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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 (ETCO2) 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, ETCO2 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 ETCO2; 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.

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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.

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During recovery from septic shock, circulating mitochondrial N-formyl peptides (mtFPs) predispose to secondary infection by occupying formyl peptide receptor 1 (FPR1) on the neutrophil (polymorphonuclear leukocyte, PMN) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mtFPs in clinical settings. Thus, we studied how to remove mtFPs from septic-shock plasma and whether such removal could preserve cell-surface FPR1 and restore sepsis-induced PMN dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mtFP removal rescued PMN FPR1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mtFP exposure. However, PMN functional recovery occurred in a stepwise fashion over 30 - 90 minutes. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model systems using blood samples obtained from patients with septic shock, anti-mtFP antibodies alone failed to eliminate mtFPs from septic-shock plasma or inhibit mtFP activity. We therefore created a beads-based anti-mtFP antibody cocktail (bb-AMfpA) by combining protein A/sepharose with antibodies specific for the most potent human mtFP chemoattractants. The bb-AMfpA treatment successfully removed those active mtFPs from septic-shock plasma. Furthermore, the bb-AMfpA treatment significantly restored chemotactic and bactericidal dysfunction of PMNs obtained from patients with septic shock who developed secondary infections. By clearing circulating mtFPs, the immobilized anti-mtFP antibody therapy prevented mtFP interactions with surface FPR1, thereby restoring [Ca2+]i-dependent PMN antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock.

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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.

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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.

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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, H2O2 were measured. Nox-1 and H2O2 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, H2O2 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.

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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.

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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.

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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.

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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.

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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.

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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.

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Background: We compared the prognostic accuracy of in-hospital mortality of the initial Sequential Organ Failure Assessment (SOFAini) score at the time of sepsis recognition and resuscitation and the maximum SOFA score (SOFAmax) 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 SOFAini and SOFAmax 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, SOFAmax increased compared with SOFAini, 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 SOFAmax (0.71; 95% confidence interval [CI], 0.69-0.72) was significantly higher than that of SOFAini (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.

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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.

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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.

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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.

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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.

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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.