Afebrile status at the time of emergency department visit is associated with delayed antibiotic therapy in patients with sepsis (revised).

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.

Temperature trajectories and mortality in hypothermic sepsis patients.

OBJECTIVES: Hypothermia is associated with poor outcomes in sepsis patients, and hypothermic sepsis patients exhibit temperature alterations during initial treatment. The objective of this study was to classify hypothermic sepsis patients based on body temperature trajectories and investigate the associations of these patients with 28-day mortality. METHODS: This was a retrospective analysis of prospectively collected data from adult sepsis or septic shock patients who visited three emergency departments between August 2014 and December 2019. Hypothermic sepsis was defined as an initial body temperature <36 °C. delta temperature was calculated by subtracting the 0 h body temperature from the 6 h body temperature. We divided the patients into three groups according to delta temperature: Group A (delta temperature ≤ 0), Group B (0 < delta temperature ≤ 1) and Group C (delta temperature > 1). The primary outcome was 28-day mortality, and a multivariable Cox proportional hazards regression model was generated. RESULTS: Among 7344 patients with sepsis or septic shock, 325 hypothermic patients were included in the analysis, and the overall mortality rate was 36%. While initial body temperature was not different between survivors and nonsurvivors, survivors exhibited a higher body temperature at 6 h. The 28-day mortality rates for Groups A, B and C were 53.1%, 36.0%, and 30.0%, respectively, and Group A had significantly higher mortality than Group C did (p < 0.05). Group C demonstrated a 44.2% decrease in 28-day mortality compared to Group A (adjusted hazard ratio of 0.558; 95% confidence interval of 0.330-0.941). CONCLUSIONS: In hypothermic sepsis patients, an increase of 1 °C or more in body temperature after the initial 6 h is associated with a reduced risk of 28-day mortality.

Circulating mitochondrial N-formyl peptides contribute to secondary nosocomial infection in patients with septic shock.

Secondary infections typically worsen outcomes of patients recovering from septic shock. Neutrophil [polymorphonuclear leukocytes (PMNs)] migration to secondarily inoculated sites may play a key role in inhibiting progression from local bacterial inoculation to secondary infection. Mitochondrial N-formyl peptide (mtFP) occupancy of formyl peptide receptor-1 (FPR1) has been shown to suppress PMN chemotaxis. Therefore, we studied the association between circulating mtFPs and the development of secondary infection in patients with septic shock. We collected clinical data and plasma samples from patients with septic shock admitted to the intensive care unit for longer than 72 h. Impacts of circulating nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) upon clinical outcomes were analyzed. Next, the role of ND6 in PMN chemotaxis was investigated using isolated human PMNs. Studying plasma samples from 97 patients with septic shock, we found that circulating ND6 levels at admission were independently and highly associated with the development of secondary infection (odds ratio = 30.317, 95% CI: 2.904 to 316.407, P = 0.004) and increased 90-d mortality (odds ratio = 1.572, 95% CI: 1.002 to 2.465, P = 0.049). In ex vivo experiments, ND6 pretreatment suppressed FPR1-mediated PMN chemotactic responses to bacterial peptides in the presence of multiple cytokines and chemokines, despite increased nondirectional PMN movements. Circulating mtFPs appear to contribute to the development of secondary infection and increased mortality in patients with septic shock who survive their early hyperinflammatory phase. The increased susceptibility to secondary infection is probably partly mediated by the suppression of FPR1-mediated PMN chemotaxis to secondary infected sites.

Trends in Healthy Life Expectancy (HALE) and Disparities by Income and Region in Korea (2008-2020): Analysis of a Nationwide Claims Database.

BACKGROUND: Healthy life expectancy is a well-recognized indicator for establishing health policy goals used in Korea's Health Plan. This study aimed to explore Koreans' healthy life expectancy and its gender, income, and regional disparities from 2008 to 2020. METHODS: This study was conducted on the entire population covered by health insurance and medical aid program in Korea. The incidence-based "years lived with disability" for 260 disease groups by gender, income level, and region was calculated employing the methodology developed in the Korean National Burden of Disease Study, and it was used as the number of healthy years lost to calculate health-adjusted life expectancy (HALE). RESULTS: Koreans' HALE increased from 68.89 years in 2008 to 71.82 years in 2020. Although the gender disparity in HALE had been decreasing, it increased to 4.55 years in 2020. As of 2020, 5.90 years out of 8.67 years of the income disparity (Q5-Q1) in HALE were due to the disparity between Q1 and Q2, the low-income groups. Income and regional disparities in HALE exhibited an increasing trend, and these disparities were higher in men than in women. CONCLUSION: A subgroup with a low health level was identified through the HALE results, and it was confirmed that improving the health level of this population can reduce health inequalities and improve health at the national level. Further exploration of the HALE calculation methodology may help in the development of effective policies such as prioritizing interventions for health risk factors.

Measuring the Burden of Disease in Korea Using Disability-Adjusted Life Years (2008-2020).

BACKGROUND: The measurement of health levels and monitoring of characteristics and trends among populations and subgroups are essential for informing evidence-based policy decisions. This study aimed to examine the burden of disease in Korea for both the total population and subgroups in 2020, as well as analyze changes in disease burden from 2008 to 2020. METHODS: We employed the methodology developed in the Korean National Burden of Disease and Injuries Study to calculate disability-adjusted life years (DALYs) by sex, causes, region, and income level from 2008 to 2020. DALYs were derived by combining years of life lost and years lived with disability. RESULTS: In 2020, the burden of disease for the Korean population was estimated to be 25,439 DALYs per 100,000 population, reflecting a 13.8% increase since 2008. The leading causes of DALYs were diabetes mellitus, followed by low back pain and ischemic stroke. A sex-specific gap reversal was observed, with the disease burden for men surpassing that of women starting in 2017. Furthermore, variations in disease burden were identified across 250 regions and income quintiles. CONCLUSION: It is imperative to establish appropriate health policies that prioritize the diseases with significantly increasing burdens and subgroups experiencing high disease burdens. The findings of this study are expected to serve as a foundation for developing healthcare policies aimed at improving the health levels of Koreans and achieving health equity.

Trends of Gaps Between Health-Adjusted Life Expectancy and Life Expectancy at the Regional Level in Korea Using a Group-Based Multi-Trajectory Modeling Approach (2008-2019).

BACKGROUND: Health-adjusted life expectancy (HALE) is an indicator of the average lifespan in good health. Through this study, we aimed to identify regional disparities in the gap between HALE and life expectancy, considering the trends that have changed over time in Korea. METHODS: We employed a group-based multi-trajectory modeling approach to capture trends in the gap between HALE and life expectancy at the regional level from 2008 to 2019. HALE was calculated using incidence-based "years lived with disability." This methodology was also employed in the Korean National Burden of Disease Study. RESULTS: Based on five different information criteria, the most fitted number of trajectory groups was seven, with at least 11 regions in each group. Among the seven groups, one had an exceptionally large gap between HALE and life expectancy compared to that of the others. This group was assigned to 17 regions, of which six were metropolitan cities. CONCLUSION: Based on the results of this study, we identified regions in which health levels have deteriorated over time, particularly within specific areas of metropolitan cities. These findings can be used to design comprehensive policy interventions for community health promotion and urban regeneration projects in the future.

Combination Therapy of Niacin and Apocynin Attenuates Lung Injury During Sepsis in Rats.

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.

Preexisting Clinical Frailty Is Associated With Worse Clinical Outcomes in Patients With Sepsis.

OBJECTIVES: Frailty is a multidimensional syndrome or state of increased vulnerability to poor resolution of homoeostasis following a stressor event. Frailty is common in patients with sepsis. Sepsis and frailty are both associated with older age and chronic medical conditions. However, there is limited evidence about the direct association between frailty and sepsis. The aim of this study is to determine the association between preexisting clinical frailty and clinical outcomes in patients with sepsis. DESIGN: A nationwide propensity score-matched cohort study analyzing data prospectively collected between September 2019 and February 2020. SETTING: Nineteen tertiary or university-affiliated hospitals in South Korea. PATIENTS: Adult patients who were diagnosed with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Frailty status was assessed using the Clinical Frailty Scale. All patients were classified as "frail" (Clinical Frailty Scale score, 5-9) or "nonfrail" (Clinical Frailty Scale score, 1-4). Propensity score matching identified comparable nonfrail patients. The primary outcome was inhospital mortality. Multivariable logistic regression analysis was used to evaluate the association between frailty and inhospital mortality. The propensity score-matched cohort comprised 468 nonfrail patients and 468 frail patients; all covariate imbalances were alleviated. In the matched cohort (mean age, 69 ± 14 yr), 27.2% had septic shock at presentation. Inhospital mortality was 34.2% in the frail group and 26.9% in the nonfrail group (p = 0.019). The adjusted odds ratio for inhospital mortality in the frail group compared with the nonfrail group was 2.00 (95% CI, 1.39-2.89; p < 0.001). Among the patients who survived to discharge, the frail group was less likely to be discharged home compared with the nonfrail group, 64.0% versus 81.3%, respectively (p < 0.001). CONCLUSIONS: In patients with sepsis, preexisting clinical frailty is associated with worse clinical outcomes than that in nonfrail patients, including inhospital mortality and discharge to home.

Hypernatremia is associated with poor long-term neurological outcomes in out-of-hospital cardiac arrest survivors.

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.

Trend of Disease Burden of North Korean Defectors in South Korea Using Disability-adjusted Life Years from 2010 to 2018.

BACKGROUND: This study aimed to examine the disease burden of North Korean defectors in South Korea by sex, age, and disease from 2000 to 2018 and to study the changes in the disease burden over time. METHODS: Based on the incidence-based disability-adjusted life year (DALY) developed in a Korean National Burden of Disease (KNBD) study, we calculated the years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) for approximately 22,753 North Korean defectors in South Korea whose claims data were available from the National Health Insurance Service (NHIS). RESULTS: In 2018, the rates of YLL, YLD, and DALY for North Korean defectors per 100,000 population was 3,763 (male 8,491; female 2,404), 37,683 (male 27,742; female 40,539), and 41,446 (male 36,233; female 42,943), respectively. Major depressive disorders constituted the highest DALY, followed by cirrhosis of the liver and low back pain. The disease burden of North Korean defectors consistently decreased from 2010 to 2018. The decrease in YLD contributed to the overall decline in DALY per 100,000 population in 2018, which decreased by 25.2% compared to that in 2010. CONCLUSION: This is the first study to measure the disease burden of North Korean defectors in South Korea. Given the decreasing or substantially increasing trends in disease burden, it is necessary to establish appropriate public health policies in a timely manner, and the results of this study provide a basis for the development of customized public health and healthcare policies for North Korean defectors in South Korea.

Prediction of Neurological Outcomes in Out-of-hospital Cardiac Arrest Survivors Immediately after Return of Spontaneous Circulation: Ensemble Technique with Four Machine Learning Models.

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.

Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker-Treated Swine.

BACKGROUND: Beta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. MATERIALS AND METHODS: Controlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage-only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). RESULTS: PoPV was well correlated with PPV in controlled hemorrhage-only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. CONCLUSIONS: The diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.

Years of Life Lost Attributable to COVID-19 in High-incidence Countries.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a major public health problem of international concern. It is important to estimate its impact of COVID-19 for health policy decision-making. We estimated the years of life lost (YLLs) due to COVID-19 in high-incidence countries. METHODS: We collected the YLLs due to COVID-19 in 30 high-incidence countries as of April 13, 2020 and followed up as of July 14, 2020. Incidence and mortality were collected using each country's formal reports, articles, and other electronic sources. The life expectancy of Japanese females by age and the UN population data were used to calculate YLLs in total and per 100,000. RESULTS: As of April 22, 2020, there were 1,699,574 YLLs due to COVID-19 in 30 high-incidence countries. On July 14, 2020, this increased to 4,072,325. Both on April 22 and July 14, the total YLLs due to COVID-19 was highest in the USA (April 22, 534,481 YLLs; July 14, 1,199,510 YLLs), and the YLLs per 100,000 population was highest in Belgium (April 22, 868.12 YLLs/100,000; July 14, 1,593.72 YLLs/100,000). YLLs due to COVID-19 were higher among males than among females and higher in those aged ≥ 60 years than in younger individuals. Belgium had the highest proportion of YLLs attributable to COVID-19 as a proportion of the total YLLs and the highest disability-adjusted life years per 100,000 population. CONCLUSION: This study estimated YLLs due to COVID-19 in 30 countries. COVID-19 is a high burden in the USA and Belgium, among males and the elderly. The YLLs are very closely related with the incidence as well as the mortality. This highlights the importance of the early detection of incident case that minimizes severe acute respiratory syndrome coronavirus-2 fatality.

Delayed endoscopy is associated with increased mortality in upper gastrointestinal hemorrhage.

OBJECTIVES: To determine the association between delayed (>24 h) endoscopy and hospital mortality in patients with upper gastrointestinal hemorrhage (UGIH). METHODS: We retrospectively analyzed all adult patients with UGIH who underwent endoscopy in a single emergency room for 2 years. The primary exposure was defined as >24 h from the ED visit to the first endoscopy. The primary outcome was defined as all cause hospital mortality. Secondary outcomes were intensive care unit admission rate, ED length of stay, and hospital length of stay. RESULTS: Among 1101 patients enrolled, 898 received endoscopy within 24 h (early group) and 203 received endoscopy after 24 h (delayed group). The hospital mortality of early and delayed group was 2.8% and 6.4%, respectively (unadjusted relative risk [RR] 2.30: 95% CI, 1.20-4.42, p = 0.012). This was significant after adjusting covariates including AIMS65 and Glasgow-Blatchford score (adjusted RR 2.23: 95% CI, 1.18-4.20, p = 0.013). Intensive care unit admission rate was not different between two groups. ED and hospital length of stay were significantly longer in delayed group. CONCLUSIONS: Endoscopy performed after 24 h was associated with increased hospital mortality in UGIH. Patients in the delayed group stayed longer in the ED and in the hospital.

Relative tachycardia is associated with poor outcomes in post-cardiac arrest patients regardless of therapeutic hypothermia.

BACKGROUND: To investigate whether the relationship between heart rate and neurological outcome is independent of therapeutic hypothermia (TH) and whether heart rate is related to hemodynamic instability post-cardiac arrest. METHODS: Retrospective review of an out-of-hospital cardiac arrest registry was performed. The primary exposure was heart rate quartiles at 24 h post-cardiac arrest. The primary outcome was a poor neurological outcome, which was defined as having a cerebral performance category (CPC) of 3-5 at 28 days. Secondary outcomes were mean blood pressure and serum lactate at 24 h and Sequential Organ Failure Assessment (SOFA) scores at admission. RESULTS: In total, 155 patients were enrolled. The proportion of patients with a poor CPC was significantly greater in higher heart rate quartiles; similar results were observed in patients who did and did not undergo TH. Serum lactate levels at 24 h were significantly higher in the 3rd and 4th quartile groups than in the 1st quartile group. Additionally, SOFA scores were significantly higher in the 4th quartile group than in the 1st and 3rd quartile groups. CONCLUSIONS: Relative tachycardia is associated with poor neurological outcomes in post-cardiac arrest patients, independent of TH, and with higher serum lactate levels and admission SOFA scores.

Niacin and Selenium Attenuate Brain Injury After Cardiac Arrest in Rats by Up-Regulating DJ-1-Akt Signaling.

OBJECTIVES: To determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Rat cortex neurons and male Sprague-Dawley rats (n = 68). INTERVENTIONS: In rat cortex neurons underwent 90 minutes of oxygen-glucose deprivation and 22.5 hours of reoxygenation, effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 µM) were investigated. The role of DJ-1 was determined using DJ-1 knockdown cells. In cardiac arrest rats, posttreatment effects of the combination therapy of niacin (360 mg/kg) and selenium (60 µg/kg) were evaluated. MEASUREMENTS AND MAIN RESULTS: In oxygen-glucose deprivation and 22.5 hours of reoxygenation cells, combination therapy synergistically activated the glutathione redox cycle by a niacin-induced increase in glutathione reductase and a selenium-induced increase in glutathione peroxidase activities and reduced hydrogen peroxide level. It increased phosphorylated Akt and intranuclear Nuclear factor erythroid 2-related factor 2 expression and attenuated neuronal injury. However, these benefits were negated by DJ-1 knockdown. In cardiac arrest rats, combination therapy increased DJ-1, phosphorylated Akt, and intranuclear nuclear factor erythroid 2-related factor 2 expression, suppressed caspase 3 cleavage, and attenuated histologic injury in the brain tissues. It also improved the 7-day Neurologic Deficit Scales from 71.5 (66.0-74.0) to 77.0 (74.-80.0) (p = 0.02). CONCLUSIONS: The combination therapy of clinically relevant doses of niacin and selenium attenuated brain injury and improved neurologic outcome in cardiac arrest rats. Its benefits were associated with reactive oxygen species reduction and subsequent DJ-1-Akt signaling up-regulation.

Prognostic performance of Emergency Severity Index (ESI) combined with qSOFA score.

OBJECTIVE: We conducted this study to investigate whether ESI combined with qSOFA score (ESI+qSOFA) predicts hospital outcome better than ESI alone in the emergency department (ED). METHODS: This was a retrospective study for patients aged over 15years who visited an ED of a tertiary referral hospital from January 1st, 2015 to December 31st, 2015. We calculated and compared predictive performances of ESI alone and ESI+qSOFA for prespecified outcomes. The primary outcome was hospital mortality, and the secondary outcome was composite outcome of in-hospital mortality and ICU admission. We calculated in-hospital mortality rates by positive qSOFA in each subgroup divided according to ESI levels (1, 2, 3, 4+5). RESULTS: 43,748 patients were enrolled. The area under receiver-operating characteristics curves were higher in ESI+qSOFA than in ESI alone for both mortality and composite outcome (0.786 vs. 0.777, P<.001 for mortality; 0.778 vs. 0.774, P<.001 for composite outcome). In each subgroup divided by ESI levels, patients with positive qSOFA had significantly higher in-hospital mortality rate compared to those with negative qSOFA (20.4% vs. 14.7%, P=.117 in ESI level 1 subgroup; 11.3% vs. 2.7%, P=.001 in ESI level 2 subgroup; 2.3% vs. 0.4%, P<.001 in ESI level 3 subgroup; 0.0% vs. 0.0% in ESI level 4 or 5 subgroup). CONCLUSION: The prognostic performance of ESI+qSOFA for in-hospital mortality was significantly higher than that of ESI alone. Within each subgroup, patients with positive qSOFA had higher in-hospital mortality compared to those with negative qSOFA.

Niacin and Selenium Attenuate Sepsis-Induced Lung Injury by Up-Regulating Nuclear Factor Erythroid 2-Related Factor 2 Signaling.

OBJECTIVES: To determine whether the combination therapy of niacin and selenium attenuates lung injury and improves survival during sepsis in rats and whether its benefits are associated with the activation of the glutathione redox cycle and up-regulation of nuclear factor erythroid 2-related factor 2. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Human lung microvascular endothelial cells and male Sprague-Dawley rats (n = 291). INTERVENTION: In lipopolysaccharide-exposed cells, the dose-related effects of niacin and selenium were assessed, and the therapeutic effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 µM) were evaluated. The role of nuclear factor erythroid 2-related factor 2 was determined using nuclear factor erythroid 2-related factor 2 knockdown cells. In endotoxemic and cecal ligation and puncture with antibiotics rats, the therapeutic effects of the posttreatments of clinically relevant doses of niacin (360 mg/kg) and selenium (60 µg/kg) were evaluated. MEASUREMENTS AND MAIN RESULTS: Combination therapy reduced the hydrogen peroxide level via the synergistic activation of the glutathione redox cycle, which involves niacin-induced increases in glutathione reductase activity, and reduced the glutathione level and a selenium-induced increase in glutathione peroxidase activity. Combination therapy contributed to the up-regulation of nuclear factor erythroid 2-related factor 2, enhancement of glutathione synthesis, and down-regulation of nuclear factor κB signaling, but nuclear factor erythroid 2-related factor 2 knockdown inhibited the enhancement of glutathione synthesis and down-regulation of the nuclear factor κB pathway. The therapeutic effects of combination therapy on endotoxemic rats were consistent with those on lipopolysaccharide-exposed cells. In addition, the posttreatment of combination therapy attenuated lung injury and improved survival in endotoxemic and cecal ligation and puncture with antibiotics rats. However, individual therapies of niacin or selenium failed to achieve these benefits. CONCLUSIONS: The combination therapy of niacin and selenium attenuated lung injury and improved survival during sepsis. Its therapeutic benefits were associated with the synergistic activation of the glutathione redox cycle, reduction of hydrogen peroxide level, and up-regulation of nuclear factor erythroid 2-related factor 2.

Plasma glutathione reductase activity and prognosis of septic shock.

BACKGROUND: Our aim was to investigate whether plasma glutathione reductase (GR) activity is well correlated with the erythrocyte-reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio and is associated with the mortality of septic shock. MATERIALS AND METHODS: This study was conducted on male Sprague-Dawley rats and patients admitted to the intensive care unit with septic shock. To induce endotoxemia in rats, vehicle or lipopolysaccharide (LPS) at dosages of 5 or 10 mg/kg were injected into a tail vein. Animals were then euthanized 6 h post-LPS. Based on the 28-d mortality, the enrolled patients were divided into the survivors and nonsurvivors. We obtained blood samples from patients at admission (0 h) and 24 h after admission to the intensive care unit. RESULTS: In endotoxemic rats, the erythrocyte GSH/GSSG ratio, erythrocyte GR activity, and plasma GR activity in the 10 mg/kg of LPS group were lower than those in the sham and 5 mg/kg of LPS groups. In patients with septic shock, decrease in plasma GR activity at 24 h was independently associated with an increase in 28-d mortality (odds ratio, 0.828; 95% confidence interval, 0.690-0.992, P = 0.041). Plasma GR activity was correlated with erythrocyte GR activity (Spearman ρ = 0.549, P < 0.001) and the erythrocyte GSH/GSSG ratio (rho = 0.367, P = 0.009) at 24 h. CONCLUSIONS: Plasma GR activity was well correlated with erythrocyte GR activity and the erythrocyte GSH/GSSG ratio, and a decrease in plasma GR activity was associated with an increase in the mortality of septic shock patients.