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Abstract Background Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes. Methods This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group ( 120%). Results The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups. Conclusions Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients. Trial registration: Not applicable.

Abstract Background Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post–cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia. Methods A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019–2022 was conducted. Adult patients without cardiac arrest whose core body temperature was

Abstract Background The 5A score including five components “Age, Activities of daily living, Arrest, Acidemia and Albumin” was developed as an easy-to-use screening tool for predicting in-hospital mortality among patients with accidental hypothermia. However, the external validity of the 5A score has not yet been evaluated. We aimed to perform an external validation of the 5A score model. Method This secondary analysis of the multicenter, prospective cohort Japanese Association for Acute Medicine-Hypothermia Study (2018–2019), which was conducted at 87 and 89 institutions throughout Japan, collected data from December 2018 to February 2019 and from December 2019 to February 2020. Adult accidental hypothermia patients whose body temperature was 35 °C or less were included in this analysis. The probability of in-hospital mortality was calculated using a logistic regression model of the 5A score. The albumin was not recorded in this database; thus, it was imputed by estimation. Predictions were compared with actual observations to evaluate the calibration of the model. Furthermore, decision-curve analysis was used to evaluate the clinical usefulness. Results Of the 1363 patients registered in the database, data of 1139 accidental hypothermia patients were included for analysis. The median [interquartile range] age was 79 [68–87] years, and there were 625 men (54.9%) in the study cohort. The predicted probability and actual observation by risk groups produced the following results: low 7% (5.4–8.6), mild 19.1% (17.4–20.8), moderate 33.2% (29.9–36.5), and high 61.9% (55.9–67.9) predicted risks, and the low 12.4% (60/483), mild 17.7% (59/334), moderate 32.6% (63/193), and high 69% (89/129) observed mortality. These results indicated that the model was well calibrated. Decision-curve analysis visually indicated the clinical utility of the 5A score model. Conclusion This study indicated that the 5A score model using estimated albumin value has external validity in a completely different dataset from that used for the 5A model development. The 5A score is potentially helpful to predict the mortality risk and may be one of the valuable information for discussing the treatment strategy with patients and their family members.

Aim The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan. Methods This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020–2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild‐to‐moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups. Results Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM‐HS). However, the severe group was significantly worse than the mild‐to‐moderate group in outcomes like in‐hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke‐like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals. Conclusions It is suggested that severe cases require a more detailed classification of degree III in the JAAM‐HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes.

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.

Aim To assess heat stroke and heat exhaustion occurrence and response during the coronavirus disease 2019 pandemic in Japan. Methods This retrospective, multicenter, registry‐based study describes and compares the characteristics of patients between the months of July and September in 2019 and 2020. Factors affecting heat stroke and heat exhaustion were statistically analyzed. Cramér’s V was calculated to determine the effect size for group comparisons. We also investigated the prevalence of mask wearing and details of different cooling methods. Results No significant differences were observed between 2019 and 2020. In both years, in‐hospital mortality rates just exceeded 8%. Individuals >65 years old comprised 50% of cases and non‐exertional onset (office work and everyday life) comprised 60%–70%, respectively. The recommendations from the Working Group on Heat Stroke Medicine given during the coronavirus disease pandemic in 2019 had a significant impact on the choice of cooling methods. The percentage of cases, for which intravascular temperature management was performed and cooling blankets were used increased, whereas the percentage of cases in which evaporative plus convective cooling was performed decreased. A total of 49 cases of heat stroke in mask wearing were reported. Conclusion Epidemiological assessments of heat stroke and heat exhaustion did not reveal significant changes between 2019 and 2020. The findings suggest that awareness campaigns regarding heat stroke prevention among the elderly in daily life should be continued in the coronavirus disease 2019 pandemic. In the future, it is also necessary to validate the recommendations of the Working Group on Heatstroke Medicine.

Abstract Recently, a letter to the editor was published to comment on the 5A score which is the prediction model for accidental hypothermia patients comparing the HOPE score. In this letter, we responded to the comments to clarify the difference between the 5A score and the HOPE score.

Aim This study describes the clinical characteristics and outcomes as well as the prognostic factors of patients with accidental hypothermia (AH) using Japan’s nationwide registry data. Methods The Hypothermia study 2018 and 2019, which included patients aged 18 years or older with a body temperature of 35°C or less, was a multicenter registry conducted at 87 and 89 institutions throughout Japan, with data collected from December 2018 to February 2019 and December 2019 to February 2020, respectively. Results In total, 1363 patients were enrolled in the registry, of which 1194 were analyzed in this study. The median (interquartile range) age was 79 (68–87) years, and the median (interquartile range) body temperature at the emergency department was 30.8°C (28.4–33.6°C). Forty‐three percent of patients with AH had a mild condition, 35.2% moderate, and 21.9% severe. AH occurred in an indoor setting in 73.4% and was caused by acute medical illness in 49.3% of patients. A total of 101 (8.5%) patients suffered from cardiopulmonary arrest on arrival at the hospital. The overall 30‐day mortality rate was 24.5%, the median (interquartile range) intensive care unit stay was 4 (2–7) days, and the median (interquartile range) hospital stay was 13 (4–27) days. In the multivariable logistic analysis, the prognostic factors were age (≥75 years old), male, activities of daily living (needing total assistance), cause of AH (trauma, alcohol), Glasgow Coma Scale score, and potassium level (>5.5 mEq/L). Conclusion The mortality rate of AH was 24.5% in Japan. The prognostic factors developed in this study may be useful for the early prediction, prevention, and awareness of severe AH.

Abstract Background The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. Methods This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. Results IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p