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Objective: In hospitals globally, the occurrence of clinical deterioration within the hospital setting poses a significant healthcare burden. Rapid clinical intervention becomes a crucial task in such cases. In this research, we propose an end-to-end deep learning architecture that interpolates high-dimensional sequential data for the early detection of clinical deterioration events., Materials and Methods: We consider the problem of detecting deterioration events with two stages: predicting the "detection" status, a pre-event state; and predicting the event from detection time. Our approach involves the development of dual-channel graph attention networks with multi-task learning strategy by jointly learning task relatedness with a shared model for multiple prediction in multivariate time-series., Results: The experiments are conducted on two clinical time-series datasets collected from intensive care units (ICUs). Our model has shown the potential performance compared to other state-of-the-art methods, in terms of the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC)., Discussion: The proposed dual-channel graph attention networks can explicitly learn the correlations in both features and time domains of multivariate time-series. Our proposed objective function also can handle the problems of learning task relations and reducing task imbalance effects in multi-task learning., Conclusion: Applying our proposed framework architecture could facilitate the implementation of early detecting in-hospital deterioration events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

COVID-19 can lead to pulmonary complications, including organizing pneumonia. Steroids are essential in treating post-COVID-19 organizing pneumonia. However, research on the clinical benefits of initiating steroid treatment early for this condition is limited. To investigate the steroid initiation time in its association with treatment duration and corticosteroid dose for treating post-COVID-19 organizing pneumonia, we analyzed the data of 91 patients with post-COVID-19 organizing pneumonia at Chonnam National University Hospital between October 2020 and December 2022. Patients were categorized into early and late groups based on time from COVID-19 diagnosis to steroid initiation time for organizing pneumonia. The mean time interval between COVID-19 infection and steroid initiation time for treating organizing pneumonia, was 18.4±8.6 days. Within the early treatment group (treatment initiated <18.4 days after COVID-19), which included 55 patients, the mean duration of steroid treatment was 43.1±18.3days. In contrast, the late treatment group (initiated ≥18.4 days after COVID-19), which consisted of 36 patients, had a longer mean duration of steroid treatment 59.1±22.6 days) (p<0.01). Regarding corticosteroid dosing, the early treatment group had an average dosage of 0.5±0.3 mg/kg/day, in contrast to the late group, which averaged 0.8±0.3 mg/kg/day (p<0.01). Regression analysis showed steroid initiation time significantly influenced treatment duration (β=0.80 , p<0.01) and dosage (β=0.03, p<0.01). The clinical benefits of early steroid treatment for post-COVID-19 organizing pneumonia may lie in its association with reduced steroid treatment duration and dosage., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2024.)

Background: A pulmonary artery-to-aorta (PA/A) ratio of ≥1 is a reliable indicator of pulmonary hypertension and is associated with an increased risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) and long-term mortality in patients with stable COPD. However, it is unclear whether a PA/A ratio of ≥1 is associated with mortality in patients hospitalized with acute exacerbation of COPD. The purpose of this study was to evaluate the clinical course and mortality of patients with PA/A ratios of ≥1 who were hospitalized with acute exacerbation of COPD., Methods: We retrospectively reviewed the medical charts of patients admitted to a tertiary referral hospital and a secondary hospital with acute exacerbation of COPD between 2016 and 2021. Chest computed tomography was used to measure the pulmonary artery (PA), aorta (A) diameter, and the PA/A ratio. The study involved 324 and 111 patients with PA/A ratios <1 and ≥1, respectively., Results: The average age in the two groups was 74.1 and 74.5 years, which was not significantly different. When compared with the group with PA/A ratios of <1, the group with PA/A ratios of ≥1 had a lower proportion of males (71.2% vs. 89.5%, P<0.001), more patients with type 2 respiratory failure (35.1% vs. 18.8%), higher high-flow nasal cannula use (10.8% vs. 4.6%), higher use of non-invasive ventilation (NIV) (21.6% vs. 7.7%), and longer hospital stay (10.9 vs. 9.5 days). In-hospital mortality was not significantly different between the two groups. A PA/A ratio of ≥1 was identified as an independent predictor of the need for high-flow nasal cannula, NIV, and intubation in COPD patients., Conclusions: Patients with PA/A ratios of ≥1 had a high incidence of type 2 acute respiratory failure and required advanced treatment, including high-flow nasal cannula, NIV, and intubation. Therefore, hospitalized patients with acute exacerbation of COPD and PA/A ratios of ≥1 require more aggressive treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-62/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Objective: Acute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome., Methods: Peripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR., Results: ARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO 2 /FiO 2 ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts., Conclusion: ARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Park, Kim, Cho, Jin, Jo, Shin, Kho, Kee and Park.)

Few studies have examined the risk factors associated with the type of acute respiratory failure (ARF) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). This study evaluated the clinical characteristics and prognosis of patients hospitalized for acute exacerbation of COPD based on the type of ARF. The medical charts of hospitalized patients with acute exacerbation of COPD between 2016 and 2021 were retrospectively reviewed. We classified ARF into 2 types: type 1 ARF with PaO2 < 60 mm Hg in room air or a ratio of arterial partial pressure to fractional inspired oxygen < 300, and type 2 ARF with PaCO2 > 45 mm Hg and arterial pH < 7.35. A total of 435 patients were enrolled in study, including 170 participants without ARF, 165 with type 1 ARF, and 100 with type 2 ARF. Compared with the non-ARF group, the frequency of high-flow nasal cannula, noninvasive ventilation, intensive care unit admissions, and in-hospital deaths was higher in the ARF group compared with the non-ARF group. The ARF group had higher 1-year mortality group (hazard ratio [HR], 2.809; 95% confidence interval [CI], 1.099-7.180; P = .031) and readmission within 1-year rates (HR, 1.561; 95% CI, 1.061-2.295; P = .024) than the non-ARF group. The type 1 ARF group had a higher risk of 1-year mortality (HR, 3.022; 95% CI, 1.041-8.774; P = .042) and hospital readmission within 1-year (HR, 2.053; 95% CI, 1.230-3.428; P = .006) compared with the non-ARF group. There was no difference in mortality and readmission rates between the type 1 and type 2 ARF groups. In conclusion, patients with type 1 ARF rather than type 2 ARF had higher mortality and readmission rates than those without ARF. The prognoses of patients with type 1 and type 2 ARF were similar., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment., Methods: We conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women)., Results: Of the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000)., Conclusions: Although most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1-2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment., (© 2023. Springer Nature Limited.)

Nontuberculous mycobacteria (NTM) are ubiquitous organisms, but can cause a chronic pulmonary infection in some patients. Therefore, there could be host factors susceptible to this disease. A structural lung disease including damages of lungs caused by previous respiratory infection has been suggested as a host factor. Here we presented a case of NTM pulmonary disease which developed in a structural lung disease caused by a rare congenital lung disease. A 46-year-old male, was transferred to our hospital with an unexpandable lung after a closed thoracostomy due to spontaneous pneumothorax. His chest computed tomography showed an absence of left pulmonary artery at the time of admission. Mycobacterial culture in sputum, bronchial washing fluid, and pleural fluid showed the growth of NTM. Mycobacterium intracellulare was isolated from all positive cultures in the specimens. Combinations of drugs for M. intracellulare pulmonary disease including azithromycin, rifampin, and ethambutol were administered for 16 months. Amikacin intra venous treatment used for 6 months after treatment initiation. Culture conversion was achieved at 4 months of treatment. There was no evidence of recurrence of NTM pulmonary disease for 6 months after treatment. In conclusion, patients who have structural lung disease need to be careful monitoring about development of NTM pulmonary disease., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 The Authors.)

Background: Hemocoagulase batroxobin is used to prevent hemostasis or bleeding in surgical and trauma patients; however, the role of batroxobin in patients with hemoptysis is not well understood. We evaluated the risk factors and prognosis of acquired hypofibrinogenemia in hemoptysis patients treated systemically with batroxobin., Methods: We retrospectively reviewed the medical charts of hospitalized patients who were administered batroxobin for hemoptysis. Acquired hypofibrinogenemia was defined as a plasma fibrinogen level >150 mg/dL at baseline, decreasing to <150 mg/dL after batroxobin administration., Results: Overall, 183 patients were enrolled, of whom 75 had acquired hypofibrinogenemia after the administration of batroxobin. There was no statistical difference in the median age of the patients in the non-hypofibrinogenemia and hypofibrinogenemia groups (72.0 vs. 74.0 years, respectively). The patients in the hypofibrinogenemia group showed a higher rate of intensive care unit (ICU) admission (11.1% vs. 22.7%; P=0.041) and tended to have more massive hemoptysis than those in the non-hyperfibrinogenemia group (23.1% vs. 36.0%; P=0.068). The patients in the hypofibrinogenemia group further showed a higher requirement for transfusion (10.2% vs. 38.7%; P<0.000) than those in the non-hyperfibrinogenemia group. Low levels of baseline plasma fibrinogen and a prolonged and higher total dose of batroxobin were associated with the development of acquired hypofibrinogenemia. Acquired hypofibrinogenemia was associated with increased 30-day mortality [hazard ratio (HR), 4.164; 95% confidence interval (CI), 1.318-13.157]., Conclusions: The plasma fibrinogen levels in patients who were administered batroxobin for hemoptysis should be monitored, and batroxobin should be discontinued if hypofibrinogenemia occurs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-717/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objective: In-hospital tuberculosis (TB) transmission remains a concern. Airborne infection isolation (AII) can be discontinued in hospitalized patients with suspected active pulmonary TB when the results of three consecutive sputum acid-fast bacilli (AFB) smears are negative. However, fiberoptic bronchoscopy can be performed in patients who may have difficulty in producing sputum samples. This study aimed to investigate the usefulness of Mycobacterium tuberculosis-polymerase chain reaction (MTB-PCR) with bronchial washing specimens in predicting AII discontinuation in hospitalized patients with suspected active pulmonary TB., Methods: We reviewed the medical charts of patients admitted to a tertiary hospital who were isolated and underwent fiberoptic bronchoscopy for suspicious pulmonary TB from January 2016 to December 2019. Patients with positive MTB-PCR results in the initial sputum examination were excluded. Criteria for discontinuing AII were defined as negative results for three consecutive AFB smears from respiratory specimens, or cases diagnosed other than TB. The study patients were divided into two groups: TB group and non-TB group., Results: In total, 166 patients were enrolled in the study. Of them, 35 patients were diagnosed with TB. There was no significant difference between the number of males in the TB (81; 61.8%) and non-TB (21; 60.0%) group. Though 139 patients had negative results on MTB-PCR using washing specimens, eight showed positive AFB culture. Of the 139 patients with negative MTB-PCR results, 138 had negative results for three consecutive AFB smears or were established to not have pulmonary TB. Therefore, the predictive accuracy of MTB-PCR with bronchial washing samples for discontinuing AII was 99.2%., Conclusion: Although a negative result from MTB-PCR with bronchial washing samples cannot exclude pulmonary TB, it can predict AII discontinuation in hospitalized patients with suspected active pulmonary TB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs., Methods: We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital., Results: Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038)., Conclusion: Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Na et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients' symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors.)

Objective: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that are engaged in a number of diseases, but their roles in acute respiratory distress syndrome (ARDS) are not fully examined yet. This study aimed to examine levels and functions of MAIT cells in patients with ARDS., Methods: Peripheral blood samples from patients with ARDS (n=50) and healthy controls (HCs, n=50) were collected. Levels of MAIT cells, cytokines, CD69, programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) were measured by flow cytometry., Results: Circulating MAIT cell levels were significantly reduced in patients with ARDS than in HCs. MAIT cell levels were inversely correlated with disease severity and mortality. Cytokine production profiles in MAIT cells showed that percentages of interleukin (IL)-17 producing MAIT cell were significantly higher in patients with ARDS than in HCs. Patients with ARDS exhibited higher expression levels of CD69, PD-1 and LAG-3 in circulating MAIT cells. Moreover, levels of MAIT cells and expression levels of CD69, PD-1 and IL-17 in MAIT cells were higher in bronchoalveolar lavage fluid samples than in peripheral blood samples. Our in vitro experiments showed that MAIT cells triggered macrophages to produce proinflammatory cytokines such as tumour necrosis factor-α, IL-1β and IL-8., Conclusions: This study demonstrates that circulating MAIT cells are numerically deficient in patients with ARDS. In addition, MAIT cells were found to be activated, migrate into lung, secrete IL-17 and then stimulate macrophages. These findings suggest that MAIT cells contribute to the worsening of inflammation in the lung of patients with ARDS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Nontuberculous mycobacteria (NTM)-associated pleuritis is a very rare disease. Here, we describe 2 cases of life-threatening Mycobacterium intracellulare-associated pleuritis in immunocompetent hosts., Patient Concerns: A 78-year-old man with sudden onset-onset dyspnea (case 1) and an 80-year-old man with cough, sputum and fever (case 2) presented to our emergency room., Diagnoses: Both the patients were diagnosed with Mycobacterium intracellulare-associated pleuritis., Intervention: In case 1, the patient underwent intubation with mechanical ventilation due to hypoxemic respiratory failure. Daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week was administered. In case 2, the patient received daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week., Outcomes: In case 1, after receiving NTM treatment for 14 months, NTM-associated pleuritis was cured, with radiologic improvement. In case 2, however, bronchopleural fistula was developed. Despite tube drainage, air leak continued. The patient refused surgical management and eventually died of respiratory failure., Lessons: Pleural effusion arising from NTM lung disease located in the subpleural area should be considered a possible cause of NTM-associated pleuritis. Drainage and a multidrug regimen are required to treat NTM, and surgical treatment should be considered when complications occur., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We report a subgroup analysis of afatinib with respect to its efficacy, safety, and the long-term survival of patients in a Named Patient Use program at a single institution., Methods: We analyzed 60 patients with stage IV non-small cell lung cancer (NSCLC) who had been treated with ≥1 line of platinum-based chemotherapy and had activating epidermal growth factor receptor (EGFR) mutations or disease control for ≥6 months with prior EGFR inhibitors. Afatinib was started on a daily dose of 50 mg, which was decreased according to the adverse events and tolerability., Results: A total of 13 patients achieved partial remission, whereas 33, 12, and two showed stable disease, had progression, and were not evaluable, respectively, resulting in an objective response rate and disease control rate of 21.7% and 76.7%, respectively. The median progression-free survival (PFS) was 5.4 (95% confidence interval [CI]: 4.0-7.7) months and median overall survival (OS) was 10.1 (8.5-13.6) months. Toxicities leading to drug discontinuation were experienced by four patients (6.7%). Grade 3 diarrhea occurred in 10 patients (16.7%), and afatinib dose reductions were required in 35 patients. The PFS and OS were significantly longer for patients whose dose was reduced to 40 or 30 mg than for those without dose reduction (7.0 vs 3.1 months and 13.5 vs 8.1 months, respectively, p < 0.05)., Conclusions: The efficacy of afatinib was similar to that identified in the global data without unexpected adverse events. Survival analyses support the currently approved dose of afatinib as first-line treatment for NSCLC., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Abstract: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP., Methods: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC)., Results: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016)., Conclusions: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality., Competing Interests: The authors have declared that no competing interests exist.

Rational: Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis., Patient Concerns: An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred., Diagnoses: The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding., Intervention: Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered., Outcomes: The plasma fibrinogen level normalized and bleeding signs did not recur., Lessons: It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167-81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582-6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301-7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

Background: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients., Methods: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value., Results: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients., Conclusions: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr.2020.04.11). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Background: The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis., Case Presentation: A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung., Conclusions: Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

Background: We correlated the tumor proportion score (TPS) of programmed cell death ligand 1 (PD-L1, SP263 or 22C3) expression with the disease control rate (DCR, partial remission and stable disease), and progression free survival (PFS) after nivolumab or pembrolizumab treatment., Methods: A total of 70 case records (55 males, 15 females) of patients with non-small cell lung cancer (NSCLC, 46 adenocarcinoma, 22 squamous cell carcinoma, and two others) were reviewed. The PD-L1 expressions were divided into High (SP263 ≥ 30%, 22C3 ≥ 80%) and Low groups (SP263 < 30%, 22C3 < 80%). In the combined analysis, the PD-L1 group was defined as High if either of the two stains was classified as High and defined as Low if both stains were classified as Low., Results: Among the patients treated with nivolumab (n = 37), the SP263 High group showed higher DCR compared to the SP263 Low group (52.6% vs. 11.1%, P = 0.024). In patients treated with pembrolizumab (n = 33), no significant difference in DCR and PFS according to PD-L1 expression was observed. In the combined analysis (n = 36), patients in the PD-L1 High group showed significantly higher DCRs than those in the PD-L1 Low group (56.1% vs. 24.1%, P = 0.028). PFS was significantly longer in the PD-L1 High group than in the Low group (medians 4.1 vs. 1.6 months, respectively, P = 0.04)., Conclusion: A high expression level of PD-L1 was correlated with a significantly higher DCR and longer PFS in NSCLC patients treated with nivolumab or pembrolizumab., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Rationale: Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza., Patient Concerns: A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia., Diagnoses: Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected., Intervention: He received peramivir plus oseltamivir and broad-spectrum antibiotics., Outcomes: The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission., Lessons: We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.

Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76-year-old man who had been treated with four doses of nivolumab because of non-small cell lung cancer (NSCLC) presented with proximal-dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes., Methods: ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR., Results: Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup., Conclusion: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer., Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays., Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736-0.916)., Conclusion: PD-L1 expression, defined as TPS ≥1%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Rationale: Current guidelines for advanced non-small cell lung cancer (NSCLC) recommend the use of targeted agents for specific driver genes after confirming genetic alterations. Although epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are usually mutually exclusive, EGFR and ALK co-alterations have been reported increasingly in cases of NSCLC. However, the optimal treatment for these cases has not been established., Patient Concerns: This case series describes three patients diagnosed with advanced non-squamous NSCLC who harbored EGFR and ALK co-alterations. The complaints for each case are as follows: 57-year-old woman with coughing and dyspnea in case 1, 32-year-old man with diplopia in case 2 and 77-year-old woman with chest discomfort in case 3., Diagnoses: Three never-smokers were diagnosed pathologically with stage IV adenocarcinoma of the lung. Subsequent molecular studies revealed the EGFR L858R mutation gene and ALK rearrangement, which were proven by real-time polymerase chain reaction and fluorescence in situ hybridization, respectively., Interventions: All 3 patients received first-line therapy with EGFR-tyrosine kinase inhibitors (TKIs). Cases 1 and 2 were treated with ALK-TKIs as second-line therapy and received additional EGFR-TKIs as third- and fourth-line regimens., Outcomes: The patients achieved partial responses to EGFR-TKIs according to radiologic findings. However, second-line ALK-TKI therapy was ineffective in cases 1 and 2., Lessons: Cases of NSCLC with concomitant EGFR mutation and ALK rearrangement are rare, and the selection of an optimal targeted therapy is challenging. Here, EGFR-TKI appeared to yield better outcomes than ALK-TKI in patients with NSCLC who harbored EGFR/ALK co-alterations.

Background: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice., Methods: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re-biopsy specimens included small biopsy, surgical tissue, or liquid-based cytology. EGFR mutation was tested using peptide nucleic acid-mediated clamping PCR., Results: Of the 230 NSCLC patients that experienced progression after EGFR-TKI therapy, 105 (45.7%) underwent re-biopsy. Re-biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re-biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re-biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR-TKIs (P < 0.001)., Conclusion: Re-biopsy in advanced NSCLC is feasible in real world clinical practice, particularly in younger patients and those who achieved a previous response to EGFR-TKIs., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Cytomegalovirus (CMV) colitis is common among immunocompromised patients, and often diagnosed by pathologic confirmation because it is associated with a diverse spectrum of clinical and endoscopic features. However, Crohn's disease has no definitive diagnostic criteria, but longitudinal ulcers and cobble stone appearance are accepted as typical endoscopic features of Crohn's disease. An 83 year-old male with a history of radiotherapy for hypopharyngeal cancer visited our hospital with a complaint of melena for 1 week. His colonoscopic exam showed multiple longitudinal ulcers along the entire colon. Most of the ulcers were longer than 4 cm, these endoscopic findings were suspected as typical endoscopic features of Crohn's disease. Pathologic reports revealed multiple inclusion bodies with CMV on immunohistochemistry. He was finally diagnosed as having CMV colitis, and received a 3 week-course of intravenous ganciclovir. A colonoscopic follow-up showed complete healing of the multiple longitudinal ulcers, and he is doing well now without further treatment.