Geriatric depression and anxiety screening via deep learning using activity tracking and sleep data.

BACKGROUND: Geriatric depression and anxiety have been identified as mood disorders commonly associated with the onset of dementia. Currently, the diagnosis of geriatric depression and anxiety relies on self-reported assessments for primary screening purposes, which is uncomfortable for older adults and can be prone to misreporting. When a more precise diagnosis is needed, additional methods such as in-depth interviews or functional magnetic resonance imaging are used. However, these methods can not only be time-consuming and costly but also require systematic and cost-effective approaches. OBJECTIVE: The main objective of this study was to investigate the feasibility of training an end-to-end deep learning (DL) model by directly inputting time-series activity tracking and sleep data obtained from consumer-grade wrist-worn activity trackers to identify comorbid depression and anxiety. METHODS: To enhance accuracy, the input of the DL model consisted of step counts and sleep stages as time series data, along with minimal depression and anxiety assessment scores as non-time-series data. The basic structure of the DL model was designed to process mixed-input data and perform multi-label-based classification for depression and anxiety. Various DL models, including the convolutional neural network (CNN) and long short-term memory (LSTM), were applied to process the time-series data, and model selection was conducted by comparing the performances of the hyperparameters. RESULTS: This study achieved significant results in the multi-label classification of depression and anxiety, with a Hamming loss score of 0.0946 in the Residual Network (ResNet), by applying a mixed-input DL model based on activity tracking data. The comparison of hyper-parameter performance and the development of various DL models, such as CNN, LSTM, and ResNet contributed to the optimization of time series data processing and achievement of meaningful results. CONCLUSIONS: This study can be considered as the first to develop a mixed-input DL model based on activity tracking data for the multi-label identification of late-life depression and anxiety. The findings of the study demonstrate the feasibility and potential of using consumer-grade wrist-worn activity trackers in conjunction with DL models to improve the identification of comorbid mental health conditions in older adults. The study also established a multi-label classification framework for identifying the complex symptoms of depression and anxiety.

Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA.

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.

Development and performance evaluation of an artificial intelligence algorithm using cell-free DNA fragment distance for non-invasive prenatal testing (aiD-NIPT).

With advances in next-generation sequencing technology, non-invasive prenatal testing (NIPT) has been widely implemented to detect fetal aneuploidies, including trisomy 21, 18, and 13 (T21, T18, and T13). Most NIPT methods use cell-free DNA (cfDNA) fragment count (FC) in maternal blood. In this study, we developed a novel NIPT method using cfDNA fragment distance (FD) and convolutional neural network-based artificial intelligence algorithm (aiD-NIPT). Four types of aiD-NIPT algorithm (mean, median, interquartile range, and its ensemble) were developed using 2,215 samples. In an analysis of 17,678 clinical samples, all algorithms showed >99.40% accuracy for T21/T18/T13, and the ensemble algorithm showed the best performance (sensitivity: 99.07%, positive predictive value (PPV): 88.43%); the FC-based conventional Z-score and normalized chromosomal value showed 98.15% sensitivity, with 40.77% and 36.81% PPV, respectively. In conclusion, FD-based aiD-NIPT was successfully developed, and it showed better performance than FC-based NIPT methods.

Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects.

Background: Statins are the most popular agents for the primary and secondary prevention of cardiovascular disease; however, the pharmacokinetic parameters and associated genetic factors in the Korean population have not been fully elucidated. This study explored the pharmacokinetic properties of atorvastatin and the association between genetic variations and atorvastatin pharmacokinetics in healthy Korean subjects. Methods: Atorvastatin (80 mg) was administered to 35 healthy Korean volunteers. Plasma levels of atorvastatin and its metabolites were measured sequentially using liquid chromatography-tandem mass spectrometry from 0 to 24 h after atorvastatin administration. Customized next-generation sequencing analysis was performed covering all coding exons of 15 genes, as well as 46 single-nucleotide variants in 29 genes related to statin pharmacokinetics. Results: The mean area under the concentration-time (AUC) and Cmax (maximum peak concentration) were 269.0 ng/ml∙h and 84.3 ng/ml, respectively, which were approximately two times higher than those reported in Caucasians. Genetic analysis revealed that eight genetic variants in ABCB1, ABCG2, APOA5, CETP, and CYP7A1 contributed to the AUC of atorvastatin. The atorvastatin AUC0-24 h prediction model was developed based on age and eight genetic variants using multivariate linear regression (adjusted R 2 = 0.878, p < 0.0001). Conclusion: This study shows that the pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorvastatin AUC0-24 h could be predicted based on age and eight genetic variants of ABCB1, ABCG2, APOA5, CETP, and CYP7A1.

Topology Optimized Prelithiated SiO Anode Materials for Lithium-Ion Batteries.

Silicon monoxide (SiO)-based materials have great potential as high-capacity anode materials for lithium-ion batteries. However, they suffer from a low initial coulombic efficiency (ICE) and poor cycle stability, which prevent their successful implementation into commercial lithium-ion batteries. Despite considerable efforts in recent decades, their low ICE and poor cycle stability cannot be resolved at the same time. Here, it is demonstrated that the topological optimization of the prelithiated SiO materials is highly effective in improving both ICE and capacity retention. Laser-assisted atom probe tomography combined with thermogravimetry and differential scanning calorimetry reveals that two exothermic reactions related to microstructural evolution are key in optimizing the domain size of the Si active phase and Li2 SiO3 buffer phase, and their topological arrangements in prelithiated SiO materials. The optimized prelithiated SiO, heat-treated at 650 °C, shows higher capacity retention of 73.4% and lower thickness changes of 68% after 300 cycles than those treated at other temperatures, with high ICE of ≈90% and reversible capacity of 1164 mAh g-1 . Such excellent electrochemical properties of the prelithiated SiO electrode originate from its optimized topological arrangement of active Si phase and Li2 SiO3 inactive buffer phase.

Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study.

Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resectable (n = 110), locally advanced (n = 78), and metastatic (n = 127) PDAC from March 2015 through January 2020. Low-depth whole-genome cell-free DNA sequencing identified genome-wide copy number alterations using instability score (I-score) to reflect genome-wide instability. Plasma cell-free and matched tumor tissue DNA from 15 patients with resectable pancreatic cancer was sequenced to assess the concordance of chromosomal copy number alteration profiles. Associations of I-score with clinical factors or survival were assessed. Seventy-six patients had high genomic instability with I-score > 7.3 in pre-treatment ctDNA; proportions of high I-score were 5.5%, 5.1%, and 52% in resectable, locally advanced, and metastatic stages, respectively. Correlation coefficients between Z-scores of plasma and tissue DNA at segment resolution were high (r2 = 0.82). Univariable analysis showed the association of I-score with progression-free survival in each stage. Multivariable analyses demonstrated that clinical stage-adjusted I-scores were significant factors for progression-free and overall survival. In these patients, ctDNA genomic I-scores provided prognostic information relevant to progression-free survival in each clinical stage.

Analysis of Health Insurance Big Data for Early Detection of Disabilities: Algorithm Development and Validation.

BACKGROUND: Early detection of childhood developmental delays is very important for the treatment of disabilities. OBJECTIVE: To investigate the possibility of detecting childhood developmental delays leading to disabilities before clinical registration by analyzing big data from a health insurance database. METHODS: In this study, the data from children, individuals aged up to 13 years (n=2412), from the Sample Cohort 2.0 DB of the Korea National Health Insurance Service were organized by age range. Using 6 categories (having no disability, having a physical disability, having a brain lesion, having a visual impairment, having a hearing impairment, and having other conditions), features were selected in the order of importance with a tree-based model. We used multiple classification algorithms to find the best model for each age range. The earliest age range with clinically significant performance showed the age at which conditions can be detected early. RESULTS: The disability detection model showed that it was possible to detect disabilities with significant accuracy even at the age of 4 years, about a year earlier than the mean diagnostic age of 4.99 years. CONCLUSIONS: Using big data analysis, we discovered the possibility of detecting disabilities earlier than clinical diagnoses, which would allow us to take appropriate action to prevent disabilities.

Effect of typhoons on the Korean national emergency medical service system.

OBJECTIVE: While the effect of typhoons on emergency medicine has been evaluated, data are scarce on their effects on the emergency medical service (EMS). This study evaluated the effect of typhoons on EMS patients and performance. METHODS: The study period was January 2010 to December 2012. Meteorological data regarding typhoons were provided by the Korean Meteorological Administration. EMS data were retrieved from the EMS database of the national emergency management agency. The database includes ambulance run sheets, which contain clinical and operational data. In this case-crossover study, the cases and controls were EMS calls on the day of typhoon warnings and calls one week prior to the typhoon warnings, respectively. RESULTS: During the study period, 11 typhoons affected Korea. A total of 14,521 cases were selected for analysis. Overall, there were no obvious differences between the case and control groups. However, there were statistically significant differences in age, place, and time requests. There were fewer patients between 0 and 15 years of age (P=0.01) and more unconscious patients (P=0.01) in the case group. The EMS operational performance, as measured by the times elapsed between call to start, call to field, and call to hospital did not differ significantly. There was also no significant difference in the time from hospital arrival between the cases (28.67, standard deviation 16.37) and controls (28.97, standard deviation 28.91) (P=0.39). CONCLUSION: Typhoons did not significantly affect the EMS system in this study. Further study is necessary to understand the reasons for this finding.

Usefulness of C-MAC video laryngoscope in direct laryngoscopy training in the emergency department: A propensity score matching analysis.

OBJECTIVES: We determined the usefulness of C-MAC video laryngoscope (C-MAC) as a safe training tool for the direct laryngoscopy technique in the emergency department. METHODS: We retrospectively analyzed an institutional airway registry of adult (≥18 years old) patients from April 2014 through October 2016. In this study, the operator used C-MAC as a direct laryngoscope (DL) with limited access to the screen, and the supervisor instructed the operator via verbal feedback while watching the screen. Patients were categorized into the DL group if a conventional DL was used and the C-DL group if a C-MAC used as a DL. RESULTS: Of 744 endotracheal intubations, 163 propensity score-matched pairs were generated (1-to-n matching: C-DL group, 163 vs. DL group, 428). For the propensity-matched groups, the overall first pass success rate was 69%, while those in the C-DL and DL groups were 79% and 65%, respectively. Overall, multiple attempts were required in 8% of patients, with 4% in the C-DL group and 9% in the DL group. The overall complication rate was 11%, with 4% in the C-DL group and 14% in the DL group. In multivariable analysis, the adjusted odds ratios of C-DL use for first pass success, multiple attempts, and complications were 2.05 (95% confidence interval [CI] 1.18-2.87, p < 0.01), 0.38 (95% CI 0.15-0.94; p < 0.01), and 0.28 (95% CI 0.12-0.63; p < 0.01), respectively. CONCLUSIONS: Our study suggests that the C-MAC could be useful for training residents in the direct laryngoscopy while ensuring patient safety in the emergency department.

Deliberate Self-harm among Young People Begins to Increase at the Very Early Age: a Nationwide Study.

BACKGROUND: Suicide in young people is one of most common cause of death; and deliberate self-harm (DSH) is important indicator of suicide. It is currently unclear how old the rate begins to increase or when it reaches to the same level with adults. The purpose of this study was to find beginning age of DSH and compare their characteristics with adults. METHODS: This study retrospectively reviewed 5 years of nationwide prospective registry named Emergency Department-based Injury In-depth Surveillance (EDIIS) registry composed of all injured patients who were admitted to twenty tertiary university hospital emergency departments. Injured patients aged 29 years or younger from January 1, 2011 to December 31, 2015 were included. Incidence rate of DSH in all age was described. Patients were stratified by age: early teenage (11-15 years), late teenage (16-19 years), and early adulthood (20-29 years). Data of early teenage group were compared to those of other groups for examining their characteristics. RESULTS: Among 588,549 injury patients, 8,400 patients reported DSH. The rate began to rise at age 11 and reach at age 16 which was equivalent to that of age 20 to 29. Early teenage had significantly higher excess mortality ratio based injury severity score (EMR-ISS) and had almost same level without significant difference in operation incidence or mortality compared to late teenage and early adulthood. CONCLUSION: DSH rate began to rise at age 11, reaching adulthood level at age 16 in Korea.

Low Accuracy of Positive qSOFA Criteria for Predicting 28-Day Mortality in Critically Ill Septic Patients During the Early Period After Emergency Department Presentation.

STUDY OBJECTIVE: We determine the diagnostic performance of positive Quick Sequential Organ Failure Assessment (qSOFA) scores for predicting 28-day mortality among critically ill septic patients during the early period after emergency department (ED) presentation. METHODS: This was a retrospective cohort study at a tertiary care academic center. We reviewed a registry of adult (≥18 years) patients who received a diagnosis of severe sepsis or septic shock during an ED stay from August 2008 through September 2014. We identified the point at which patients met 2 or more of the 3 qSOFA criteria (indicating a positive qSOFA score) simultaneously during the initial 24 hours. The diagnostic performance of positive qSOFA score for predicting 28-day mortality was assessed (on ED arrival and within 3, 6, and 24 hours after ED presentation). RESULTS: A total of 1,395 patients were included, and the overall 28-day mortality was 15%. For patients with positive qSOFA score, 28-day mortality was 23% (95% confidence interval [CI] 19% to 28%) on ED arrival, 20% (95% CI 17% to 23%) at 3 hours, 20% (95% CI 17% to 22%) at 6 hours, and 17% (95% CI 15% to 20%) at 24 hours. Positive qSOFA score for predicting 28-day mortality had a sensitivity, specificity, and area under the receiver operating curve, respectively, of 39% (95% CI 32% to 46%), 77% (95% CI 75% to 80%), and 0.58 (95% CI 0.55 to 0.62) on ED arrival; 68% (95% CI 62% to 75%), 52% (95% CI 49% to 55%), and 0.60 (95% CI 0.57 to 0.63) within 3 hours; 82% (95% CI 76% to 87%), 41% (95% CI 38% to 44%), and 0.61 (95% CI 0.58 to 0.64) within 6 hours; and 91% (95% CI 86% to 94%), 23% (95% CI 21% to 25%), and 0.57 (95% CI 0.54 to 0.59) within 24 hours. CONCLUSION: The diagnostic performance of positive qSOFA score for predicting 28-day mortality was low in critically ill septic patients, particularly during the early period after ED presentation. The study requires further prospective validation because of limitations with its retrospective design and use of single-center data.

Coronary angiography is related to improved clinical outcome of out-of-hospital cardiac arrest with initial non-shockable rhythm.

OBJECTIVE: Coronary angiography (CAG) for survivors of out-of-hospital cardiac arrest (OHCA) enables early identification of coronary artery disease and revascularization, which might improve clinical outcome. However, little is known for the role of CAG in patients with initial non-shockable cardiac rhythm. METHODS: We investigated clinical outcomes of successfully resuscitated 670 adult OHCA patients who were transferred to 27 hospitals in Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES), a Korean nationwide multicenter registry. The primary outcome was 30-day survival with good neurological outcome. Propensity score matching and inverse probability of treatment weighting analyses were performed to account for indication bias. RESULTS: A total of 401 (60%) patients showed initial non-shockable rhythm. CAG was performed only in 13% of patients with non-shockable rhythm (53 out of 401 patients), whereas more than half of patients with shockable rhythm (149 out of 269 patients, 55%). Clinical outcome of patients who underwent CAG was superior to patients without CAG in both non-shockable (hazard ratio (HR) = 3.6, 95% confidence interval (CI) = 2.5-5.2) and shockable rhythm (HR = 3.7, 95% CI = 2.5-5.4, p < 0.001, all). Further analysis after propensity score matching or inverse probability of treatment weighting showed consistent findings (HR ranged from 2.0 to 3.2, p < 0.001, all). CONCLUSIONS: Performing CAG was related to better survival with good neurological outcome of OHCA patients with initial non-shockable rhythms as well as shockable rhythms.

The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit outside the Emergency Department.

A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation. We evaluated the utility of the FRIDU during 1 year of operation. We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively. No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges.

Impact of early coronary angiography on the survival to discharge after out-of-hospital cardiac arrest.

OBJECTIVE: Acute myocardial infarction is a major cause of out-of-hospital cardiac arrest (OHCA). Coronary angiography (CAG) enables diagnostic confirmation of coronary artery disease and subsequent revascularization, which might improve the prognosis of OHCA survivors. Non-randomized data has shown a favorable impact of CAG on prognosis for this population. However, the optimal timing of CAG has been debated. METHODS: The clinical outcomes of 607 OHCA patients registered in CAPTURES (Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance), a nationwide multicenter registry performed in 27 hospitals, were analyzed. Early CAG was defined as CAG performed within 24 hours of emergency department admission. The primary outcome was survival to discharge, with neurologically favorable status defined by cerebral performance category scores ≤2. RESULTS: Compared to patients without CAG (n=469), patients who underwent early CAG (n=138) were younger, more likely to be male, and more likely to have received bystander cardiopulmonary resuscitation, pre-hospital defibrillation, and revascularization (P<0.01 for all). Analysis of 115 propensity score-matched pairs showed that early CAG is associated with a 2.3-fold increase in survival to discharge with neurologically favorable status (P<0.001, all). Survival to discharge increased consistently according to the time interval between emergency department visit and CAG (P<0.05). CONCLUSION: Early CAG of OHCA patients was associated with better survival and favorable neurologic outcomes at discharge. However, there was no clear time threshold for CAG that predicted survival to discharge.

Emergency medical service personnel need to improve knowledge and attitude regarding prehospital sepsis care.

OBJECTIVE: We aimed to evaluate the knowledge and attitudes of emergency medical service (EMS) personnel pertaining to sepsis. We also compared EMS personnel's knowledge of sepsis and their intention to engage in prehospital sepsis management. METHODS: The survey was conducted during education conferences for EMS personnel in December 2013 and January 2015 in Seoul, Korea. The questionnaire composed of 10 questions relevant to sepsis, was distributed on-scene, and was retrieved by investigators after the conference. We classified subjects into active and passive groups based on intent to participate in prehospital sepsis care. RESULTS: A total of 271 questionnaires were distributed; 255 EMS personnel (94%) completed the survey, 126 (49%) of whom were first-degree emergency medical technicians (EMTs). Less than 75% of subjects provided clinically relevant responses to questions about the definitions of sepsis, tachycardia, tachypnea, hypotension, hypothermia, fluid resuscitation, and vasopressor. Only 15% of participants had suspected that a patient had sepsis, and 9% reported that they could identify patients with sepsis during transportation. Overall, first-degree EMTs showed higher levels of knowledge and a positive attitude to sepsis compared with non-first-degree EMTs. Sixty percent of the participants reported that they were actively involved in prehospital sepsis care. The active group showed significantly higher levels of knowledge and more positive responses to the clinical impact of prehospital sepsis care. CONCLUSION: Our study showed that is a substantial portion of EMS personnel lacks appropriate level of knowledge on sepsis care. We also found that the intention to engage in sepsis management was associated with appropriate knowledge of sepsis.

Role of coronary angiography for out-of-hospital cardiac arrest survivors according to postreturn of spontaneous circulation on an electrocardiogram.

Survivors of out-of-hospital cardiac arrest (OHCA) have high mortality and morbidity. An acute coronary event is the most common cause of sudden cardiac death. For this reason, coronary angiography is an important diagnostic and treatment strategy for patients with postcardiac arrest. This study aimed to identify the correlation between postreturn of spontaneous circulation (ROSC) on an electrocardiogram (ECG) and results of coronary angiography of OHCA survivors.We collected data from our OHCA registry from January 2010 to November 2014. We categorized OHCA survivors into 2 groups according to post-ROSC ECG results. Emergent coronary artery angiography (CAG) (CAG performed within 12 hours after cardiac arrest) was performed in patients who showed ST segment elevation or new onset of left bundle branch block (LBBB) in post-ROSC ECG. For other patients, the decision for performing CAG was made according to agreement between the emergency physician and the cardiologist.During the study period, 472 OHCA victims visited our emergency department and underwent cardiopulmonary resuscitation. Among 198 OHCA survivors, 82 patients underwent coronary artery intervention. Thirty-one (70.4%) patients in the ST segment elevation or LBBB group and 10 (24.4%) patients in the nonspecific ECG group had coronary artery lesions (P < .01). Seven (18.4%) patients in the nonspecific ECG group showed coronary spasm.OHCA survivors without ST segment elevation or new onset LBBB still have significant coronary lesions in CAG. If there is no other obvious arrest cause in patients without significant changes in post ROSC ECG, CAG should be considered to rule out the possibility of coronary artery problems, including coronary spasm.

Association between Body Temperature Patterns and Neurological Outcomes after Extracorporeal Cardiopulmonary Resuscitation.

We evaluated the association of body temperature patterns with neurological outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). Between December 2013 and December 2015, we enrolled 48 patients with cardiac arrest who survived for at least 24 hours after ECPR. Based on their body temperature patterns and the intention to control fever, we divided the patients into those in whom fever was actively controlled (N = 25), those with normothermia (N = 17), and those with unintended hypothermia (N = 6). The primary outcome was the Cerebral Performance Categories (CPC) scale at discharge. Of the 48 ECPR patients, 23 patients (47.9%) had good neurological outcomes (CPC 1 and 2) and 27 patients (56.3%) survived to discharge. The normothermia group showed a pattern of higher temperatures compared with the other groups during 48 hours after ECPR. Not only poor neurological outcomes but also intensive care unit (ICU) mortality occurred more often in the unintended hypothermia group than in the other two groups, regardless of the fever control strategy (p = 0.023 and p = 0.002, respectively). There were no differences in neurological outcomes and ICU mortality between the actively controlled fever group and the normothermia group (p = 0.845 and p = 0.616, respectively). Unintentionally sustained hypothermia may be associated with poor neurological outcomes after ECPR. These findings suggest that patients who are unable to generate a fever following ECPR may incur severe hypoxic brain injury.

Neutrophil-to-lymphocyte ratio as a prognostic marker in critically-ill septic patients.

BACKGROUND: We evaluated the associations between the neutrophil-to-lymphocyte ratio (NLR) or changes in NLR and outcomes in septic patients. METHODS: Patients who met the criteria for severe sepsis or septic shock were categorized into five groups according to the quintile of initial NLR value. We defined two risk groups according to NLR value and changes in NLR during the first two days (defined as the persistently low NLR group and the persistently high NLR group). The primary outcome was 28-day mortality. RESULTS: A total of 1395 patients were included. The median initial NLR values from Quintile 1 to Quintile 5 were as follows: 0.2 (IQR [interquartile range], 0.1-0.7), 3.4 (IQR, 2.6-4.7), 8.6 (IQR, 7.1-9.9), 15.4 (IQR, 13.3-17.8), and 31.0 (IQR, 24.6-46.8), respectively. The 28-day mortality values for the same groups were as follows: 24.4%, 12.2%, 11.1%, 11.8%, and 16.1% (P<.01). Cox regression analysis showed that inclusion in Quintile 1 or Quintile 5 was a significant risk factor predicting 28-day mortality compared to Quintile 3 (adjusted hazard ratio [HR]: 1.79 (95% confidence interval [CI], 1.15-2.78) in Quintile 1; 1.67 (95% CI, 1.04-2.66) in Quintile 5). The analysis indicated that persistently low NLR (adjusted HR: 2.25, 95% CI, 1.63-3.11) and persistently high NLR (adjusted HR: 2.65, 95% CI, 1.64-4.29) were significant risk factors. CONCLUSIONS: In summary, the initial NLR measured at ED admission was independently associated with 28-day mortality in patients with severe sepsis and septic shock. In addition, change in NLR may prove to be a valuable prognostic marker.

IVAG: An Integrative Visualization Application for Various Types of Genomic Data Based on R-Shiny and the Docker Platform.

Next-generation sequencing (NGS) technology has become a trend in the genomics research area. There are many software programs and automated pipelines to analyze NGS data, which can ease the pain for traditional scientists who are not familiar with computer programming. However, downstream analyses, such as finding differentially expressed genes or visualizing linkage disequilibrium maps and genome-wide association study (GWAS) data, still remain a challenge. Here, we introduce a dockerized web application written in R using the Shiny platform to visualize pre-analyzed RNA sequencing and GWAS data. In addition, we have integrated a genome browser based on the JBrowse platform and an automated intermediate parsing process required for custom track construction, so that users can easily build and navigate their personal genome tracks with in-house datasets. This application will help scientists perform series of downstream analyses and obtain a more integrative understanding about various types of genomic data by interactively visualizing them with customizable options.

Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock.

BACKGROUND: We aimed to evaluate the impact of metformin use on lactate kinetics in patients with severe sepsis and septic shock. METHODS: We analyzed data from a registry that included patients who presented to the emergency department and met criteria for severe sepsis or septic shock. Patients were divided into two groups based on metformin use. We compared lactate concentrations, lactate clearance (LC), and normalization at 6 h (H6) and 24 h (H24) after the initial (H0) measurement. Propensity score matching, multiple logistic, and linear regression analysis via a generalized estimating equations method were used. RESULTS: Of 1,318 patients, 71 patients were in the metformin use group and all 71 were selected in a one to two propensity matching. Metformin users showed significantly higher lactate levels at H0 (5.3 vs. 4.4 mmol/L) and H6 (3.8 vs. 2.9 mmol/L) in all patients, although in the matched subset, the effect was marginal (H0, 5.3 vs. 4.9 mmol/L; H6, 3.8 vs. 3.2 mmol/L; H24, 2.7 vs. 2.4 mmol/L). Mean LC (H6, 29% vs. 34%; H24, 43% vs. 49%) and normalization rate (H6, 27% vs. 28%; H24, 49% vs. 52%) were also not significantly different. Although metformin use appeared to be associated with higher lactate levels before using the propensity score method, no significant association was found between metformin use and lactate kinetics variables in the balanced matched subset data. CONCLUSIONS: Lactate levels in metformin users were initially elevated in the early phase of resuscitation from severe sepsis and septic shock. However, there was no significant difference in lactate levels, LC, and normalization over the initial 24 h period based on metformin use.