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Objective Right ventricular heart failure (RVHF) is a critical complication in patients with respiratory failure, particularly among those who transitioned to lung transplantation using venovenous (VV) extracorporeal membrane oxygenation (ECMO). In these patients, both cardiac and respiratory functions are supported using venoarterial or venoarterial-venous ECMO. However, these modalities increase the risk of device-related complications, such as thromboembolism, bleeding, and limb ischemia, and they may disturb early rehabilitation. Due to these limitations, a right ventricular assist device with an oxygenator (Oxy-RVAD) using ECMO may be considered for patients with RVHF with VV ECMO. Design A retrospective case series and literature review. Setting A single tertiary care university hospital. Participants The study comprised lung transplantation candidates on ECMO bridging who developed right-sided heart failure. Interventions An RVAD with ECMO. Measurements and Main Results Of eight patients who underwent the study protocol, seven were bridged successfully to lung transplantation (BTT), and all patients with BTT were discharged, with a 30-day survival rate of 100% (7/7 patients). The 180-day survival rate was 85% (6/7 patients). Conclusions The study suggested that Oxy-RVAD using ECMO may be a viable option for bridging patients with RVHF to lung transplantation. Trial Registration Retrospectively registered.

OBJECTIVES To investigate the impact of normothermia on compliance with sepsis bundles and in-hospital mortality in patients with sepsis who present to emergency departments. DESIGN Retrospective multicenter observational study. PATIENTS Nineteen university-affiliated hospitals of the Korean Sepsis Alliance participated in this study. Data were collected regarding patients who visited emergency departments for sepsis during the 1-month period. The patients were divided into three groups based on their body temperature at the time of triage in the emergency department (i.e., hypothermia [ 38°C]). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 64,021 patients who visited emergency departments, 689 with community-acquired sepsis were analyzed (182 hyperthermic, 420 normothermic, and 87 hypothermic patients). The rate of compliance with the total hour-1 bundle was lowest in the normothermia group (6.0% vs 9.3% in hyperthermia vs 13.8% in hypothermia group; p = 0.032), the rate for lactate measurement was lowest in the normothermia group (62.1% vs 73.1% vs 75.9%; p = 0.005), and the blood culture rate was significantly lower in the normothermia than in the hyperthermia group (p < 0.001). The in-hospital mortality rates in the hyperthermia, normothermia, and hypothermia groups were 8.5%, 20.6%, and 30.8%, respectively (p < 0.001), but there was no significant association between compliance with sepsis bundles and in-hospital mortality. However, in a multivariate analysis, compared with hyperthermia, normothermia was significantly associated with an increased in-hospital mortality (odds ratio, 2.472; 95% CI, 1.005-6.080). This association remained significant even after stratifying patients by median lactate level. CONCLUSIONS Normothermia at emergency department triage was significantly associated with an increased risk of in-hospital mortality and a lower rate of compliance with the sepsis bundle. Despite several limitations, our findings suggest a need for new strategies to improve sepsis outcomes in this group of patients.

Right heart decompensation is a fatal complication in patients with respiratory failure, particularly in those transitioned to lung transplantation using veno-venous extracorporeal membrane oxygenation (V-V ECMO). In these patients, veno-arterial (V-A ECMO) or veno-arterialvenous extracorporeal membrane oxygenation (V-AV ECMO) is used to support both cardiac and respiratory function. However, these processes may increase the risk of device-related complications such as bleeding, thromboembolism, and limb ischemia. In the present case, a 64-year-old male patient with idiopathic pulmonary fibrosis developed respiratory failure and commenced treatment with V-V ECMO as a bridge to lung transplantation. Unfortunately, the patient developed right heart decompensation and required both cardiac and respiratory support during treatment with V-V ECMO. Instead of adding arterial cannulation, he was switched to a novel configuration, a right ventricular assist device with an oxygenator (Oxy- RVAD) using ECMO, with drainage cannulation from the femoral vein and return cannulation to the main pulmonary artery. The patient was successfully bridged to lung transplantation without serious complications after 10 days of Oxy-RVAD support. To the best of our knowledge, this is an extreme rare and challenging case of Oxy-RVAD using ECMO in a patient successfully bridged to lung transplantation.

An outbreak of fatal humidifier disinfectant lung injuries (HDLI) occurred in Korea. Human studies on mechanisms underlying HDLI have yet to be conducted. This study aimed to investigate methylation changes and their potential role in HDLI after exposure to HDs containing polyhexamethylene guanidine-phosphate. DNA methylation analysis was performed in blood samples from 10 children with HDLI and 10 healthy children using Infinium Human MethylationEPIC BeadChip. Transcriptome analysis was performed using lung tissues from 5 children with HDLI and 5 controls. Compared to healthy controls, 92 hypo-methylated and 79 hyper-methylated CpG sites were identified in children with HDLI at the statistical significance level of |Δβ|>0.2 and p

Background It is unclear whether the administration of antibiotics within 1 hour could improve patient outcomes in sepsis, and whether the association of time to antibiotics administration and clinical outcomes are different for sepsis and septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3,035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI], 0.61–0.99; p=0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI, 0.44–0.99; p=0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI, 0.64–1.15; p=0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p=0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

OBJECTIVES To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN Prospective, multicenter, observational study. SETTING Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS None. MEASUREMENT AND MAIN RESULTS The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65). CONCLUSIONS Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

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

Background: Hospitalized patients can develop septic shock at any time. Therefore, it is important to identify septic patients in hospital wards and rapidly perform the optimal treatment. Although the sepsis bundle has already been reported to improve survival rates, the controversy over evidence of the effect of in-hospital sepsis continues to exist. We aimed to estimate the outcomes and bundle compliance of patients with septic shock in hospital wards managed through the rapid response system (RRS). Methods: A retrospective cohort study of 976 patients with septic shock managed through the RRS at an academic, tertiary care hospital in Korea from 2008 to 2017. Results: Of the 976 enrolled patients, the compliance of each sepsis bundle was high (80.8–100.0%), but the overall success rate of the bundle was low (58.3%). The compliance rate for achieving the overall sepsis bundle increased from 26.5% to 70.0%, and the 28-day mortality continuously decreased from 50% to 32.1% over 10 years. We analyzed the two groups according to whether they completed the overall sepsis bundle or not. Of the 976 enrolled patients, 569 (58.3%) sepsis bundles were completed, whereas 407 (41.7%) were incomplete. The complete bundle group showed lower 28-day mortality than the incomplete bundle group (37.1% vs. 53.6%, p &lt, 0.001). In the multivariate multiple logistic regression model, the 28-day mortality was significantly associated with the complete bundle (adjusted odds ratio (OR), 0.61, 95% confidence intervals (CI), 0.40–0.91, p = 0.017). The obtaining of blood cultures (adjusted OR, 0.45, 95% CI, 0.33–0.63, p &lt, 0.001) and lactate re-measurement (adjusted OR, 0.69, 95% CI, 0.50–0.95, p = 0.024) in each component of the sepsis bundle were associated with the 28-day mortality. Conclusions: The rapid response system provides improving sepsis bundle compliances and survival in patients with septic shock in hospital wards.

Background Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea. Methods This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study. Results Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P

Background Although extracorporeal membrane oxygenation (ECMO) has been used for the treatment of acute high-risk pulmonary embolism (PE), there are limited reports which focus on this approach. Herein, we described our experience with ECMO in patients with acute high-risk PE. Methods We retrospectively reviewed medical records of patients diagnosed with acute high-risk PE and treated with ECMO between January 2014 and December 2018. Results Among 16 patients included, median age was 51 years (interquartile range [IQR], 38 to 71 years) and six (37.5%) were male. Cardiac arrest was occurred in 12 (75.0%) including two cases of out-of-hospital arrest. All patients underwent veno-arterial ECMO and median ECMO duration was 1.5 days (IQR, 0.0 to 4.5 days). Systemic thrombolysis and surgical embolectomy were performed in seven (43.8%) and nine (56.3%) patients, respectively including three patients (18.8%) received both treatments. Overall 30-day mortality rate was 43.8% (95% confidence interval, 23.1% to 66.8%) and 30-day mortality rates according to the treatment groups were ECMO alone (33.3%, n=3), ECMO with thrombolysis (50.0%, n=4) and ECMO with embolectomy (44.4%, n=9). Conclusions Despite the vigorous treatment efforts, patients with acute high-risk PE were related to substantial morbidity and mortality. We report our experience of ECMO as rescue therapy for refractory shock or cardiac arrest in patients with PE.

Lung cancer screening with low-dose computed tomography reduced mortality in selected high risk patients. However, the use of chest radiography for lung cancer screening in Asian populations is still controversial. We investigated the effectiveness of chest radiographic surveillance using a nationwide health service data in South Korea.Data from the Korean National Health Insurance Service examinee cohort of 2004 to 2013 were examined, and 63,228 patients with lung cancer were identified, 38,494 (57%) of whom underwent chest radiography screening. The others did not undergo lung cancer screening and were considered as a control group. Clinical data including age, smoking, screening intervals, lung cancer stages, treatments, and survival were collected. Survival gain from surveillance after adjustment for lead-time bias based on the sojourn time was calculated. Cox-proportional hazard analyses were performed to evaluate the effectiveness of screening and to determine the appropriate screening interval for chest radiography surveillance.Early lung cancer was found in 38% of patients receiving chest radiography versus 26% of those without surveillance. A patient age of more than 65 years (hazard ratio [HR], 1.53; 95% confidence limits [CL], 1.50-1.56), male (HR, 1.66; 95% CL, 1.62-1.70), and high lung cancer stages at the time of diagnosis were independent factors associated with mortality (each, P 0.001). Chest radiography surveillance was a factor for decreasing mortality in female (HR, 0.81; 95% CL, 0.77-0.84, P 0.001), with mortality reduction of 10% at the 3- and 5-year survival time-points. In female patients, chest radiography surveillance at intervals of less than 3 years was an independent predictor of improved survival.Surveillance chest radiography increased survival in a female screened population in South Korea. Chest radiography intervals of less than 3 years may help to detect lung cancer in female patients.

Although guidelines have recommended that patients with chronic thromboembolic pulmonary hypertension (CTEPH) should be managed by a multidisciplinary team (MDT), there is a lack of clinical data indicating that the MDT improves CTEPH management.The study aimed to identify the effect of an MDT on CTEPH management.We divided the study period into pre-MDT and post-MDT eras and compared the implementation rates of major diagnostic and therapeutic procedures.Of 116 patients with CTEPH, 42 (36.2%) were diagnosed in the post-MDT era. The implementation rates of right heart catheterization (10.8% vs. 97.6%, p0.001) and pulmonary endarterectomy (32.4% vs. 59.5%, p0.005) were significantly increased in the post-MDT era. Balloon pulmonary angioplasty was not performed in the pre-MDT era but was performed in the post-MDT era.The MDT appears to be associated with improved CTEPH management.

Purpose Monocyte distribution width (MDW) has been suggested as an early biomarker of sepsis, but few studies have compared MDW with conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT). This study evaluated MDW as a biomarker for sepsis and compared it with CRP and PCT. Materials and methods Patients aged 18–80 years who visited the emergency department were screened and prospectively enrolled in a tertiary medical center. Complete blood count, MDW, CRP, and PCT were examined. Diagnostic performance for sepsis was tested using the area under the curve (AUC) of receiver operating characteristic (ROC) curves, sensitivity, and specificity. Results In total, 665 patients were screened, and 549 patients with valid laboratory test results were included in the analysis. The patients were categorized into three groups according to the Sepsis-3 criteria: non-infection, infection, and sepsis. MDW showed the highest value in the sepsis group (median [interquartile range], 24.0 [20.8–27.8]). The AUC values for MDW, CRP, PCT, and white blood cells for predicting sepsis were 0.71 (95% confidence interval [CI], 0.67–0.75), 0.75 (95% CI, 0.71–0.78], 0.76 (95% CI, 0.72–0.79, and 0.61 (95% CI, 0.57–0.65), respectively. With the optimal cutoff value of the cohort, the sensitivity was 83.0% for MDW (cutoff, 19.8), 69.7% for CRP (cutoff, 4.0), and 76.6% for PCT (cutoff, 0.05). The combination of quick Sequential Organ Failure Assessment (qSOFA) with MDW improved the AUC (0.76; 95% CI, 0.72–0.80) to a greater extent than qSOFA alone (0.67; 95% CI, 0.62–0.72). Conclusions MDW reflected a diagnostic performance comparable to that of conventional diagnostic markers, implying that MDW is an alternative biomarker. The combination of MDW and qSOFA improves the diagnostic performance for early sepsis.

Background: Under the Food and Drug Administration’s drug development tool qualification program, fibrinogen is the first biomarker drug development tool used in chronic obstructive pulmonary disease (COPD). However, the correlation between fibrinogen and exacerbations among Korean patients with COPD remains unclear. Methods: In this retrospective cross-sectional study, we included patients with COPD for whom plasma fibrinogen assessment results, without exacerbation, were available. Then, we compared subgroups according to fibrinogen level (threshold: 350 mg/dL). We used multivariate linear regression analysis to investigate the clinical phenotype of COPD with high fibrinogen level, analyzed the correlation between the COPD severity indexes and fibrinogen level. Results: Of 140 patients, we confirmed 48 (34.3%) patients in the high-level fibrinogen group. The high-level group demonstrated a medical history of more exacerbations than the low-level group. Lung functions [forced expiratory volume in 1 s (FEV 1 ), forced vital capacity, and 6-minute walk distance] were more deteriorated in the high-level group. Multivariate regression analysis revealed that fibrinogen level was associated with high COPD assessment test score, and experience of exacerbation. Fibrinogen level exhibited a statistically significant positive correlation with COPD severity indexes. Conclusions: High fibrinogen level seems to reflect frequent exacerbation and severe symptomatic phenotypes in Korean patients with COPD.

Ina Jeong,1,* Jae-Hyun Lim,2,* Dong Kyu Oh,3 Woo Jin Kim,4 Yeon-Mok Oh3 1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea; 2Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Purpose: As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues. Patients and methods: First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity

Background and objective Despite the ongoing intense debate on the definition of airflow limitation by spirometry in the elderly population, there have only been few studies comparing the fixed ratio and the Z-score of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) in terms of long-term mortalities. In this study, we aimed to identify the proper method for accurately defining the airflow limitation in terms of long-term mortality prediction in the elderly population. Methods Data were collected from the Third National Health and Nutrition Examination Survey in the US. Non-Hispanic Caucasians aged 65-80 years were included. The receiver operating characteristic (ROC) curves of both methods were plotted and compared for 10-year all-cause, respiratory, and COPD mortalities. Results Of 1,331 subjects, the mean age was 71.7 years and 805 (60.5%) were males. For the 10-year all-cause mortality, the area under the curve (AUC) of the fixed ratio was significantly greater than that of the Z-score of FEV1/FVC, but both showed poor prediction performance (0.633 vs 0.616, p

Despite the increasing use of high-flow nasal cannulas (HFNCs) to treat critically ill patients, data on their effectiveness for sepsis patients remains very limited. We studied a prospective cohort of sepsis patients from the Korean Sepsis Registry (18 intensive care units (ICUs)). Patients started on HFNC therapy for hypoxemia within the first three ICU days were enrolled. HFNC failure was defined as intubation or ICU death, and the primary outcome was early HFNC failure occurring within 72 h of HFNC initiation. Of 901 patients with sepsis admitted to the ICU, 206 who received HFNC therapy were finally included (117 with pneumonia vs. 89 with non-pneumonia sepsis, median age, 71.0 (63.0–78.0) years, PaO2/FiO2 ratio, 160.2 (107.9–228.2) mm Hg, septic shock, n = 81 (39.3%)). During HFNC therapy, 72 (35.0%) patients were intubated and 51 (24.8%) died. HFNC failure developed in 95 (46.1%) patients, and among them, early failure rate was 85.3% (81/95). On multivariate analysis, an immunocompromised state (odds ratio (OR) = 2.730), use of a combination of antibiotics (OR = 0.219), and the PaO2/FiO2 ratio (OR = 0.308) were significantly associated with early HFNC failure in pneumonia sepsis patients. However, in non-pneumonia sepsis patients, lactate levels (OR = 1.532) were significantly associated with early HFNC failure. In conclusion, a high proportion of sepsis patients experience HFNC failure, usually within 72 h after therapy initiation, which emphasizes the importance of close monitoring. Furthermore, unlike in pneumonia sepsis, organ failure (i.e., lactate) might serve as a prognostic marker in non-pneumonia sepsis (i.e., type IV respiratory failure).

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are difficult to manage with very poor survival and due to universal recurrence after liver transplantation, they have been excluded from indication. Conformer radiation therapy (RT) has been shown to be effective in the treatment of HCC but only few trials have been reported as bridge to liver transplantation (LT) in HCC with PVTT. The purpose of our study was to evaluate the possibility of applying living donor liver transplantation (LDLT) following successful downstaging using RT in advanced HCC with PVTT. Among 1360 patients who received LT at our institution between May 1996 and March 2013, 5 received RT and they were compared with a propensity score matched group of 10 patients receiving RT alone according to sex, age, tumor size and number, dose of RT, level of AFP and location of PVTT. Objective tumor response after RT was evaluated with CT and/or MRI according to modified RECIST criteria. There is no difference in clinical characteristics between both groups. Two recipients showed disease progression, but in RT alone group, all patients are shown tumor ingrowths or intra-, extra-hepatic metastasis. LDLT following RT group's OS was 1055 days and that of RT alone group's was 367 days with significant statistically difference. Conclusion: LDLT following RT can be treatment of choice for PVTT in selective patients like solitary HCC with below Vp3 PVTT and good tumor response, and we suggest that this warrants further testing in a randomized, controlled, multi-center trial. And when doing bile duct anastomosis in RT recipients, hepaticojejunostomy was recommended to prevent biliary complication. This article is protected by copyright. All rights reserved.

Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.

The efficacy of antithrombin (AT) administration in patients with septic shock and disseminated intravascular coagulation (DIC) was uncertain. This study aimed to investigate whether high-dose AT administration improves outcomes in patients with septic shock and DIC. This observational, prospective cohort study included consecutive adult septic shock patients with DIC who showed AT activity

Background The current early warning scores may be insufficient for medical emergency teams (METs) to use in assessing the severity and the prognosis of activated patients. We evaluated the predictive powers of the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) for 28-day mortality and to analyze predictors of 28-day mortality in general ward patients who activate the MET. Methods Adult general ward inpatients who activated the MET in a tertiary referral teaching hospital between March 2009 and December 2016 were included. The demographic and clinical characteristics and physiologic parameters at the time of MET activation were collected, and MEWS and NEWS were calculated. Results A total of 6,729 MET activation events were analyzed. Patients who died within 28 days were younger (mean age 60 vs 62 years), were more likely to have malignancy (72% vs 53%), were more likely to be admitted to the medical department rather than the surgical department (93% vs 80%), had longer intervals from admission to MET activation (median, 7 vs 5 days), and were less likely to activate the MET during nighttime hours (5 PM to 8 AM) (61% vs 66%) compared with those who did not die within 28 days (P < 0.001 for all comparisons). The areas under the receiver operating characteristic curves of MEWS and NEWS for 28-day mortality were 0.58 (95% CI, 0.56–0.59) and 0.60 (95% CI, 0.59–0.62), which were inferior to that of the logistics regression model (0.73; 95% CI, 0.72–0.74; P < 0.001 for both comparisons). Conclusions Both the MEWS and NEWS had poor predictive powers for 28-day mortality in patients who activated the MET. A new scoring system is needed to stratify the severity and prognosis of patients who activated the MET.

A 65-year-old male was bridged to lung transplantation with veno-venous extracorporeal membrane oxygenation (ECMO). After experiencing heparin-induced thrombocytopaenia, heparin was replaced with argatroban. After 24 days, bilateral sequential lung transplantation was performed with argatroban anticoagulation. Intraoperative argatroban doses ranged between 0.4 and 0.6 μg/kg/min, resulting in activated clotting time of 169–216 s and activated partial thromboplastin time of 45–75 s. The patient was weaned from ECMO immediately after lung transplantation, and no bleeding or thrombotic complications were observed. He was discharged home on postoperative day 140.

Supplemental Digital Content is available in the text, There is ongoing controversy about how to address the growing demand for intensive care for critically ill elderly patients. We investigated resource utilization patterns and mortality rates according to age among critically ill patients. We retrospectively analyzed the medical records of patients admitted to a medical intensive care unit (ICU) in a tertiary referral teaching hospital between July 2006 and June 2015. Patients were categorized into non-elderly (age

Background: Vitamin C has shown several beneficial effects on sepsis in preclinical studies. However, clinical data supporting these reports are scarce. This study aimed to evaluate whether adjunctive intravenous vitamin C therapy could reduce hospital mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. Methods: For this retrospective cohort study, consecutive medical ICU patients with severe sepsis or septic shock requiring mechanical ventilation were included. The study patients were classified into the vitamin C or control groups depending on the administration of intravenous vitamin C (2 g every 8 hours). The primary outcome was hospital mortality. Results: Thirty-five patients in the vitamin C group and 40 patients in the control group were included. The two groups were comparable in regards to the baseline characteristics at ICU admission. The hospital mortality was 46% (16 of 35 patients) in the vitamin C group and 40% (16 of 40 patients) in the control group, showing a statistically nonsignificant difference (P=0.62). The mortality at 90 days after ICU admission (60% vs . 48%) did not significantly differ between groups. The median time to shock reversal was 3 days [interquartile range (IQR), 2 to 5 days] in both groups. The changes in the Sepsis-related Organ Failure Assessment (SOFA) scores during the first 4 ICU days were −1.4±3.3 and −1.4±3.0 in the vitamin C and control groups, respectively. Conclusions: Adjunctive intravenous vitamin C therapy alone did not reduce hospital mortality in mechanically ventilated patients with severe sepsis or septic shock.

Partial liver grafts used in living donor liver transplantation (LDLT) may have multiple hepatic artery (HA) stumps. This study was designed to validate the safety of partial reconstruction of multiple HAs in pediatric LDLT cases. From January 2000 to June 2014, 136 pediatric LDLT recipients were categorized into three groups: single HA group (Group 1, n = 74), multiple HAs with total reconstruction group (Group 2, n = 23), and multiple HAs with partial reconstruction group (Group 3, n = 39). Partial reconstruction was performed only when there was pulsatile back-bleeding after larger HA reconstruction and sufficient intrahepatic arterial flow was confirmed by Doppler ultrasound (DUS). There was no significant difference in biliary complication rate, artery complication rate, patient survival, and graft survival among these groups. Risk factor analysis revealed that the presence of multiple HAs and partial reconstruction of multiple HAs were not risk factors of biliary anastomosis stricture. In conclusion, partial reconstruction of HAs during pediatric LDLT using a left liver graft with multiple HA stumps does not increase the risk of biliary anastomosis stricture or affect graft survival when intrahepatic arterial communication is confirmed by pulsatile back-bleeding and DUS.

Allergic contact dermatitis (ACD) is an inflammatory skin disease and regarded as a prototype of T-cell mediated delayed-type hypersensitivity reactions. Aroma Oil Complex (AOC) is composed of lavender true oil, chamomile roman oil and tea tree oil. This study was performed to assess the effects of AOC in a canine model of ACD. ACD was induced on the back of dogs induced by sensitization and repeated application by 2,4-dinitro-1-chlorobenzene (DNCB). Topical treatment of AOC was applied once a day for 8 days and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, skin thickness and erythema index, were measured every two days during experimental periods. Histopathology and immunohistochemistry were performed to evaluate the anti-inflammatory effect. In skin biophysical parameters, TEWL, skin hydration, skin thickness and erythema index were significantly increased, with a maximum increase appeared on day 2 (p < 0.05). After the completion of AOC treatment, skin biophysical parameters were significantly reached those of baseline in a time-dependent manner (p < 0.05). In histopathology, marked increases of epidermal thicknesses were induced after DNCB challenge with numerous inflammatory cell infiltrations and edematous changes, decreases of connective tissue occupied regions in dermis. In addition, marked increases of cytokine - tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-immunoreactivities in the dermis and of apoptotic markers - caspase-3 and PARP-immunoreactivities in the epidermis were observed in DNCB control as compared with intact control, respectively (p < 0.01). The decrease of infiltrated inflammatory cells and related decreases of pro-inflammatory cytokine immunoreactivities were observed in AOC treated skin (p < 0.01). Based on these findings, AOC may have anti-inflammatory and alleviatory effects in the allergic contact dermatitis.

The efficacy and safety of osimertinib were demonstrated in clinical trials; however, real-world clinical data, particularly the resistance profile, are limited. Here, we investigated the efficacy, safety, and resistance profile of osimertinib in real-world practice. We reviewed medical records of T790M mutation-positive lung cancer patients who started osimertinib between February 2016 and June 2017. Molecular pathologic data of biopsy samples obtained after acquisition of resistance to osimertinib were also analyzed. The study included 23 patients with a median age of 59 years. The median follow-up duration was 11.9 months (IQR, 4.7-15.8). Objective response was achieved in 17 (73.9%) patients, and the disease was controlled in 22 (95.7%) patients. Median progression-free survival (PFS) was 7.4 months (95% CI, 3.6-11.0). Adverse events were minimal except for one case of pneumonitis. Of 14 patients experiencing disease progression, 10 underwent re-biopsy. The T790M mutation disappeared in seven patients (70%), and one showed wild-type conversion. PFS was shorter in the T790M-loss group than in the T790M-persistent group (4.4 vs. 7.7 months). Two patients with small cell transformation responded well to subsequent chemotherapy. One patient developed a C797S mutation that became undetectable after two cycles of gemcitabine and cisplatin followed by six cycles of pembrolizumab, after which the patient responded well to osimertinib. In conclusion, osimertinib showed favorable efficacy and safety in real-world practice comparable to those observed in clinical trials. Repeat biopsy after the acquisition of resistance to osimertinib is helpful to direct further treatment strategies.

Low-tidal volume (TV) mechanical ventilation is an important manipulation in managing patients with acute respiratory distress syndrome (ARDS). However, there is no definite evidence to support the use of this intervention in patients with viral etiologies.A retrospective observational study of 104 patients with ARDS caused by pandemic influenza A/H1N1 infection admitted to 28 intensive care units (ICUs) in Korea was performed. Patients were categorized into 3 groups according to the TV they received: TV less than or equal to 7 mL/kg, TV greater than 7 mL/kg but less than or equal to 9 mL/kg, or TV greater than 9 mL/kg.The mean age was 55.1 years, and 55.8% were male (n = 58). Patients with TV greater than 9 mL/kg showed higher 28-day ICU mortality than the 2 other groups (vs TV7 mL/kg, P = .007 and vs 7 mL/kgTV ≤ 9 mL/kg, P = .004, respectively). Patients with TV less than or equal to 7 mL/kg required ventilators, ICU admissions, and hospitalizations for fewer days than those with TV greater than 7 mL/kg (11.4 vs 6.1 days for 28-day ventilator-free days, 9.7 vs 4.9 days for 28-day ICU-free days, and 5.2 vs 2.4 days for 28-day hospital-free days, respectively). Tidal volume greater than 9 mL/kg (hazard rate, 2.459; P = .003) and Sequential Organ Failure Assessment score (hazard rate, 1.158; P = .014) were significant predictors of 28-day ICU mortality.Low-TV mechanical ventilation still benefits patients with ARDS caused by viral pneumonia.

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin.

Since the wireless technologies based on the IP have been developed recently, a variety of mobile services has been proposed. For broadcasting services to utilize network resources efficiently, there is a need to support handover of multicast traffic in mobile networks. In this paper, we add a network function block to solve the tunnel convergence problem, and propose a new fast handover scheme to reduce handover latency for PMIPv6 networks with multicast function. With the simulation result, we show that our fast handover scheme has better performance than the draft in the IETF in the viewpoint of handover latency and multicast service disruption.

Purpose Percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) has some limitations such as poor sonic window and injury to adjacent organs. The laparoscopic approach has been suggested as an alternative option. The aim of this study was to show the safety and efficacy of laparoscopic RFA for single, small (≤3 cm), and primary or recurrent HCC that is not suitable for percutaneous RFA or surgical resection. Methods We reviewed the cases of 37 patients (32 men and 5 women, mean age 61 ± 8.1 years) who underwent laparoscopic RFA for single, small HCC (≤3 cm) that was unsuitable for percutaneous RFA or surgical resection. Results The technical success rate was 94.6% and 34 patients (95%) had no complications. There were no conversions to open RFA and no operative mortality. The primary effectiveness rate 1 month after the procedure was 100%. The overall recurrence rates at 3, 6, 12, and 24 months after the laparoscopic RFA were 8.1%, 14.4%, 25%, and 35.7%, respectively. The local tumor progression rate was 4.2% at 6 months and 8.7% at 9 months. Conclusion Laparoscopic RFA is a safe and effective treatment for HCC cases that are unsuitable for percutaneous RFA.

We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer., Graphical Abstract

A 61-year-old woman came to the hospital with dyspnea and pleural effusion on chest radiography. She underwent repeated thoracentesis, transbronchial lung biopsy, bronchoalveolar lavage, and thoracoscopic pleural biopsy with talc pleurodesis, but diagnosis of her was uncertain. Positron emission tomography showed multiple lymphadenopathies, so she underwent endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes. Here, we report a case of malignant pleural mesothelioma that was eventually diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. This is an unusual and first case in Korea.

Disseminated Mycobacterium avium complex (MAC) infection can occur in immunocompromised patients, and rarely in immunocompetent subjects. Due to the extensive distribution of the disease, clinical presentation of disseminated MAC may mimic malignancies, and thorough examinations are required in order to make accurate diagnosis. We report a case of disseminated Mycobacterium intracellulare disease in an immunocompetent patient, which involved the lung, lymph nodes, spleen, and multiple bones. F-18 fluorodeoxyglucose positron-emission tomography imaging showed multiple hypermetabolic lesions, which are suggestive of typical hematogenous metastasis. However, there was no evidence of malignancy in serial biopsies, and M. intracellulare was repeatedly cultured from respiratory specimens and bones. Herein, we should know that disseminated infection can occur in the immunocompetent subjects, and it can mimic malignancies.

【Background: Primary non-Hodgkin's lymphoma of the lung is a rare entity. It is represented commonly as marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, radiologic findings, management and prognosis have not been well defined. Methods: We reviewed the medical records of 24 patients with primary pulmonary lymphoma between January 1995 and September 2008; all diagnoses had been confirmed based on pathology. Results: The median follow-up time was 42.3 months (range, 0.1~131.2 months). Five (20.8%) patients were asymptomatic, 17 (70.8%) patients had pulmonary symptoms, and the remaining 2 (8.3%) patients presented with constitutional symptoms. There were 16 (66.7%) patients with MALT lymphoma, 4 (16.7%) patients with diffuse large B-cell lymphoma and 4 (16.7%) patients with lymphoma that had not received a WHO classification. Radiologic findings of primary pulmonary lymphoma were diverse and multiple nodule or consolidation was the most common finding regardless of pathologic lymphoma type. PET scan was carried out in 13 (54.2%) patients and all lesions showed notable FDG uptake. MALT lymphoma showed a trend of better prognosis (3-year survival, 78.8% vs. 70.0%; 5-year survival, 78.8% vs. 52.5%; p=0.310) than non-MALT lymphoma. Conclusion: Primary non-Hodgkin's lymphoma of the lung occurs with nonspecific clinical features and radiologic findings. MALT lymphoma is the most common pathologic type of primary pulmonary lymphoma. This entity of lymphoma appears to have a good prognosis and in this study, there was a trend of better outcome than non-MALT lymphoma.】