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Few studies assessed the use of endobronchial ultrasound (EBUS)-guided re-biopsy for detecting the T790M mutation after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure.A total of 2996 EBUS procedures were performed during the study period (January 2019-June 2022). In total, 44 consecutive patients who underwent EBUS-guided re-biopsy (56 procedures) for detecting the T790M mutation were analyzed. The success rates and T790M mutation frequencies were analyzed according to the re-biopsy site and EBUS method. Multivariate logistic regression analyses were used to identify factors affecting the likelihood of the T790M mutation.The success rates for the mutation analyses using EBUS with a guide-sheath (EBUS-GS), EBUS guided transbronchial needle aspiration (EBUS-TBNA), and EBUS-GS with EBUS-TBNA for re-biopsy were 80.6% (29/36), 93.3% (14/15), and 100% (5/5), respectively. Patients who underwent lymph node biopsy using EBUS-TBNA had an increased rates of the T790M mutation compared with those undergoing lung biopsy using EBUS-GS (EBUS-TBNA, 60.0%; EBUS-GS with EBUS-TBNA, 40.0%; EBUS-GS, 11.1%; p 0.001). In multivariate analysis, the use of a first-generation EGFR-TKI (odds ratio [OR], 4.29; 95% confidence interval [CI], 1.05-17.58; p = 0.043) was associated with occurrence of the T790M mutation. Re-biopsy of the metastatic site tended to be associated with a higher T790M mutation rate. Mild hemoptysis occurred in 3.6% (2/56) of the patients.EBUS-guided re-biopsy can be used for detecting the T790M mutation in patients who failed EGFR-TKI therapy. The T790M mutation frequency differed according to the re-biopsy site. The use of a first-generation EGFR-TKI was an independent predictor of the T790M mutation.

Background Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. Methods This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco Results The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco Conclusions In this study, approximately one quarter of the ED-SCLC patients had DLco

Background: Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea.Methods: A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement).Results: The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers.Conclusion: Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Background : Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) has improved the diagnostic yield of bronchoscopic biopsy of peripheral pulmonary lesions (PPLs). The diagnostic yield and complications of RP-EBUS-TBLB for PPLs vary depending on the technique, such as using a guide sheath (GS) or fluoroscopy. We investigated the utility of RP-EBUS-TBLB using a GS without fluoroscopy for diagnosing PPLs. Methods We retrospectively reviewed data from 537 patients who underwent RP-EBUS-TBLB of PPLs from January 2019 to July 2020. TBLB was performed using RP-EBUS with a GS and without fluoroscopy. The diagnostic yield and complications were assessed. All lung lesions without a definitive diagnosis were excluded from analyses. Multivariable logistic regression analyses were used to identify factors affecting the diagnostic yields. Results The overall diagnostic accuracy, sensitivity, specificity, positive predictive, and negative predictive values were 93.0% (462/497), 89.7% (305/340), 100% (157/157), 100% (305/305), and 81.8% (157/192), respectively. In multivariable analyses, the size of the lesion (≥20 mm; odds ratio [OR], 2.20; 95% confidence interval [CI], 1.03-4.72; p = 0.043) and having the probe within the lesion (OR, 3.08; 95% CI, 1.47-6.44; p = 0.003) were associated with diagnostic success. Pneumothorax occurred in 2.2% (12/537) of cases and chest tube insertion was required in 0.6% (3/537) of patients. Conclusions When diagnosing PPLs, RP-EBUS-TBLB using a GS without fluoroscopy is a highly accurate diagnostic method that does not cause exposure to radiation with acceptable complication rates. Lesions ≥ 20 mm and having the probe within the lesion improve diagnostic success.

Background: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. Methods: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite out comes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clini cal features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. Results: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pres sure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P

Background Limited studies have been performed to assess readmission following hospitalization for community-acquired pneumonia (CAP) in an Asian population. We evaluated the rates, reasons, and risk factors for 30-day readmission following hospitalization for CAP in the general adult population of Korea. Methods We performed a retrospective observational study of 1,021 patients with CAP hospitalized at Yeungnam University from March 2012 to February 2014. The primary end point was all-cause hospital readmission within 30 days following discharge after the initial hospitalization. Hospital readmission was classified as pneumonia-related or pneumonia-unrelated readmission. Results During the study period, 862 patients who survived to hospital discharge were eligible for inclusion and among them 72 (8.4%) were rehospitalized within 30 days. In the multivariable analysis, pneumonia-related readmission was associated with para/hemiplegia, malignancy, pneumonia severity index class ≥4 and clinical instability ≥1 at hospital discharge. Comorbidities such as chronic lung disease and chronic kidney disease, treatment failure, and decompensation of comorbidities were associated with the pneumonia-unrelated 30-day readmission rate. Conclusion Rehospitalizations within 30 days following discharge were frequent among patients with CAP. The risk factors for pneumonia-related and -unrelated readmission were different. Aspiration prevention, discharge at the optimal time, and close monitoring of comorbidities may reduce the frequency of readmission among patients with CAP.

Infectious complications after endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are rare but serious. Here, we report a very rare case of delayed onset of mediastinitis with tracheomediastinal fistula after EBUS‐TBNA. Surgical debridement was performed, antibiotics were administered, and the postoperative course of the patient was good. Careful monitoring is needed to prevent the possible development of infectious complications after EBUS‐TBNA., We report a rare case of delayed onset of mediastinitis with tracheomediastinal fistula after endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA). To our knowledge, tracheomediastinal fistula after EBUS‐TBNA is rarely reported. Surgical debridement was performed, antibiotics were administered, and the postoperative course of the patient was good.

Background Despite the increasing prevalence of chronic obstructive pulmonary disease (COPD) worldwide, knowledge and awareness of COPD remain extremely low. This prospective study aimed to demonstrate the effectiveness of organized educational intervention. Patients and methods The study participants included patients diagnosed with COPD and receiving inhaler treatment. In this prospective study, the patients made three sequential visits to the hospital (baseline, 1 month, 3 months). On their first and second visits, patients received systematic education about COPD. On their first and third visits, each patient was evaluated using a COPD Assessment Test, COPD Knowledge Questionnaire, Hospital Anxiety and Depression Scale, and Rosenberg Self-Esteem Scale. Results Fifty-five participants were enrolled in the study. The mean COPD knowledge score before and after education was 12.51±3.19 and 17.89±1.37, respectively, indicating a significant increase in the score post-education (P

Supplemental Digital Content is available in the text., Objective This study aimed to investigate the relationship between blood pressure variability (BPV) and clinical outcomes in patients with coronavirus disease 2019 (COVID-19) and hypertension. Methods A total of 136 patients hospitalized with COVID-19 were enrolled in this study. Patients were grouped according to the presence of hypertension and BPV. Mean arterial pressure (MAP) measured at 8 a.m. and 8 p.m. was analyzed, and BPV was calculated as the coefficient of variation of MAP (MAPCV). High BPV was defined as MAPCV values above the median. We compared the age, level of C-reactive protein (CRP), creatine kinase-MB (CK-MB), N-terminal pro-B type natriuretic peptide (NT-proBNP), creatinine and in-hospital mortality and investigated the relationship among the groups. Results COVID-19 patients with hypertension were older (70 ± 12 vs. 53 ± 17 years; P < 0.001), had higher levels of CRP (9.4 ± 9.2 vs. 5.3 ± 8.2 mg/dL; P = 0.009), MAPCV (11.4 ± 4.8 vs. 8.9 ± 3.2; P = 0.002), and higher in-hospital mortality (19.6% vs. 5.9%; P = 0.013) than those without hypertension. There was a proportional relationship between BPV and age, levels of CRP, CK-MB, NT-proBNP, creatinine and in-hospital mortality (all, P < 0.05). In Cox regression analysis, advanced age [≥80 years, hazard ratio (HR) 10.4, 95% confidence interval (CI) 2.264–47.772, P = 0.003] and higher MAPCV (HR 1.617, 95% CI, 1.281–2.040, P < 0.001) were significantly associated with in-hospital mortality. Conclusion High BPV in COVID-19 patients with hypertension is significantly associated with in-hospital mortality. Advanced age and systemic inflammation are proportional to high BPV. Additional attention is needed for COVID-19 patients with hypertension and high BPV.

Jong Geol Jang, Jin Hong Chung, Kyeong-Cheol Shin, Hyun Jung Jin, Kwan Ho Lee, June Hong Ahn Department of Internal Medicine, Division of Pulmonology and Allergy, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of KoreaCorrespondence: Kwan Ho Lee; June Hong AhnDepartment of Internal Medicine, Division of Pulmonology and Allergy, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu, 42415, Republic of KoreaTel +82-53-640-6601; +82-53-640-6577Fax +82-53-620-3849Email ghlee@med.yu.ac.kr; fireajh@gmail.comObjective: Critical inhaler handling errors are associated with an increased risk of adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). However, real-world data on inhaler device handling techniques and the risk factors for critical inhaler errors in the Asian population have been examined in only a few studies. We evaluated the rates and risk factors for critical inhaler errors in the COPD population in Korea.Methods: COPD patients were prospectively enrolled from January 2018 to November 2019. An advanced practice nurse evaluated their inhaler technique. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (DPIs; Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair), a soft mist inhaler (SMI; Respimat), and pressurized metered dose inhalers (pMDIs).Results: The percentage critical errors for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 60.0%, 41.0%, 27.8%, 12.5%, 44.4%, 45.5%, and 55.0%, respectively. In the multivariate analyses, female sex, short COPD duration, dissatisfaction with the inhaler (assessed by FSI-10), and moderate acute exacerbations (AEs) in the prior year were independent risk factors for any critical error in the DPI group. In the SMI group, a low education level and frequent AEs in the prior year were independent risk factors for any critical error, whereas a high COPD assessment test (CAT) score was the only risk factor in the pMDI group.Conclusion: Critical inhaler errors are common among patients with COPD, regardless of their preferred inhaler device. The rates and risk factors for critical inhaler errors differed among patients using different devices. Optimal device selection considering the risk factors of inhaler misusage will improve disease control in COPD patients.Keywords: COPD, inhalation therapy, error, risk factor

Background The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound–guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. Methods We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. Results The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16–5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02–5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26–129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64–80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. Conclusion RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable., Graphical Abstract

Jong Geol Jang, June Hong Ahn, Hyun Jung Jin Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, South KoreaCorrespondence: Jong Geol JangDivision of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Respiratory Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-Ro, Namgu, Daegu, 42415, Republic of KoreaTel +82-53-620-4367Fax +82-53-620-4367Email jang83@ynu.ac.krPurpose: Severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) that require hospitalization and emergency department visits are associated with considerable morbidity and mortality. Respiratory viral infection is an important cause of severe AECOPD. We evaluated the incidence and prognostic factors of viral infection in severe AECOPD.Patients and Methods: We performed a retrospective study of 262 cases of severe AECOPD in 192 patients who required hospitalization and emergency department visits at a tertiary teaching hospital in Daegu, Korea. A multiplex polymerase chain reaction panel using a nasopharyngeal swab sample was performed to detect viral infection.Results: Viral infection was detected in 108 events (41.2%) from 96 patients. The most common virus was rhinovirus/enterovirus (27.5%), followed by influenza virus (22.5%), respiratory syncytial virus (13.3%), parainfluenza virus (12.5%), coronavirus (12.5%), metapneumovirus (7.5%), and adenovirus (4.2%). Virus-positive exacerbations, compared to virus-negative exacerbations, had a higher frequency of symptoms of rhinopharyngitis, higher neutrophil count and C-reactive protein (CRP) level, and lower eosinophil count. Multivariate analysis demonstrated that elevated CRP levels (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.24– 6.15), symptoms of rhinopharyngitis (OR, 1.98; 95% CI, 1.03– 3.78), low eosinophil count (OR, 1.74; 95% CI, 1.03– 2.92), and inhaled corticosteroid (ICS) use (OR, 1.70; 95% CI 1.04– 2.80) were associated with viral infection in severe AECOPD.Conclusion: The incidence of viral infection in severe AECOPD was 41.2%, and the most commonly detected virus was rhinovirus/enterovirus. Increased CRP level, symptoms of rhinopharyngitis, low eosinophil count, and use of ICS were associated with viral infection in severe AECOPD.Keywords: chronic obstructive pulmonary disease, exacerbation, viral infection, multiplex polymerase chain reaction, risk factors

Background It is difficult to distinguish subtle differences shown in computed tomography (CT) images of coronavirus disease 2019 (COVID-19) and bacterial pneumonia patients, which often leads to an inaccurate diagnosis. It is desirable to design and evaluate interpretable feature extraction techniques to describe the patient's condition. Methods This is a retrospective cohort study of 170 confirmed patients with COVID-19 or bacterial pneumonia acquired at Yeungnam University Hospital in Daegu, Korea. The Lung and lesion regions were segmented to crop the lesion into 2D patches to train a classifier model that could differentiate between COVID-19 and bacterial pneumonia. The K-means algorithm was used to cluster deep features extracted by the trained model into 20 groups. Each lesion patch cluster was described by a characteristic imaging term for comparison. For each CT image containing multiple lesions, a histogram of lesion types was constructed using the cluster information. Finally, a Support Vector Machine classifier was trained with the histogram and radiomics features to distinguish diseases and severity. Results The 20 clusters constructed from 170 patients were reviewed based on common radiographic appearance types. Two clusters showed typical findings of COVID-19, with two other clusters showing typical findings related to bacterial pneumonia. Notably, there is one cluster that showed bilateral diffuse ground-glass opacities (GGOs) in the central and peripheral lungs and was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia patients with 95% reported for severity classification. The CT quantitative parameters represented by the values of cluster 8 were correlated with existing laboratory data and clinical parameters. Conclusion Deep chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. The constructed histogram features improved accuracy for both diseases and severity classification, and showed correlations with laboratory data and clinical parameters. The constructed histogram features can provide guidance for improved analysis and treatment of COVID-19., Graphical Abstract

In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm., Graphical abstract

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’ blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

Inhaler education for chronic obstructive pulmonary disease (COPD) patients improves inhaler technique and adherence. However, the effects of such education on the quality of life and inhaler satisfaction remain unclear. Here, we evaluated inhaler handling and adherence, and changes in quality of life and inhaler satisfaction, after repeated education for COPD patients. We prospectively enrolled COPD patients who had used inhalers for over 1 month and evaluated the effects of repeated education. Three visits were made over 6 months; an advanced practice nurse evaluated inhaler technique and adherence, and instructed the patients in inhaler technique during face-to-face sessions. Inhaler technique and adherence were assessed at every visits, and the modified Medical Research Council (mMRC) test, COPD Assessment Test (CAT), EuroQol-5D (EQ-5D), Patient Health Questionnaire (PHQ-9), and Feeling of Satisfaction with Inhaler questionnaire (FSI-10) were administered before (visit 1) and after two educational sessions (visit 3). A total of 261 COPD patients (308 inhalers) were included. Education significantly reduced the proportion of critical errors after two educational sessions (visit 3), from 43.2 to 8.8% (p

Background Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. Methods We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. Results Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90–193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35–88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45–452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64–1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. Conclusion In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19., Graphical Abstract

Background The case fatality rate of coronavirus disease 2019 (COVID-19) is estimated to be between 4.3% and 11.0%. Currently there is no effective antiviral treatment for COVID-19. Thus, early recognition of patients at high risk is important. Methods We performed a retrospective observational study of 110 patients with severe acute respiratory syndrome coronavirus 2 infection. We compared the effectiveness of three scoring systems: the Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) systems, for predicting the prognosis of COVID-19. The area under the receiver operating characteristic curve (AUROC) was used for these assessments, and Kaplan-Meier survival curves were used to identify the cumulative risk for 28-day mortality according to the NEWS stratification. Results For predicting 28-day mortality, NEWS was superior to qSOFA (AUROC, 0.867 vs. 0.779, P < 0.001), while there was no significant difference between NEWS and SIRS (AUROC, 0.867 vs. 0.639, P = 0.100). For predicting critical outcomes, NEWS was superior to both SIRS (AUROC, 0.918 vs. 0.744, P = 0.032) and qSOFA (AUROC, 0.918 vs. 0.760, P = 0.012). Survival time was significantly shorter for patients with NEWS ≥ 7 than for patients with NEWS < 7. Conclusion Calculation of the NEWS at the time of hospital admission can predict critical outcomes in patients with COVID-19. Early intervention for high-risk patients can thereby improve clinical outcomes in COVID-19 patients., Graphical Abstract

Objectives: The effects of inhaler education in chronic obstructive pulmonary disease (COPD) patients remain unclear. The objective of this study was to evaluate techniques and adherence in using inhaler devices and to investigate the effects of repeated education using inhaler device handling in COPD patients. Methods: We prospectively enrolled COPD patients who used their particular inhaler device for more than 1 month and evaluated the efficacy of repeated education for COPD. The educational intervention was 6-month education program of three visits, during which subjects were tested their inhaler technique and adherence, taught about inhaler technique face-to-face by advanced practice nurse. Inhaler technique, adherence, mMRC, COPD assessment tests (CAT), EuroQol-5D (EQ-5D), patient health questionnaire (PHQ-9), and feeling of satisfaction with inhaler questionnaire (FSI-10) were compared before and after education. Results: A total of 261 COPD patients performing a total of 308 inhaler devices were included in the study. 244 (93.5%) were men and the mean age was 69.8 ± 7.7. At least one errors were observed in 267 (86.7%) and at least one critical inhaler errors were observed in 43.2% (133/308). Education significantly decreased in percentage of incorrect techniques, incorrect critical techniques and poor adherence (86.7% vs 39.3%, p

Rationale: Small cell carcinoma (SCC) occurs mostly in the lung, and small cell lung cancer accounts for 13% of newly diagnosed lung cancers. Only 2.5% of SCC occurs in extrapulmonary sites, and SCC of pleural origin is especially very uncommon. Patient concerns: An 85-year-old man presenting with progressive dyspnea for more than 7 days. Diagnoses: Computed tomography scan of the chest showed massive pleural effusion and diffuse nodular thickening of the pleura on the right chest. Sonography-guided needle biopsy of the pleural mass was performed and histologic and immunohistochemical findings revealed SCC. Since no parenchymal lung lesion was observed, the patient was finally diagnosed with SCC of the pleura (SCCP). Interventions: Due to the patient's old age and poor performance status, chemotherapy was not performed and only drainage of pleural effusion was conducted for symptom relief. Outcomes: Dyspnea improved after pleural effusion drainage. The patient was discharged and transferred to a local medical center for hospice care. Lessons: Although primary SCCP is extremely rare, SCCP should also be considered as well as mesothelioma in case of presence of a pleural-based mass with massive pleural effusion.

Introduction: The effects of inhaler education in chronic obstructive pulmonary disease (COPD) patients remain unclear. Objectives: The purpose of this study was to evaluate techniques and adherence in using inhaler devices and to investigate the effects of educational intervention using inhaler in COPD patients. Methods: We prospectively enrolled COPD patients who used their particular inhaler device for more than 1 month and evaluated the efficacy of educational intervention for COPD. Results: A total of 75 COPD patients (61.2 ± 18.6 predicted FEV1) performing a total of 94 inhaler devices were included in the study. 70 (93.3%) were men and the mean age was 69.3 ± 7.0. Respimat users (n=42, 44.7%) were the highest among the enrolled patients. Education significantly decreased in percentage of incorrect techniques and poor adherence (94.7% vs 51.6%, P Conclusions: Face-to-face inhaler technique education by advanced practice nurse significantly improved the inhaler technique, adherence and feeling of satisfaction with inhaler.

Introduction: Identification of the reasons and risk factors associated with readmission is important concerning discharge planning. Aims: The purpose of this study was to clarify the rates, reasons and risk factors associated with 30 day readmission following hospitalization for community-acquired pneumonia (CAP). Methods: We performed a retrospective observational study of 1,021 patients with CAP who were hospitalized at Yeungnam University Hospital. Hospital readmission was classified as (1) pneumonia-related readmission or (2) pneumonia-unrelated readmission. Results: Of the 862 patients who survived to hospital discharge, 72 (8.4%) were rehospitalized within 30 days following discharge. Pneumonia-related causes accounted for 37.5% (27 patients) and pneumonia-unrelated causes accounted for 62.5% (45 patients) of the total reasons for 30 day readmission. In the multivariable analysis, pneumonia related hospital readmission was associated with para/hemiplegia, malignancy, pneumonia severity index (PSI) class ≥4 and clinical instability ≥1 at hospital discharge. Underlying comorbidities such as chronic lung disease, chronic kidney disease, hospitalization for ≥2 days during the preceding 90 days, treatment failure and decompensation of comorbidities were associated with pneumonia-unrelated hospital readmission within 30 days. Conclusions: Identification of the risk factors associated with hospital readmission in two different groups might have implications for discharge planning and follow up of patients with CAP.

In the diagnosis of lung lesions, computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) has a high diagnostic yield and a low complication rate. The procedure is usually performed by interventional radiologists, but the diagnostic yield and safety of CT-guided PTNB when performed by pulmonologists have not been evaluated. A retrospective study of 239 patients who underwent CT-guided PTNB at Yeungnam University Hospital between March 2017 and April 2018 was conducted. A pulmonologist performed the procedure using a co-axial technique with a 20-gauge needle. Then diagnostic yield and safety were assessed. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of malignancy were 96.1% (171/178), 100% (46/46), 100% (171/171), and 86.8% (46/53), respectively. The diagnostic accuracy was 96.9% (217/224) and the overall complication rate was 33.1% (82/248). Pneumothorax, hemoptysis, and hemothorax occurred in 27.0% (67/248), 5.2% (13/248), and 0.8% (2/248) of the patients, respectively. Univariate analyses revealed that pneumothorax requiring chest tube insertion was a significant risk factor (odds ratio, 25.0, p &lt, 0.001) for diagnostic failure. CT-guided PTNB is a safe procedure with a high diagnostic accuracy, even when performed by an inexperienced pulmonologist. The results were similar to those achieved by interventional radiologists as reported in previously published studies.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

The transcription factor nuclear factor-κB (NF-κB) signaling is a mediator of viral infection-mediated inflammation and SET-domain containing 6 (SETD6) is known as a methyltransferase that suppresses the activity of NF-κB signaling. However, the downside of the SETD6 is that it cannot be directly utilized as an inflammatory regulator due to the short half-life and poor intracellular delivery. Here, a ferritin nanocage-based delivery system is presented that can maintain the activity of SETD6 in vivo. According to the analysis of severe COVID-19 patients’ peripheral blood mononuclear cells (PBMCs), the SETD6 expression is downregulated while that of NF-κB is upregulated. By engineering the structure of ferritin, a protein scaffold is fabricated in which short ferritin is decorated with cell-penetrating peptide and nuclear-localizing TAT-NBD peptide together with SETD6, termed TFS. The TFS enhances the SETD6 level and reduces the NF-κB signaling in PBMCs of severe COVID-19 patients and subsequently suppresses the cytokine storm. When the TFS is intravenously administered in the cytokine storm mouse model, the survival rate is rescued and the lung tissue damage and cytokine expression are also inhibited. These results indicate that the ferritin nanocage-based peptide delivery system allows stable in vivo delivery and efficient suppression of NF-κB signaling-mediated inflammation.

Although some information on the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a few selected cases has been reported, data on the clinical characteristics and outcomes of patients hospitalized therewith in South Korea are lacking. We conducted a retrospective single-center study of 98 consecutive hospitalized patients with confirmed SARS-CoV-2 infection at Yeungnam University Medical Center in Daegu, South Korea. Sixty patients were women (61.2%), and the mean age was 55.4±17.1 years. Thirteen patients (13.3%) were treated in the intensive care unit (ICU). The mean interval from symptom onset to hospitalization was 7.7±4.5 days. Patients who received ICU care were significantly older and were more likely to have diabetes mellitus. The National Early Warning Score on the day of admission was significantly higher in patients requiring ICU care. Acute respiratory distress syndrome (13/13 patients; 100%), septic shock (9/13; 69.2%), acute cardiac injury (9/13; 69.2%), and acute kidney injury (8/13; 61.5%) were more common in patients who received ICU care. All patients received antibiotic therapy, and most (97/98 patients; 99.0%) received antiviral therapy (lopinavir/ritonavir). Hydroxychloroquine was used in 79 patients (80.6%), and glucocorticoid therapy was used in 18 patients (18.4%). In complete blood counts, lymphopenia was the most common finding (40/98 patients; 40.8%). Levels of all proinflammatory cytokines were significantly higher in ICU patients. As of March 29, 2020, the mortality rate was 5.1%. Here, we report the clinical characteristics and laboratory findings of SARS-CoV-2 patients in South Korea up to March 29, 2020.

There are no proven therapeutics for Coronavirus disease 2019 (COVID-19) pneumonia outbreak. We observed and analyzed the clinical efficacy of the most used hydroxychloroquine (HCQ) for 30 days. In this study, administration of HCQ

SETTING Hospitalised patients with community-acquired pneumonia (CAP) in a tertiary referral hospital in South Korea. OBJECTIVE To determine the burden of vitamin D deficiency in patients hospitalised with CAP and to investigate whether vitamin D deficiency affected clinical outcomes. DESIGN Serum 25-hydroxyvitamin D (25[OH]D) levels were measured at admission; vitamin D deficiency was defined as 25(OH)D

Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor that arises from mesenchymal tissue underlying the mesothelial layer of the pleura. It usually has an indolent clinical course. The hypoglycemia that accompanies SFTP was first described by Doege and Potter independently in 1930, hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to be ~4%. In this report, we present a typical case of DPS that was cured through complete surgical resection.

Hyaluronic acid is widely used in medical procedures, particularly in cosmetic procedures administered by physicians or nonmedical personnel. The materials used for cosmetic procedures by physicians as well as illegally by non-medical personnel can cause nonthrombotic pulmonary embolism (NTPE). We report the case of a woman with acute respiratory failure, neurologic symptoms and petechiae after an illegal procedure of hyaluronic acid dermal filler performed by an unlicensed medical practitioner 3 days before symptom onset. Although a few cases of NTPE after injection of hyaluronic acid have been reported yet, this is the first typical case showing a NTPE manifestation after the facial injection of hyaluronic acid.

Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma has been rarely reported, whereas only a few cases of Cushing syndrome accompanied by opportunistic infections have been reported. We experienced a patient with pheochromocytoma with ectopic Cushing syndrome complicated by invasive aspergillosis. A 35-year-old woman presented with typical Cushingoid features. Her basal plasma cortisol, ACTH, and 24-hour urine free cortisol levels were significantly high, and 24-hour urine metanephrine and catecholamine levels were slightly elevated. The endogeneous cortisol secretion was not suppressed by either low- or high-dose dexamethasone. Abdominal computed tomography (CT) revealed a heterogeneous enhancing mass measuring approximately 2.5 cm in size in the left adrenal gland. No definitive mass lesion was observed on sellar magnetic resonance imaging. On fluorine-18 fluorodeoxyglucose positron emission tomography/CT, a hypermetabolic nodule was observed in the left upper lung. Thus, we performed a percu- taneous needle biopsy, which revealed inflammation, not malignancy. Thereafter, we performed a laparo- scopic left adrenalectomy, and its pathologic finding was a pheochromocytoma with positive immunohisto- staining for ACTH. After surgery, the biochemistry was normalized, but the clinical course was fatal despite intensive care because of the invasive aspergillosis that included the lungs, retina, and central nervous system.