Comparison of Dual-Dispatch Protocols on Return of Spontaneous Circulation in Patients with Out-of-Hospital Cardiac Arrest: A Nationwide Observational Study.

Objective: In South Korea, the National Fire Agency (NFA) conducted a pilot project on the advanced life support (ALS) protocol, including epinephrine administration, to improve the survival rate of out-of hospital cardiac arrest (OHCA). Therefore, this study aimed to evaluate the effect of the ALS protocol of NFA on prehospital return of spontaneous circulation (PROSC) in patients with OHCA. Methods: This study was conducted on patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to the ALS protocol, which was divided into dedicated ALS(DA), smartphone-based ALS(SALS), and non-dedicated ALS(Non-DA), and the main analysis factor was PROSC. Multivariate logistic regression analysis was performed. Results: During the study period, a total of 18,031 adult patients with OHCA were treated by the emergency medical service (EMS), including 7,520 (41.71 %) DA, 2,622 (14.54 %) SALS, and 7,889 (43.75 %) Non-DA. The prehospital ROSC ratio was 13.19% for the DA, 11.17% for the SALS, and 7.91% for the Non-DA ambulance (P < 0.01). Compared with that of the DA group, the odds ratio (95% confidence interval [CI]) for PROSC ratio in the SALS and Non-DA groups were 0.97 (0.82-1.15) and 0.57 (0.50-0.65), respectively. It was shown that the PROSC ratio of the DA group was higher than that of the Non-DA group and was not lower than that of the SALS group. Conclusion: ALS protocol intervention was associated with difference in PROSC rates. Therefore, continuous efforts on the systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.

The Impact of the COVID-19 Outbreak on Emergency Medical Service: An Analysis of Patient Transportations and Time Intervals.

BACKGROUND: This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the Emergency Medical Service (EMS) system in South Korea. The study focused on the differences in EMS time intervals following the COVID-19 outbreak, particularly for patients with fever. METHODS: A retrospective analysis of EMS patient transportation data from 2017 to 2022 was conducted using the national EMS database. RESULTS: Starting from the year 2020, coinciding with the COVID-19 outbreak, all EMS time intervals experienced an increase. For the years 2017 to 2022, the mean response time interval values were 8.6, 8.6, 8.6, 10.2, 12.8, and 11.4 minutes, and the mean scene time interval values were 7.1, 7.2, 7.4, 9.0, 9.8, and 10.9 minutes. The mean transport time interval (TTI) values were 12.1, 12.3, 12.4, 14.2, 16.9, and 16.2 minutes, and the mean turnaround time interval values were 27.6, 27.9, 28.7, 35.2, 42.0, and 43.1 minutes. Fever (≥ 37.5°C) patients experienced more pronounced prolongations in EMS time intervals compared to non-fever patients and had a higher probability of being non-transported. The mean differences in TTI between fever and non-fever patients were 0.8, 0.8, 0.8, 4.3, 4.8, and 3.2 minutes, respectively, from 2017 to 2022. Furthermore, the odds ratios for fever patients being transported to the emergency department were 2.7, 2.9, 2.8, 1.1, 0.8, and 0.7, respectively, from 2017 to 2022. CONCLUSION: The study findings highlight the significant impact of the COVID-19 outbreak on the EMS system and emphasize the importance of ongoing monitoring to evaluate the burden on the EMS system.

Production of a 135-residue long N-truncated human keratinocyte growth factor 1 in Escherichia coli.

BACKGROUND: Palifermin (trade name Kepivance®) is an amino-terminally truncated recombinant human keratinocyte growth factor 1 (KGF-1) with 140 residues that has been produced using Escherichia coli to prevent and treat oral mucositis following radiation or chemotherapy. In this study, an amino-terminally shortened KGF-1 variant with 135 residues was produced and purified in E. coli, and its cell proliferation activity was evaluated. RESULTS: We expressed soluble KGF-1 fused to thioredoxin (TRX) in the cytoplasmic fraction of E. coli to improve its production yield. However, three N-truncated forms (KGF-1 with 140, 138, and 135 residues) were observed after the removal of the TRX protein from the fusion form by cleavage of the human enterokinase light chain C112S (hEKL C112S). The shortest KGF-1 variant, with 135 residues, was expressed by fusion with TRX via the hEKL cleavage site in E. coli and purified at high purity (> 99%). Circular dichroism spectroscopy shows that purified KGF-1135 had a structure similar to that of the KGF-1140 as a random coiled form, and MCF-7 cell proliferation assays demonstrate its biological activity. CONCLUSIONS: We identified variations in N-terminus-truncated KGF-1 and selected the most stable form. Furthermore, by a simple two-step purification, highly purified KGF-1135 was obtained that showed biological activity. These results demonstrate that KGF-1135 may be considered an alternative protein to KGF-1.

Impact of COVID-19 on Out-of-Hospital Cardiac Arrest in Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health crisis that has had a significant impact on emergency medical services (EMS). Several studies have reported an increase in the incidence of out-of-hospital cardiac arrest (OHCA) and a decreased survival due to COVID-19, which has been limited to a short period or has been reported in some regions. This study aimed to investigate the effect of COVID-19 on OHCA patients using a nationwide database. METHODS: We included adult OHCA patients treated by EMS providers from January 19, 2019 to January 20, 2021. The years before and after the first confirmed case in Korea were set as the non-COVID-19 and COVID-19 periods, respectively. The main exposure of interest was the COVID-19 period, and the primary outcome was prehospital return of spontaneous circulation (ROSC). Other OHCA variables were compared before and after the COVID-19 pandemic and analyzed. We performed a multivariable logistic regression analysis to understand the independent effect of the COVID-19 period on prehospital ROSC. RESULTS: The final analysis included 51,921 eligible patients, including 25,355 (48.8%) during the non-COVID-19 period and 26,566 (51.2%) during the COVID-19 period. Prehospital ROSC deteriorated during the COVID-19 period (10.2% vs. 11.1%, P = 0.001). In the main analysis, the adjusted odds ratios (AORs) for prehospital ROSC showed no significant differences between the COVID-19 and non-COVID-19 periods (AOR [95% confidence interval], 1.02 [0.96-1.09]). CONCLUSION: This study found that the proportion of prehospital ROSC was lower during the COVID-19 period than during the non-COVID-19 period; however, there was no statistical significance when adjusting for potential confounders. Continuous efforts are needed to restore the broken chain of survival in the prehospital phase and increase the survival rate of OHCA patients.

High-level production of keratinocyte growth factor 2 in Escherichia coli.

Recombinant human keratinocyte growth factor 2 (KGF-2), also known as repifermin, is used in various therapeutic applications. However, KGF-2 production has not been optimized for facilitating large-scale production. Therefore, we attempted to attain high-level production of bioactive KGF-2. KGF-2 was fused with 6HFh8 (6HFh8-KGF-2) at the tobacco etch virus protease cleavage site. The 6HFh8-KGF-2 was expressed in Escherichia coli with high expression levels of approximately 33% and 20% of soluble protein in flask culture and 5 L fermentation, respectively. 6HFh8-KGF-2 was purified via nickel affinity chromatography. To maintain a stable form of KGF-2, the conditions of the cleavage reaction were optimized based on the isoelectric point. KGF-2 was purified via ion-exchange chromatography to high purity (>99%) with an optimal purification yield (91%). Circular dichroism spectroscopy demonstrated that purified KGF-2 had a secondary structure and thermal stability similar to that of commercial KGF-2. Bioactivity assays indicated that purified KGF-2 could induce MCF-7 cell proliferation in the same manner as commercial KGF-2. These results demonstrate that bioactive KGF-2 was overexpressed in E. coli and purified to high quality. Our findings indicated that bioactive KGF-2 can be produced in large quantities in E. coli.

The number and level of first-contact emergency medical services crew and clinical outcomes in out-of-hospital cardiac arrest with dual dispatch response.

OBJECTIVE: This study aimed to evaluate the association between the number and level of emergency medical technicians (EMTs) in the first-contact emergency medical services (EMS) unit and the clinical outcomes of out-of-hospital cardiac arrest (OHCA) with a dual dispatch response. METHODS: Adult nontraumatic EMS-treated OHCAs between 2015 and 2018 in a nationwide database, were enrolled. The main exposure was the number and certification level of first-contact EMS crew: three versus two members, proportion of EMT intermediate level (EMT-I) over 50% versus under or equal to 50%. Good neurologic recovery was selected as the primary outcome. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios and confidence intervals. RESULTS: A total of 26,867 patients were enrolled and analyzed. Good neurologic recovery was different across the study groups: 5.4% in the two-member crews, 7.2% in the three-member crews, 5.9% in the low EMT-I proportion crews, and 6.8% in the high EMT-I proportion crews. In the main analysis, statistically significant differences for favorable outcomes were found between the three-member and two-member crews, and the high EMT-I proportion and low EMT-I proportion crews; for good neurologic recovery, adjusted odds ratios (95% confidence interval) were 1.23 (1.06-1.43) for three-member crews, and 1.28 (1.17-1.40) for a high EMT-I proportion. CONCLUSION: The higher number and level of first-contact EMS crew was associated with better neurologic recovery in adult nontraumatic OHCA with a dual-dispatched EMS response.

Biological Influence of Pulmonary Disease Conditions Induced by Particulate Matter on Microfluidic Lung Chips.

Particulate matter (PM10)-induced respiratory illnesses are difficult to investigate in trans-well culture systems. Microphysiological systems offer the capacity to mimic these phenomena to analyze any possible hazards that PM10 exposure poses to respiratory system of Humans. This study proposes an on-chip healthy human lung distal airway model that efficiently reconstitutes in vivo-like environmental conditions in a microfluidic device. The lung-on-chip model comprises a TEER sensor chip and portable microscope for continuous monitoring. To determine the efficacy of our model, we assessed the response to exposure to three PM environmental conditions (mild, average, and severe) and analyzed the relevant in vivo physiological and toxicological data using the airway model. Our results revealed significant increases in the levels of the IL-13, IL-6, and MUC5AC pathological biomarkers, which indicate increased incidences of on-chip asthma and chronic obstructive pulmonary disease conditions. Overall, we deduced that this model will facilitate the identification of potential therapeutics and the prevention of chronic life-threatening toxicities and pandemics such as COVID-19. The proposed system provides basic data for producing an improved in organ-on-chip technology. Supplementary Information: The online version contains supplementary material available at 10.1007/s13206-022-00068-x.

SperoPredictor: An Integrated Machine Learning and Molecular Docking-Based Drug Repurposing Framework With Use Case of COVID-19.

The global spread of the SARS coronavirus 2 (SARS-CoV-2), its manifestation in human hosts as a contagious disease, and its variants have induced a pandemic resulting in the deaths of over 6,000,000 people. Extensive efforts have been devoted to drug research to cure and refrain the spread of COVID-19, but only one drug has received FDA approval yet. Traditional drug discovery is inefficient, costly, and unable to react to pandemic threats. Drug repurposing represents an effective strategy for drug discovery and reduces the time and cost compared to de novo drug discovery. In this study, a generic drug repurposing framework (SperoPredictor) has been developed which systematically integrates the various types of drugs and disease data and takes the advantage of machine learning (Random Forest, Tree Ensemble, and Gradient Boosted Trees) to repurpose potential drug candidates against any disease of interest. Drug and disease data for FDA-approved drugs (n = 2,865), containing four drug features and three disease features, were collected from chemical and biological databases and integrated with the form of drug-disease association tables. The resulting dataset was split into 70% for training, 15% for testing, and the remaining 15% for validation. The testing and validation accuracies of the models were 99.3% for Random Forest and 99.03% for Tree Ensemble. In practice, SperoPredictor identified 25 potential drug candidates against 6 human host-target proteomes identified from a systematic review of journals. Literature-based validation indicated 12 of 25 predicted drugs (48%) have been already used for COVID-19 followed by molecular docking and re-docking which indicated 4 of 13 drugs (30%) as potential candidates against COVID-19 to be pre-clinically and clinically validated. Finally, SperoPredictor results illustrated the ability of the platform to be rapidly deployed to repurpose the drugs as a rapid response to emergent situations (like COVID-19 and other pandemics).

Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation.

The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease modeling. Conventionally, spheroid culture is carried out in static conditions, making the media nutrient-deficient around the spheroid periphery. The current approach tries to enhance the capacity of the spheroid culture platform by integrating the perfusion channel for dynamic culture conditions. A pro-inflammatory hepatic model was emulated using a coculture of HepG2 cell line, fibroblasts, and endothelial cells for validating the spheroid culture plate with a perfusable channel across the spheroid well. Enhanced proliferation and metabolic capacity of the microphysiological model were observed and further validated by metabolic assays. A comparative analysis of static and dynamic conditions validated the advantage of spheroid culture with dynamic media flow. Hepatic spheroids were found to have improved proliferation in dynamic flow conditions as compared to the static culture platform. The perfusable culture system for spheroids is more physiologically relevant as compared to the static spheroid culture system for disease and drug analysis.

Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips.

The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS.

Impact of age on the outcomes of extracorporeal cardiopulmonary resuscitation: analysis using inverse probability of treatment weighting.

OBJECTIVES: Patient selection is crucial to improving the outcomes of extracorporeal cardiopulmonary resuscitation (ECPR). However, ECPR's efficacy with older patients remains unknown. METHODS: We reviewed patients who underwent extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest from January 2006 to December 2018. Exclusion criteria were age <18 years, cannulation failure and ECMO applied at another hospital. We divided patients into 2 groups with an age cut-off of 66 years, using the Contal and O'Quigley method for overall survival. We performed inverse probability of treatment weighting (IPTW) between the 2 groups and set the primary outcome as overall survival. RESULTS: We included 318 patients in our study (≤66 years, n = 199; >66 years, n = 119). Before IPTW, we observed that the older group had a higher frequency of diabetes, hypertension, and myocardial infarction. In the young group, more patients had out-of-hospital cardiac arrest as compared with the older group. The hospital mortality rate was 55% (48.7% in the young group, 65.5% in the older group; P = 0.004). In the multivariable analysis after IPTW, the older group showed worse outcomes in overall survival [hazard ratio (HR) = 2.02; 95% confidence interval (CI), 1.50-2.70; P < 0.001] and neurological outcomes at discharge (odds ratio = 2.95; 95% CI, 1.69-5.14; P = <0.001). ECMO insertion during catheterization (HR = 0.57; 95% CI, 0.36-0.90; P = 0.015) and recovery of spontaneous circulation before pump-on (HR = 0.67; 95% CI, 0.50-0.89; P = 0.007) were positive predictors, but initial asystole rhythm, non-cardiac cause (HR = 2.39; 95% CI, 1.59-3.61; P < 0.001), out-of-hospital cardiac arrest (HR = 1.86; 95% CI, 1.24-2.79; P = 0.003) and prolonged cardiopulmonary resuscitation to pump-on time (HR = 1.01; 95% CI, 1.01-1.02; P < 0.001) were negative predictors for overall survival. CONCLUSIONS: Older patients who had ECPR had significantly worse survival and neurological outcomes. For patients older than age 66 years, more careful patient selection is critically important for improving the efficacy of ECPR.

Multiplex PCR-Based Nanopore Sequencing and Epidemiological Surveillance of Hantaan orthohantavirus in Apodemus agrarius, Republic of Korea.

Whole-genome sequencing of infectious agents enables the identification and characterization of emerging viruses. The MinION device is a portable sequencer that allows real-time sequencing in fields or hospitals. Hantaan orthohantavirus (Hantaan virus, HTNV), harbored by Apodemus agrarius, causes hemorrhagic fever with renal syndrome (HFRS) and poses a critical public health threat worldwide. In this study, we aimed to evaluate the feasibility of using nanopore sequencing for whole-genome sequencing of HTNV from samples having different viral copy numbers. Amplicon-based next-generation sequencing was performed in A. agrarius lung tissues collected from the Republic of Korea. Genomic sequences of HTNV were analyzed based on the viral RNA copy numbers. Amplicon-based nanopore sequencing provided nearly full-length genomic sequences of HTNV and showed sufficient read depth for phylogenetic analysis after 8 h of sequencing. The average identity of the HTNV genome sequences for the nanopore sequencer compared to those of generated from Illumina MiSeq revealed 99.8% (L and M segments) and 99.7% (S segment) identities, respectively. This study highlights the potential of the portable nanopore sequencer for rapid generation of accurate genomic sequences of HTNV for quicker decision making in point-of-care testing of HFRS patients during a hantavirus outbreak.

Expression and purification of soluble and active human enterokinase light chain in Escherichia coli.

Human enterokinase light chain (hEKL) specifically cleaves the sequence (Asp)4-Lys↓X (D4K), making this a frequently used enzyme for site-specific cleavage of recombinant fusion proteins. However, hEKL production from Escherichia coli is limited due to intramolecular disulphide bonds. Here, we present strategies to obtain soluble and active hEKL from E. coli by expressing the hEKL variant C112S fused with maltose-binding protein (MBP) through D4K and molecular chaperons including GroEL/ES. The fusion protein self-cleaved in vivo, thereby removing the MBP in the E. coli cells. Thus, the self-cleaved hEKL variant was released into the culture medium. One-step purification using HisTrap™ chromatography purified the hEKL variant exhibiting an enzymatic activity of 3.1 × 103 U/mL (9.934 × 105 U/mg). The approaches presented here greatly simplify the purification of hEKL from E. coli without requiring refolding processes.

Impact of a Multidisciplinary Team Approach on Extracorporeal Circulatory Life Support-Bridged Heart Transplantation.

BACKGROUND: The number of heart transplantations (HTx) is increasing annually. Due to advances in medical and surgical support, the outcomes of HTx are also improving. Extracorporeal circulatory life support (ECLS) provides patients with decompensated heart failure a chance to undergo HTx. A medical approach involving collaboration among experienced experts in different fields should improve the outcomes and prognosis of ECLSbridged HTx. METHODS: From December 2003 to December 2018, 1,465 patients received ECLS at Samsung Medical Center. We excluded patients who had not undergone HTx or underwent repeated transplantations. Patients younger than 18 years were excluded. We also excluded patients who received an implantable durable left ventricular assist device before HTx. In total, 91 patients were included in this study. A multidisciplinary team approach began in March 2013 at our hospital. We divided the patients into 2 groups depending on whether they were treated before or after implementation of the team approach. RESULTS: The 30-day mortality rate was significantly higher in the pre-ECLS team group than in the post-ECLS team group (n=5, 18.5% vs. n=2, 3.1%; p=0.023). The 1-year survival rate was better in the post-ECLS team group than in the pre-ECLS team group (n=57, 89.1% vs. n=19, 70.4%; p=0.023). CONCLUSION: We found that implementing a multidisciplinary team approach improved the outcomes of ECLS-bridged HTx. Team-based care should be adapted at HTx centers that perform high-risk HTx.

Effective production of human growth factors in Escherichia coli by fusing with small protein 6HFh8.

BACKGROUND: Growth factors (GFs) are signaling proteins that affect cellular processes such as growth, proliferation, and differentiation. GFs are used as cosmeceuticals, exerting anti-wrinkle, anti-aging, and whitening effects, and also as pharmaceuticals to treat wounds, growth failure, and oral mucositis. However, in mammalian and bacterial cells, low productivity and expression in inclusion bodies, respectively, of GFs does not satisfy the consumer demand. Here, we aimed to develop a bacterial expression system that produces high yields of soluble GFs that can be purified in their native forms. RESULTS: We present Fh8, an 8-kDa peptide from Fasciola hepatica with an N-terminal hexa-histidine (6HFh8), as a fusion partner for enhanced human GF production in recombinant Escherichia coli. The fusion partner harboring a tobacco etch virus (TEV) protease cleavage site was fused to the N-terminus of 10 human GFs: acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), epidermal growth factor (EGF), human growth hormone (hGH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor 165 (VEGF165), keratinocyte growth factor 1 (KGF-1), placental growth factor (PGF), stem cell factor (SCF), and tissue inhibitor of metalloproteinase 1 (TIMP-1). The fusion proteins were expressed in E. coli under the control of T7 promoter at three temperatures (25 °C, 30 °C, and 37 °C). All individual fusion proteins, except for SCF and TIMP-1, were successfully overexpressed in cytoplasmic soluble form at more than one temperature. Further, the original aFGF, IGF-1, EGF, and VEGF165 proteins were cleaved from the fusion partner by TEV protease. Five-liter fed-batch fermentation approaches for the 6HFh8-aFGF (lacking disulfide bonds) and 6HFh8-VEGF165 (a cysteine-rich protein) were devised to obtain the target protein at concentrations of 9.7 g/l and 3.4 g/l, respectively. The two GFs were successfully highly purified (> 99% purity). Furthermore, they exerted similar cell proliferative effects as those of their commercial equivalents. CONCLUSIONS: We demonstrated that 6HFh8-GF fusion proteins could be overexpressed on a g/l scale in the cytoplasm of E. coli, with the GFs subsequently highly purified and maintaining their biological activity. Hence, the small protein 6HFh8 can be used for efficient mass-production of various GFs.

Intractable Coronary Spasm Requiring Percutaneous Coronary Intervention after Coronary Artery Bypass Grafting in a Patient with Moyamoya Disease.

Moyamoya disease (MMD) is characterized by progressive steno-occlusive lesions of the distal or proximal branch of the internal carotid arteries, and cerebrovascular symptoms are its major complications. Extracranial vascular involvement including the coronary artery has been reported, and some case reports have described variant angina or myocardial infarction. However, no report has yet described a case of myocardial infarction after coronary artery bypass grafting (CABG). Here, we present a patient with MMD who suffered cardiac arrest caused by myocardial infarction due to a coronary spasm after offpump CABG and who was discharged successfully after treatment with a veno-arterial extracorporeal membrane oxygenator and percutaneous coronary intervention.

Implementation of Venoarterial Extracorporeal Membrane Oxygenation in Nonintubated Patients.

BACKGROUND: Although extracorporeal membrane oxygenation (ECMO) is generally performed percutaneously, the technology is deployed under sedation and necessitates endotracheal intubation. However, in some patients, the use of venoarterial (VA) ECMO without intubation may be beneficial. Herein, we describe our experiences with VA ECMO performed without prior endotracheal intubation. METHODS: A total of 783 patients treated with VA ECMO at a single center between January 2013 and July 2018 were reviewed retrospectively. We included patients who underwent successful VA ECMO implementation without prior endotracheal intubation, and excluded those who were younger than 18 years, had ongoing cardiopulmonary resuscitation status, and had poor quality of the vessels needed for percutaneous cannulation. The primary study outcome was in-hospital survival. RESULTS: In total, 50 patients were included in this study, 94% of whom showed cardiogenic shock. The mean age of the study participants was 56.3±14.5 years. The median VA ECMO support time was 7 days (range, 2-13 days). Twenty-one patients (42%) did not receive ventilator care during the VA ECMO support period, while 29 patients (58%) progressed to intubation after VA ECMO implementation. The rates of survival at discharge and weaning success were 82% (n=41) and 92% (n=46), respectively, and 80% (n=40) of patients presented good Glasgow-Pittsburgh Cerebral Performance Categories scores at discharge. CONCLUSION: Even in patients with cardiogenic shock, percutaneous VA ECMO can be introduced safely without prior endotracheal intubation by an experienced care team. The application of nonintubated VA ECMO might be a feasible strategy in selected cases.

Phylogeographic diversity and hybrid zone of Hantaan orthohantavirus collected in Gangwon Province, Republic of Korea.

BACKGROUND: Hantaan orthohantavirus (Hantaan virus, HTNV), harbored by Apodemus agrarius (the striped field mouse), causes hemorrhagic fever with renal syndrome (HFRS) in humans. Viral genome-based surveillance at new expansion sites to identify HFRS risks plays a critical role in tracking the infection source of orthohantavirus outbreak. In the Republic of Korea (ROK), most studies demonstrated the serological prevalence and genetic diversity of orthohantaviruses collected from HFRS patients or rodents in Gyeonggi Province. Gangwon Province is a HFRS-endemic area with a high incidence of patients and prevalence of infected rodents, ROK. However, the continued epidemiology and surveillance of orthohantavirus remain to be investigated. METHODOLOGY/PRINCIPAL FINDINGS: Whole-genome sequencing of HTNV was accomplished in small mammals collected in Gangwon Province during 2015-2018 by multiplex PCR-based next-generation sequencing. To elucidate the geographic distribution and molecular diversity of viruses, we conducted phylogenetic analyses of HTNV tripartite genomes. We inferred the hybrid zone using cline analysis to estimate the geographic contact between two different HTNV lineages in the ROK. The graph incompatibility based reassortment finder performed reassortment analysis. A total of 12 HTNV genome sequences were completely obtained from A. agrarius newly collected in Gangwon Province. The phylogenetic and cline analyses demonstrated the genetic diversity and hybrid zone of HTNV in the ROK. Genetic exchange analysis suggested the possibility of reassortments in Cheorwon-gun, a highly HFRS-endemic area. CONCLUSIONS/SIGNIFICANCE: The prevalence and distribution of HTNV in HFRS-endemic areas of Gangwon Province enhanced the phylogeographic map for orthohantavirus outbreak monitoring in ROK. This study revealed the hybrid zone reflecting the genetic diversity and evolutionary dynamics of HTNV circulating in Gangwon Province. The results arise awareness of rodent-borne orthohantavirus diseases for physicians in the endemic area of ROK.

Evaluation of performance characteristics of portal monitor for radiation emergency.

For evaluating the counting efficiency of a portal monitor, we use a137Cs radiation point source (1 µCi) to subsequently establish it effective measurable area. Through simulation, we estimate the appropriate distance from potentially contaminated individuals in the scanning queue to the monitoring individual. When this distance is over 10 m, the counting efficiency was below 0.01%. We find that the triage can be applied to roughly 180 individuals per hour during mass casualties.