no statistically significant differences in both pooled sensitivities (p = 0.48) and specificities (p = 0.57) between procalcitonin and presepsin. Conclusion Our meta-analysis provided evidence that the diagnostic accuracy of procalcitonin and presepsin in detecting infection was similar and that both are useful for early diagnosis of sepsis and subsequent reduction of mortality in critically ill adult patients. Systematic review registration The study was registered in PROSPERO under the registration number CRD42016035784.

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.

Aim Self‐inflicted injury, as one reason to visit the emergency department, is an important issue in emergency medicine around the world. However, the impact of changes in social systems, such as medical reimbursement revision, on ambulance transport for self‐inflicted injury remains unclear. The aim of this study was to assess the impact of medical reimbursement revision on the emergency transport of self‐inflicted injury patients using nationwide ambulance records. Methods This was a retrospective observational study from April 2012 to March 2016. We analyzed nationwide ambulance records in Japan, and included self‐inflicted injury, drug poisoning, and drug overdose patients transported to hospitals by ambulance. The primary outcome of this study was age‐adjusted number of self‐inflicted injury patients transported by ambulance in each month per 1 million standard populations. To assess the impact of the medical reimbursement revision in 2014, we calculated the R2, regression coefficients and 95% confidence interval (CI) using interrupted time series analysis. Results This study included 148,873 patients. The R2 for the interrupted time series model was 0.821. The regression coefficient for the time trend before the medical reimbursement revision was 0.167 (95% CI, 0.090 to 0.244; p

Aim The quick Sequential Organ Failure Assessment (qSOFA) was proposed for use as a simple screening tool for sepsis. In this study, we evaluated the relationship between the prehospital use of qSOFA and prognosis in patients with sepsis or suspected sepsis using the population‐based Osaka Emergency Information Research Intelligent Operation Network (ORION) registry, which compiles prehospital ambulance data and in‐hospital information. Methods The study enrolled 437,974 patients in the ORION registry from January 1 to December 31, 2016. We selected hospitalized patients with sepsis or suspected sepsis using the appropriate codes from the International Classification of Diseases revision 10. We excluded patients with: (i) missing data (outcome, Japan Coma Scale, respiratory rate, and blood pressure); (ii) respiratory rate ≥60/min; and (iii) blood pressure ≥250 mmHg. These measures were evaluated by ambulance personnel when they first contacted the patient in the prehospital setting. The primary end‐point was discharge to death. Results In total, 12,646 patients (median age, 78 [interquartile range, 65–85] years; male, n = 6,760 [53.5%]) were eligible for our analysis. In a multivariable logistic regression analysis adjusted for confounding factors, the proportion of patients discharged to death was significantly higher for those evaluated as qSOFA positive (≥2 points) than qSOFA negative (≤1 point) (265/2,250 [11.78%] vs. 415/10,396 [3.99%]; adjusted odds ratio 2.91; 95% confidence interval, 2.47–3.43; P

BACKGROUND:Dysglycemia is frequently observed in patients with sepsis. However, the relationship between dysglycemia and outcome is inconsistent. We evaluate the clinical characteristics, glycemic abnormalities, and the relationship between the initial glucose level and mortality in patients with sepsis. METHODS:This is a retrospective sub-analysis of a multicenter, prospective cohort study. Adult patients with severe sepsis (Sepsis-2) were divided into groups based on blood glucose categories (

Abstract Background This study was performed to gain insights into novel therapeutic approaches for acute systemic inflammation in heatstroke. Bone marrow-derived mononuclear cells (BMMNCs) secrete anti-inflammatory proteins and have protective effects against acute inflammation. Recent evidence suggested that transplantation of BMMNCs can reduce the acute tissue injury caused by regional myocardial reperfusion and the lung dysfunction induced by lipopolysaccharides. We evaluated whether BMMNCs attenuate systemic inflammatory response induced by severe heatstroke. Material and methods Anesthetized 12-week-old male Wistar rats were subjected to heat stress (41.8 °C for 30 min) with/without transplantation of BMMNCs. Bone marrow cells were harvested from the femur and tibia of other Wistar rats. BMMNCs were separated by density centrifugation, dissolved in phosphate-buffered saline (PBS), and injected intravenously immediately after heat stress (HS-BMMNCs group). The control group was administered an equal volume of PBS, and the sham group underwent the same procedure without heat stress. Results Seven-day survival improved significantly in the HS-BMMNCs group versus control group (83.3% vs 41.7%). Transplantation of BMMNCs significantly suppressed serum levels of pro-inflammatory mediators, such as tumor necrosis factor-alpha, interleukin-6 and histone H3 at 3, 6, and 12 h after heat stress. Besides, the elevation of serum syndecan-1, a main component of the vascular endothelial glycocalyx layer, in the BMMNCs group was significantly suppressed compared to that in the control group at 6 and 12 h after heat stress. Histological analysis revealed that edema of the alveolar septum and vascular endothelial injury in the lung were evident in the control group 6 h after heat stress, whereas the morphological alteration was ameliorated in the HS-BMMNCs group. Also, histological analysis using BMMNCs derived from green fluorescent protein transgenic rats showed that the transplanted BMMNCs migrated into lung, kidney, and spleen at 24 h after heat stress but did not engraft to host tissues. Conclusion Transplantation of BMMNCs attenuated acute systemic inflammation and vascular endothelial injury, reduced organ dysfunction, and improved survival in a rat heatstroke model. These findings provide a possible therapeutic strategy against critical heatstroke.

Abstract Background Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. Methods This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. Results In total, 1184 patients (median age 73 years, interquartile range (IQR) 64–81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6–11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21–26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12–46) days. Approximately 37% of the patients were discharged home after recovery. Conclusion Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. Trial registration UMIN-CTR, UMIN000019742. Registered on 16 November 2015.

Optimizing diagnostic criteria to detect specific patients likely to benefit from anticoagulants is warranted. A cutoff of 5 points for the International Society on Thrombosis and Haemostasis overt disseminated intravascular coagulation (DIC) scoring system was determined in the original article, but its validity was not evaluated. This study aimed to explore the optimal cutoff points of DIC scoring systems and evaluate the effectiveness of early intervention with anticoagulants. We used a nationwide retrospective registry of consecutive adult patients with sepsis in Japan to develop simulated survival data, assuming anticoagulants were conducted strictly according to each cutoff point. Estimated treatment effects of anticoagulants for in-hospital mortality and risk of bleeding were calculated by logistic regression analysis with inverse probability of treatment weighting using propensity scoring. Of 2663 patients with sepsis, 1247 patients received anticoagulants and 1416 none. The simulation model showed no increase in estimated mortality between 0 and 3 cutoff points, whereas at ≥4 cutoff points, mortality increased linearly. The estimated bleeding tended to decrease in accordance with the increase in cutoff points. The optimal cutoff for determining anticoagulant therapy may be 3 points to minimize nonsurvival with acceptable bleeding complications. The findings of the present study suggested a beneficial association of early intervention with anticoagulant therapy and mortality in the patients with sepsis-induced DIC. Present cutoff points of DIC scoring systems may be suboptimal for determining the start of anticoagulant therapy and delay its initiation.