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: To examine whether niacin attenuates lung inflammation and improves survival during sepsis and to determine whether the beneficial effects of niacin are associated with downregulation of the nuclear factor (NF)-[kappa]B pathway. [ABSTRACT FROM AUTHOR]

During recovery from septic shock, circulating mitochondrial N-formyl peptides predispose to secondary infection by occupying formyl peptide receptor 1 on the neutrophil (polymorphonuclear leukocyte) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mitochondrial N-formyl peptides in clinical settings. Thus, we studied how to remove mitochondrial N-formyl peptides from septic-shock plasma and whether such removal could preserve cell-surface formyl peptide receptor 1 and restore sepsis-induced polymorphonuclear leukocyte dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mitochondrial N-formyl peptide removal rescued polymorphonuclear leukocyte formyl peptide receptor 1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mitochondrial N-formyl peptide exposure. However, polymorphonuclear leukocyte functional recovery occurred in a stepwise fashion over 30 to 90 min. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model, systems using blood samples obtained from patients with septic shock, antimitochondrial N-formyl peptide antibodies alone failed to eliminate mitochondrial N-formyl peptides from septic-shock plasma or inhibit mitochondrial N-formyl peptide activity. We therefore created a beads-based antimitochondrial N-formyl peptide antibody cocktail by combining protein A/sepharose with antibodies specific for the most potent human mitochondrial N-formyl peptide chemoattractants. The beads-based antimitochondrial N-formyl peptide antibody cocktail treatment successfully removed those active mitochondrial N-formyl peptides from septic-shock plasma. Furthermore, the beads-based antimitochondrial N-formyl peptide antibody cocktail treatment significantly restored chemotactic and bactericidal dysfunction of polymorphonuclear leukocytes obtained from patients with septic shock who developed secondary infections. By clearing circulating mitochondrial N-formyl peptides, the immobilized antimitochondrial N-formyl peptide antibody therapy prevented mitochondrial N-formyl peptide interactions with surface formyl peptide receptor 1, thereby restoring [Ca2+]i-dependent polymorphonuclear leukocyte antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock., Competing Interests: Conflict of interest statement. W.Y.K., Y.S.J., G.J.S., S.H.K., A.L., J.Y.K., H.Y.K., H.P., T.K., and K.S.K. are inventors on a patent application submitted by Seoul National University that covers “Blood perfusion device to reduce secondary infection in hospital”. The authors have declared no additional conflict of interest exists., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Background: Early risk stratification is crucial due to septic patients' heterogeneity. Serum albumin level may reflect the severity of sepsis and host status. This study aimed to evaluate the prognostic ability of the initial sequential organ failure assessment (SOFA) score alone and combined with serum albumin levels for predicting 28-day mortality in patients with septic shock. Methods: We conducted an observational study using a prospective, multicenter registry of septic shock patients between October 2015 and May 2022 from 12 emergency departments in the Korean Shock Society and the results were validated by examining those from the septic shock cohort in Asan Medical Center. The primary outcome was 28-day mortality. The area under the receiver operating characteristic (ROC) curve was used to compare the predictive values of SOFA score alone and SOFA score combined with serum albumin level. Results: Among 5805 septic shock patients, 1529 (26.3%) died within 28 days. Mortality increased stepwise with decreasing serum albumin levels (13.6% in albumin ≥3.5, 20.7% in 3.5-3.0, 29.7% in 3.0-2.5, 44.0% in 2.5-2.0, 56.4% in <2.0). The albumin SOFA score was calculated by adding the initial SOFA score to the 4 points assigned for albumin levels. ROC analysis for predicting 28-day mortality showed that the area under the curve for the albumin SOFA score was 0.71 (95% CI 0.70-0.73), which was significantly higher than that of the initial SOFA score alone (0.68, 95% CI: 0.67-0.69). Conclusions: The combination of the initial SOFA score with albumin can improve prognostic accuracy for patients with septic shock, suggesting the albumin SOFA score may be used as an early mortality stratification tool.

Objectives: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients., Methods: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records., Results: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01)., Conclusions: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim of the Study: We evaluated whether an artificial intelligence (AI)-driven robot cardiopulmonary resuscitation (CPR) could improve hemodynamic parameters and clinical outcomes., Methods: We developed an AI-driven CPR robot which utilizes an integrated feedback system with an AI model predicting carotid blood flow (CBF). Twelve pigs were assigned to the AI robot group (n = 6) and the LUCAS 3 group (n = 6). They underwent 6 min of CPR after 7 min of ventricular fibrillation. In the AI robot group, the robot explored for the optimal compression position, depth and rate during the first 270-second period, and continued CPR with the optimal setup during the next 90-second period and beyond. The primary outcome was CBF during the last 90-second period. The secondary outcomes were coronary perfusion pressure (CPP), end-tidal carbon dioxide level (ETCO 2 ) and return of spontaneous circulation (ROSC)., Results: The AI model's prediction performance was excellent (Pearson correlation coefficient = 0.98). CBF did not differ between the two groups [estimate and standard error (SE), -23.210 ± 20.193, P = 0.250]. CPP, ETCO 2 level and rate of ROSC also did not show difference [estimate and SE, -0.214 ± 7.245, P = 0.976 for CPP; estimate and SE, 1.745 ± 3.199, P = 0.585 for ETCO 2 ; 5/6 (83.3%) vs. 4/6 (66.7%), P = 1.000 for ROSC)., Conclusion: This study provides proof of concept that an AI-driven CPR robot in porcine cardiac arrest is feasible. Compared to a LUCAS 3, an AI-driven CPR robot produced comparable hemodynamic and clinical outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Gil Joon Suh reports financial support was provided by National Research Foundation of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study introduces a novel system that can simulate diverse mechanical properties of the human chest to enhance the experience of CPR training by reflecting realistic chest conditions of patients., Methods: The proposed system consists of Variable stiffness mechanisms (VSMs) and Variable damper (VD) utilizing stretching silicone bands and dashpot dampers with controllable valves to modulate stiffness and damping, respectively. Cyclic loading was applied with a robot manipulator to the system. Compression force and displacement were measured and analyzed to evaluate the system's mechanical response. Long-term stability of the system was also validated., Results: A non-linear response of the human chest under compression is realized through this design. Test results indicated non-linear force-displacement curves with hysteresis, similar to those observed in the chest of patients. Controlling the VSM and VD allowed for intentional changes in the slope and area of curves that are related to stiffness and damping, respectively. Stiffness and damping of the system were computed using performance test results. The stiffness ranged from 5.34 N/mm to 13.59 N/mm and the damping ranges from 0.127 N[Formula: see text] s/mm to 0.511 N[Formula: see text] s/mm. These properties cover a significant portion of the reported mechanical properties of the human chests. The system demonstrated satisfactory stability even when it was subjected to maximum stiffness conditions of the long-term compression test., Conclusion: The system is capable of emulating the mechanical properties and behavior of the human chests, thereby enhancing the CPR training experience., (© 2024 The Authors.)

Purpose: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock., Materials and Methods: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated., Results: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17)., Conclusion: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Ischemia-reperfusion (IR) injury is implicated in various clinical diseases. Kallistatin attenuates oxidative stress, and its deficiency has been associated with poor neurological outcomes after cardiac arrest. The present study investigated the antioxidant mechanism through which kallistatin prevents IR injury., Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with small interfering RNA (siRNA) targeting the human kallistatin gene (SERPINA4). Following SERPINA4 knockdown, the level of kallistatin expression was measured. To induce IR injury, HUVECs were exposed to 24 h of oxygen-glucose deprivation and reoxygenation (OGD/R). To evaluate the effect of SERPINA4 knockdown on OGD/R, cell viability and the concentration of kallistatin, endothelial nitric oxide synthase (eNOS) and total NO were measured., Results: SERPINA4 siRNA transfection suppressed the expression of kallistatin in HUVECs. Exposure to OGD/R reduced cell viability, and this effect was more pronounced in SERPINA4 knockdown cells compared with controls. SERPINA4 knockdown significantly reduced kallistatin concentration regardless of OGD/R, with a more pronounced effect observed without OGD/R. Furthermore, SERPINA4 knockdown significantly decreased eNOS concentrations induced by OGD/R (P<0.01) but did not significantly affect the change in total NO concentration (P=0.728)., Conclusion: The knockdown of SERPINA4 resulted in increased vulnerability of HUVECs to OGD/R and significantly affected the change in eNOS level induced by OGD/R. These findings suggest that the protective effect of kallistatin against IR injury may contribute to its eNOS-promoting effect.

Sex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245-1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118-1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413-0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock., (© 2024. The Author(s).)

The purpose of study was to evaluate that kallistatin deficiency causes excessive production of reactive oxygen species and exacerbates neuronal injury after cardiac arrest. For in vitro study, kallistatin knockdown human neuronal cells were given ischemia-reperfusion injury, and the oxidative stress and apoptosis were evaluated. For clinical study, cardiac arrest survivors admitted to the ICU were divided into the good (CPC 1-2) and poor (CPC 3-5) 6-month neurological outcome groups. The serum level of kallistatin, Nox-1, H 2 O 2 were measured. Nox-1 and H 2 O 2 levels were increased in the kallistatin knockdown human neuronal cells with ischemia-reperfusion injury (p < 0.001) and caspase-3 was elevated and apoptosis was promoted (SERPINA4 siRNA: p < 0.01). Among a total of 62 cardiac arrest survivors (16 good, 46 poor), serum kallistatin were lower, and Nox-1 were higher in the poor neurological group at all time points after admission to the ICU (p = 0.013 at admission; p = 0.020 at 24 h; p = 0.011 at 72 h). At 72 h, H 2 O 2 were higher in the poor neurological group (p = 0.038). Kallistatin deficiency exacerbates neuronal ischemia-reperfusion injury and low serum kallistatin levels were associated with poor neurological outcomes in cardiac arrest survivors., (© 2024. The Author(s).)

Background: Recently, we developed a chest compression device that can move the chest compression position without interruption during CPR and be remotely controlled to minimize rescuer exposure to infectious diseases. The purpose of this study was to compare its performance with conventional mechanical CPR device in a mannequin and a swine model of cardiac arrest., Materials and Methods: A prototype of a remote-controlled automatic chest compression device (ROSCER) that can change the chest compression position without interruption during CPR was developed, and its performance was compared with LUCAS 3 in a mannequin and a swine model of cardiac arrest. In a swine model of cardiac arrest, 16 male pigs were randomly assigned into the two groups, ROSCER CPR (n = 8) and LUCAS 3 CPR (n = 8), respectively. During 5 minutes of CPR, hemodynamic parameters including aortic pressure, right atrial pressure, coronary perfusion pressure, common carotid blood flow, and end-tidal carbon dioxide partial pressure were measured., Results: In the compression performance test using a mannequin, compression depth, compression time, decompression time, and plateau time were almost equal between ROSCER and LUCAS 3. In a swine model of cardiac arrest, coronary perfusion pressure showed no difference between the two groups (p = 0.409). Systolic aortic pressure and carotid blood flow were higher in the LUCAS 3 group than in the ROSCER group during 5 minutes of CPR (p < 0.001, p = 0.008, respectively). End-tidal CO2 level of the ROSCER group was initially lower than that of the LUCAS 3 group, but was higher over time (p = 0.022). A Kaplan-Meier survival analysis for ROSC also showed no difference between the two groups (p = 0.46)., Conclusion: The prototype of a remote-controlled automated chest compression device can move the chest compression position without interruption during CPR. In a mannequin and a swine model of cardiac arrest, the device showed no inferior performance to a conventional mechanical CPR device., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis., (© 2023. The Author(s).)

Abstract: Objective: This study aimed to test whether the prognostic value of tryptophanyl-tRNA synthetase 1 (WARS1) for 28-day mortality in patients with sepsis was affected by monocytopenia. Methods: A prospective analysis of retrospectively collected samples from 74 sepsis patients was performed. WARS1, C-reactive protein (CRP), and procalcitonin were measured at admission and 24 and 72 h after admission. The prognostic value of WARS1, CRP, and procalcitonin for 28-day mortality was compared using repeated measures analysis of variance and the area under the receiver operating characteristic curve (AUROC). All analyses were performed in patients with or without monocytopenia, defined as an absolute monocyte count less than 0.1 × 10 9 cells/L. Results: WARS1 levels differed significantly between survivors and nonsurvivors when all patients and patients without monocytopenia were assessed ( P = 0.008, P < 0.001, respectively). In contrast, the WARS1 level did not differ between survivors and nonsurvivors with monocytopenia. C-reactive protein and procalcitonin levels were not different between survivors and nonsurvivors regardless of whether they had monocytopenia. The AUROCs of WARS1 at admission and 24 h for mortality were significantly higher in patients without monocytopenia (0.830, 0.818) than in patients with monocytopenia (0.232, 0.196; P < 0.001, both). When patients without monocytopenia were analyzed, the AUROCs of WARS1 for mortality were 0.830 and 0.818 at admission and 24 h, respectively, which were significantly higher than those of CRP (0.586, 0.653) and procalcitonin (0.456, 0.453) at the same time points ( P = 0.024 and 0.034, respectively). Conclusion: WARS1 is a useful biomarker for prognosis in sepsis patients without monocytopenia., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Background: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients., Methods: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively., Results: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677-0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611-0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715-0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration., Conclusion: In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: It is important to be able to predict the chance of survival to hospital discharge upon ED arrival in order to determine whether to continue or terminate resuscitation efforts after out of hospital cardiac arrest. This study was conducted to develop and validate a simple scoring rule that could predict survival to hospital discharge at the time of ED arrival., Methods: This was a multicenter retrospective cohort study based on a nationwide registry (Korean Cardiac Arrest Research Consortium) of out of hospital cardiac arrest (OHCA). The study included adult OHCA patients older than 18 years old, who visited one of 33 tertiary hospitals in South Korea from September 1st, 2015 to June 30th, 2020. Among 12,321 screened, 5471 patients were deemed suitable for analysis after exclusion. Pre-hospital ROSC, pre-hospital witness, shockable rhythm, initial pH, and age were selected as the independent variables. The dependent variable was set to be the survival to hospital discharge. Multivariable logistic regression (LR) was performed, and the beta-coefficients were rounded to the nearest integer to formulate the scoring rule. Several machine learning algorithms including the random forest classifier (RF), support vector machine (SVM), and K-nearest neighbor classifier (K-NN) were also trained via 5-fold cross-validation over a pre-specified grid, and validated on the test data. The prediction performances and the calibration curves of each model were obtained. Pre-processing of the registry was done using R, model training & optimization using Python., Results: A total of 5471 patients were included in the analysis. The AUROC of the scoring rule over the test data was 0.7620 (0.7311-0.7929). The AUROCs of the machine learning classifiers (LR, SVM, k-NN, RF) were 0.8126 (0.7748-0.8505), 0.7920 (0.7512-0.8329), 0.6783 (0.6236-0.7329), and 0.7879 (0.7465-0.8294), respectively., Conclusion: A simple scoring rule consisting of five, binary variables could aid in the prediction of the survival to hospital discharge at the time of ED arrival, showing comparable results to conventional machine learning classifiers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although the Surviving Sepsis Campaign guidelines provide standardized and generalized guidance, they are less individualized. This review focuses on recent updates in the hemodynamic management of septic shock. Monitoring and intervention for septic shock should be personalized according to the phase of shock. In the salvage phase, fluid resuscitation and vasopressors should be given to provide life-saving tissue perfusion. During the optimization phase, tissue perfusion should be optimized. In the stabilization and de-escalation phases, minimal fluid infusion and safe fluid removal should be performed, respectively, while preserving organ perfusion. There is controversy surrounding the use of restrictive versus liberal fluid strategies after initial resuscitation. Fluid administration after initial resuscitation should depend upon the patient's fluid responsiveness and requires individualized management. A number of dynamic tests have been proposed to monitor fluid responsiveness, which can help clinicians decide whether to give fluid or not. The optimal timing for the initiation of vasopressor agents is unknown. Recent data suggest that early vasopressor initiation should be considered. Inotropes can be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion despite adequate volume status and arterial blood pressure. Venoarterial extracorporeal membrane oxygenation should be considered for refractory septic shock with severe cardiac systolic dysfunction.

Background: We compared the prognostic accuracy of in-hospital mortality of the initial Sequential Organ Failure Assessment (SOFA ini ) score at the time of sepsis recognition and resuscitation and the maximum SOFA score (SOFA max ) using the worst variables in the 24 h after the initial score measurement in emergency department (ED) patients with septic shock., Methods: This was a retrospective observational study using a multicenter prospective registry of septic shock patients in the ED between October 2015 and December 2019. The primary outcome was in-hospital mortality. The prognostic accuracies of SOFA ini and SOFA max were evaluated using the area under the receiver operating characteristic (AUC) curve., Results: A total of 4860 patients was included, and the in-hospital mortality was 22.1%. In 59.7% of patients, SOFA max increased compared with SOFA ini , and the mean change of total SOFA score was 2.0 (standard deviation, 2.3). There was a significant difference in in-hospital mortality according to total SOFA score and the SOFA component scores, except cardiovascular SOFA score. The AUC of SOFA max (0.71; 95% confidence interval [CI], 0.69-0.72) was significantly higher than that of SOFA ini (AUC, 0.67; 95% CI, 0.66-0.69) in predicting in-hospital mortality. The AUCs of all scores of the six components were higher for the maximum values., Conclusion: The prognostic accuracy of the initial SOFA score at the time of sepsis recognition was lower than the 24-h maximal SOFA score in ED patients with septic shock. Follow-up assessments of organ failure may improve discrimination of the SOFA score for predicting mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Oxidative stress contributes to tissue injury through reactive oxygen species-dependent signaling pathways during sepsis. We studied therapeutic benefits of the combination therapy of niacin, which increased reduced glutathione levels, and apocynin, which suppressed reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity, in septic rats., Materials and Methods: Polymicrobial sepsis was induced through cecal ligation and puncture (CLP) with antibiotics in male Sprague-Dawley rats (n = 189). The rats were randomly divided into sham, CLP, CLP + niacin, CLP + apocynin, and CLP + niacin + apocynin groups. Six hours after CLP, vehicle, niacin (360 mg/kg through the orogastric tube), and/or apocynin (20 mg/kg through intraperitoneal injection) were administered. The occurrence of mortality for 72 h after CLP was observed. Next, a separate set of animals was euthanized at 24 h post-CLP for lung tissue analyses., Results: Combination therapy with niacin and apocynin significantly improved survival in rats with sepsis (75.0% versus 28.8%, P = 0.006) but monotherapy with niacin or apocynin did not. Monotherapy with niacin and apocynin appeared to increase NADPH levels and decrease Nox levels and activity, respectively, but failed to show statistical significances. However, combination therapy significantly decreased Nox levels and activity, increased NADPH and glutathione levels, decreased intranuclear nuclear factor-κB (NF-κB) p65 levels, reduced inflammatory cytokine expression and malondialdehyde levels, and attenuated histological lung injuries., Conclusions: Combination therapy with niacin and apocynin synergistically attenuated lung injuries and improved survival in rats with sepsis through niacin-induced glutathione redox cycle activation and apocynin-induced Nox suppression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A reliable prognostic score for minimizing futile treatments in advanced cancer patients with septic shock is rare. A machine learning (ML) model to classify the risk of advanced cancer patients with septic shock is proposed and compared with the existing scoring systems. A multi-center, retrospective, observational study of the septic shock registry in patients with stage 4 cancer was divided into a training set and a test set in a 7:3 ratio. The primary outcome was 28-day mortality. The best ML model was determined using a stratified 10-fold cross-validation in the training set. A total of 897 patients were included, and the 28-day mortality was 26.4%. The best ML model in the training set was balanced random forest (BRF), with an area under the curve (AUC) of 0.821 to predict 28-day mortality. The AUC of the BRF to predict the 28-day mortality in the test set was 0.859. The AUC of the BRF was significantly higher than those of the Sequential Organ Failure Assessment score and the Acute Physiology and Chronic Health Evaluation II score (both p < 0.001). The ML model outperformed the existing scores for predicting 28-day mortality in stage 4 cancer patients with septic shock. However, further studies are needed to improve the prediction algorithm and to validate it in various countries. This model might support clinicians in real-time to adopt appropriate levels of care.

This study aimed to determine the impact of modifications in emergency department (ED) practices caused by the coronavirus disease 2019 (COVID-19) pandemic on the clinical outcomes and management of patients with septic shock. We performed a retrospective study. Patients with septic shock who presented to the ED between 1 January 2018 and 19 January 2020 were allocated to the pre-COVID-19 group, whereas those who presented between 20 January 2020 and 31 December 2020 were assigned to the post-COVID-19 group. We used propensity score matching to compare the sepsis-related interventions and clinical outcomes. The primary outcome measure was in-hospital mortality. Of the 3697 patients included, 2254 were classified as pre-COVID-19 and 1143 as post-COVID-19. A total of 1140 propensity score-matched pairings were created. Overall, the in-hospital mortality rate was 25.5%, with no statistical difference between the pre- and post-COVID-19 groups (p = 0.92). In a matched cohort, the post-COVID-19 group had delayed lactate measurement, blood culture test, and infection source control (all p < 0.05). There was no significant difference in time to antibiotics (p = 0.19) or vasopressor administration (p = 0.09) between the groups. Although sepsis-related interventions were delayed during the COVID-19 pandemic, there was no significant difference in the in-hospital mortality between the pre- and post-COVID-19 groups.

We aimed to evaluate correlation and agreement between noninvasive brain temperature (T BN ) and invasive brain temperature (T BI ) measurement during targeted temperature management (TTM) in a swine cardiac arrest model. Defibrillation attempts were provided after 5 minutes of ventricular fibrillation and 12 minutes of cardiopulmonary resuscitation in five pigs. After return of spontaneous circulation, TTM was provided with induction and maintenance phases with a target temperature of 33°C for 6 hours and a rewarming phase with a rewarming rate of 1°C/h for 4 hours. T BN and T BI were measured using a double sensor method and an intracranial catheter, respectively. Pulmonary artery temperature (T P ), esophageal temperature (T E ), and rectal temperature (T R ) were measured. Primary outcomes were correlation and agreement between T BN and T BI and secondary outcomes were correlation and agreement among T BN and other temperatures. The Pearson correlation coefficient (PCC) between T BN and T BI was 0.95 ( p  < 0.001) during the whole TTM phases. PCCs between T BN and T BI during the induction, maintenance, and rewarming phases were 0.91 ( p  < 0.001), 0.88 ( p  < 0.001), and 0.94 ( p  < 0.001) and 95% limits of agreement (LoAs) between T BN and T BI were (-0.27°C to 0.78°C), (-0.18°C to 0.54°C), and (-0.93°C to 0.88°C), respectively. Correlation between T BN and T BI during the maintenance phase was higher than correlation between T BN and T E (PCC = 0.74, p  < 0.001) or T P (PCC = 0.81, p  < 0.001). The 95% LoAs were narrowest between T BN and T P in the induction phase (-0.58 to 0.11), between T BN and T BI in the maintenance phase (-0.54 to 0.18), and between T BN and T R in the rewarming phase (-0.96 to 0.84). Noninvasive brain temperature showed good correlation with invasive brain temperature during TTM in a swine cardiac arrest model. Correlation was highest during the rewarming phase and lowest during the maintenance phase. Agreement between the two measurements was not clinically acceptable.

Background: Brain oedema after cardiac arrest is strongly associated with poor neurological outcomes. Excessive sodium supplementation may increase serum osmolarity and facilitate brain oedema development in cardiac arrest survivors. We aimed to investigate the association of serum sodium levels with long-term neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors., Methods: This retrospective observational study used a multicentre prospective cohort registry of OHCA survivors collected between December 2013 and February 2018. We analyzed the association of serum sodium levels at the return of spontaneous circulation (ROSC) (Sodium 0H) and at 24 h after ROSC (Sodium 24H) with 1-year neurological outcomes in OHCA survivors. Patients with 1-year cerebral performance categories (CPC) 1 and 2 were included in the good outcome group while those with CPC 3, 4, and 5 were included in the poor outcome group., Results: Among 277 patients, 84 (30.3%) and 193 (69.7%) were in the good and poor outcome groups, respectively. Compared with the good outcome group, the poor outcome group showed significantly higher Sodium 24H levels (140 mEq/L vs. 137.4 mEq/L, p < 0.001). Increased serum sodium levels per 1 mEq/L increased the risk of poor 1-year CPC by 13% (adjusted odds ratio = 1.13; 95% CI, 1.04⎼1.23; p = 0.004)., Conclusions: Relatively high Sodium 24H levels showed a strong and independent association with poor long-term neurological outcomes in OHCA survivors. These findings may be applied in therapeutic strategies for improving neurological outcomes in OHCA survivors., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% ( n = 18/77) vs. 13.6% ( n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08-6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness., Competing Interests: The authors declare no conflict of interest.

Background: The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score., Methods: We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock., Results: We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%)., Conclusions: Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality., (© 2022. The Author(s).)

Objective: We investigated the effects of a quick Sequential Organ Failure Assessment (qSOFA)-negative result (qSOFA score <2 points) at triage on the compliance with sepsis bundles among patients with sepsis who presented to the emergency department (ED)., Methods: Prospective sepsis registry data from 11 urban tertiary hospital EDs between October 2015 and April 2018 were retrospectively reviewed. Patients who met the Third International Consensus Definitions for Sepsis and Septic Shock criteria were included. Primary exposure was defined as a qSOFA score ≥2 points at ED triage. The primary outcome was defined as 3-hour bundle compliance, including lactate measurement, blood culture, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration. Multivariate logistic regression analysis to predict 3-hour bundle compliance was performed., Results: Among the 2,250 patients enrolled in the registry, 2,087 fulfilled the sepsis criteria. Only 31.4% (656/2,087) of the sepsis patients had qSOFA scores ≥2 points at triage. Patients with qSOFA scores <2 points had lower lactate levels, lower SOFA scores, and a lower 28-day mortality rate. Rates of compliance with lactate measurement (adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.29-0.75), antibiotics administration (aOR, 0.64; 95% CI, 0.52-0.78), and 30 mL/kg crystalloid administration (aOR, 0.62; 95% CI, 0.49-0.77) within 3 hours from triage were significantly lower in patients with qSOFA scores <2 points. However, the rate of compliance with blood culture within 3 hours from triage (aOR, 1.66; 95% CI, 1.33-2.08) was higher in patients with qSOFA scores <2 points., Conclusion: A qSOFA-negative result at ED triage is associated with low compliance with lactate measurement, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration within 3 hours in sepsis patients.

Septic shock patients who survive past the acute period are associated with an increased risk of long-term mortality. However, factors for predicting late death remain unclear. We aimed to investigate the prognostic factors associated with late mortality in septic shock patients with 28-day survival after admission. This retrospective observational study used a prospective, multi-center registry of septic shock patients between October 2015 and December 2019 involving 12 emergency departments (EDs) from the Korean Shock Society. Adult septic shock patients visiting the ED with 28-day survival after admission were included. Among 4624 septic shock patients, 3588 (77.6%) who survived past day 28 were analyzed. The 90-day mortality rate was 14.2%. Non-survivors were older (66.8 vs. 68.9 years; p = 0.032) and had higher lactate levels (3.7 vs. 4.0 mmol/L; p = 0.028) than survivors. Pulmonary and hepatobiliary infections and a history of malignancy (27.7 vs. 57.5%; p < 0.001) were more frequent in the non-survivor group than in the survivor group. Independent risk factors for late death on multivariate regression analysis were age; malignancy; and hemoglobin, blood urea nitrogen, and albumin levels. The length of intensive care unit stay and Sequential Organ Failure Assessment score were independently associated with late death. Approximately, one-seventh of septic shock patients who survived past day 28 of admission died by day 90. Physicians must pay attention to survivors with these risk factors during the post-acute period as they have an increased mortality risk., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background: The code stroke system is designed to identify stroke patients who may benefit from reperfusion therapy. It is essential for emergency physicians to rapidly distinguish true strokes from stroke mimics to activate code stroke. This study aimed to investigate the clinical and neurological characteristics that can be used to differentiate between stroke and stroke mimics in the emergency department (ED)., Methods: We conducted a retrospective observational study of code stroke patients in the ED from January to December 2019. The baseline characteristics and the clinical and neurological features of stroke mimics were compared with those of strokes., Results: A total of 409 code stroke patients presented to the ED, and 125 (31%) were diagnosed with stroke mimics. The common stroke mimics were seizures (21.7%), drug toxicity (12.0%), metabolic disorders (11.2%), brain tumors (8.8%), and peripheral vertigo (7.2%). The independent predictors of stroke mimics were psychiatric disorders, dizziness, altered mental status, and seizure-like movements, while current smoking, elevated systolic blood pressure, atrial fibrillation on the initial electrocardiogram, hemiparesis as a symptom, and facial palsy as a sign suggested a stroke. In addition, the likelihood of a stroke in code stroke patients tended to increase as the number of accompanying deficits increased from the following set of seven focal neurological deficits: hemiparesis (or upper limb monoparesis), unilateral limb sensory change, facial palsy, dysarthria, aphasia (or neglect), visual field defect, and oculomotor disorder ( P < 0.001)., Conclusion: Some clinical and neurological characteristics have been identified to help differentiate stroke mimics from true stroke. In particular, the likelihood of stroke tended to increase as the number of accompanying focal neurological deficits increased., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Nighttime hospital admission is often associated with increased mortality risk in various diseases. This study investigated compliance rates with the Surviving Sepsis Campaign (SSC) 3-h bundle for daytime and nighttime emergency department (ED) admissions and the clinical impact of compliance on mortality in patients with septic shock., Methods: We conducted an observational study using data from a prospective, multicenter registry for septic shock provided by the Korean Shock Society from 11 institutions from November 2015 to December 2017. The outcome was the compliance rate with the SSC 3-h bundle according to the time of arrival in the ED., Results: A total of 2049 patients were enrolled. Compared with daytime admission, nighttime admission was associated with higher compliance with the administration of antibiotics within 3 h (adjusted odds ratio (adjOR), 1.326; 95% confidence interval (95% CI), 1.088-1.617, p = 0.005) and with the complete SSC bundle (adjOR, 1.368; 95% CI, 1.115-1.678; p = 0.003), likely to result from the increased volume of all patients and sepsis patients admitted during daytime hours. The hazard ratios of the completion of SSC bundle for 28-day mortality and in-hospital mortality were 0.750 (95% CI 0.590-0.952, p = 0.018) and 0.714 (95% CI 0.564-0.904, p = 0.005), respectively., Conclusion: Septic shock patients admitted to the ED during the daytime exhibited lower sepsis bundle compliance than those admitted at night. Both the higher number of admitted patients and the higher patients to medical staff ratio during daytime may be factors that are responsible for lowering the compliance., (© 2022. The Author(s).)

Introduction: We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock., Methods: This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate., Results: Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve., Conclusion: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β., Trial Registration: NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: We aimed to investigate the association between initial fluid resuscitation in septic shock patients with isolated hyperlactatemia and outcomes., Methods: This multicenter prospective study was conducted using the data from the Korean Shock Society registry. Patients diagnosed with isolated hyperlactatemia between October 2015 and December 2018 were included and divided into those who received 30 mL/kg of fluid within 3 or 6 h and those who did not receive. The primary outcome was in-hospital mortality; the secondary outcomes were intensive care unit (ICU) admission, length of ICU stay, mechanical ventilation, and renal replacement therapy (RRT)., Results: A total of 608 patients were included in our analysis. The administration of 30 mL/kg crystalloid within 3 or 6 h was not significantly associated with in-hospital mortality in multivariable logistic regression analysis ([OR, 0.8; 95% CI, 0.52-1.23, p = 0.31], [OR, 0.96; 95% CI, 0.59-1.57, p = 0.88], respectively). The administration of 30 mL/kg crystalloid within 3-h was not significantly associated with mechanical ventilation and RRT ([OR, 1.19; 95% CI, 0.77-1.84, p = 0.44], [OR, 1.2; 95% CI, 0.7-2.04, p = 0.5], respectively). However, the administration of 30 mL/kg crystalloid within 6 h was associated with higher ICU admission and RRT ([OR, 1.57; 95% CI, 1.07-2.28, p = 0.02], [OR, 2.08; 95% CI, 1.19-3.66, p = 0.01], respectively)., Conclusions: Initial fluid resuscitation of 30 mL/kg within 3 or 6 h was neither associated with an increased or decreased in-hospital mortality in septic shock patients with isolated hyperlactatemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Acute diverticulitis (AD) is a common disease with various outcomes. When AD is diagnosed in the emergency department (ED), the ED clinician must determine the patient's treatment strategy whether the patient can be discharged, needs to be admitted to the general ward, ICU, or needs surgical consultation. This study aimed to identify potential risk factors for clinically important outcomes (CIOs) and to develop a prediction model for CIOs in AD to aid clinical decision making in the ED., Methods: Retrospective data from between 2013 and 2017 in an ED in an urban setting were reviewed for adult AD. Potential risk factors were age, sex, past medical history, symptoms, physical exams, laboratory results, and imaging results. A CIO was defined as a case with one of the following outcomes: hospital death, ICU admission, surgery or invasive intervention, and admission for 7 or more days. The prediction model for CIOs was developed using potential risk factors. Model discrimination and calibration were assessed using the area under the curve (AUC) and 95% confidence intervals (CIs) and the Hosmer-Lemeshow (HL) test, respectively. Model validation was conducted using 500 random bootstrap samples., Results: Of the final 337 AD patients, 63 patients had CIOs. Six potential factors (age, abdominal pain (≥ 3 days), anorexia, rebound tenderness, white blood cell count (> 15,000/μl), C-reactive protein (> 10 mg/dL), and CT findings of a complication) were used for the final model. The AUC (95% CI) for CIOs was 0.875 (0.826-0.923), and χ 2 was 2.969 (p-value = 0.936) with the HL test. Validation using bootstrap samples resulted in an optimism-corrected AUC of 0.858 (0.856-0.861)., Conclusion: A prediction model for clinically important outcomes of AD visiting a single ED showed good discrimination and calibration power with an acceptable range., Competing Interests: Declaration of Competing Interest Nothing to declare is in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Low serum cholesterol is known to be associated with poor prognosis in sepsis patients. On the other hand, there have been few studies on the association between high serum cholesterol, one of the major risk factors for cardiovascular adverse events, and prognosis of sepsis patients. We investigated the relationship between the serum total cholesterol concentration and outcome of sepsis patients., Methods: We conducted a multicenter retrospective cohort study at the emergency departments (EDs) of three urban tertiary teaching hospitals. Patients were divided into three groups according to the initial serum total cholesterol concentration: low cholesterol (cholesterol <120 mg/dL), normal cholesterol (cholesterol 120-200 mg/dL), and high cholesterol (cholesterol >200 mg/dL). Multivariable Cox proportional hazard regression model was used to identify the independent association between the serum total cholesterol concentrations and mortality at 28 days., Results: A total of 4,512 patients were included in the final analysis. The mortality at 28 days of the low, normal, and high cholesterol groups were 24.1%, 14.5%, and 20.5%, respectively (P<0.001). Both the low and high cholesterol groups had a higher risk of death than the normal cholesterol group (low cholesterol group [hazard ratio (HR), 1.46; 95% confidence interval (CIs), 1.25-1.71] and high cholesterol group (HR, 1.57; 95% CI, 1.14-2.16)., Conclusions: Both low and high serum total cholesterol concentrations were associated with higher mortality at 28 days in sepsis patients.

Aim of Study: To investigate whether regional cerebral oxygen saturation (rSO 2 ) differs in out-of-hospital cardiac arrest (OHCA) survivors undergoing targeted temperature management (TTM) 36 °C versus 33 °C., Methods: A randomized clinical trial was conducted at intensive care units in two referral hospitals. Fifty-seven comatose OHCA survivors were randomized into either a 36 °C or 33 °C group. Patients were cooled and maintained at an oesophageal temperature of either 36 °C or 33 °C for 24 hours, rewarmed at a rate of 0.25 °C/hour, and maintained at <37.5 °C until 72 hours. During 72 hours of TTM, rSO 2 was continuously monitored on the left forehead using near-infrared spectroscopy (INVOS TM 5100C). The rSO 2 level at 72 hours was compared between the two groups. Next, serial rSO 2 levels for 72 hours were compared using mixed effects regression. The association between rSO 2 levels and 6-month neurological outcomes was also evaluated., Results: There were no significant differences in the rSO 2 level at 72 hours between the 36 °C and 33 °C groups (p = 0.372). Furthermore, serial rSO 2 levels for 72 hours of TTM were not different between the two groups (p = 0.733). However, low rSO 2 levels, particularly at 24 hours of TTM, were significantly associated with poor 6-month neurological outcomes (odds ratio = 0.899, 95% confidence interval: 0.831-0.974). The area under the receiver operating characteristic curve of the rSO 2 level at 24 hours for poor neurological outcomes was 0.800., Conclusions: Regardless of target temperatures, low rSO 2 levels during TTM were significantly associated with poor 6-month neurological outcomes in OHCA survivors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of the study was to investigate the diagnostic accuracy of initial and post-fluid resuscitation lactate levels in predicting 28 day mortality., Materials and Methods: We retrospectively analyzed a multi-center registry of suspected septic shock cases that was prospectively collected between October 2015 and December 2018 from 11 Emergency Departments. The primary outcome was 28 day mortality. The diagnostic performance of the initial and post-fluid resuscitation lactate levels as a predictor for 28 day mortality was assessed., Results: A total of 2568 patients were included in the final analysis. The overall 28 day mortality rate was 23%. The area under the receiver operating characteristic curve (AUROC) of initial lactate for predicting 28 day mortality was 0.66 (95% CI, 0.64-0.69) and that of after fluid administration lactate was 0.70 (95% CI, 0.67-0.72), and there was a significant difference (p < 0.001). The optimal cutoff point of lactate after fluid administration was 4.4 mmol/L. Compared with this, the Sepsis-3 definition with a lactate level of 2 mmol/L or more was relatively more sensitive and less specific for predicting 28 day mortality., Conclusion: The post-fluid resuscitation lactate level was more accurate than the initial lactate level in predicting 28 day mortality in patients with suspected septic shock., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts of interest or funding sources to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We performed this study to establish a prediction model for 1-year neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients who achieved return of spontaneous circulation (ROSC) immediately after ROSC using machine learning methods., Methods: We performed a retrospective analysis of an OHCA survivor registry. Patients aged ≥ 18 years were included. Study participants who had registered between March 31, 2013 and December 31, 2018 were divided into a develop dataset (80% of total) and an internal validation dataset (20% of total), and those who had registered between January 1, 2019 and December 31, 2019 were assigned to an external validation dataset. Four machine learning methods, including random forest, support vector machine, ElasticNet and extreme gradient boost, were implemented to establish prediction models with the develop dataset, and the ensemble technique was used to build the final prediction model. The prediction performance of the model in the internal validation and the external validation dataset was described with accuracy, area under the receiver-operating characteristic curve, area under the precision-recall curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Futhermore, we established multivariable logistic regression models with the develop set and compared prediction performance with the ensemble models. The primary outcome was an unfavorable 1-year neurological outcome., Results: A total of 1,207 patients were included in the study. Among them, 631, 139, and 153 were assigned to the develop, the internal validation and the external validation datasets, respectively. Prediction performance metrics for the ensemble prediction model in the internal validation dataset were as follows: accuracy, 0.9620 (95% confidence interval [CI], 0.9352-0.9889); area under receiver-operator characteristics curve, 0.9800 (95% CI, 0.9612-0.9988); area under precision-recall curve, 0.9950 (95% CI, 0.9860-1.0000); sensitivity, 0.9594 (95% CI, 0.9245-0.9943); specificity, 0.9714 (95% CI, 0.9162-1.0000); PPV, 0.9916 (95% CI, 0.9752-1.0000); NPV, 0.8718 (95% CI, 0.7669-0.9767). Prediction performance metrics for the model in the external validation dataset were as follows: accuracy, 0.8509 (95% CI, 0.7825-0.9192); area under receiver-operator characteristics curve, 0.9301 (95% CI, 0.8845-0.9756); area under precision-recall curve, 0.9476 (95% CI, 0.9087-0.9867); sensitivity, 0.9595 (95% CI, 0.9145-1.0000); specificity, 0.6500 (95% CI, 0.5022-0.7978); PPV, 0.8353 (95% CI, 0.7564-0.9142); NPV, 0.8966 (95% CI, 0.7857-1.0000). All the prediction metrics were higher in the ensemble models, except NPVs in both the internal and the external validation datasets., Conclusion: We established an ensemble prediction model for prediction of unfavorable 1-year neurological outcomes in OHCA survivors using four machine learning methods. The prediction performance of the ensemble model was higher than the multivariable logistic regression model, while its performance was slightly decreased in the external validation dataset., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Objective: Metabolic acidosis is commonly associated with the disease severity in patients with sepsis or septic shock. This study was performed to investigate the association between serum total carbon dioxide (TCO 2) concentration and 28-day mortality in patients with sepsis., Methods: This study was a multicenter retrospective cohort study of patients with sepsis or septic shock. The relationships between serum TCO 2 and 28-day mortality, bicarbonate, pH, lactate, and anion gap were determined with cubic spline curves. The patients were divided into four groups according to their serum TCO 2 concentration: Group I (TCO 2  > 20 mmol/l), Group II (15 < TCO 2  ≤ 20 mg/dl), Group III (10 < TCO 2  ≤ 15 mmol/l), and Group IV (TCO 2  ≤ 10 mmol/l)., Results: A total of 3168 patients were included in the analysis, and the overall mortality rate was 24.1%. Serum TCO 2 concentrations below 20 mmol/l showed an almost linear correlation with mortality as well as with lactate, bicarbonate, and pH. The 28-day mortality rates of Group I, II, III, and IV were 18.3%, 23.6%, 32.6%, and 50.0%, respectively (p < .001). In Multivariable Cox proportional hazard regression analysis, the groups with lower serum TCO 2 concentrations had a higher risk of 28-day mortality compared with Group I: Group II (Hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.11-1.64), Group III (HR, 1.74; 95% CI, 1.37-2.21), and Group IV (HR, 2.72; 95% CI, 2.03-3.64)., Conclusions: Serum TCO 2 concentrations of 20 mmol/l or less were associated with 28-day mortality in patients with sepsis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)