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Background Ventilator-dependent patients in the intensive care unit (ICU) who are difficult to wean from invasive mechanical ventilation (IMV) have been increasing in number. However, data on the clinical outcomes of difficult-to-wean patients are lacking. We aimed to evaluate clinical outcomes in patients discharged from the ICU with tracheostomy and ventilator dependency. Methods We retrospectively investigated clinical course and survival in patients requiring home mechanical ventilation (HMV) with a tracheostomy and difficulty weaning from IMV during medical ICU admission from September 2013 through August 2016 at Severance Hospital, Yonsei University, Seoul, Korea. Results Of 84 difficult-to-wean patients who were started on HMV in the medical ICU, 72 survived, were discharged from the ICU, and were included in this analysis. HMV was initiated after a median of 23 days of IMV, and the successful weaning rate was 46% (n=33). In-hospital mortality rate was significantly lower in the successfully weaned group than the unsuccessfully weaned group (0% vs. 23.1%, respectively; P=0.010). Weaning rates were similar according to primary diagnosis, but high body mass index (BMI), low Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score at ICU admission, and absence of neuromuscular disease were associated with weaning success. After a median follow-up of 4.6 months (range, 1-27 months) for survivors, 3-month (n=64) and 6-month (n=59) survival rates were 82.5% and 72.2%, respectively. Survival rates were higher in the successfully weaned group than the unsuccessfully weaned group at 3 months (96.4% vs. 69.0%; P=0.017) and 6 months (84.0% vs. 62.1%; P=0.136) following ICU discharge. Conclusions In summary, 46% of patients who started HMV were successfully weaned from the ventilator in general wards. High BMI, low APACHE II score, and absence of neuromuscular disease were factors associated with weaning success.

Background Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. Methods This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. Results Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. Conclusions Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients. Electronic supplementary material The online version of this article (10.1186/s13054-018-2211-x) contains supplementary material, which is available to authorized users.

Background Physical function may influence perioperative outcomes of lung transplantation. We investigated the feasibility of a pulmonary rehabilitation program initiated in the immediate postoperative period at an intensive care unit (ICU) for patients who underwent lung transplantation. Methods We retrospectively evaluated 22 patients who received pulmonary rehabilitation initiated in the ICU within 2 weeks after lung transplantation at our institution from March 2015 to February 2016. Levels of physical function were graded at the start of pulmonary rehabilitation and then weekly throughout rehabilitation according to criteria from our institutional pulmonary rehabilitation program: grade 1, bedside (G1); grade 2, dangling (G2); grade 3, standing (G3); and grade IV, gait (G4). Results The median age of patients was 53 years (range, 25 to 73 years). Fourteen patients (64%) were males. The initial level of physical function was G1 in nine patients, G2 in seven patients, G3 in four patients, and G4 in two patients. Patients started pulmonary rehabilitation at a median of 7.5 days (range, 1 to 29 days) after lung transplantation. We did not observe any rehabilitation-related complications during follow-up. The final level of physical function was G1 in six patients, G3 in two patients, and G4 in 14 patients. Fourteen of the 22 patients were able to walk with or without assistance, and 13 of them maintained G4 until discharge; the eight remaining patients never achieved G4. Conclusions Our results suggest the feasibility of early pulmonary rehabilitation initiated in the ICU within a few days after lung transplantation.

Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor-α, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells. In LPS-induced murine lung injury model, total cell counts, polymorphonuclear leukocytes counts, and pro-inflammatory cytokine levels in the BALF were significantly lower and histologically detected lung injury was less common in the group treated with IGF-1 receptor monoclonal antibody compared to the non-treated group. On western blotting, RIP3 and phosphorylated MLKL expressions were relatively decreased in the IGF-1 receptor monoclonal antibody group compared to the non-treated group. IGF-1 may be associated with RIP3-mediated necroptosis in vitro, while blocking of the IGF-1 pathway may reduce LPS-induced lung injuries in vivo.

Background Extracorporeal membrane oxygenation (ECMO) has been widely used for hemodynamic support during lung transplantation (LTx). We evaluated the risk factors associated with failure of weaning from ECMO in the operating room during LTx. Methods We retrospectively reviewed 74 consecutive patients who had undergone LTx from March 2013 to February 2016. Patients who underwent single LTx, multiorgan transplantation, and LTx for pulmonary hypertension were excluded. All operations were performed under ECMO support. Clinical data of donor, recipient, and intraoperative parameters were reviewed. Results Younger donors (40 ± 11 versus 45 ± 10 years, p = 0.047), donors with shorter mechanical ventilation (125 ± 74 versus 160 ± 80 minutes, p = 0.066) and donors with higher Pao 2 at 100% oxygen (455 ± 87 mm Hg versus 399 ± 88 mm Hg, p = 0.008) were significantly different in the ECMO weaning group than in the weaning failure group. Of the recipients, the number of patients who had preoperative ECMO support were significantly fewer in the successful weaning group than in the weaning failure group (11.9% versus 34.4%, p = 0.061). The operation time was significantly shorter in the weaning group than in the weaning failure group (392 ± 66 versus 435 ± 82 minutes, p = 0.014). In multivariate logistic regression analysis, the independent risk factors for ECMO weaning were donor age (odds ratio 1.101, 95% confidence interval: 1.030 to 1.177, p = 0.005), donor Pao 2 (odds ratio 0.992, 95% confidence interval: 0.984 to 0.999, p = 0.034), and operation time (odds ratio 1.010, 95% confidence interval: 1.000 to 1.019, p = 0.043). Conclusions Our results showed that younger donor age, high Pao 2 , and shorter operation time were factors related to successful ECMO weaning in the operating room after LTx.

Background: Lung transplantation is the last treatment option for end-stage lung disease, and the number of lung transplantations has been steadily increasing. Hyperbilirubinemia is a rare complication after lung transplantation. The aim of this study was to review rare causes of hyperbilirubinemia after lung transplantation at our center. Methods: In this single-center study, we retrospectively reviewed the records of 116 consecutive lung transplantation patients who underwent lung transplantation at Severance Hospital and Gangnam Severance Hospital of Yonsei University College of Medicine in South Korea between December 22, 2010 and January 1, 2016. Hyperbilirubinemia was defined as a total bilirubin level exceeding 5 mg/dL for at least 3 days after lung transplantation. Results: Hyperbilirubinemia occurred in 33 patients (28.4%) who received lung transplants at our institution. Twenty-four cases involved common causes such as drug toxicity, biliary tract stone, sepsis, and bleeding. However, rare causes of hyperbilirubinemia including hemophagocytic lymphohistiocytosis (HLH), thrombotic microangiopathy (TMA), and ischemic cholangiopathy were observed in 9 (7.8%) patients during the study period. All patients with hyperbilirubinemia due to a rare cause died despite aggressive treatment. Conclusion: Causes of hyperbilirubinemia after lung transplantation are varied, and the prognosis of patients with hyperbilirubinemia arising from rare causes was poor. Therefore, early evaluation and management of hyperbilirubinemia after lung transplantation is important to improve patient outcomes.

The aim of this single-center study is to review the transplant outcomes of patients receiving lung transplantation (LTx) using intraoperative extracorporeal membrane oxygenation (ECMO) according to the perioperative use of ECMO.We retrospectively reviewed the transplant outcomes of 107 consecutive patients who underwent LTx using intraoperative ECMO between March 2013 and August 2016 at Severance Hospital of Yonsei University (Seoul, Korea).Patients were divided into the following three groups according to the use of perioperative ECMO: only intraoperative ECMO (n=47) or extended post-operative ECMO but no bridging and no postoperative ECMO re-implantation (secondary ECMO; n=28) as Group A (n=75); bridging ECMO without secondary ECMO (n=14) as Group B; and secondary ECMO with (n=7) or without (n=11) bridging as Group C. Baseline demographics were comparable among the three groups. The mean duration of preoperative ECMO bridging was 16.4±15.6 (n=21). After a median of 17.7 months (range, 3.1-40.9 months) for survivors, the one year overall survival (OS) rates after LTx for the three groups were 76.3%±5.2% for Group A, 59.9%±14.3% for Group B, and 14.0%±9.0% for Group C (P0.0001). The secondary ECMO (Group C) was established a mean of 7.9±5.3 days after LTx. The main cause of secondary ECMO was acute respiratory failure from pneumonia, and the main cause of death was infection-related events.Our data suggests that the use of perioperative ECMO, including its extended postoperative use during LTx, is feasible and has favorable outcomes. However, as shown by the poor survival outcome after secondary ECMO, the development of solid strategy to reduce the need for secondary ECMO implantation after LTx seems important.

Background: Most studies about the risk factors of 1-year mortality after lung transplantation were performed on non-Asians. This study aimed to evaluate the perioperative factors related to the 1-year mortality after lung transplantation in Korea. Methods: Sixty-eight consecutive patients who underwent lung transplantation without preoperative extracorporeal membrane oxygenation treatment at 1 tertiary hospital in South Korea between October 24, 2012, and October 16, 2015, were analyzed retrospectively. Results: Forty-four patients (64.7%) lived for >1 year after lung transplantation. The median age of all patients was 55 years (range, 16–75 years), and men accounted for 57.4%. The major cause of lung transplantation was idiopathic pulmonary fibrosis (48.5%); the other causes were interstitial lung disease related to connective tissue disease (17.6%) and bronchiolitis obliterans after stem cell transplantation (14.7%). In univariate analysis, higher median age (52 vs . 61.5 years, P vs . 79.2%, P=0.007), lower preoperative albumin level ( vs . 45.8%, P=0.049), need for renal replacement therapy (RRT) after surgery (4.5% vs . 37.5%, P=0.001), and postoperative delta neutrophil index (DNI) >5.5 higher than the preoperative DNI (22.7% vs . 70.8%, P Conclusions: Recipients with advanced age should be carefully selected, and patients who need RRT or with increased DNI after transplantation should be managed accordingly.

Background In many clinical disorders, there is a relationship between the ratio of the diameter of the main pulmonary artery (mPA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study was to determine if the mPA/Ao ratio at diagnosis is associated with the clinical characteristics and outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed the diameters of the pulmonary artery and aorta on chest CT, clinical characteristics, and results of other examinations in 303 patients at the time of initial diagnosis of IPF at our tertiary care center between 2011 and 2015. The primary outcomes were death and lung transplantation. The patients were followed up until June 2017. Results One hundred and eight patients (35.6%) died and 58 (19.1%) underwent lung transplantation during follow-up. The mean mPA and Ao diameters were 28.3 mm and 34.0 mm, respectively, and the mean mPA/Ao ratio was 0.84. Thirty-one patients (10.2%) had an mPA/Ao ratio > 1.0 and 182 (60.1%) had an mPA/Ao ratio > 0.8. Patients with an mPA/Ao ratio > 0.8 had a lower DLco value than those with an mPA/Ao ratio ≤ 0.8. In Kaplan-Meier analysis, patients with an mPA/Ao ratio > 1.0 or > 0.8 had worse outcomes than those with an mPA/Ao ratio ≤ 1.0 and ≤ 0.8, respectively. Conclusions A higher mPA/Ao ratio based on 1.0 and 0.8 is associated with unfavorable prognosis in patients with IPF.

Background: Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods: We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). Results: Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions: Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

Background Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. Method We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. Results The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0–14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203–0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983–0.993; p < 0.001) independently predicted prognosis. Conclusions Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.

Currently, lung transplantation (LTX) is considered to be a curative treatment option in patients with end-stage lung disease. Although pulmonary hypertension (PH), confirmed by cardiac catheterization, is a prognostic factor in patients undergoing LTX, the prognostic value of PH in Asian lung transplant recipients remains uncertain. In this study, we aimed to determine whether PH before LTX may serve as a prognostic factor for survival in Asian patients.The medical records of 50 patients [male, 27; female, 23; mean age, 51.0 (41.0-60.0) years], who received preoperative right heart catheterization (RHC) and echocardiography before single or double LTX at Severance Hospital between January 2010 and December 2014, were reviewed. The relationship between 1-year survival after LTX and PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest] was evaluated.The mean right ventricular systolic pressure and mPAP were 48.5 (22.8) and 30.0 (24.0-40.0) mmHg. Of the 50 patients, 17 (34.0%) died within a year after LTX. The 1-year survival rate among patients with mPAP ≥25 mmHg (58.8%) was lower than the survival rate among patients with mPAP25 mmHg (87.5%). Pre-transplantation mPAP of ≥25 mmHg was associated with post-transplantation survival [hazard ratio (HR), 4.832; 95% confidence interval (CI), 1.080-21.608, P=0.039]. The presence of preoperative PH was also associated with an increased risk of postoperative complications.Confirmation of PH via preoperative cardiac catheterization was associated with the prognosis of the patient after LTX. Clinicians should consider the necessity for early transplantation surgery before the mPAP reaches ≥25 mmHg.

Background Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. Methods A single-center retrospective study was conducted. The study included 76 patients who received a lung transplant at a tertiary hospital in South Korea between January 2010 and March 2015. Results Nine patients (11.8%) had class I and/or class II panel-reactive antibodies greater than 50%. Twelve patients (15.8%) had anti-HLA antibodies with a low mean fluorescence intensity (MFI, 1000–3000), 7 (9.2%) with a moderate MFI (3000–5000), and 12 (15.8%) with a high MFI (> 5000). Ten patients (13.2%) had suspected donor-specific antibodies (DSA), and 60% (6/10) of these patients had antibodies with a high MFI. In an analysis of outcomes, high-grade (≥2) primary graft dysfunction (PGD) was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI values than in patients with low MFI values (39.4% vs. 14.0%, p = 0.011). Of 20 patients who survived longer than 2 years and evaluated for pBOS after transplant, potential bronchiolitis obliterans syndrome (pBOS) or BOS was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI than in patients with low MFI, although this difference was not statistically significant (50.0% vs. 14.3%, p = 0.131). Conclusions The prevalence of anti-HLA antibodies with high MFI was not high in Korea. However, the MFI was relatively high in patients with DSA. Anti-HLA antibodies with moderate-to-high MFI values were related to high-grade PGD. Therefore, recipients with high MFI before lung transplantation should be considered for desensitization and close monitoring.

Background: Pulmonary involvement is common in connective tissue disease (CTD), and respiratory failure is a major cause of morbidity and mortality in CTD-related interstitial lung disease (CTD-ILD). Lung transplantation is thus important for these patients. However, survival, outcomes, and management of these patients after transplantation have been debated. The aim of this study was to evaluate the outcomes for CTD-ILD compared to those for idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods: We performed a single-centre retrospective study of 62 patients with CTD-ILD or IPF who underwent lung transplantation at a tertiary hospital in South Korea between October 2012 and October 2016. Results: Patients with CTD-ILD (n=15) were younger (46 vs . 60 years, P=0.001) and were less likely to be male (33.3% vs . 76.6%, P=0.004) than were patients with IPF (n=47). The 1-year cumulative survival rate was 80.0% for CTD-ILD and 59.6% for IPF (log-rank P=0.394). There was no difference in the cumulative survival rate (log-rank P=0.613) of age- and sex-matched patients with CTD-ILD (n=15) and IPF (n=15). The incidence of primary graft dysfunction was similar (P=0.154), and 2 (18.2%) patients developed possible CTD flare. Conclusions: Patients with CTD-ILD and those with IPF who underwent lung transplantation had similar survival rates.

Multiple cytokines and inflammatory markers control TB infection. We aimed to investigate the changes in multiple cytokines and inflammatory markers in active TB patients following anti-TB drug therapy. Twenty-nine patients with active TB were recruited prospectively between December 2010 and July 2017. Blood samples were collected before (T0), after 2 months (T2), and at the end of anti-TB treatment (Tend). We measured the levels of Interferon (IFN)-γ, interleukin (IL)-2, IL-12, IL-10, IL-13 and tumor necrosis factor (TNF)-α in supernatants collected from the QuantiFERON-TB Gold In-Tube assay (QFT-GIT), as well as the WBC, neutrophil, platelet count and neutrophil to lymphocyte ratio (NLR) in whole blood. Compared with baseline levels, WBC, neutrophil, and platelet counts were significantly lower following treatment. In addition, the NLR after treatment significantly decreased compared with baseline, whereas the IL-2/IFN-γ ratio increased after treatment. In conclusion, the levels of IL-2/IFN-γ ratios in the supernatant and the NLR might be useful biomarkers to evaluate the effectiveness of drug therapy in active TB patients.

OBJECTIVES: Lung transplantation is a well-established treatment of end-stage lung disease; however, it is limited by a shortage of donor lungs. To overcome this problem, donation after cardiac death (DCD) and ex vivo lung perfusion (EVLP) are being widely investigated. In this study, the effect of hydrogen gas, a known antioxidant, was investigated on a DCD lung model during EVLP. METHODS: Ten pigs were randomized into either a control (n= 5) or a hydrogen group (n= 5). After fibrillation by electric shock, no further treatment was administered in order to induce warm ischaemic injury for 1 h. The lungs were then procured, followed by 4 h of EVLP. During EVLP, the lungs were ventilated with room air in the control group, and with 2% hydrogen gas in the hydrogen group. Oxygen capacity (OC), pulmonary vascular resistance (PVR) and peak airway pressure (PAP) were measured every hour, and the expressions of interleukin-1 beta (IL-1β), IL-6 (IL-6), IL-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were evaluated in lung tissue after EVLP. Pathological evaluations were performed using lung injury severity (LIS) scores and the wet/dry ratio was also measured. RESULTS: The OC in the hydrogen group was higher than in the control group, but the difference was not statistically significant (P= 0.0862). PVR (P= 0.0111) and PAP (P= 0.0189) were statistically significantly lower in the hydrogen group. Compared with the control group, the hydrogen group had a statistically significantly lower expression of IL-1β (P= 0.0317), IL-6 (P= 0.0159), IL-8 (P= 0.0195) and TNF-α (P= 0.0159). The LIS scores (P= 0.0358) and wet/dry ratios (P= 0.040) were also significantly lower in the hydrogen group. CONCLUSIONS: Hydrogen gas inhalation during EVLP improved the function of DCD lungs, which may increase the utilization of DCD lungs.

The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation). The cell counts and protein concentration in the bronchoalveolar lavage fluid (BALF), changes in histopathology, Ashcroft score, hydroxyproline assay, expression of several signal pathway proteins including EphA2-EphrinA1, and PI3K-Akt, and cytokine levels were compared among the groups. We found that bleomycin significantly increased the protein concentration in the BALF, Ashcroft score in lung tissue, and hydroxyproline contents in lung lysates. Furthermore, bleomycin upregulated EphA2, EphrinA1, PI3K 110γ, Akt, IL-6 and TNF-α. However, administration of ATRA attenuated the upregulation of EphA2-EphrinA1 and PI3K-Akt after bleomycin instillation, and decreased pulmonary fibrosis. In addition, ATRA suppressed IL-6 and TNF-α production induced by bleomycin-induced injury. Collectively, these data suggest that ATRA attenuates bleomycin-induced pulmonary fibrosis by regulating EphA2-EphrinA1 and PI3K-Akt signaling.

Background: Lung transplantation (LTx) is a life-saving treatment for patients with end-stage lung disease; however, the shortage of donor lungs has been a major limiting factor to increasing the number of LTx. Growing experience following LTx using donor lungs after cardiac death (DCD) has been promising, although concerns remain. The purpose of this study was to develop a DCD lung harvest model using an ex vivo lung perfusion (EVLP) system and to assess the function of presumably damaged lungs harvested from the DCD donor in pigs. Methods: The 40 kg pigs were randomly divided into the control group with no ischemic lung injury (n=5) and the study group (n=5), which had 1 hour of warm ischemic lung injury after cardiac arrest. Harvested lungs were placed in the EVLP circuit and oxygen capacities (OC), pulmonary vascular resistance (PVR), and peak airway pressure (PAP) were evaluated every hour for 4 hours. At the end of EVLP, specimens were excised for pathologic review and wet/dry ratio. Results: No statistically significant difference in OC (P=0.353), PVR (P=0.951), and PAP (P=0.651) was observed in both groups. Lung injury severity score (control group vs. study group: 0.700±0.303 vs. 0.870±0.130; P=0.230) and wet/dry ratio (control group vs. study group: 5.89±0.97 vs. 6.20±0.57; P=0.560) also showed no statistically significant difference between the groups. Conclusions: The function of DCD lungs assessed using EVLP showed no difference from that of control lungs without ischemic injury; therefore, utilization of DCD lungs can be a new option to decrease the number of deaths on the waiting list.

Background Cardiac surgery with cardiopulmonary bypass (CPB) is a known risk factor for acute respiratory distress syndrome (ARDS). We aimed to analyze the treatment outcome in patients who required veno-venous extracorporeal membrane oxygenation (VV-ECMO) for postcardiotomy ARDS despite other rescue modalities. Methods We retrospectively reviewed the outcomes in 13 patients (mean age, 54.7±5.9 years) who received VV-ECMO support for refractory ARDS after cardiac surgery between March 2013 and February 2016 at Severance Hospital, Yonsei University (Seoul, Korea). Results At the start of VV-ECMO, the average lung injury score was 3.0±0.2, and the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score was -4±1.1. Although 7 patients initiated VV-ECMO support within 24 h from operation, the remaining 6 started at a median of 8.5 days (range, 5-16 days). Nine (69.3%) patients were successfully weaned from VV-ECMO. After a median follow-up duration of 14.5 months (range, 1.0-33.0 months) for survivors, the 1-year overall survival was 58.6%±14.4%. The differences in the overall survival from VV-ECMO according to the RESP score risk classes were borderline significant (100% in class III, 50%±25% in class IV, and 20%±17.9% in class V; P=0.088). Conclusions VV-ECMO support can be a feasible rescue strategy for adult patients who develop refractory ARDS after a cardiac surgery. Additionally, the RESP score seems a valuable prognostic tool for post-ECMO survival outcome in this patient population as well.

Purpose Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. Materials and Methods We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs.

AIM: To examine incidence of tuberculosis (TB) in gastrectomy patients and investigate the risk factors for developing TB after gastrectomy in patients with gastric cancer. METHODS: A retrospective cohort study of gastrectomy patients with gastric cancer was performed at a university-affiliated hospital in Seoul, South Korea between January 2007 and December 2009. We reviewed patient medical records and collected data associated with the risk of TB, surgery, and gastric cancer. Standardized incidence ratios (SIRs) of TB were calculated to compare the incidence of TB in gastrectomy patients with that in the general Korean population, and risk factors for TB after gastrectomies were analyzed. RESULTS: Among the 1776 gastrectomy patients, 0.9% (16/1776) developed post-gastrectomy TB, with an incidence of 223.7 cases per 100000 patients per year. The overall incidence of TB in gastrectomy patients, adjusted by sex and age, was significantly higher than that in the general population (SIR = 2.22, 95%CI: 1.27-3.60). Previous TB infection [odds ratio (OR) = 7.1, P < 0.001], lower body mass index (BMI) (kg/m2; OR = 1.21, P = 0.043) and gastrectomy extent (total gastrectomy vs subtotal gastrectomy) (OR = 3.48, P = 0.017) were significant risk factors for TB after gastrectomy in a multivariate analysis. CONCLUSION: TB incidence after gastrectomy is higher than that in the general population. Previous TB infection, lower BMI, and total gastrectomy are risk factors for TB after gastrectomy in patients with gastric cancer.