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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.

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 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

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.

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

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

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

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.

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.

【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.】