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Background Tranexamic acid (TXA) reduces surgical bleeding and reduces death from bleeding after trauma and childbirth. However, its effects on thrombotic events and seizures are less clear. We conducted a systematic review and meta-analysis to examine the safety of TXA in bleeding patients. Methods For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials from inception until June 1, 2020. We included randomized trials comparing intravenous tranexamic acid and placebo or no intervention in bleeding patients. The primary outcomes were thrombotic events, venous thromboembolism, acute coronary syndrome, stroke and seizures. A meta-analysis was performed using a random effects model and meta-regression analysis was performed to evaluate how effects vary by dose. We assessed the certainty of evidence using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Results A total of 234 studies with 102,681 patients were included in the meta-analysis. In bleeding patients, there was no evidence that TXA increased the risk of thrombotic events (RR = 1.00 [95% CI 0.93–1.08]), seizures (1.18 [0.91–1.53]), venous thromboembolism (1.04 [0.92–1.17]), acute coronary syndrome (0.88 [0.78–1.00]) or stroke (1.12 [0.98–1.27]). In a dose-by-dose sensitivity analysis, seizures were increased in patients receiving more than 2 g/day of TXA (3.05 [1.01–9.20]). Meta-regression showed an increased risk of seizures with increased dose of TXA ( p  = 0.011). Conclusion Tranexamic acid did not appear to increase the risk of thrombotic events in bleeding patients. However, because there may be dose-dependent increase in the risk of seizures, very high doses should be avoided.

Many systematic reviews have been published regarding anticoagulant therapy in sepsis, among which there is substantial heterogeneity. This study aimed to provide an overview of existing systematic reviews of randomized controlled trials by using a comprehensive search method. We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. Of 895 records screened, 19 systematic reviews were included. The target agent was as follows: antithrombin (n = 4), recombinant thrombomodulin (n = 3), heparin (n = 3), recombinant activated protein C (n = 8), and all anticoagulants (n = 1). Antithrombin did not improve mortality in critically ill patients but indicated a beneficial effect in sepsis-induced disseminated intravascular coagulation (DIC), although the certainty of evidence was judged as low. Recombinant thrombomodulin was associated with a trend in reduced mortality in sepsis with coagulopathy with no increased risk of bleeding, although the difference was not statistically significant and the required information size for any declarative judgement insufficient. Although three systematic reviews showed potential survival benefits of unfractionated heparin and low-molecular-weight heparin in patients with sepsis, trials with low risk of bias were lacking, and the overall impact remains unclear. None of the meta-analyses of recombinant activated protein C showed beneficial effects in sepsis. In summary, a beneficial effect was not observed in overall sepsis in poorly characterized patient groups but was observed in sepsis-induced DIC or sepsis with coagulopathy in more specific patient groups. This umbrella review of anticoagulant therapy suggests that characteristics of the target populations resulted in heterogeneity among the systematic reviews.

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.

Backgrounds Intestinal ischemia of strangulated small bowel obstruction (SSBO) requires prompt identification and early intervention. This study aimed to evaluate the risk factors and develop a prediction model of intestinal ischemia requiring bowel resection in SSBO. Methods This was a single-center, retrospective cohort study of consecutive patients underwent emergency surgery for SSBO from April 2007 to December 2021. Univariate analysis was performed to identify the risk factors for bowel resection in these patients. Two clinical scores (with contrasted computed tomography [CT] and without contrasted CT) were developed to predict intestinal ischemia. The scores were validated in an independent cohort. Results A total of 127 patients were included, 100 in the development cohort (DC) and 27 in the validation cohort (VC). Univariate analysis showed that high white blood cell count (WBC), low base excess (BE), ascites and reduced bowel enhancement were significantly associated with bowel resection. The ischemia prediction score (IsPS) comprised 1 point each for WBC ≥ 10,000/L, BE ≤ -1.0 mmol/L, ascites, and 2 points for reduced bowel enhancement. The simple IsPS (s-IsPS, without contrasted CT) of 2 or more had a sensitivity of 69.4%, specificity of 65.4%. The modified IsPS (m-IsPS, with contrasted CT) of 3 or more had a sensitivity of 86.7%, specificity of 76.0%. AUC of s-IsPS was 0.716 in DC and 0.812 in VC, and AUC of m-IsPS was 0.838 and 0.814. Conclusion IsPS predicted possibility of ischemic intestinal resection with high accuracy and can help in the early identification of intestinal ischemia in SSBO.

Background Shift work is common in healthcare, especially in emergency and intensive care, to maintain the quality of patient care. Night shifts are linked to health risks such as cardiovascular disease, metabolic disorders, and poor mental health. It has been suggested that inflammatory responses due to the disruption of circadian rhythm may contribute to health risks, but the detailed mechanisms remain unclear. This study aimed to analyze changes in gene expression in whole blood of healthcare workers before and after a night shift and investigate the molecular pathogenesis of these changes and their impact on health. Methods This was a single-center, prospective, observational study of four medical doctors working night shifts in the emergency department. Blood samples from the subjects were collected before and after the night shift, and RNA sequencing was performed to analyze changes in gene expression in whole blood. The data obtained were analyzed via Ingenuity Pathway Analysis (IPA) core analysis that included canonical pathway analysis, upstream regulator analysis, and functional network analysis. RNA bulk deconvolution was performed to estimate the relative abundance of immune cells. The IPA analysis match feature was also used to assess similarities of gene expression patterns with other diseases. Results We identified 302 upregulated and 78 downregulated genes ( p  < 0.05, |log2-fold change|> 0.5) as genes whose expression changed after the night shift. Canonical pathway analysis revealed that Toll-like receptors and other innate immune response pathways were activated. Upstream regulator analysis and functional network analysis also consistently indicated a predicted activation of innate immune and inflammatory responses. RNA bulk deconvolution showed changes in the proportions of several immune cells. IPA analysis match indicated that gene expression patterns after night shifts were highly correlated with several diseases, including major depressive disorder, in terms of immune and inflammatory responses. Conclusion The results revealed that innate immune and inflammatory responses are elicited after night shifts in healthcare workers and that gene expression patterns correlate with several diseases in terms of immune and inflammatory responses. These findings suggest that shift work may affect health risks through innate immune and inflammatory responses.

IntroductionTranexamic acid (TXA) is a synthetic derivative of the amino acid lysine that inhibits fibrinolysis by blocking lysine-binding sites on plasminogen, which contribute to reduced bleeding, the need for transfusion and mortality. Although there is reliable evidence of the efficacy of TXA, its effects on other important outcomes, adverse events, including thrombotic events and seizure, remain uncertain.Methods and analysisWe will conduct a systematic review and meta-analysis of randomised controlled trials with the objective of evaluating the incidence of thrombotic adverse events and seizure and how the effect of TXA varies by dose and underlying disease. We will include patients with bleeding in any underlying disease. We will search MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials for randomised controlled trials. The planned date of our systematic search is 1 June 2020. We will follow the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Subgroup and sensitivity analyses will be performed to explore residual heterogeneity and inconsistency. Meta-regression analysis will be carried out to investigate the association between the incidence of adverse events and the TXA dose. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study will not involve primary data collection, and formal ethics approval will therefore not be required. We aim to publish this systematic review in a peer-review journal.Trial registration numberUMIN000039611.

IntroductionThe optimal target of mean arterial pressure (MAP) for better outcomes in patients with vasodilatory shock remains a matter of debate. Although catecholamines are generally used to maintain target blood pressure in hypotensive patients with vasodilatory shock, the adverse effects of catecholamines must also be considered. We will perform a systematic review and meta-analysis of randomised controlled trials (RCTs) to assess the certainty of evidence determining the optimal target of MAP control for patients with vasodilatory shock in critically ill settings.Methods and analysisThis study protocol was registered in the University Hospital Medical Information Network Clinical Trials Registry. We will include only RCTs that evaluated the two different comparators for target MAP to be maintained for clinical outcomes of all-cause mortality: organ dysfunction and adverse events in critically ill adult patients with vasodilatory shock. We will search the electronic bibliographic databases of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials in November 2020. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data. We will report study characteristics and assess methodological quality using the Cochrane Risk-of-Bias 2 tool. If pooling is appropriate, we will calculate relative risks with 95% CIs for all outcome measures. Clinical and methodological subgroup and sensitivity analyses will be performed to explore heterogeneity. Overall certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study will not involve primary data collection, and formal ethics approval will therefore not be required. We aim to publish this systematic review in a peer-reviewed journal.Trial registration numberUMIN000042624.

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.

Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on the Japan Septic Disseminated Intravascular Coagulation retrospective study. We used the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score to calculate the ΔDIC score as ((DIC score on Day 3) − (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ΔDIC was more than 0. The secondary outcome was the actual predictive accuracy of ΔDIC (predicted ΔDIC−real ΔDIC). We used the machine-learning methods, such as random forests (RF), support vector machines (SVM), and neural networks (NN); their predictive accuracies were compared with those of conventional methods. In total, 1017 patients were included. Regarding DIC progression, predictive accuracy of the multiple linear regression, RF, SVM, and NN models was 63.7%, 67.0%, 64.4%, and 59.8%, respectively. The difference between predicted ΔDIC and real ΔDIC was 2.05, 1.54, 2.24, and 1.77 for the multiple linear regression, RF, SVM, and NN models, respectively. RF had the highest predictive accuracy.

Background The Sequential Organ Failure Assessment (SOFA)-2 score was developed to better reflect contemporary critical care practice by incorporating modern organ support modalities and updated thresholds based on recent data. However, the generalizability of this framework to intensive care unit (ICU) populations beyond the development cohort, particularly across organ support subgroups and major disease categories, remains uncertain. We aimed to evaluate the external validity of SOFA-2 using the OneICU database, a large Japanese critical care database with comprehensive domain-level data. Methods Adult ICU stays between February 2013 and August 2025 were included and classified into two cohorts: those with complete SOFA-1 and SOFA-2 component data on the day of ICU admission, and those with complete SOFA-2 data on that day. Discriminatory performance for ICU mortality was evaluated using the area under the receiver operating characteristic curve (AUROC) and compared between SOFA-1 and SOFA-2 using the DeLong test. Subgroup analyses were performed by major organ support device use and across disease categories. Results Among 152,883 eligible ICU stays, 67,116 had complete SOFA-1 and SOFA-2 data, and 121,443 had complete SOFA-2 data. SOFA-2 showed a slightly higher AUROC for ICU mortality than SOFA-1 (0.859 vs. 0.853; p  < 0.001), although the absolute difference was small. Across subgroups defined by mechanical circulatory support use, SOFA-2 showed higher discrimination than SOFA-1. Discrimination was similar in other device-defined subgroups and in patients readmitted to the ICU. SOFA-2 also demonstrated good discrimination across major diagnostic groups. Conclusions SOFA-2 showed similar discrimination for ICU mortality compared with SOFA-1 and maintained broadly comparable performance across clinically relevant subgroups, supporting its applicability for early severity assessment in heterogeneous ICU populations.