Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation.

BACKGROUND: Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. METHODS: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. RESULTS: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029-1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). CONCLUSIONS: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.

Automatic Segmentation and Radiologic Measurement of Distal Radius Fractures Using Deep Learning.

Background: Recently, deep learning techniques have been used in medical imaging studies. We present an algorithm that measures radiologic parameters of distal radius fractures using a deep learning technique and compares the predicted parameters with those measured by an orthopedic hand surgeon. Methods: We collected anteroposterior (AP) and lateral X-ray images of 634 wrists in 624 patients with distal radius fractures treated conservatively with a follow-up of at least 2 months. We allocated 507 AP and 507 lateral images to the training set (80% of the images were used to train the model, and 20% were utilized for validation) and 127 AP and 127 lateral images to the test set. The margins of the radius and ulna were annotated for ground truth, and the scaphoid in the lateral views was annotated in the box configuration to determine the volar side of the images. Radius segmentation was performed using attention U-Net, and the volar/dorsal side was identified using a detection and classification model based on RetinaNet. The proposed algorithm measures the radial inclination, dorsal or volar tilt, and radial height by index axes and points from the segmented radius and ulna. Results: The segmentation model for the radius exhibited an accuracy of 99.98% and a Dice similarity coefficient (DSC) of 98.07% for AP images, and an accuracy of 99.75% and a DSC of 94.84% for lateral images. The segmentation model for the ulna showed an accuracy of 99.84% and a DSC of 96.48%. Based on the comparison of the radial inclinations measured by the algorithm and the manual method, the Pearson correlation coefficient was 0.952, and the intraclass correlation coefficient was 0.975. For dorsal/volar tilt, the correlation coefficient was 0.940, and the intraclass correlation coefficient was 0.968. For radial height, it was 0.768 and 0.868, respectively. Conclusions: The deep learning-based algorithm demonstrated excellent segmentation of the distal radius and ulna in AP and lateral radiographs of the wrist with distal radius fractures and afforded automatic measurements of radiologic parameters.

Methylprednisolone pulse therapy for critically ill patients with COVID-19: a cohort study.

BACKGROUND: The guidelines recommend the use of dexamethasone 6 mg or an equivalent dose in patients with coronavirus disease 2019 (COVID-19) who require supplemental oxygen. Given that the severity of COVID-19 varies, we investigated the effect of a pulse dose of corticosteroids on the clinical course of critically ill patients with COVID-19. METHODS: This single-center, retrospective cohort study was conducted between September and December 2021, which was when the Delta variant of the COVID-19 virus was predominant. We evaluated the mortality and oxygenation of severe to critical COVID-19 cases between groups that received dexamethasone 6 mg for 10 days (control group) and methylprednisolone 250 mg/day for 3 days (pulse group). RESULTS: Among 44 patients, 14 and 30 patients were treated with control steroids and pulse steroids, respectively. There was no difference in disease severity, time from COVID-19 diagnosis to steroid administration, or use of remdesivir or antibacterial agents between the two groups. The pulse steroid group showed a significant improvement in oxygenation before and after steroid treatment (P<0.001) compared with the control steroid group (P=0.196). There was no difference in in-hospital mortality (P=0.186); however, the pulse steroid group had a lower mortality rate (23.3%) than the control steroid group (42.9%). There was a significant difference in the length of hospital stay between both two groups (P=0.039). CONCLUSIONS: Pulse steroids showed no mortality benefit but were associated with oxygenation improvement and shorter hospital stay than control steroids. Hyperglycemia should be carefully monitored with pulse steroids.

A case of granulocyte colony-stimulating factor producing lung adenocarcinoma with anaplastic lymphoma kinase gene rearrangements.

A 49-year-old woman was diagnosed with lung adenocarcinoma, stage IIIB, with increased leukocytes and neutrophils. Positron emission tomography showed dense uptake in right lung, but not in the bone marrow or bone. Biopsy revealed positive anaplastic lymphoma kinase (ALK) gene rearrangements. First-line ALK inhibitor, crizotinib, was used for 9 weeks and its effect was limited. Second-line ALK inhibitor did not show effect. Positive immunostaining and high serum granulocyte colony-stimulating factor (G-CSF) levels confirmed G-CSF-producing lung adenocarcinoma. The patient died after 4.5 months of diagnosis. This is the first reported case of G-CSF-producing lung cancer with ALK rearrangements.

Change in management and outcome of mechanical ventilation in Korea: a prospective observational study.

BACKGROUND/AIMS: There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. METHODS: International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. RESULTS: Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016. CONCLUSION: There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Comparison of clinical features and prognosis in patients with cryptogenic and secondary organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) can be diagnosed pathologically, and cryptogenic OP (COP) and secondary OP (SOP) have been classified by cause and particular underlying context. Because it is clinically difficult to differentiate between COP and SOP, this study investigated characteristics that could distinguish between COP and SOP. METHODS: The medical records of patients who underwent lung biopsy for a diagnosis of OP at a single tertiary hospital from January 2016 to December 2018 were retrospectively reviewed. RESULTS: Eighty-five patients had pathologically proven OP, including 16 diagnosed with COP and 69 diagnosed with SOP. The most common cause of SOP was infectious pneumonia, observed in 57 (82.6%) of the 69 patients, followed by cancer and radiation pneumonitis. The pathogens causing infectious pneumonia were identified in 45 (65.2%) patients. There were no differences in age, sex, and lung function between the COP and SOP groups. Median body mass index was significantly lower (P = 0.030), and median time from symptom onset to hospital admission significantly shorter (P = 0.006), in the SOP than in the COP group. Fever was more common in the SOP group (P = 0.024), and CURB 65, an index of pneumonia severity, tended to be higher in the SOP group (P = 0.017). Some laboratory results differed significantly between the two groups. Lymphocyte counts in bronchoalveolar lavage (BAL) fluid were significantly higher in the COP than in the SOP group (P = 0.012). Radiologic findings showed that effusion was more common in the SOP group (P = 0.036). There were no between-group differences in steroid use, 30 day and in-hospital mortality rates, and rates of OP outcomes and recurrences. Pneumonia recurrence rate was significantly higher in SOP patients who were than were not treated with steroids (P = 0.035). CONCLUSIONS: Infection is the main cause of SOP. Symptom onset is more rapid in patients with SOP than with COP. Some blood and BAL fluid test results differed significantly in the COP and SOP groups. Pleural effusion was more common in the SOP group but there were no differences in clinical course. Recurrence in patients with SOP was more common in those who were than were not treated with steroids.

Prognostic Implication of Baseline Sarcopenia for Length of Hospital Stay and Survival in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of sarcopenia on clinical outcomes of coronavirus disease 2019 (COVID-19) is not clearly determined yet. We aimed to investigate the association between baseline sarcopenia and clinical outcomes in patients with COVID-19. METHODS: All hospitalized adult patients with COVID-19 who had baseline chest computed tomography (CT) scans at a Korean university hospital from February 2020 to May 2020 were included. The main outcome was time from hospital admission to discharge. Death was considered as a competing risk for discharge. Baseline skeletal muscle cross-sectional area at the level of the 12th thoracic vertebra was measured from chest CT scans. The lowest quartile of skeletal muscle index (skeletal muscle cross-sectional area divided by height-squared) was defined as sarcopenia. RESULTS: Of 121 patients (median age, 62 years; 44 men; 29 sarcopenic), 7 patients died and 86 patients were discharged during the 60-day follow-up. Patients with sarcopenia showed a longer time to discharge (median, 55 vs 28 days; p < .001) and a higher incidence of death (17.2% vs 2.2%; p = .004) than those without sarcopenia. Baseline sarcopenia was an independent predictor of delayed hospital discharge (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [95% CI], 0.23-0.96), but was not independently associated with mortality in patients with COVID-19 (aHR, 3.80; 95% CI, 0.48-30.26). The association between baseline sarcopenia and delayed hospital discharge was consistent in subgroups stratified by age, sex, comorbidities, and severity of COVID-19. CONCLUSIONS: Baseline sarcopenia was independently associated with a prolonged hospital stay in patients with COVID-19. Sarcopenia could be a prognostic marker in COVID-19.

Clinical features and prognostic factors of critically ill patients with COVID-19 in Daegu, South Korea: A multi-center retrospective study.

ABSTRACT: To describe the clinical and demographic characteristics of critically ill patients with COVID-19 in Daegu, South Korea, and to explore the risk factors for in-hospital mortality in these patients.Retrospective cohort study of 110 critically ill patients with COVID-19 admitted to the ICU in Daegu, South Korea, between February 18 and April 5, 2020. The final date of follow-up was April 20, 2020.A total of 110 patient medical records were reviewed. The median age was 71 years (interquartile range [IQR] = 63-78 years). During the study period, 47 patients (42.7%) died in the hospital. The most common SARS-CoV-2 infection related complication was acute respiratory distress syndrome (ARDS) in 95 patients (86.4%). Of the 79 patients (71.8%) who received invasive mechanical ventilation, 46 (58.2%) received neuromuscular blockade injection, and 19 (24.1%) received ECMO treatment. All patients received antibiotic injection, 99 patients (90%) received hydroxychloroquine, 96 patients (87.3%) received lopinavir-ritonavir antiviral medication, and 14 patients (12.7%) received other antiviral agents, including darunavir-cobicistat and emtricitabine-tenofovir. In the multivariable logistic regression model, the odds ratio of in-hospital death was higher with APACHE II score (OR = 1.126; 95% CI = 1.014-1.252; P  = .027).The in-hospital mortality rate of critically ill patients with COVID-19 was approximately 40%. Higher APACHE II score at admission was an independent risk factor for death in these patients.

Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019.

BACKGROUND/AIMS: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. METHODS: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. RESULTS: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. CONCLUSION: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.

Experience of percutaneous tracheostomy in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious disease that causes respiratory failure. Tracheostomy is an essential procedure in critically ill COVID-19 patients; however, it is an aerosol-generating technique and thus carries the risk of infection transmission. We report our experience with percutaneous tracheostomy and its safety in a real medical setting. METHODS: During the COVID-19 outbreak, 13 critically ill patients were admitted to the intensive care unit (ICU) at Daegu Catholic University Medical Center between February 24 and April 30, 2020. Seven of these patients underwent percutaneous tracheostomy using Ciaglia Blue Rhino. The medical environment, percutaneous tracheostomy method, and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results were retrospectively reviewed. After treatment, the COVID-19 infection status of healthcare personnel was investigated by RT-PCR. RESULTS: The ICU contained negative pressure cohort areas and isolation rooms, and healthcare personnel wore a powered air-purifying respirator system. We performed seven cases of percutaneous tracheostomy in the same way as in patients without COVID-19. Five patients (71.4%) tested positive for COVID-19 by RT-PCR at the time of tracheostomy. The median cycle threshold value for the RNA-dependent RNA polymerase was 30.60 (interquartile range [IQR], 25.50-36.56) in the upper respiratory tract and 35.04 (IQR, 28.40-36.74) in the lower respiratory tract. All healthcare personnel tested negative for COVID-19 by RT-PCR. CONCLUSIONS: Percutaneous tracheostomy was performed with conventional methods in the negative pressure cohort area. It was safe to perform percutaneous tracheostomy in an environment of COVID-19 infection.

Normothermia in Patients With Sepsis Who Present to Emergency Departments Is Associated With Low Compliance With Sepsis Bundles and Increased In-Hospital Mortality Rate.

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 [< 36°C] vs normothermia [36-38°C] vs hyperthermia [> 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.

Pulmonary tuberculosis presenting secondary organizing pneumonia with organized polypoid granulation tissue: case series and review of the literature.

BACKGROUND: Secondary organizing pneumonia (SOP) is difficult to distinguish from cryptogenic organizing pneumonia (COP) considering various clinical situations. SOP caused by Mycobacterium tuberculosis is rare; indeed, it has not been reported as a sequela of disseminated tuberculosis. METHODS: From January 2016 to December 2018, we identified six cases of tuberculosis-associated SOP in which Mycobacterium tuberculosis was revealed by microbiological examination; one of the cases was miliary tuberculosis. RESULTS: Of the six cases, 17% were positive for acid fast bacillus (AFB) stain, but 100% were positive for M. tuberculosis polymerase chain reaction (MTB PCR) and AFB culture. In all cases, transbronchial lung biopsy was performed and organizing pneumonia was confirmed pathologically. All survived after treatment with anti-tuberculosis therapy. CONCLUSIONS: Pulmonary tuberculosis, which shows OP in lung biopsy, is diagnosed through MTB PCR and AFB culture, and the prognosis is thought to be good.

Clinical Significance of Timing of Intubation in Critically Ill Patients with COVID-19: A Multi-Center Retrospective Study.

The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, p = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis (p = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.

Characteristics, management and clinical outcomes of patients with sepsis: a multicenter cohort study in Korea.

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<0.001). Hospital mortality was 43.2% and 18.5% in sepsis patients with and without shock, respectively. Of the 703 patients who survived to discharge, 61.5% were discharged to home and 38.6% were transferred to other hospitals or facilities. CONCLUSIONS: This study found the prevalence of sepsis in adult patients visiting an ED in Korea was 1.5% (15.2/1,000 patients). Patients with sepsis, especially septic shock, had a high mortality and were often referred to step-down centers after acute and critical care.

Utility of Radial Probe Endobronchial Ultrasound-Guided Transbronchial Lung Biopsy in Diffuse Lung Lesions.

BACKGROUND: Radial probe endobronchial ultrasound (R-EBUS) is widely used for diagnosing peripheral pulmonary lesions. However, the utility of R-EBUS-guided transbronchial lung biopsy (TBLB) for diffuse lung lesions (DLLs) remains unknown. We designed this study to evaluate the utility of R-EBUS-guided TBLB in DLLs. METHODS: This retrospective study enrolled patients admitted from January 2016 to November 2017 who underwent TBLB for DLLs. The R-EBUS-guided TBLB and blind TBLB groups were compared. DLL was defined as any lung disorder that involved more than one segment of the lung. In both the groups, fluoroscopy and guided sheath were not used during TBLB. RESULTS: A total of 127 patients underwent TBLB for DLLs (67 patients in the R-EBUS-guided TBLB group and 60 in the blind TBLB group). There were no differences in age, sex, and comorbid illnesses between the two groups. Furthermore, there was no difference in the TBLB diagnostic yield of the two groups (p=0.660) although more samples were collected from the R-EBUS-guided TBLB group (p=0.003). Procedure time was significantly longer in the R-EBUS-guided TBLB group than in the blind TBLB group (p<0.001). Thus, incidence of pneumothorax was significantly lower in the R-EBUS-guided TBLB group than in the blind TBLB group (p=0.032). CONCLUSION: Diagnostic yield in DLLs did not differ between the R-EBUS-guided TBLB and blind TBLB groups. Findings show that R-EBUS-guided TBLB in DLLs may reduce risk of pneumothorax.

Effectiveness and Safety of High-Flow Nasal Cannula Oxygen Delivery during Bronchoalveolar Lavage in Acute Respiratory Failure Patients.

BACKGROUND: Bronchoalveolar lavage (BAL) is a necessary procedure for diagnosis of various lung diseases. High-flow nasal cannula (HFNC) oxygen delivery was recently introduced. This study aimed to investigate the safety and effectiveness of HFNC oxygen supply during BAL procedure in patients with acute respiratory failure (ARF). METHODS: Patients who underwent BAL while using HFNC at a partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2; PF) ratio of 300 or below among patients who had been admitted from March 2013 to May 2017 were retrospectively investigated. RESULTS: Thirty-three BAL procedures were confirmed. Their baseline PF ratio was 166.1±46.7. FiO2 values before, during, and after BAL were 0.45±0.12, 0.74±0.19, and 0.57±0.14, respectively. Flow (L/min) values before, during, and after BAL were 26.5±20.3, 49.0±7.2, and 40.8±14.2, respectively. Both FiO2 and flow during and after the procedure were significantly different from those before the procedure (both p<0.001). Oxygen saturation levels before, during, and after BAL measured by pulse oximeter were 94.8±2.9, 94.6±3.5, and 95.2±2.8%, respectively. There were no significant differences in oxygen saturation among the three groups. Complications of BAL procedure included transient hypoxemia, hypotension, and fever. However, there was no endotracheal intubation within 24 hours. Baseline PF ratio in "without HFNC" group was significantly higher than that in "with HFNC" group. There were no differences in complications between the two groups. CONCLUSION: The use of HFNC during BAL procedure in ARF patients was effective and safe. However, there were no significant differences in oxygen saturation level and complications comparing "without HFNC" group in mild ARF. More studies are needed for moderate to severe ARF patients.

Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells.

BACKGROUND: Mistletoe extract of Visucm album extract (VAE) contains many biologically active components and has been reported to be not only a complementary and alternative medicine, but also a potent therapeutic agent for many types of cancer. PURPOSE: In this study, we examined the effect of VAE on expression and activation of Axl and scrutinized the involvement of Axl in the anti-cancer activity of VAE in parental and chemo-resistant non-small cell lung cancer (NSCLC) cells. METHODS: The levels of Axl protein and mRNA were determined by Western blot analysis and RT-PCR, respectively. Phosphorylation of Axl upon Gas6 stimulation was observed by Western blot analysis. For ectopic expression or gene silencing of Axl, the recombinant plasmid, pcDNA3-Axl, or specific siRNA targeting Axl were transfected into A549 and H460 cells using Lipofectamine 2000, respectively. The anti-cancer activity of mistletoe extract was examined against the parental cells and each of their cisplatin- or erlotinib-resistant cells using trypan blue exclusion assays and colony formation assay. RESULTS: The levels of Axl mRNA were also reduced by VAE treatment, implying the transcriptional downregulation of Axl expression by VAE. In addition, the phosphorylation of Axl protein upon its ligand, Gas6, stimulation was found to be abrogated by VAE. We next found cytotoxic effect of VAE on both the parental NSCLC cells and their variants which are resistant to cisplatin (A549/CisR and H460/CisR) or erlotinib (H460/ER and H1975/ER). Treatment of these cells with VAE caused a dose-dependent decrease of cell viability and clonogenicity. This anti-proliferative effect of VAE was attenuated in Axl-overexpressing cells, while it was augmented in cells transfected Axl specific siRNA. Next, we also found that in cisplatin-resistant cells and erlotinib-resistant cells, VAE treatment decreased Axl protein level, colonogenicity. The levels of several cell cycle regulator, p21 and apoptosis related protein, X-linked inhibitor of apoptosis, was found to be induced and reduced by VAE treatment, respectively. CONCLUSION: Taken together, our data provide that VAE targets Axl to suppress cell proliferation and to circumvent cisplatin- and erlotinib-resistance in NSCLC cells.

Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.