Hyperkalemia Detection in Emergency Departments Using Initial ECGs: A Smartphone AI ECG Analyzer vs. Board-Certified Physicians.

BACKGROUND: Hyperkalemia is a potentially fatal condition that mandates rapid identification in emergency departments (EDs). Although a 12-lead electrocardiogram (ECG) can indicate hyperkalemia, subtle changes in the ECG often pose detection challenges. An artificial intelligence application that accurately assesses hyperkalemia risk from ECGs could revolutionize patient screening and treatment. We aimed to evaluate the efficacy and reliability of a smartphone application, which utilizes camera-captured ECG images, in quantifying hyperkalemia risk compared to human experts. METHODS: We performed a retrospective analysis of ED hyperkalemic patients (serum potassium ≥ 6 mmol/L) and their age- and sex-matched non-hyperkalemic controls. The application was tested by five users and its performance was compared to five board-certified emergency physicians (EPs). RESULTS: Our study included 125 patients. The area under the curve (AUC)-receiver operating characteristic of the application's output was nearly identical among the users, ranging from 0.898 to 0.904 (median: 0.902), indicating almost perfect interrater agreement (Fleiss' kappa 0.948). The application demonstrated high sensitivity (0.797), specificity (0.934), negative predictive value (NPV) (0.815), and positive predictive value (PPV) (0.927). In contrast, the EPs showed moderate interrater agreement (Fleiss' kappa 0.551), and their consensus score had a significantly lower AUC of 0.662. The physicians' consensus demonstrated a sensitivity of 0.203, specificity of 0.934, NPV of 0.527, and PPV of 0.765. Notably, this performance difference remained significant regardless of patients' sex and age (P < 0.001 for both). CONCLUSION: Our findings suggest that a smartphone application can accurately and reliably quantify hyperkalemia risk using initial ECGs in the ED.

Serum total carbon dioxide as a prognostic factor for 28-day mortality in patients with sepsis.

OBJECTIVE: Metabolic acidosis is commonly associated with the disease severity in patients with sepsis or septic shock. This study was performed to investigate the association between serum total carbon dioxide (TCO2) concentration and 28-day mortality in patients with sepsis. METHODS: This study was a multicenter retrospective cohort study of patients with sepsis or septic shock. The relationships between serum TCO2 and 28-day mortality, bicarbonate, pH, lactate, and anion gap were determined with cubic spline curves. The patients were divided into four groups according to their serum TCO2 concentration: Group I (TCO2 > 20 mmol/l), Group II (15 < TCO2 ≤ 20 mg/dl), Group III (10 < TCO2 ≤ 15 mmol/l), and Group IV (TCO2 ≤ 10 mmol/l). RESULTS: A total of 3168 patients were included in the analysis, and the overall mortality rate was 24.1%. Serum TCO2 concentrations below 20 mmol/l showed an almost linear correlation with mortality as well as with lactate, bicarbonate, and pH. The 28-day mortality rates of Group I, II, III, and IV were 18.3%, 23.6%, 32.6%, and 50.0%, respectively (p < .001). In Multivariable Cox proportional hazard regression analysis, the groups with lower serum TCO2 concentrations had a higher risk of 28-day mortality compared with Group I: Group II (Hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.11-1.64), Group III (HR, 1.74; 95% CI, 1.37-2.21), and Group IV (HR, 2.72; 95% CI, 2.03-3.64). CONCLUSIONS: Serum TCO2 concentrations of 20 mmol/l or less were associated with 28-day mortality in patients with sepsis.

The index of oxygenation to respiratory rate as a prognostic factor for mortality in Sepsis.

OBJECTIVES: An index combining respiratory rate and oxygenation (ROX) has been introduced, and the ROX index is defined as the ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate. In sepsis, hypoxemia and tachypnea are commonly observed. We performed this study to investigate the association between the ROX index and 28-day mortality in patients with sepsis or septic shock. METHODS: This retrospective study included 2862 patients. The patients were divided into three groups according to the ROX index: Group I (ROX index >20), Group II (ROX index >10 and ≤ 20), and Group III (ROX index ≤10). RESULTS: The median ROX index was significantly lower in the nonsurvivors than in the survivors (12.8 and 18.2, respectively) (p < 0.001). The 28-day mortality rates in Groups I, II and III were 14.5%, 21.3% and 34.4%, respectively (p < 0.001). In the multivariable Cox regression analysis, Group III had an approximately 40% higher risk of death than Group I during the 28-day period (hazard ratio = 1.41, 95% confidence interval 1.13-1.76). The area under the curve of the ROX index was significantly higher than that of the quick Sequential Organ Failure Assessment score (p < 0.001). CONCLUSIONS: The ROX index was lower in nonsurvivors than in survivors, and a ROX index less than or equal to 10 was an independent prognostic factor for 28-day mortality in patients with sepsis or septic shock. Therefore, the ROX index could be used as a prognostic marker in sepsis.

Antibiotic prescription consistent with guidelines in emergency department is associated with 30-day survival in severe community-acquired pneumonia.

BACKGROUND: The selection of initial empirical antibiotics is an important issue in the treatment of severe community-acquired pneumonia (CAP). This study aimed to investigate whether empirical antibiotic prescription concordant with guidelines in the emergency department (ED) affects 30-day mortality in patients with severe CAP. METHODS: We conducted a retrospective analysis of adult patients with severe CAP who were hospitalized in the ED. Severe CAP was defined according to the criteria of the 2007 Infectious Diseases Society of America/American Thoracic Society guidelines. Patients were divided into two groups according to whether they were prescribed empirical antibiotics concordant with guidelines. Multivariable Cox proportional hazard regression analysis was performed to identify the independent association between the prescription of initial empirical antibiotics concordant with the guidelines and 30-day mortality. Propensity score matching was performed to reduce selection bias between groups and Kaplan-Meier survival analysis was performed to analyze the time-to-event of 30-day survival. RESULTS: In total, 630 patients were hospitalized in the ED for severe CAP, and 179 (28.4%) died within 30 days. Antibiotics consistent with guidelines were prescribed to 359 (57.0%) patients. The 30-day mortality was significantly higher in the guideline-discordant group (p = 0.003) and multivariable Cox proportional hazard regression analysis revealed that the prescription of antibiotics discordant with the guidelines was independently associated with 30-day mortality (hazard ratio 1.43, 95% CI 1.05-1.93). After propensity score matching, there were 255 patients in each group. The 30-day mortality was lower in the group prescribed guideline-concordant antibiotics than in the group prescribed guideline-discordant antibiotics (23.9% vs. 33.3%, p = 0.024). Kaplan-Meier survival analysis showed that antibiotic prescription concordant with the guidelines resulted in higher survival rates at 30 days (p = 0.002). CONCLUSIONS: The prevalence of antibiotic prescription consistent with guidelines for severe CAP seemed to be low in the ED, and this variable was independently associated with 30-day survival.

Developing neural network models for early detection of cardiac arrest in emergency department.

BACKGROUND: Automated surveillance for cardiac arrests would be useful in overcrowded emergency departments. The purpose of this study is to develop and test artificial neural network (ANN) classifiers for early detection of patients at risk of cardiac arrest in emergency departments. METHODS: This is a single-center electronic health record (EHR)-based study. The primary outcome was the development of cardiac arrest within 24 h after prediction. Three ANN models were trained: multilayer perceptron (MLP), long-short-term memory (LSTM), and hybrid. These were compared to other classifiers including the modified early warning score (MEWS), logistic regression, and random forest. We used AUROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the comparison. RESULTS: During the study period, there were a total of 374,605 ED visits and 2,910,321 patient status updates. The ANN models (MLP, LSTM, and hybrid) achieved higher AUROC (AUROC: 0.929, 0.933, and 0.936; 95% confidential interval: 0.926-0.932, 0.930-0.936, and 0.933-0.939, respectively) compared to the non-ANN models, and the hybrid model exhibited the best performance. The ANN classifiers displayed higher performance in most of the test characteristics when the threshold levels of the classifiers were fixed to display the same positive result as those at the three MEWS thresholds (score ≥ 3, ≥4, and ≥5), and when compared with each other. CONCLUSIONS: The ANN improves upon MEWS and conventional machine learning algorithms for the prediction of cardiac arrests in emergency departments. The hybrid ANN model utilizing both baseline and sequence information achieved the best performance.

Moderate to severe hyperphosphataemia as an independent prognostic factor for 28-day mortality in adult patients with sepsis.

BACKGROUND: Ischaemic tissue injury caused by tissue hypoperfusion is one of the major consequences of sepsis. Phosphate concentrations are elevated in ischaemic tissue injury. This study was performed to investigate the association of phosphate concentrations with mortality in patients with sepsis. METHODS: This was a retrospective cohort study of patients with sepsis conducted at an urban, tertiary care emergency department (ED) in Korea. Patients with sepsis arriving between March 2010 and April 2017 were stratified into four groups according to the initial phosphate concentration at presentation to the ED: group I (hypophosphataemia, phosphate <2 mg/dL), group II (normophosphataemia, phosphate 2-4 mg/dL), group III (mild hyperphosphataemia, phosphate 4-6 mg/dL), group IV (moderate to severe hyperphosphataemia, phosphate ≥6 mg/dL). Multivariable Cox proportional hazard regression analyses were performed to evaluate the independent association of initial phosphate concentration with 28-day mortality. RESULTS: Of the 3034 participants in the study, the overall mortality rate was 21.9%. The 28-day mortality rates were group I (hypophosphataemia) 14.6%, group II 17.4% (normophosphataemia), group III (mild hyperphosphataemia) 29.2% and group IV (moderate to severe hyperphosphataemia) 51.4%, respectively (p<0.001). In the multivariable analyses, patients with severe hyperphosphataemia had a significantly higher risk of death than those with normal phosphate levels (HR 1.59; 95% CI 1.23 to 2.05). Mortality in the other groups was not significantly different from mortality in patients with normophosphataemia. CONCLUSIONS: Moderate to severe hyperphosphataemia was associated with 28-day mortality in patients with sepsis. Phosphate level could be used as a prognostic indicator in sepsis.

Prolonged stay in the emergency department is an independent risk factor for hospital-acquired pressure ulcer.

It is not easy to ensure optimal prevention of hospital-acquired pressure ulcer (HAPU) in crowded emergency departments (EDs). We hypothesised that a prolonged ED length of stay (LOS) is associated with an increased risk of HAPU. This is a single-centre observational study. Prospectively collected HAPU surveillance data were analysed. Adult (aged ≥20 years) patients admitted through the ED from April 1, 2013 to December 31, 2016 were included. The primary outcome was the development of HAPU within a month. Covariates included demographics, comorbidities, conditions at triage, initial laboratory results, primary ED diagnosis, critical ED interventions, and ED dispositions. The association between ED LOS and HAPU was modelled using logistic and extended Cox regression. A total of 48 641 admissions were analysed. The crude odds ratio (OR) and hazard ratio (HR) for HAPU were increased to 1.44 (95% CI, 1.20-1.72) and 1.21 (95% CI, 1.02-1.45), respectively, in ED LOS ≥24 hours relative to ED LOS <6 hours. In multivariable logistic regression, ED LOS ≥12 and ≥24 hours were associated with higher risk of HAPU, with ORs of 1.30 (95% CI, 1.05-1.60) and 1.80 (95% CI, 1.45-2.23) relative to ED LOS <6 hours, respectively. The extended Cox regression showed that the risk lasted up to a week, with HRs of 1.42 (95% CI, 1.07-1.88) and 1.92 (95% CI, 1.44-2.57) relative to ED LOS <6 hours, respectively. In conclusion, Prolonged ED LOS is independently associated with HAPU. Shorter ED LOS should be pursued as a goal in a multifaceted solution for HAPU.

Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury.

The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation is poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.Using a custom-made intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualisation of the pulmonary microcirculation and circulating cells in vivo We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that this decrease resulted from the generation of dead space, which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behaviour, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved hypoxaemia.Using the intravital lung imaging system, we observed that Mac-1-upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation that was recovered by a Mac-1 inhibitor in sepsis-induced ALI.

Characterization of Fecal Peritonitis-Induced Sepsis in a Porcine Model.

BACKGROUND: Although there are well-established small-animal sepsis models, the longitudinal assessment of hemodynamic variables, laboratory values, and blood culture in a single living sepsis model is limited. Therefore, we aimed to comprehensively characterize fecal peritonitis-induced sepsis in a porcine model. MATERIALS AND METHODS: Autologous feces (1 g/kg) was administered into the peritoneum of 11 male pigs (49 ± 8 kg). The pigs were monitored up to 12 h with full fluid and vasopressor support to maintain the mean arterial pressure at >65 mm Hg. Longitudinal blood culture and laboratory values were obtained at defined time intervals. The cytokine levels in plasma were analyzed. Furthermore, a clinical registry of sepsis patients at a single emergency department was used to compare the Sepsis-related Organ Failure Assessment scores with those of the porcine model. RESULTS: The hyperdynamic phase of increasing cardiac output with decreasing systemic vascular resistance was maintained until 2 h, followed by the reverse (hypodynamic phase). With the escalating requirement for fluid and vasopressor, the lactate level progressively increased while the platelet count, urine output, and serum albumin level consistently decreased. Bacteremia developed 7 h (median) after the administration of feces, and Escherichia coli was the most common pathogen. The pattern of Sepsis-related Organ Failure Assessment scores with prominent cardiovascular failure was comparable to clinical data. CONCLUSIONS: We implemented a porcine fecal peritonitis-induced sepsis model that demonstrates culture-proven bacteremia and multiple organ failure, particularly cardiovascular system failure. This model could facilitate the development of technologies for the early diagnosis of bacterial pathogens in blood.

Effect of Electrical Vagus Nerve Stimulation on Cerebral Blood Flow and Neurological Outcome in Asphyxial Cardiac Arrest Model of Rats.

BACKGROUND: Vagus nerve stimulation (VNS) during post-resuscitation may increase recovery of cerebral blood flow (CBF) and reduce neurological injury. OBJECTIVE: This study was designed to investigate the effect of electrical VNS on neurological outcomes following cardiac arrest (CA). METHODS: Male Sprague-Dawley rats (n = 48) were subjected to the asphyxial CA model and blindly allocated to the VN isolation (CA + VN isolation) or VNS group (CA + VNS group). Cardiopulmonary resuscitation was initiated 450 s after pulseless electrical arrest, and the left cervical vagus nerve was electrically stimulated (0.05 mA, 1 Hz) for 3 h in the CA + VNS group. The neurological deficit score (NDS) and overall performance category (OPC) were assessed at 24 h after resuscitation, and histological injury of the hippocampus was evaluated. Independent experiments were performed to evaluate the effect of VNS on global cortical CBF after resuscitation using laser speckle Doppler imaging through a thinned skull window from pre-arrest to 6 h after resuscitation. RESULTS: The baseline characteristics were not significantly different between the two groups. The NDS was significantly higher, and the OPC was substantially lower in the CA + VNS group (p = 0.022 and p = 0.049, respectively) supported by decrease in histological injury of the hippocampal CA1 region. CBF in the early period of post-return of spontaneous circulation (ROSC) was significantly higher in the CA + VNS group (p < 0.05 at post-ROSC 2 h and 4 h), and 4-hydroxynonenal was significantly lower in the CA + VNS group (p = 0.026). CONCLUSIONS: VNS improved cerebral perfusion and neurological outcomes at 24 h after ROSC in an asphyxial CA model of rats.

Dynamic Changes in Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis with Respect to Antibiotic Susceptibility.

Purpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.

Extracorporeal Blood Treatment Using Functional Magnetic Nanoclusters Mitigates Organ Dysfunction of Sepsis in Swine.

Mitigating sepsis-induced severe organ dysfunction with magnetic nanoparticles has shown remarkable advances in extracorporeal blood treatment. Nevertheless, treating large septic animals remains challenging due to insufficient magnetic separation at rapid blood flow rates (>6 L h-1) and limited incubation time in an extracorporeal circuit. Herein, superparamagnetic nanoclusters (SPNCs) coated with red blood cell (RBC) membranes are developed, which promptly capture and magnetically separate a wide range of pathogens at high blood flow rates in a swine sepsis model. The SPNCs exhibited an ultranarrow size distribution of clustered iron oxide nanocrystals and exceptionally high saturation magnetization (≈ 90 emu g-1) close to that of bulk magnetite. It is also revealed that CD47 on the RBCs allows the RBC-SPNCs to remain at a consistent concentration in the blood by evading innate immunity. The uniform size distribution of the RBC-SPNCs greatly enhances their effectiveness in eradicating various pathogenic materials in extracorporeal blood. The use of RBC-SPNCs for extracorporeal treatment of swine infected with multidrug-resistant E. coli is validated and found that severe bacteremic sepsis-induced organ dysfunction is significantly mitigated after 12 h. The findings highlight the potential application of RBC-SPNCs for extracorporeal therapy of severe sepsis in large animal models and potentially humans.

MONITORING OF PULMONARY EDEMA USING ULTRASOUND RADIOFREQUENCY SIGNAL.

ABSTRACT: Objectives: Excessive accumulation of extravascular lung water impairs respiratory gas exchange and results in respiratory distress. Real-time radiofrequency signals of ultrasound can continuously and quantitatively monitor excessive lung water. This study aims to evaluate the availability of continuous real-time quantitative pulmonary edema monitoring using ultrasound radiofrequency signals and compare it with Pa o2 (partial pressure of arterial oxygen)/F io2 (fraction of inspired oxygen) (PF) ratio, conventional lung ultrasound, and the Hounsfield unit of chest computed tomography. Methods: Male Yorkshire pigs (40.5 ± 0.5 kg) were anesthetized and mechanically ventilated. A balanced crystalloid was administered to induce hydrostatic pulmonary edema. Three different infusion rates of 2, 4, and 6 mL/kg per minute were tested to determine the infusion rate for the appropriate swine model. The chest computed tomography and ultrasonography with radiofrequency signals were taken every 5 min during the full inspiration. The ultrasonography scans with radiofrequency signals were measured at the intercostal space where the line crossing the two armpits and the right anterior axillary line intersected. Results: The infusion rate of fluid for the pulmonary edema model was determined to be 6 mL/kg per minute, and a total of four pigs were tested at an injection rate of 6 mL/kg. The adjusted R2 values of regression analysis between the radiofrequency signal and computer tomography Hounsfield score were 0.990, 0.993, 0.988, and 0.993 (all P values <0.05). All radiofrequency signal changes preceded changes in PF ratio or lung ultrasound changes. The area under the receiver operating characteristic curve of the radiofrequency signal for predicting PF ratio <300 was 0.88 (95% confidence interval, 0.82-0.93). Conclusion: We evaluated ultrasound radiofrequency signals to assess pulmonary edema in a swine model that can worsen gradually and showed that quantitative ultrasound radiofrequency signal analysis could assess pulmonary edema and its progression before PF ratio or lung ultrasound changes.

ASSOCIATIONS OF THE SERUM ALBUMIN CONCENTRATION AND SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE AT DISCHARGE WITH 1-YEAR MORTALITY IN SEPSIS SURVIVORS: A RETROSPECTIVE COHORT STUDY.

ABSTRACT: Introduction: This study was performed to investigate the predictors of 1-year mortality at discharge in sepsis survivors. Methods: This study was a retrospective analysis of patients with sepsis and septic shock at a single center. Patients who survived hospitalization for sepsis or septic shock between January 2016 and December 2017 were included in this study. Age, sex, body mass index, laboratory results such as blood cell count, C-reactive protein (CRP) and albumin levels, the Sequential Organ Failure Assessment (SOFA) score at the time of discharge and site of infection were compared between the survivors and nonsurvivors at 1 year postdischarge. Multivariate logistic regression was performed to identify the predictors of 1-year mortality. Results: During the study period, 725 sepsis patients were included in the analysis, 64 (8.8%) of whom died within the first year. The nonsurvivors were older and had a lower body mass index and a higher SOFA score at discharge than the survivors ( P < 0.05). Among the laboratory results at discharge, hemoglobin, platelet counts, and albumin concentrations were lower in the nonsurvivors than in the survivors, whereas CRP was higher in the nonsurvivors than in the survivors. In the multivariate logistic regression analysis, serum albumin <2.5 mg/dL and SOFA score ≥2 at discharge were identified as independent prognostic factors for 1-year mortality (odds ratio, 2.616; 95% confidence interval, 1.437-4.751 for albumin <2.5 mg/dL and 2.106, 1.199-3.801 for SOFA score ≥2, respectively). Conclusions: A low serum albumin concentration of <2.5 mg/dL and a high SOFA score of ≥2 at the time of discharge were prognostic factors for 1-year mortality in survivors of sepsis.

Discovery of Novel, Thienopyridine-Based Tyrosine Kinase Inhibitors Targeting Tumorigenic RON Splice Variants.

Herein, we report the identification, structural optimization, and biological efficacy of thieno[2,3-b]pyridines as potent inhibitors of splice variants of the tyrosine kinase recepteur d'origine nantais (RON). Among synthesized compounds, compound 15f exhibited excellent in vitro kinase inhibition and antiproliferative activity, as well as in vivo antineoplastic efficacy against RON splice variant-expressing tumors. Moreover, compound 15f with excellent pharmacokinetics demonstrated significant activity with greater tumor growth inhibition (74.9% at 10 mg/kg) than compounds 2 and 4 in a patient-derived xenograft model. Collectively, 15f represents a promising, novel anticancer agent targeting RON splice variants.

The Prognostic Value of the Modified Surprise Question in Critically Ill Emergency Department Patients.

Objective: The initiation of palliative care (PC) in the emergency department (ED) is effective in improving the quality of life for seriously ill patients. This study aimed to evaluate the prognostic value of the modified surprise question (mSQ), "Would you be surprised if this patient died in the next 30 days?" as a trigger for initiating PC in critically ill ED patients. Methods: We conducted a prospective cohort study over a 6-month period in an ED, during which 22 emergency residents answered the mSQ for critically ill ED patients (Korean Triage and Acuity Scale 1 or 2). The primary outcome was the accuracy of the positive mSQ (negative response to the mSQ) in predicting 30-day mortality, and logistic regression analysis was performed to identify the prognostic factors. Results: A total of 300 patients were enrolled, and the positive mSQ group included 118 (39.3%) patients. The 30-day mortality rate of the cohort was 10.0%. The sensitivity, specificity, positive predictive value, and negative predictive value of the positive mSQ were 83.3%, 65.6%, 21.2%, and 97.3%, respectively, with a c-statistic of 0.74 and a positive likelihood ratio of 2.42. In a multivariable analysis controlling for clinically relevant variables, the odds ratio for 30-day mortality of the positive mSQ was 4.76 (95% confidence interval, 1.61-14.09; P = .005). Conclusions: The mSQ may be valuable for identifying critically ill ED patients with an increased risk of 30-day mortality. Therefore, it may be utilized as a trigger for PC consultation in the ED.

High blood viscosity in acute ischemic stroke.

Background: The changes in blood viscosity can influence the shear stress at the vessel wall, but there is limited evidence regarding the impact on thrombogenesis and acute stroke. We aimed to investigate the effect of blood viscosity on stroke and the clinical utility of blood viscosity measurements obtained immediately upon hospital arrival. Methods: Patients with suspected stroke visiting the hospital within 24 h of the last known well time were enrolled. Point-of-care testing was used to obtain blood viscosity measurements before intravenous fluid infusion. Blood viscosity was measured as the reactive torque generated at three oscillatory frequencies (1, 5, and 10 rad/sec). Blood viscosity results were compared among patients with ischemic stroke, hemorrhagic stroke, and stroke mimics diagnosed as other than stroke. Results: Among 112 enrolled patients, blood viscosity measurements were accomplished within 2.4 ± 1.3 min of vessel puncture. At an oscillatory frequency of 10 rad/sec, blood viscosity differed significantly between the ischemic stroke (24.2 ± 4.9 centipoise, cP) and stroke mimic groups (17.8 ± 6.5 cP, p < 0.001). This finding was consistent at different oscillatory frequencies (134.2 ± 46.3 vs. 102.4 ± 47.2 at 1 rad/sec and 39.2 ± 11.5 vs. 30.4 ± 12.4 at 5 rad/sec, Ps < 0.001), suggesting a relationship between decreases in viscosity and shear rate. The area under the receiver operating curve for differentiating cases of stroke from stroke mimic was 0.79 (95% confidence interval, 0.69-0.88). Conclusion: Patients with ischemic stroke exhibit increases in whole blood viscosity, suggesting that blood viscosity measurements can aid in differentiating ischemic stroke from other diseases.

Calix[4]pyrrole-based heteroditopic ion-pair receptor that displays anion-modulated, cation-binding behavior.

A new ditopic ion-pair receptor 1 was designed, synthesized, and characterized. Detailed binding studies served to confirm that this receptor binds fluoride and chloride ions (studied as their tetraalkylammonium salts) and forms stable 1:1 complexes in CDCl(3). Treatment of the halide-ion complexes of 1 with Group I and II metal ions (Li(+), Na(+), K(+), Cs(+), Mg(2+), and Ca(2+); studied as their perchlorate salts in CD(3)CN) revealed unique interactions that were found to depend on both the choice of the added cation and the precomplexed anion. In the case of the fluoride complex [1⋅F](-) (preformed as the tetrabutylammonium (TBA(+)) complex), little evidence of interaction with the K(+) ion was seen. In contrast, when this same complex (i.e., [1⋅F](-) as the TBA(+) salt) was treated with the Li(+) or Na(+) ions, complete decomplexation of the receptor-bound fluoride ion was observed. In sharp contrast to what was seen with Li(+), Na(+), and K(+), treating complex [1⋅F](-) with the Cs(+) ion gave rise to a stable, receptor-bound ion-pair complex [Cs⋅1⋅F] that contains the Cs(+) ion complexed within the cup-like cavity of the calix[4]pyrrole, which in turn was stabilized in its cone conformation. Different complexation behavior was observed in the case of the chloride complex [1⋅Cl](-). In this case, no appreciable interaction was observed with Na(+) or K(+). In addition, treating [1⋅Cl](-) with Li(+) produces a tightly hydrated dimeric ion-pair complex [1⋅LiCl(H(2)O)](2) in which two Li(+) ions are bound to the crown moiety of the two receptors. In analogy to what was seen in the case of [1⋅F](-), exposure of [1⋅Cl](-) to the Cs(+) ion gives rise to an ion-pair complex [Cs⋅1⋅Cl] in which the cation is bound within the cup of the calix[4]pyrrole. Different complexation modes were also observed when the binding of the fluoride ion was studied by using the tetramethylammonium and tetraethylammonium salts.

Oligoether-strapped calix[4]pyrrole: an ion-pair receptor displaying cation-dependent chloride anion transport.

A ditopic ion-pair receptor (1), which has tunable cation- and anion-binding sites, has been synthesized and characterized. Spectroscopic analyses provide support for the conclusion that receptor 1 binds fluoride and chloride anions strongly and forms stable 1:1 complexes ([1·F](-) and [1·Cl](-)) with appropriately chosen salts of these anions in acetonitrile. When the anion complexes of 1 were treated with alkali metal ions (Li(+), Na(+), K(+), Cs(+), as their perchlorate salts), ion-dependent interactions were observed that were found to depend on both the choice of added cation and the initially complexed anion. In the case of [1·F](-), no appreciable interaction with the K(+) ion was seen. On the other hand, when this complex was treated with Li(+) or Na(+) ions, decomplexation of the bound fluoride anion was observed. In contrast to what was seen with Li(+), Na(+), K(+), treating [1·F](-) with Cs(+) ions gave rise to a stable, host-separated ion-pair complex, [F·1·Cs], which contains the Cs(+) ion bound in the cup-like portion of the calix[4]pyrrole. Different complexation behavior was seen in the case of the chloride complex, [1·Cl](-). Here, no appreciable interaction was observed with Na(+) or K(+). In contrast, treating with Li(+) produces a tight ion-pair complex, [1·Li·Cl], in which the cation is bound to the crown moiety. In analogy to what was seen for [1·F](-), treatment of [1·Cl](-) with Cs(+) ions gives rise to a host-separated ion-pair complex, [Cl·1·Cs], in which the cation is bound to the cup of the calix[4]pyrrole. As inferred from liposomal model membrane transport studies, system 1 can act as an effective carrier for several chloride anion salts of Group 1 cations, operating through both symport (chloride+cation co-transport) and antiport (nitrate-for-chloride exchange) mechanisms. This transport behavior stands in contrast to what is seen for simple octamethylcalix[4]pyrrole, which acts as an effective carrier for cesium chloride but does not operates through a nitrate-for-chloride anion exchange mechanism.

Vagus Nerve Stimulation Improves Mitochondrial Dysfunction in Post-cardiac Arrest Syndrome in the Asphyxial Cardiac Arrest Model in Rats.

Cerebral mitochondrial dysfunction during post-cardiac arrest syndrome (PCAS) remains unclear, resulting in a lack of therapeutic options that protect against cerebral ischemia-reperfusion injury. We aimed to assess mitochondrial dysfunction in the hippocampus after cardiac arrest and whether vagus nerve stimulation (VNS) can improve mitochondrial dysfunction and neurological outcomes. In an asphyxial cardiac arrest model, male Sprague-Dawley rats were assigned to the vagus nerve isolation (CA) or VNS (CA + VNS) group. Cardiopulmonary resuscitation was performed 450 s after pulseless electrical activity. After the return of spontaneous circulation (ROSC), left cervical VNS was performed for 3 h in the CA + VNS group. Mitochondrial respiratory function was evaluated using high-resolution respirometry of the hippocampal tissue. The neurologic deficit score (NDS) and overall performance category (OPC) were assessed at 24, 48, and 72 h after resuscitation. The leak respiration and oxidative phosphorylation capacity of complex I (OXPHOS CI) at 6 h after ROSC were significantly higher in the CA + VNS group than in the CA group (p = 0.0308 and 0.0401, respectively). Compared with the trends of NDS and OPC in the CA group, the trends of those in the CA + VNS group were significantly different, thus suggesting a favorable neurological outcome in the CA + VNS group (p = 0.0087 and 0.0064 between times × groups interaction, respectively). VNS ameliorated mitochondrial dysfunction after ROSC and improved neurological outcomes in an asphyxial cardiac arrest rat model.