Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study.

BACKGROUND: The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated. METHODS: This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed. RESULTS: BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively. CONCLUSIONS: A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

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.

Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.

BACKGROUND: Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. METHODS: This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. RESULTS: Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61-0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44-0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64-1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. CONCLUSION: Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

BACES Score for Predicting Mortality in Nontuberculous Mycobacterial Pulmonary Disease.

Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed.Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease.Methods: We included patients age ≥20 years with newly diagnosed nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort.Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m2 (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval, 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval, 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5.Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense.

Association of plasma exosomes with severity of organ failure and mortality in patients with sepsis.

Current sepsis biomarkers may be helpful in determining organ failure and evaluating patient clinical course; however, direct molecular biomarkers to predict subsequent organ failure have not yet been discovered. Exosomes, a small population of extracellular vesicles, play an important role in the inflammatory response, coagulation process and cardiac dysfunction in sepsis. Nonetheless, the association of plasma exosome with severity and mortality of sepsis is not well known. Therefore, the overall levels of plasma exosome in sepsis patients were assessed and whether exosome levels were associated with organ failure and mortality was evaluated in the present study. Plasma level of exosomes was measured by ELISA. Among 220 patients with sepsis, 145 (66%) patients were diagnosed with septic shock. A trend of increased exosome levels in control, sepsis and septic shock groups was observed (204 µg/mL vs 525 µg/mL vs 802 µg/mL, P < 0.001). A positive linear relationship was observed between overall exosome levels and Sequential Organ Failure Assessment (SOFA) score in the study cohorts (r value = 0.47). When patients were divided into two groups according to best cut-off level, a statistical difference in 28- and 90-day mortality between patients with high and low plasma exosomes was observed. Elevated levels of plasma exosomes were associated with severity of organ failure and predictive of mortality in critically ill patients with sepsis.

Impact of diffusing lung capacity before and after neoadjuvant concurrent chemoradiation on postoperative pulmonary complications among patients with stage IIIA/N2 non-small-cell lung cancer.

BACKGROUND AND OBJECTIVE: This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. METHODS: We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco < 80% predicted and DLco < 60% predicted, respectively. RESULTS: On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36-3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68-8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. CONCLUSIONS: The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease.

Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression-free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry-based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26-0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31-0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry-defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab.

Prevalence of and risk factors for pulmonary complications after curative resection in otherwise healthy elderly patients with early stage lung cancer.

BACKGROUND AND OBJECTIVE: The prevalence of lung cancer has been increasing in healthy elderly patients with preserved pulmonary function and without underlying lung diseases. We aimed to determine the prevalence of and risk factors for postoperative pulmonary complications (PPCs) in healthy elderly patients with non-small cell lung cancer (NSCLC) to select optimal candidates for surgical resection in this subpopulation. METHODS: We included 488 patients older than 70 years with normal spirometry results who underwent curative resection for NSCLC (stage IA-IIB) between 2012 and 2016. RESULTS: The median (interquartile range) age of our cohort was 73 (71-76) years. Fifty-two patients (10.7%) had PPCs. Severe PPCs like acute respiratory distress syndrome, pneumonia, and respiratory failure had prevalences of 3.7, 3.7, and 1.4%, respectively. Compared to patients without PPCs, those with PPCs were more likely to be male and current smokers; have a lower body mass index (BMI), higher American Society of Anesthesiologists (ASA) classification, more interstitial lung abnormalities (ILAs), and higher emphysema index on computed tomography (CT); and have undergone pneumonectomy or bilobectomy (all p < 0.05). On multivariate analysis, ASA classification ≥3, lower BMI, ILA, and extent of resection were independently associated with PPC risk. The short-term all-cause mortality was significantly higher in patients with PPCs. CONCLUSIONS: Curative resection for NSCLC in healthy elderly patients appeared feasible with 10% PPCs. ASA classification ≥3, lower BMI, presence of ILA on CT, and larger extent of resection are predictors of PPC development, which guide treatment decision-making in these patients.

Disease severity and activity in bronchiectasis: A paradigm shift in bronchiectasis management.

Bronchiectasis has an increasing prevalence and substantial clinical and economic burden. Therefore, physicians should identify patients with bronchiectasis at high risk of disease progression to ensure optimal management in advance. The heterogeneity of bronchiectasis means it is unlikely that any single parameter could identify high-risk patients, therefore disease severity is usually assessed using validated composite tools, such as the Bronchiectasis Severity Index, FACED, and Bronchiectasis Aetiology Comorbidity Index, to predict long-term outcomes in bronchiectasis. Disease severity, however, implies an advanced process with lung destruction. Earlier intervention may prevent disease progression and improve outcomes. To identify patients at risk, rather than patients with established advanced disease, we need to shift our focus from disease severity to disease activity. Disease activity denotes the activation level of underlying pathophysiological processes and can be measured using clinical presentations and biomarkers. This review discusses a paradigm shift in bronchiectasis management, focusing on disease activity rather than severity, to prevent disease progression.

Outcomes of Intermittent Multidrug IV Therapy for Refractory Mycobacterium abscessus Pulmonary Disease.

BACKGROUND: No studies have reported therapies for the treatment of patients with refractory Mycobacterium abscessus pulmonary disease (MAB-PD). We implemented intermittent multidrug IV therapy (IMIT) through repeated hospitalizations for patients with MAB-PD who were refractory to antibiotics for more than 12 months. RESEARCH QUESTION: What are the effects of IMIT on patients with refractory MAB-PD? STUDY DESIGN AND METHODS: The IV antibiotics administered for IMIT included amikacin, imipenem, and tigecycline, and the outcomes for 36 patients who underwent IMIT for refractory MAB-PD were evaluated. Patients were repeatedly hospitalized and administered IMIT on recurrent symptoms or radiographic evidence of deterioration, while maintaining oral/inhaled antibiotics. RESULTS: Of the 36 patients, 26 (72%) had M abscessus subspecies abscessus (herein, M abscessus)-PD, and 10 (28%) had M abscessus subspecies massiliense (herein, M massiliense)-PD. The median number of hospitalizations for IMIT was two (interquartile range, 1-3) for patients with M abscessus-PD and one (interquartile range, 1-2) for patients with M massiliense-PD. At least one negative culture result and culture conversion were observed in 62% and 12% of patients with M abscessus-PD, and in 80% and 60% of patients with M massiliense-PD, respectively. Symptomatic improvement was observed in all patients, and radiologic improvement, including cavity amelioration or no deterioration, was observed in 42% and 70% of patients with M abscessus-PD and with M massiliense-PD, respectively. No resistance to clarithromycin or amikacin was acquired. INTERPRETATION: IMIT with intermittent hospitalization can be a beneficial palliative treatment for patients with refractory MAB-PD. This therapy alleviated symptoms, slowed radiologic progression, and reduced the bacterial burden in some patients. However, radiologic and microbiological responses to IMIT were more apparent in M massiliense-PD than in M abscessus-PD.

Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis.

Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.

Association of resistance training and moderate-to-vigorous physical activity with clinical outcomes in men with airflow limitation: a nationwide population-based study.

Aerobic moderate-to-vigorous physical activity (MVPA) is recommended for individuals with chronic diseases. However, the association between resistance training (RT) in addition to moderate to vigorous physical activity (MVPA) and sleep duration, as well as respiratory symptoms, in patients with chronic obstructive pulmonary disease has not been thoroughly investigated. This population-based cross-sectional study used data from the Korea National Health and Nutrition Examination Survey between 2014 and 2019. A total of 61,754 individuals were identified and men with airflow limitation (FEV1/FVC < 0.7) who engaged in aerobic MVPA were selected (n = 794). Weighted percentages and odds ratio (OR) of sleep problems (≤ 5 or ≥ 9 h), chronic cough, and chronic sputum were estimated. A multivariate-adjusted complex sample logistic regression model was used to calculate ORs and 95% confidence intervals (CI). Subgroup analyses were conducted using the forced expiratory volume (FEV1) % of the predicted value (%pred) ≥ 80 vs. < 80. The percentages of sleep problems, chronic cough, and chronic sputum production were lower in men who underwent aerobic MVPA + RT than in those who underwent aerobic MVPA alone. The multivariable-adjusted OR of sleep problems was 0.44 (95% CI 0.25-0.77) in individuals undergoing aerobic MVPA + RT compared to aerobic MVPA alone. The ORs of chronic cough and sputum were 0.35 (95% CI 0.13-0.94) and 0.51 (95% CI 0.30-0.87), respectively. These associations were only significant in individuals with FEV1 < 80% pred. Compared with aerobic MVPA alone, aerobic MVPA + RT was associated with appropriate sleep duration and a decrease in chronic cough and sputum in male with airflow limitation. This was more pronounced in individuals with a FEV1 < 80% pred.

Association of moderate-to-vigorous physical activity with reduction of acute exacerbation in COPD patients using a dual ultra-long-acting bronchodilators.

Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

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 of miliary pulmonary metastases in non-small cell lung cancer.

BACKGROUND: The prognosis of miliary pulmonary metastases (MPM), which are characterized as randomly disseminated, innumerable, and small metastatic nodules, has been considered as being poor. The purpose of this study was to evaluate the clinical characteristics and survival of MPM in patients with non-small cell lung cancer (NSCLC). METHODS: This retrospective study included NSCLC patients with MPM and nonmiliary pulmonary metastases (NMPM) detected during staging evaluation between 2000 and 2020. MPM was defined as >50 bilaterally distributed metastatic pulmonary nodules (<1 cm in diameter), and NMPM was defined as the presence of ≤15 metastatic pulmonary nodules regardless of size. Baseline characteristics, genetic alterations and overall survival (OS) rates were compared between the two groups. RESULTS: Twenty-six patients with MPM and 78 patients with NMPM were analyzed. The median number of patients who smoked was significantly lower in the MPM group than in the NMPM group (0 vs. 8 pack years, p = 0.030). The frequency of EGFR mutation was significantly higher in the MPM group (58%) than in the NMPM group (24%; p = 0.006). There was no significant difference in 5-year OS between the MPM and the NMPM group by the log-rank test (p = 0.900). CONCLUSION: MPM in NSCLC were significantly related to EGFR mutation. The OS rate of the MPM group was not inferior to that of the NMPM group. The presence of EGFR mutations should be thoroughly evaluated for NSCLC patients with initial presentation of MPM.

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.

Prognostic value of pretherapeutic FDG PET/CT in non-small cell lung cancer with pulmonary lymphangitic carcinomatosis.

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.

Expeditious Resolution of Giant Bullae with Endobronchial Valves and Percutaneous Catheter Insertion.

As bullae contribute to decreased lung function in chronic obstructive pulmonary disease (COPD) patients, effective decompression of large bullae is important. Bronchoscopic lung volume reduction via endobronchial one-way valves is less invasive and has a lower mortality rate than lung volume reduction surgery. We report the case of a 48-year-old male who presented with giant bullae that were expeditiously resolved with endobronchial valves and percutaneous catheter insertion. Three days later, imaging revealed marked decreases in the extent of bullae and atelectasis of the contralateral lung without any complications, including air leakage or pneumothorax. Combination of endobronchial valves and percutaneous catheter insertion might be helpful to accelerate the release of large bullae and to achieve improved lung function and higher levels of physical activity in patients with COPD.