Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer.

Purpose: To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection. Methods: Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity. Results: The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028). Conclusion: Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.

Impact of preserved ratio impaired spirometry on coronary artery calcium score progression: a longitudinal cohort study.

Background: Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC). Methods: This retrospective cohort study included 11 420 participants aged ≥40 years with forced expiratory volume in 1 s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted, were further divided by low FVC (FVC <80% predicted). We estimated the 5-year progression rates of CAC by comparing participants with and without PRISm at baseline using mixed linear models. Results: Of the 11 420 participants, 8536 (75%), 811 (7%) and 2073 (18%) had normal spirometry, PRISm with normal FVC and PRISm with low FVC, respectively. During the mean (range) follow-up of 6.0 (0.5-17.2) years, the multivariable adjusted ratio of 5-year CAC progression rates comparing participants with PRISm to those with normal spirometry was 1.08 (95% CI 1.04-1.13). This rate was higher in participants with PRISm with low FVC (1.21 (95% CI 1.12-1.30)) than in those with normal FVC. Conclusion: In this longitudinal cohort study of subjects without a history of CVD, PRISm was significantly associated with CAC progression, which was more evident in the group with PRISm and low FVC.

Clinical characteristics and outcomes of hypersensitivity pneumonitis in South Korea.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood. OBJECTIVES: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea. DESIGN: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea. METHODS: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines. RESULTS: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort. CONCLUSION: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

The impact of deep learning reconstruction in low dose computed tomography on the evaluation of interstitial lung disease.

To evaluate the effect of the deep learning model reconstruction (DLM) method in terms of image quality and diagnostic agreement in low-dose computed tomography (LDCT) for interstitial lung disease (ILD), 193 patients who underwent LDCT for suspected ILD were retrospectively reviewed. Datasets were reconstructed using filtered back projection (FBP), adaptive statistical iterative reconstruction Veo (ASiR-V), and DLM. For image quality analysis, the signal, noise, signal-to-noise ratio (SNR), blind/referenceless image spatial quality evaluator (BRISQUE), and visual scoring were evaluated. Also, CT patterns of usual interstitial pneumonia (UIP) were classified according to the 2022 idiopathic pulmonary fibrosis (IPF) diagnostic criteria. The differences between CT images subjected to FBP, ASiR-V 30%, and DLM were evaluated. The image noise and BRISQUE scores of DLM images was lower and SNR was higher than that of the ASiR-V and FBP images (ASiR-V vs. DLM, p < 0.001 and FBP vs. DLR-M, p < 0.001, respectively). The agreement of the diagnostic categorization of IPF between the three reconstruction methods was almost perfect (κ = 0.992, CI 0.990-0.994). Image quality was improved with DLM compared to ASiR-V and FBP.

Prognostic implication of downregulated exosomal miRNAs in patients with sepsis: a cross-sectional study with bioinformatics analysis.

BACKGROUND: Despite the understanding of sepsis-induced extracellular vesicles (EVs), such as exosomes, and their role in intercellular communication during sepsis, little is known about EV contents such as microRNA (miRNA), which modulate important cellular processes contributing to sepsis in body fluids. This study aimed to analyze the differential expression of exosomal miRNAs in plasma samples collected from sepsis patients and healthy controls, and to identify potential miRNA regulatory pathways contributing to sepsis pathogenesis. METHODS: Quantitative real-time PCR-based microarrays were used to profile plasma exosomal miRNA expression levels in 135 patients with sepsis and 11 healthy controls from an ongoing prospective registry of critically ill adult patients admitted to the intensive care unit. The identified exosomal miRNAs were tested in an external validation cohort (35 sepsis patients and 10 healthy controls). And then, functional enrichment analyses of gene ontology, KEGG pathway analysis, and protein-protein interaction network and cluster analyses were performed based on the potential target genes of the grouped miRNAs. Finally, to evaluate the performance of the identified exosomal miRNAs in predicting in-hospital and 90-day mortalities of sepsis patients, receiver operating characteristic curve (ROC) and Kaplan-Meier analyses were performed. RESULTS: Compared with healthy controls, plasma exosomes from sepsis patients showed significant changes in 25 miRNAs; eight miRNAs were upregulated and 17 downregulated. Additionally, the levels of hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p were significantly lower in sepsis patients than in healthy controls (p < 0.0001). These four miRNAs were confirmed in an external validation cohort. In addition, the most common pathway for these four miRNAs were PI3K-Akt and mitogen-activated protein kinase (MAPK) signaling pathways based on the KEGG analysis. The area under the ROC of hsa-let-7f-5p, miR-331-3p, miR-301a-3p, and miR-335-5p level for in-hospital mortality was 0.913, 0.931, 0.929, and 0.957, respectively (p < 0.001), as confirmed in an external validation cohort. Also, the Kaplan-Meier analysis showed a significant difference in 90-day mortality between sepsis patients with high and low miR-335-5p, miR-301a-3p, hsa-let-7f-5p, and miR-331-3p levels (p < 0.001, log-rank test). CONCLUSION: Among the differentially-expressed miRNAs detected in microarrays, the top four downregulated exosomal miRNAs (hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p) were identified as independent prognostic factors for in-hospital and 90-day mortalities among sepsis patients. Bioinformatics analysis demonstrated that these four microRNAs might provide a significant contribution to sepsis pathogenesis through PI3K-Akt and MAPK signaling pathway.

Bioinformatics Analysis of Gene Expression Profiles for Diagnosing Sepsis and Risk Prediction in Patients with Sepsis.

: Although early recognition of sepsis is essential for timely treatment and can improve sepsis outcomes, no marker has demonstrated sufficient discriminatory power to diagnose sepsis. This study aimed to compare gene expression profiles between patients with sepsis and healthy volunteers to determine the accuracy of these profiles in diagnosing sepsis and to predict sepsis outcomes by combining bioinformatics data with molecular experiments and clinical information. We identified 422 differentially expressed genes (DEGs) between the sepsis and control groups, of which 93 immune-related DEGs were considered for further studies due to immune-related pathways being the most highly enriched. Key genes upregulated during sepsis, including S100A8, S100A9, and CR1, are responsible for cell cycle regulation and immune responses. Key downregulated genes, including CD79A, HLA-DQB2, PLD4, and CCR7, are responsible for immune responses. Furthermore, the key upregulated genes showed excellent to fair accuracy in diagnosing sepsis (area under the curve 0.747-0.931) and predicting in-hospital mortality (0.863-0.966) of patients with sepsis. In contrast, the key downregulated genes showed excellent accuracy in predicting mortality of patients with sepsis (0.918-0.961) but failed to effectively diagnosis sepsis.In conclusion, bioinformatics analysis identified key genes that may serve as biomarkers for diagnosing sepsis and predicting outcomes among patients with sepsis.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea: A Nationwide Multicenter Survey.

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

Impact of interstitial lung abnormalities on postoperative pulmonary complications and survival of lung cancer.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown. RESEARCH QUESTION: This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer. STUDY DESIGN AND METHODS: A matched case-control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage. RESULTS: Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p<0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p<0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p<0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002). CONCLUSIONS: The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival.

Efficacy of Combining Multiple Electromagnetic Navigation Bronchoscopy Modalities for Diagnosing Lung Nodules.

Electromagnetic navigation bronchoscopy (ENB) is one of the non-invasive methods used for lung nodule biopsy. We evaluated the efficacy of combining radial endobronchial ultrasound (R-EBUS)-guided transbronchial lung biopsy (TBLB) with ENB-guided TBLB or transbronchial needle aspiration (TBNA) for diagnosing lung nodules. Forty patients with a lung nodule underwent ENB-TBLB or TBNA, followed by R-EBUS-TBLB if available. The final diagnosis was benign or malignant, depending on the surgical pathology or 24-month follow-up computed tomography (CT). We compared the sensitivity, negative predictive value, and accuracy between combinations of procedures. The mean nodule size was 21.65 mm, and 60.0% of the nodules were solid. The bronchus was within the nodule in 67.5% and 65.0% of cases examined using CT and R-EBUS, respectively. The accuracies of ENB-TBLB alone, ENB-TBLB/TBNA, and R-EBUS-TBLB plus ENB-TBLB/TBNA were 74.4%, 82.5%, and 90.0%, respectively. The sensitivity levels of the aforementioned procedures were 69.8%, 78.8%, and 87.9%, respectively. Among 21 patients who underwent both ENB-TBLB and R-EBUS-TBLB, the latter revealed malignant cells in three of nine patients (33.3%) with benign ENB-TBLB results. Combined ENB-TBLB/TBNA and R-EBUS-TBLB had increased sensitivity and diagnostic accuracy for lung nodules. ENB and R-EBUS are complementary; using both modalities improves the sensitivity and accuracy of lung nodule diagnoses.

Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis.

Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between mtDNA and essential necroptosis mediators in prospectively enrolled patients with sepsis. Plasma mtDNA copy number was measured using quantitative PCR assay and necroptosis mediators, including receptor-interacting protein kinase-3 (RIPK3), mixed lineage domain-like pseudokinase (MLKL), and high-mobility group box 1 (HMGB1), were measured by ELISA. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive ability of mtDNA copy number as a predictor of hospital mortality. Among the 142 patients with sepsis, the mtDNA copy number was significantly higher in non-survivors than in survivors (median, 4040 copies/µL vs. 2585 copies/µL; p < 0.001), and the area under the ROC curve was 0.73 (95% CI, 0.64−0.82) for the relationship between mtDNA and hospital mortality. Furthermore, the correlation between mtDNA copy number and each necroptosis mediator was excellent (p < 0.001 for all): RIPK3 (r = 0.803), MLKL (r = 0.897), and HMGB1 (r = 0.603). The plasma mtDNA copy number was highly correlated with essential necroptosis mediators, suggesting that mtDNA propagates necroptosis and increases sepsis mortality.

Clinical utility of EBUS-TBNA of hilar, interlobar, and lobar lymph nodes in patients with primary lung cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS-TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. METHODS: This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS-TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS-TBNA who did not undergo surgical sampling/clinical follow-up or who received radiotherapy/chemotherapy were excluded. RESULTS: The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS-TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs <10 mm than ≥10 mm in size (90.1% vs. 97.8%; p < 0.001). There was no significant difference in diagnostic performance according to the nodal station (10 vs. 11/12) and left- versus right-sided LNs. The diagnostic sensitivity (100 vs. 95.5%; p = 0.221) and specificity (100 vs. 100%) of N3 LNs was not significantly different from those of N1 LNs. In this study, eight (8/91, 8.8%) patients with cN1 NSCLC received neoadjuvant treatment based on the results of EBUS-TBNA. CONCLUSION: EBUS-TBNA accurately evaluates station 10/11/12 LNs of both N1 and N3 disease. The diagnostic performances of EBUS-TBNA for station 10/11/12 LNs seem to be comparable to those of EBUS-TBNA for mediastinal LNs.

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.

Clinical characteristics and prognostic factors of fibrotic nonspecific interstitial pneumonia.

AIM: Several studies have reported favorable outcomes of nonspecific interstitial pneumonia (NSIP); however, its prognosis and prognostic factors remain unclear. This study aimed to determine the outcomes of fibrotic NSIP and the prognostic factors for progression, relapse, and survival. METHODS: In this retrospective study, we reviewed the clinical data of 204 patients diagnosed with fibrotic NSIP by surgical lung biopsy at Samsung Medical Center. The factors associated with survival and disease progression or relapse were determined using Cox proportional hazard analysis. RESULTS: The median age of patients was 54 years and 67 (33%) patients were male. Also, 47 patients (23%) were current or ex-smokers. In all, 141 (69%) patients were diagnosed with idiopathic NSIP, while 63 (31%) patients were associated with connective tissue diseases. Progression or relapse was observed in 100 (49%) patients. The 5-year and 10-year survival rates were 94.6% and 90.4%, respectively. The factors associated with disease progression and relapse were diffusing capacity for carbon monoxide (DLco) <60% [adjusted hazard ratio (HR), 1.739; 95% confidence interval (CI), 1.036-2.921; p = 0.036], bronchoalveolar lavage (BAL) lymphocyte >15% (adjusted HR, 0.592; 95% CI, 0.352-0.994; p = 0.047), and treatment with corticosteroid and azathioprine (adjusted HR, 0.556; 95% CI, 0.311-0.955; p = 0.048). Disease progression or relapse was associated with mortality (adjusted HR, 7.135; 95% CI, 1.499-33.971; p = 0.014). CONCLUSION: Preserved lung function, BAL lymphocytosis, and treatment with corticosteroids and azathioprine were associated with lower risks of disease progression and relapse, which were risk factors for mortality.

Prospective Study of Proton Therapy for Lung Cancer Patients with Poor Lung Function or Pulmonary Fibrosis.

PBT has a unique depth-dose curve with a Bragg peak that enables one to reduce the dose to normal lung tissue. We prospectively enrolled 54 patients with non-small cell lung cancer treated with definitive PBT. The inclusion criteria were forced expiratory volume in 1 s (FEV1) ≤ 1.0 L or FEV1 ≤ 50% of predicted or diffusing capacity of the lungs for carbon monoxide (DLco) ≤ 50%, or pulmonary fibrosis. The primary endpoint was grade ≥ 3 pulmonary toxicity, and secondary endpoints were changes in pulmonary function and quality of life. The median age was 71.5 years (range, 57-87). Fifteen (27.8%) and fourteen (25.9%) patients had IPF and combined pulmonary fibrosis and emphysema, respectively. The median predicted forced vital capacity (FVC), FEV1, and DLco were 77% (range, 42-104%), 66% (range, 31-117%), and 46% (range, 23-94%), respectively. During the follow-up (median, 14.7 months), seven (13.0%) patients experienced grade ≥ 3 pulmonary toxicity. Seven months after the completion of PBT, patients with IPF or non-IPF interstitial lung disease (ILD) experienced a decrease in the FVC but the decrease in DLco was not significant. Under careful monitoring by pulmonologists, PBT could be a useful treatment modality for lung cancer patients with poor lung function or pulmonary fibrosis.

Clinical Features, Diagnosis, Management, and Outcomes of Idiopathic Pulmonary Fibrosis in Korea: Analysis of the Korea IPF Cohort (KICO) Registry.

BACKGROUND: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. METHODS: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. RESULTS: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. CONCLUSION: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

Retraction notice to: "Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management" [Eur. J. Radiol. Open 8C (2021) 100311].

[This retracts the article DOI: 10.1016/j.ejro.2020.100311.].

Exosomal CD63 in critically ill patients with sepsis.

CD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the association of exosomal CD63 with the severity and mortality of sepsis is not well known. Therefore, in the present study, the overall levels of exosomal CD63 were evaluated to ascertain whether they were associated with organ failure and mortality in patients with sepsis. Exosomal CD63 was measured from prospectively enrolled critically-ill patients with sepsis (n = 217) and healthy control (n = 20). To detect and quantify exosomes in plasma, a commercially available enzyme-linked immunosorbent assay kit was used according to the manufacturer's protocol. The total number of exosomal CD63 was determined by quantifying the immunoreactive CD63. The association between plasma levels of exosomal CD63 and sequential organ failure assessment (SOFA) score was assessed by a linear regression method. The best cut-off level of exosomal CD63 for 28-day mortality prediction was determined by Youden's index. Among 217 patients with sepsis, 143 (66%) patients were diagnosed with septic shock. Trends of increased exosomal CD63 levels were observed in control, sepsis, and septic-shock groups (6.6 µg/mL vs. 42 µg/mL vs. 90 µg/mL, p < 0.001). A positive correlation between exosomal CD63 and SOFA scores was observed in patients with sepsis (r value = 0.35). When patients were divided into two groups according to the best cut-off level, the group with higher exosomal CD63 levels (more than 126 µg/mL) was significantly associated with 28-day and in-hospital mortality. Moreover, the Kaplan-Meier survival method showed a significant difference in 90-day survival between patients with high- and low-exosomal CD63 levels (log-rank p = 0.005). Elevated levels of exosomal CD63 were associated with the severity of organ failure and predictive of mortality in critically ill patients with sepsis.

Infectious complications of EBUS-TBNA: A nested case-control study using 10-year registry data.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a standard procedure, but little is known about its infectious complications. The aim of this study is to evaluate the incidence and risk factors of infectious complications of EBUS-TBNA and its clinical course, including effects on anti-cancer treatment. METHODS: This is a nested case-control study of patients who received EBUS-TBNA and were followed for at least 2 months at Samsung Medical Center from August 2009 to April 2019. Patients with clinical symptoms of infection and correlating chest images were defined as the infection group (n = 33). The controls were randomly selected from patients without infectious complication. Multivariate logistic regression with backward selection was used to identify the risk factors of infectious complications. RESULTS: Of the 6826 patients, 33 (0.48%) infectious complications were identified, comprising pneumonia (n = 20) and mediastinal infections (n = 13). Target lesions with necrotic features on chest computed tomography (CT) scan (adjusted odds ratio [aOR], 3.08; 95% confidence interval [CI], 1.49-6.40; P = 0.002) and procedures that were performed via the esophagus (aOR, 3.19; 95% CI, 1.47-6.88; P = 0.003) were independently associated with infectious complications. Among patients ultimately diagnosed with cancer, the infection group tended to refuse anti-cancer treatment compared to controls (32/459, 7.0% vs. 5/30, 16.7%; P = 0.066). However, among the patients who received anti-cancer treatment, there was no delay in onset of treatment. CONCLUSIONS: Infectious complications of EBUS-TBNA are rare; however, attention should be paid if the target lesion appears necrotic on chest CT or if the procedure is performed via the esophagus. Although it was not conclusive due to its rarity, patients with infectious complications tended not to receive anti-cancer treatment.

Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes.

The role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.