Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

Enhancing the interferon-γ release assay through omission of nil and mitogen values.

PURPOSE: To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. METHODS: This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. RESULTS: Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09-0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06-0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05-0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. CONCLUSION: The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Different neuroprognostication thresholds of neuron-specific enolase in shockable and non-shockable out-of-hospital cardiac arrest: a prospective multicenter observational study in Korea (the KORHN-PRO registry).

BACKGROUND: Serum neuron-specific enolase (NSE) is the only recommended biomarker for multimodal prognostication in postcardiac arrest patients, but low sensitivity of absolute NSE threshold limits its utility. This study aimed to evaluate the prognostic performance of serum NSE for poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors based on their initial rhythm and to determine the NSE cutoff values with false positive rate (FPR) < 1% for each group. METHODS: This study included OHCA survivors who received targeted temperature management (TTM) and had serum NSE levels measured at 48 h after return of spontaneous circulation in the Korean Hypothermia Network, a prospective multicenter registry from 22 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. The primary outcome was poor outcome at 6 month, defined as a cerebral performance category of 3-5. RESULTS: Of 623 patients who underwent TTM with NSE measured 48 h after the return of spontaneous circulation, 245 had an initial shockable rhythm. Median NSE level was significantly higher in the non-shockable group than in the shockable group (104.6 [40.6-228.4] vs. 25.9 [16.7-53.4] ng/mL, P < 0.001). Prognostic performance of NSE assessed by area under the receiver operating characteristic curve to predict poor outcome was significantly higher in the non-shockable group than in the shockable group (0.92 vs 0.86). NSE cutoff values with an FPR < 1% in the non-shockable and shockable groups were 69.3 (sensitivity of 42.1%) and 102.7 ng/mL (sensitivity of 76%), respectively. CONCLUSION: NSE prognostic performance and its cutoff values with FPR < 1% for predicting poor outcome in OHCA survivors who underwent TTM differed between shockable and non-shockable rhythms, suggesting postcardiac arrest survivor heterogeneity. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02827422.

Performance analysis considering endpoints for three accelerated diagnostic protocols for chest pain.

INTRODUCTION: The modified accelerated diagnostic protocol (ADP) to assess patients with chest pain symptoms using troponin as the only biomarker (mADAPT), the History, ECG, Age, Risk factors, and Troponin (HEART) pathway, and the Emergency Department Assessment of Chest Pain Rule (EDACS)-ADP, are the three most well-known ADPs for patients with chest pain. These ADPs define major adverse cardiac event (MACE) as components of acute myocardial infarction, revascularization, and death; unstable angina is not included as an endpoint. METHODS: We performed a single-center prospective observational study comparing the performance of these 3 ADPs for patients with 30-day MACE with and without unstable angina. We hypothesized that these ADPs will have high sensitivities for MACE without unstable angina, a definition used for score derivation studies. However, when unstable angina is included in the MACE, their performances would be lower than the acceptable rate of >99% sensitivity. RESULTS: A total of 1,214 patients were included in the analysis. When unstable angina was not included in the endpoint, sensitivities for MACE were 99.1% (95% confidence interval [CI]: 96.7-99.9%), 99.5% (95% CI: 97.4-100%), and 100% (95% CI: 98.3-100%) for mADAPT, EDACS-ADP, and HEART pathway, respectively. The HEART pathway had the highest proportion of patients classified as low risk (39.2%, 95% CI: 35.8-42.9%), followed by EDACS-ADP (31.3%, 95% CI: 28.2-34.6%) and mADAPT (29.3%, 95% CI: 26.4-32.5%). However, when unstable angina was included in the MACE, sensitivities were 96.6% (95% CI: 94.4-98.1%) for mADAPT, 97.3% (95% CI: 95.3-98.6%) for EDACS-ADP, and 97.3% (95% CI: 95.3-98.6%) for the HEART pathway, respectively. There were 15 false-negative cases with mADAPT, and 12 false-negative cases each for EDACS-ADP and HEART pathway. CONCLUSION: All three ADPs-mADAPT, EDACS-ADP, and HEART pathway-were similarly accurate in their discriminatory performance for the risk stratification of ED patients presenting with possible ACS when unstable angina was not included in the endpoint. The HEART pathway showed the best combination of sensitivity and proportion of patients that can be classified as safe for early discharge. However, when unstable angina was added to the endpoint, all three ADPs did not show appropriate safety levels and their performances were lower than the acceptable risk of MACE.

Association Between Body Weight Changes and Subsequent Development of Out-of-Hospital Cardiac Arrest: A Population-Based Nested Case-Control Study.

BACKGROUND: Body weight is a modifiable demographic factor. Although the association of body mass index (BMI) categories with sudden cardiac death was reported, dynamic changes of BMI and the risk of cardiac arrest remain unknown. This study aimed to evaluate the association between the out-of-hospital cardiac arrest (OHCA) occurrence within a year and the percent changes of BMI preceding the OHCA. METHODS: This population-based nested case-control study used the National Health Insurance Service Data of Korea. In all, 24,465 patients with non-traumatic OHCA between 2010 and 2018, who underwent national health check-up twice (one within a year and the other within 2-4 years before OHCA) and 32,434 controls without OHCA, were matched for age and sex. The association between the risk of OHCA and BMI percent change stratified by sex was investigated. RESULTS: All the BMI percent changes of ≥ 5% significantly increased the OHCA occurrence with a reverse J-shaped association. Compared to individuals with a stable weight, those with severe (> 15%) BMI decrease had the highest odds ratio (OR) of 4.29 (95% confidence intervals [CIs], 3.72-4.95) for OHCA occurrence followed by those with moderate (10-15%) weight loss (OR, 2.80; 95% CI, 2.55-3.08) and those with severe (> 15%) weigh gain (OR, 2.24; 95% CI, 1.96-2.57), respectively. The impact of weight loss on the cardiac arrest occurrence was more prominent in men, while the impact of weight gain was more prominent in women. CONCLUSION: Significant weight changes increase the risk of OHCA within a year with a reverse J-shaped association. Significant weight loss might be a warning sign for OHCA especially for men.

Association between the number of prehospital defibrillation attempts and a sustained return of spontaneous circulation: a retrospective, multicentre, registry-based study.

BACKGROUND: Currently, there is no consensus on the number of defibrillation attempts that should be made before transfer to a hospital in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the association between the number of defibrillations and a sustained prehospital return of spontaneous circulation (ROSC). METHODS: A retrospective analysis of a multicentre, prospectively collected, registry-based study in Republic of Korea was conducted for OHCA patients with prehospital defibrillation. The primary outcome was sustained prehospital ROSC, and the secondary outcome was a good neurological outcome at hospital discharge, defined as Cerebral Performance Category score 1 or 2. Cumulative incidence of sustained prehospital ROSC and good neurological outcome according to number of defibrillations were examined. Multivariable logistic regression analysis was used to examine whether the number of defibrillations was independently associated with the outcomes. RESULTS: Excluding 172 patients with missing data, a total of 1983 OHCA patients who received prehospital defibrillation were included. The median time from arrest to first defibrillation was 10 (IQR 7-15) min. The numbers of patients with sustained prehospital ROSC and good neurological outcome were 738 (37%) and 549 (28%), respectively. Sustained ROSC rates decreased as the number of defibrillation attempts increased from the first to the sixth (16%, 9%, 5%, 3%, 2% and 1%, respectively). The cumulative sustained ROSC rate, and good neurological outcome rate from initial defibrillation to sixth defibrillation were 16%, 25%, 30%, 34%, 36%, 36% and 11%, 18%, 22%, 25%, 26%, 27%, respectively. With adjustment for clinical characteristics and time to defibrillation, a higher number of defibrillations was independently associated with a lower chance of a sustained ROSC (OR 0.81, 95% CI 0.76 to 0.86) and a lower chance of good neurological outcome (OR 0.86, 95% CI 0.80 to 0.92). CONCLUSIONS: We observed no significant increase in ROSC after five defibrillations, and no absolute increase in ROSC after seven defibrillations. These data provide a starting point for determination of the optimal defibrillation strategy prior to consideration for prehospital extracorporeal cardiopulmonary resuscitation (ECPR) or conveyance to a hospital with an ECPR capability. TRIAL REGISTRATION NUMBER: NCT03222999.

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Augmented-Medication CardioPulmonary Resuscitation Trials in out-of-hospital cardiac arrest: a pilot randomized controlled trial.

BACKGROUND: Previously conducted physician-centered trials on the usefulness of vasopressin have yielded negative results; thus, patient-oriented trials have been warranted. We hypothesize that Augmented-Medication CardioPulmonary Resuscitation could be helpful for selected patients with out-of-hospital cardiac arrest (OHCA). METHODS: This is a double-blind, single-center, randomized, placebo-controlled trial conducted in the emergency department in a tertiary, university-affiliated hospital in Seoul, Korea. A total of 148 adults with non-traumatic OHCA who had initial diastolic blood pressure (DBP) < 20 mm Hg via invasive arterial monitoring during the early cardiac compression period were randomly assigned to two groups. Patients received a dose of 40 IU of vasopressin or placebo with initial epinephrine. The primary endpoint was a sustained return of spontaneous circulation. Secondary endpoints were survival discharge, and neurologic outcomes at discharge. RESULTS: Of the 180 included patients, 32 were excluded, and 148 were enrolled in the trial. A sustained return of spontaneous circulation was achieved by 27 patients (36.5%) in the vasopressin group and 24 patients (32.4%) in the control group (risk difference, 4.1%; P = .60). Survival discharge and good neurologic outcomes did not differ between groups. The trial group had significantly higher median DBPs during resuscitation than the control group (16.0 vs. 14.5 mm Hg, P < 0.01). There was no difference in end-tidal carbon dioxide, acidosis, and lactate levels at baseline, 10 min, and end-time. CONCLUSION: Among patients with refractory vasodilatory shock in OHCA, administration of vasopressin, compared with placebo, did not significantly increase the likelihood of return of spontaneous circulation.

Polyopes affinis Suppressed IFN-γ- and TNF-α-Induced Inflammation in Human Keratinocytes via Down-Regulation of the NF-κB and STAT1 Pathways.

Polyopes affinis is a red algal species commonly found on the South coast and near Jeju Island, Korea. This study aimed to determine whether P. affinis extracts can inhibit the pathogenesis of T-helper-2 (Th2)-mediated inflammation in a human keratinocyte cell line of atopic dermatitis (AD). Cells were incubated with 10 ng/mL of interferon gamma (IFN-γ) and 10 ng/mL of tumor necrosis factor-alpha (TNF-α) at various concentrations of PAB (10, 30, and 60 µg/mL) and PAA (100, 500, and 1000 µg/mL) extracts. A gene-ontology (GO)-enrichment analysis revealed that PAB significantly enriched the genes associated with biological processes such as cell adhesion, immune response, inflammation, and chemokine-mediated pathways. PAB suppressed the expression of the secretory proteins and mRNAs that are associated with the thymus and the production of activation-regulated chemokines (TARC/CCL17) and macrophage-derived chemokines (MDC/CCL22). The effect of the extract on mitogen-activated protein kinases (MAPKs) was related to its inhibition of TARC/CCL17 and MDC/CCL22 production by blocking NF-κB and STAT1 activation. These results suggest that seaweed extract may improve AD by regulating pro-inflammatory chemokines. In conclusion, we first confirmed the existence of phloroglucinol, a polyphenol formed from a precursor called phlorotannin, which is present in PAB, and this result proved the possibility of PAB being used as a treatment for AD.

Types of cancer and outcomes in patients with cancer requiring admission from the emergency department: A nationwide, population-based study, 2016-2017.

BACKGROUND: Emergency department (ED) utilization and emergency admissions by patients with cancer have increased. The authors aimed to evaluate the characteristics of patients with cancer admitted through the ED and determine whether cancer types are related to in-hospital mortality. METHODS: The National Emergency Department Information System database of patients visiting EDs in South Korea between 2016 and 2017 was analyzed. Among 6,179,088 adult patients who presented to an ED with nontraumatic medical illness, patients with cancer were identified. The primary outcome was in-hospital mortality. RESULTS: Patients with cancer accounted for 6.8% of ED visits, and 239,630 patients (57.0%) were admitted to the hospital (intensive care unit [ICU], 9.5%; others, 90.5%). The prevalent cancers requiring hospitalization were lung cancer (15.7%), liver cancer (14.2%), and colon cancer (11.6%). The commonest reasons for admission other than cancer-related medical problems (41.4%) were pneumonia (4.8%) and hepatobiliary infection (2.8%). Overall in-hospital mortality was 16.1% (ICU, 28.3%; general wards, 14.8%); lung cancer (22.9%), liver cancer (19.7%), and leukemia/multiple myeloma (17.8%) showed the highest mortality rates. The highest odds for mortality were for lung cancer (adjusted odds ratio [OR], 2.227; 95% confidence interval [CI], 2.124-2.335; P < .001) and liver cancer (adjusted OR, 1.839; 95% CI, 1.751-1.930; P < .001), which were referenced to genitourinary cancer by multivariable logistic regression analysis. CONCLUSIONS: More than half of the patients with cancer visiting EDs were admitted to the hospital with a mortality rate of 16.1%. Physicians treating patients with cancer and policymakers and planners designing health systems should understand the different prevalences and outcomes of oncological emergencies by cancer type to improve patient care.

Characteristics and clinical outcomes of culture-negative and culture-positive septic shock: a single-center retrospective cohort study.

BACKGROUND: We evaluated the characteristics and outcomes of culture-negative versus culture-positive septic shock. METHODS: We performed a retrospective observational study of data from a prospective registry from 2014 to 2018. A total of 2,499 adult patients with septic shock were enrolled. The primary outcome was 90-day mortality, and the secondary outcomes were the length of hospital stay, a requirement for mechanical ventilation or renal replacement therapy, and in-hospital mortality. RESULTS: Of 1,718 patients with septic shock, 1,012 (58.9%) patients were culture-positive (blood 803, urine 302, sputum 102, others 204) and the median pathogen detection time was 9.5 h (aerobic 10.2 h and anaerobic 9.0 h). The most common site of culture-positive infection was the hepatobiliary tract (39.5%), while for the culture-negative it was the lower respiratory tract (38.2%). The culture-negative group had a lower mean body temperature (37.3 vs 37.7 ℃), lactate (2.5 vs. 3.2 mmol/L), C-reactive protein (11.1 vs 11.9 mg/dL), and sequential organ failure assessment score (7.0 vs. 8.0) than that of the culture-positive group. However, 90-day mortality between the groups was not significantly different (32.7 vs 32.2%, p = 0.83), and the other clinical outcomes also did not differ significantly. Moreover, a shorter culture detection time was correlated with a higher sequential organ failure assessment score but not with mortality. CONCLUSION: Patients with septic shock are frequently culture-negative, especially in cases where the infection focus is in the lower respiratory tract. Although culture-negative was associated with a degree of organ dysfunction, it was not an independent predictor of death.

Background frequency can enhance the prognostication power of EEG patterns categories in comatose cardiac arrest survivors: a prospective, multicenter, observational cohort study.

BACKGROUND: We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns ("highly malignant," "malignant," and "benign") according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. METHODS: This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3-5) at 1 month. RESULTS: Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the "highly malignant" pattern (40.7%) was most prevalent, followed by the "benign" (33.9%) and "malignant" (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with "malignant" patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of "highly malignant" or "malignant" EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. CONCLUSIONS: The "highly malignant" patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422 . Registered 11 September 2016-Retrospectively registered.

Comparison of the CAD consortium and updated Diamond-Forrester scores for predicting obstructive coronary artery disease.

OBJECTIVE: Current guidelines recommend the use of the updated Diamond-Forrester (DF) method and Coronary Artery Disease (CAD) Consortium models to assess the pretest probability of obstructive CAD. The present study aimed to compare the performance of these models among patients with chest pain evaluated in an emergency department (ED). METHODS: We compared three scores (DF, CAD consortium basic, and clinical) among 1247 consecutive patients with chest pain who underwent coronary computed tomographic angiography (CTA). Invasive angiography was performed to confirm the stenosis for those who showed obstructive CAD on CTA, if clinically indicated. Primary outcome was the presence of obstructive CAD (≧50% stenosis). RESULTS: Overall, 426 (34.2%) patients were diagnosed with obstructive CAD. The expected prevalence of CAD was underestimated by the CAD consortium clinical model (23.4%) and overestimated by the DF model (53.1%). For the prediction of obstructive CAD, the CAD consortium clinical model had superior area under the receiver-operating curve (0.754), followed by the CAD consortium basic (0.736), and finally, the DF model (0.718). Whereas the CAD consortium models more accurately classified patients without any CAD or nonobstructive CAD as low-risk patients, the DF model more accurately classified high-risk patients with obstructive CAD. The net reclassification improvement of CAD consortium basic and clinical models were 24.7% and 27.9%, respectively. CONCLUSIONS: Compared with the DF model, the CAD consortium clinical model appears to improve the prediction of low-risk patients with <15% probability of having obstructive CAD. However, this model needs caution when using in high-risk population.

The Prevalence and Emergency Department Utilization of Patients Who Underwent Single and Double Inter-hospital Transfers in the Emergency Department: a Nationwide Population-based Study in Korea, 2016-2018.

BACKGROUND: Inter-hospital transfer (IHT) for emergency department (ED) admission is a burden to high-level EDs. This study aimed to evaluate the prevalence and ED utilization patterns of patients who underwent single and double IHTs at high-level EDs in South Korea. METHODS: This nationwide cross-sectional study analyzed data from the National Emergency Department Information System for the period of 2016-2018. All the patients who underwent IHT at Level I and II emergency centers during this time period were included. The patients were categorized into the single-transfer and double-transfer groups. The clinical characteristics and ED utilization patterns were compared between the two groups. RESULTS: We found that 2.1% of the patients in the ED (n = 265,046) underwent IHTs; 18.1% of the pediatric patients (n = 3,556), and 24.2% of the adult patients (n = 59,498) underwent double transfers. Both pediatric (median, 141.0 vs. 208.0 minutes, P < 0.001) and adult (median, 189.0 vs. 308.0 minutes, P < 0.001) patients in the double-transfer group had longer duration of stay in the EDs. Patient's request was the reason for transfer in 41.9% of all IHTs (111,076 of 265,046). Unavailability of medical resources was the reason for transfer in 30.0% of the double transfers (18,920 of 64,054). CONCLUSION: The incidence of double-transfer of patients is increasing. The main reasons for double transfers were patient's request and unavailability of medical resources at the first-transfer hospitals. Emergency physicians and policymakers should focus on lowering the number of preventable double transfers.

NXP031 Improves Cognitive Impairment in a Chronic Cerebral Hypoperfusion-Induced Vascular Dementia Rat Model through Nrf2 Signaling.

Vascular dementia (VaD) is a progressive cognitive impairment caused by a reduced blood supply to the brain. Chronic cerebral hypoperfusion (CCH) is one cause of VaD; it induces oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, damaging several brain regions. Vitamin C plays a vital role in preventing oxidative stress-related diseases induced by reactive oxygen species, but it is easily oxidized and loses its antioxidant activity. To overcome this weakness, we have developed a vitamin C/DNA aptamer complex (NXP031) that increases vitamin C's antioxidant efficacy. Aptamers are short single-stranded nucleic acid polymers (DNA or RNA) that can interact with their corresponding target with high affinity. We established an animal model of VaD by permanent bilateral common carotid artery occlusion (BCCAO) in 12 week old Wistar rats. Twelve weeks after BCCAO, we injected NXP031 into the rats intraperitoneally for two weeks at moderate (200 mg/4 mg/kg) and high concentrations (200 mg/20 mg/kg). NXP031 administration alleviates cognitive impairment, microglial activity, and oxidative stress after CCH. NXP031 increased the expression of basal lamina (laminin), endothelial cell (RECA-1, PECAM-1), and pericyte (PDGFRß); these markers maintain the BBB integrity. We found that NXP031 administration activated the Nrf2-ARE pathway and increased the expression of SOD-1 and GSTO1/2. These results suggest that this new aptamer complex, NXP031, could be a therapeutic intervention in CCH-induced VaD.

Development and validation of the VitaL CLASS score to predict mortality in stage IV solid cancer patients with septic shock in the emergency department: a multi-center, prospective cohort study.

BACKGROUND: Clinical decision-making of invasive high-intensity care for critically ill stage IV cancer patients in the emergency department (ED) is challenging. A reliable and clinically available prognostic score for advanced cancer patients with septic shock presented at ED is essential to improve the quality of intensive care unit care. This study aimed to develop a new prognostic score for advanced solid cancer patients with septic shock available early in the ED and to compare the performance to the previous severity scores. METHODS: This multi-center, prospective cohort study included consecutive adult septic shock patients with stage IV solid cancer. A new scoring system for 28-day mortality was developed and validated using the data of development (January 2016 to December 2017; n = 469) and validation sets (January 2018 to June 2019; n = 428). The developed score's performance was compared to that of the previous severity scores. RESULTS: New scoring system for 28-day mortality was based on six variables (score range, 0-8): vital signs at ED presentation (respiratory rate, body temperature, and altered mentation), lung cancer type, and two laboratory values (lactate and albumin) in septic shock (VitaL CLASS). The C-statistic of the VitaL CLASS score was 0.808 in the development set and 0.736 in the validation set, that is superior to that of the Sequential Organ Failure Assessment score (0.656, p = 0.01) and similar to that of the Acute Physiology and Chronic Health Evaluation II score (0.682, p = 0.08). This score could identify 41% of patients with a low-risk group (observed 28-day mortality, 10.3%) and 7% of patients with a high-risk group (observed 28-day mortality, 73.3%). CONCLUSIONS: The VitaL CLASS score could be used for both risk stratification and as part of a shared clinical decision-making strategy for stage IV solid cancer patients with septic shock admitting at ED within several hours.

Prognostic accuracy of the sequential organ failure assessment (SOFA) and quick SOFA for mortality in cancer patients with sepsis defined by systemic inflammatory response syndrome (SIRS).

PURPOSE: We aimed to assess the prognostic accuracy of SOFA and qSOFA scores in cancer patients with sepsis, and also to determine if the addition of hyperlactatemia to qSOFA increases the accuracy in predicting the 30-day mortality. MATERIAL AND METHOD: We consecutively included adult active cancer patients (age ≥ 18 years) with sepsis defined by SIRS who visited the emergency department (ED) from May 1st to July 30th, 2017. Data were collected retrospectively through reviewing medical records. The SOFA and qSOFA scores were calculated with the initial variables at the time of ED admission. The primary endpoint was 30-day mortality. RESULT: Of 1137 screened, 301 were included. The 30-day mortality was 14.3% (43 patients). Among the total 301, the SOFA score was ≥ 2 in 168 and qSOFA ≥ 2 in 23. For those with SOFA ≥ 2 and < 2, the mortality was 23.2% and 3%, respectively (P < 0.001). For those with qSOFA ≥ 2 and < 2, the mortality was 47.8% and 11.5%, respectively (P < 0.001). The AUROC of 30-day mortality for qSOFA was lower than that for SOFA (0.66 (95% CI, 0.56-0.75) vs. 0.79 (95% CI, 0.72-0.87), P = 0.004)). However, the combination of qSOFA with lactate ≥ 2 threshold considerably enhanced a discrimination capacity for mortality with an AUROC 0.77 (95% CI, 0.69-0.85), which was similar to SOFA (P = 0.11). CONCLUSION: In cancer patients with sepsis, qSOFA was inferior to SOFA in predicting mortality. However, adding lactate to qSOFA resulted in greater prognostic accuracy for short-term mortality, comparable with SOFA.

Thromboelastography for prediction of hemorrhagic transformation in patients with acute ischemic stroke.

BACKGROUND: Thromboelastography (TEG) provides a rapid assessment of the hemostatic processes of a patient in emergency settings. There are limited data on TEG as a predictive tool for hemorrhagic transformation in patients with acute ischemic stroke. We investigated whether TEG values on admission could predict hemorrhagic transformation in patients with acute ischemic stroke. METHODS: TEG was performed prospectively in 772 patients who satisfied the criteria of the critical pathway for acute stroke that have neurologic symptoms in 6 h at the emergency department between March and December 2018. After excluding 114 patients, 628 patients were evaluated, and finally, 205 patients with acute ischemic stroke were included. The primary outcome is hemorrhagic transformation, defined as the presence of blood in brain on follow-up imaging study and secondary outcome is neurological deterioration, defined as a 2-point increase on the National Institutes of Health Stroke Scale (NIHSS) within 72 h of stroke onset. RESULTS: Of the 205 ischemic stroke patients (mean age 67 ±â€¯13 years, 66.3% male), hemorrhagic transformation was identified in 28 (13.7%) patients, and neurological deterioration was occurred in 24 (11.7%), and both events in 9 (4.4%). The TEG value of R (reaction time) <5 min was significantly higher in patients with hemorrhagic transformation than in patients without hemorrhagic transformation (81.1% vs. 60.5%, p = 0.027), and based on multivariable analysis, this was an independent predictor of hemorrhagic transformation (odds ratio 3.215 [95% confidence interval: 1.153-8.969]). CONCLUSIONS: In patients with acute ischemic stroke, TEG value of R < 5 min can identify patients who have an increased risk of hemorrhagic transformation during hospitalization.

Identifying low-risk chest pain in the emergency department: Obstructive coronary artery disease and major adverse cardiac events.

BACKGROUND: Accurate risk stratification for obstructive coronary artery disease (CAD) and major cardiac adverse events (MACE) is important in emergency departments. We compared six established chest pain risk scores (the HEART score, CAD basic model, CAD clinical model, TIMI, GRACE, uDF) for prediction of obstructive CAD and MACE. METHODS: Patients who presented to the emergency department with chest pain or symptoms of suspected CAD and underwent coronary computed tomographic angiography were analyzed. The primary endpoint was adverse outcomes including the presence of obstructive CAD (≥50% stenosis) and the occurrence of MACE within 6 weeks. We compared the risk scores by the area under the receiver-operating characteristic curve (AUC) and calculated their respective net reclassification index (NRI). RESULTS: Adverse outcomes occurred in 285 (28.4%) out of the 1002 patients included. For the prediction of adverse outcomes, the AUC of the HEART score (0.792) was superior to those of the CAD clinical model (0.760), CAD basic model (0.749), TIMI (0.749), uDF (0.703), and GRACE (0.653). In terms of the NRI, the HEART score significantly improved the reclassification abilities of the uDF (0.39), GRACE score (0.27), CAD basic model (0.11), TIMI (0.10), and CAD clinical model (0.08) (all P < 0.05). The HEART score also had the highest negative predictive value as well (0.893). CONCLUSIONS: The HEART score was superior to other cardiac risk scores in predicting both obstructive CAD and MACE. However, due to the high false-negative rate (11%) of the HEART score, its use for identifying low-risk patients should be considered with caution.