Chronic cavitary pulmonary aspergillosis: Serial clinical and CT findings correlated with antifungal treatment and patient response.

BACKGROUND: Chronic cavitary pulmonary aspergillosis (CCPA) is the most common form of chronic pulmonary aspergillosis. OBJECTIVE: We hypothesise that by observing serial clinical and CT findings of CCPA patients with antifungal therapy, factors helping predict responses to antifungal therapy could be withdrawn. METHODS: A total of 31 patients with CCPA who received antifungal therapy for greater than six months and who had serial CT studies were included. Clinical finding analyses were performed at initial and last follow-up CT acquisition dates. Clinical characteristics and CT features were compared between clinically improving or stable and deteriorating groups. RESULTS: With antifungal therapy, neutrophil-to-lymphocyte ratio (2.66 vs. 5.12, p = .038) and serum albumin (4.40 vs. 3.85 g/dl, p = .013) and CRP (1.10 vs. 42.80 mg/L, p = .007) were different between two groups. With antifungal therapy, meaningful CT change, regardless of clinical response grouping, was decrease in cavity wall thickness (from 13.70 mm to 8.28 mm, p < .001). But baseline (p = .668) and follow-up (p = .278) cavity wall thickness was not different between two groups. In univariate analysis, initial maximum diameter of cavity (p = .028; HR [0.983], 95% CI [0.967-0.998]) and concurrent NTM infection (p = .030; HR [0.20], 95% CI [0.05-0.86]) were related factors for poor clinical response. CONCLUSIONS: With antifungal therapy, cavities demonstrate wall thinning. Of all clinical and radiological findings and their changes, initial large cavity size and concurrent presence of NTM infection are related factors to poor response to antifungal therapy.

Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea.

BACKGROUND: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. METHODS: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan-Meier curve analyses for survival were performed. RESULTS: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63-81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan-Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). CONCLUSIONS: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.

Empiric Anti-Pseudomonal ß-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching.

BACKGROUND: There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric anti-pseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. METHODS: This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019. Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem ß-lactam monotherapy and fluoroquinolone combination therapy groups. Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. RESULTS: In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286). There was no significant difference in 30-day mortality between the two groups (16.8% vs. 18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782-3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. CONCLUSION: Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to ß-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.

Prognostic factors for survival after bronchoscopic intervention in patients with airway obstruction due to primary pulmonary malignancy.

BACKGROUND: Malignant central airway obstruction (MCAO) occurs in 20-30% of patients with primary pulmonary malignancy. Although bronchoscopic intervention is widely performed to treat MCAO, little data exist on the prognosis of interventional bronchoscopy. Therefore, we evaluated the clinical outcomes and prognostic factors of bronchoscopic interventions in patients with MCAO due to primary pulmonary malignancy. METHODS: This retrospective study was conducted at a university hospital and included 224 patients who received interventional bronchoscopy from 2004 to 2017, excluding patients with salivary gland-type tumor. A multivariable Cox proportional hazard regression analysis was used to identify independent prognostic factors associated with survival after the first bronchoscopic intervention. RESULTS: Among 224 patients, 191 (85.3%) were males, and the median age was 63 years. The most common histological type of malignancy was squamous cell carcinoma (71.0%). Technical success was achieved in 93.7% of patients. Acute complications and procedure-related death occurred in 15.6 and 1.3% of patients, respectively. The median survival time was 7.0 months, and survival rates at one year and two years were 39.7 and 28.3%, respectively. Poor survival was associated with underlying chronic pulmonary disease, poor performance status, extended lesion, extrinsic or mixed lesion, and MCAO due to disease progression and not receiving adjuvant treatment after bronchoscopic intervention. CONCLUSIONS: Interventional bronchoscopy could be a safe and effective procedure for patients who have MCAO due to primary pulmonary malignancy. In addition, we found several prognostic factors for poor survival after intervention, which will help clinicians determine the best candidates for bronchoscopic intervention.

The association of delta neutrophil index with the prognosis of acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is associated with infective triggers including bacterial or viral in many cases, and pneumonia is a major contributor to hospitalization for AECOPD and has a close relationship with poor outcomes. Increased delta neutrophil index (DNI) can be useful in the detection of COPD patients with pneumonia. METHODS: A retrospective cohort study was performed to investigate the mortality rate of the patients who were re-admitted within 6 months after discharge from the hospital due to AECOPD with or without CAP. We analyzed the difference of cumulative survival rate according to serum DNI level and readmission duration. RESULTS: Finally, 140 AECOPD patients with community-acquired pneumonia (CAP) and 174 AECOPD patients without CAP were enrolled during 6 months, respectively. The mean age was 72.2 ± 9.4 year-old, and 240 patients (76.4%) were male. When comparing the cumulative survival rate according to readmission duration (≤ 30 vs >  30 days) and DNI level (< 3.5 vs ≥ 3.5%), AECOPD patients with readmission ≤30 days and DNI ≥ 3.5% showed the lowest cumulative survival rate compared to other groups (P <  0.001). Multivariate analysis revealed readmission duration ≤30 days (HR 7.879, 95% CI 4.554-13.632, P <  0.001); and serum DNI level (HR 1.086, 95% CI 1.043-1.131, P <  0.001) were significantly associated with the mortality of AECOPD patients during 6 months. The area under the curve for readmission (≤ 30 days) + DNI level (≥ 3.5%) was 0.753 (95% CI 0.676-0.830, P <  0.001) with a sensitivity of 73.7% and a specificity of 67.3%. CONCLUSION: AECOPD patients who were readmitted ≤30 days and DNI ≥ 3.5% showed higher mortality. DNI level can be used as a predictor of prognosis in AECOPD patients who were readmitted after discharge.

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

BACKGROUND: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. METHODS: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. RESULTS: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. CONCLUSIONS: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Impact of Bronchiectasis on Postoperative Pulmonary Complications after Extra-Pulmonary Surgery in Patients with Airflow Limitation.

The impact of bronchiectasis on the occurrence of postoperative pulmonary complications (PPC) after extra-pulmonary surgery in patients with airflow limitation is not well elucidated. A retrospective analysis of 437 patients with airflow limitations, including 62 patients with bronchiectasis, was conducted. The analysis revealed that bronchiectasis was associated with increased PPC (adjusted odds ratio [aOR], 2.73; P = 0.001), which was especially significant in patients who did not use bronchodilators (aOR, 3.24; P = 0.002). Our study indicates that bronchiectasis is associated with an increased risk of PPC following extra-pulmonary surgery in patients with airflow limitation, and bronchodilators may prevent PPC in these patients.

Correction to: Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

Following publication of the original.

Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

BACKGROUND: Endosonography with needle aspiration (EBUS/EUS-NA) is recommended as the first choice for mediastinal nodal assessment in non-small cell lung cancer (NSCLC). It is important to maintain adequate negative predictive value of the procedure to avoid unnecessary additional surgical staging, but there are few studies on the influence of operator-related factors including competency on false negative results. This study aims to compare the false negative rate of individual operators and whether it changes according to accumulation of experience. METHODS: This is a retrospective study of NSCLC patients who were N0/N1 by EBUS/EUS-NA and confirmed by pathologic staging upon mediastinal lymph node dissection (n = 705). Patients were divided into a false negative group (finally confirmed as pN2/N3) and a true negative group (pN0/N1). False negative rates of six operators and whether these changed according to accumulated experience were analyzed. RESULTS: There were 111 (15.7%) false negative cases. False negative rates among six operators ranged from 8.3 to 21.4%; however, there were no statistical differences before and after adjustment for patient characteristics and procedure-related factors (P = 0.346 and P = 0.494, respectively). In addition, false negative rates did not change as each operator accumulated experience (P for trend = 0.632). CONCLUSIONS: Our data suggest that there would be no difference in false negative rates regardless of which operator performs the procedure assuming that the operators have completed a certain period of observation and have performed procedures under the guidance of an expert.

Early readmission and mortality in acute exacerbation of chronic obstructive pulmonary disease with community-acquired pneumonia.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are important causes of hospital admission and mortality. Pneumonia is a major contributor to hospitalization for AECOPD and has a close relationship with poor outcomes. We performed a prospective cohort study to evaluate the prognosis of AECOPD patients with or without community-acquired pneumonia (CAP) who hospitalized from January 2012 to December 2015. We investigated mortality and readmission rates within 6 months after the first admission between two groups and analyzed the difference of survival rate according to readmission duration (≤30 vs. >30 days) or intensive care unit (ICU) treatment. Total 308 AECOPD patients (134 with CAP and 174 without CAP) were enrolled. The mean age was 72.3 ± 9.5 years old, and 235 patients (76.3%) were male. The 180-day mortality was higher in AECOPD with CAP than without CAP (24.6% vs. 13.2%; hazard ratio (HR): 1.982; 95% CI: 1.164-3.375; p = 0.012). However, readmission rate showed no significant difference between two groups (51.5% vs. 46.6%; HR: 1.172; 95% CI: 0.850-1.616; p = 0.333). It showed a significantly lower survival rate in AECOPD with CAP rather than without CAP when were readmitted within 30 days (HR: 1.738; 95% CI:1.063-3.017; p = 0.031). According to ICU treatment, survival rate was not significantly different between two groups. Multivariate analysis revealed the readmission within 30 days ( p < 0.001), serum hemoglobin concentration ( p = 0.010), and albumin level ( p = 0.049) were significantly associated with 180-day mortality of AECOPD with CAP. AECOPD with CAP showed lower survival rate than AECOPD without CAP during 6 months. Early readmission within 30 days was significantly associated with an increased risk of mortality.

Interventional bronchoscopy in malignant central airway obstruction by extra-pulmonary malignancy.

BACKGROUND: Interventional bronchoscopy is considered an effective treatment option for malignant central airway obstruction (MCAO). However, there are few reports of interventional bronchoscopy in patients with MCAOs due to extra-pulmonary malignancy. Therefore, the objective of this study was to investigate treatment outcomes and prognostic factors for bronchoscopic intervention in patients with MCAO due to extra-pulmonary malignancy. METHODS: We retrospectively analyzed consecutive 98 patients with MCAO due to extra-pulmonary malignancy who underwent interventional bronchoscopy between 2004 and 2014 at Samsung Medical Center (Seoul, Korea). RESULTS: The most common primary site of malignancy was esophageal cancer (37.9%), followed by thyroid cancer (16.3%) and head & neck cancer (10.2%). Bronchoscopic interventions were usually performed using a combination of mechanical debulking (84.7%), stent insertion (70.4%), and laser cauterization (37.8%). Of 98 patients, 76 (77.6%) patients had MCAO due to progression of malignancy, and 42 (42.9%) patients had exhausted all other anti-cancer treatment at the time of bronchoscopic intervention. Technical success was achieved in 89.9% of patients, and acute complications and procedure-related deaths occurred in 20.4% and 3.1% of patients, respectively. Reduced survival was associated with MCAO due to cancer other than thyroid cancer or lymphoma, mixed lesions, and not receiving adjuvant treatment after bronchoscopic intervention. CONCLUSIONS: Bronchoscopic intervention could be a safe and effective procedure for MCAO due to end-stage extra-pulmonary malignancies. In addition, we identified possible prognostic factors for poor survival after intervention, which could guide clinicians select candidates that will benefit from bronchoscopic intervention.

Clinical significance of differentiating post-intubation and post-tracheostomy tracheal stenosis.

BACKGROUND AND OBJECTIVE: Post-intubation tracheal stenosis (PITS) and post-tracheostomy tracheal stenosis (PTTS) are serious complications in mechanically ventilated patients. Although the aetiologies and mechanisms of PITS and PTTS are quite different, little is known about the clinical impact of differentiating one from the other. METHODS: We retrospectively conducted a chart review of 117 patients with PITS and 88 patients with PTTS who were treated with interventional bronchoscopy at Samsung Medical Center between January 2004 and December 2013. RESULTS: Compared to patients with PITS, patients with PTTS had a lower BMI, poorer performance status and more frequent neurological aetiologies, mid-to-lower tracheal lesions, total obstruction and mixed stenosis types. Although there were no differences in the number of patients who received silicone stents between the two groups, Montgomery T-tubes were more frequently used in the PTTS group than in the PITS group. The final success rate without surgery, mortality or tracheostomy in situ was higher in the PITS group than in the PTTS group (76.9% vs 63.6%, P = 0.043). Additionally, airway prosthesis removal was achieved in 46.2% of patients in the PITS group and in 33.0% of the PTTS group (P = 0.063). CONCLUSION: There were significant differences between PITS and PTTS in terms of patient and stenosis characteristics, treatment modalities and clinical outcomes. Therefore, PITS and PTTS should be considered two different entities.

Airflow limitation severity and post-operative pulmonary complications following extra-pulmonary surgery in COPD patients.

BACKGROUND AND OBJECTIVE: The association between airflow limitation severity and post-operative pulmonary complications (PPCs) among COPD patients undergoing extra-pulmonary surgery is unknown. We evaluated the association between forced expiratory volume in 1 s (FEV1 ) and PPC in COPD patients undergoing extra-pulmonary surgery. METHODS: Using prospective cohort of PPC evaluation for extra-pulmonary surgery, we identified 694 COPD patients who conducted PPC evaluation before extra-pulmonary surgery between March 2014 and January 2015 at a tertiary hospital, Seoul, Korea. RESULTS: The overall incidence of PPC was 24.4%. The incidence of PPC in quintiles 1-5 of FEV1 (% predicted) was 31.4, 25.8, 23.7, 21.6 and 19.7%, respectively (P for trend: 0.019). In fully adjusted multivariable models, the relative risks (RRs, 95% CI) for PPC comparing participants in quintiles 1-4 of FEV1 (% predicted) with those in quintile 5 were 1.69 (1.03-2.79), 1.41 (0.83-2.37), 1.26 (0.75-2.11) and 1.30 (0.76-2.22), respectively (P for trend: 0.046). The association of severe airflow limitation with respiratory failure and post-operative exacerbations was stronger in participants who did not use bronchodilators compared with those who did. CONCLUSION: We found a progressive and significant relationship between severity of airflow limitation and the incidence of PPC in COPD patients undergoing extra-pulmonary surgery. Furthermore, perioperative bronchodilator use was associated with a reduced risk of respiratory failure and post-operative exacerbations in patients with severe airflow limitation.

Impact of Respiratory Bacterial Findings on Patients with Chronic Pulmonary Aspergillosis.

Background: Distinct bacterial strains may affect the prognosis of patients with chronic respiratory diseases. However, little is known about the clinical significance of respiratory bacteria in patients with chronic pulmonary aspergillosis (CPA), a progressive and debilitating disease caused by Aspergillus spp. Objectives: This study aimed to analyze data obtained from CPA patients and their sputum or bronchial washing samples and investigate the prevalence and composition of respiratory bacteria and clinical implications. Patients and Methods. We retrospectively reviewed the data of patients diagnosed with CPA between March 2019 and February 2023 in a tertiary referral hospital. We assessed the clinical characteristics and overall and pneumonia-specific survival rates of patients with CPA based on the presence of bacteria. Results and Conclusions. We included 142 patients with CPA. The most commonly identified bacteria were Klebsiella pneumoniae (22.5%), followed by Pseudomonas aeruginosa (21.8%) and Escherichia coli (4.2%). Patients with isolated bacteria had a higher prevalence of older age, female sex, diabetes, and a history of extrathoracic malignancy than those without isolated bacteria (P = 0.024, 0.013, 0.021, and 0.034, respectively). Furthermore, over a median follow-up of 11 (4-21) months, the pneumonia-specific mortality rate was 13.4% (19/142), which was higher in patients with isolated bacteria than in those without (P = 0.045, log-rank test). Particularly, patients with the presence of P. aeruginosa had a significantly higher mortality rate from pneumonia than those without the presence of P. aeruginosa (adjusted hazard ratio, 3.34; P = 0.015). In conclusion, CPA patients with isolated bacteria, especially P. aeruginosa, showed higher mortality rates due to pneumonia. Performing tests to identify bacteria in the lower respiratory tract of patients with CPA may be helpful in predicting future prognosis. Further studies are required to validate these findings in diverse ethnic groups.

Clinical characteristics and drug resistance profile of patients with endobronchial tuberculosis in South Korea: single-center experience.

BACKGROUND: Tuberculosis (TB) is a major infectious disease worldwide; there has been a significant increase in the number of elderly patients with TB, largely contributing to TB-related mortality. Although endobronchial tuberculosis (EBTB) is a unique form of pulmonary TB, available data on the clinical characteristics and drug susceptibility (DST) patterns of patients with EBTB are scarce. METHODS: We evaluated the clinical characteristics of patients with EBTB in South Korea and the culture-based DST patterns of EBTB. Further, the DST patterns were compared between elderly (≥65 years) and young (<65 years) patients. We retrospectively reviewed data of patients with EBTB who had the results of DST and were diagnosed between January 2013 and December 2019 at a tertiary referral hospital in South Korea. Phenotypic DST of 15 first-line and second-line anti-TB drugs was performed using Mycobacterium tuberculosis isolates prior to treatment. RESULTS: Of the 230 patients with EBTB, 69% were in elderly patients (≥65 years). Any-resistance occurred in 24 patients (10.4%), while multi-drug resistance (MDR) and extensive drug resistance (XDR) were observed in six patients (2.6%). Compared to that of the elderly treatment-naïve patients, previously treated elderly patients had a significantly higher proportion of resistance to rifampin (14.3% vs. 2.2%; P=0.031), ethambutol (9.5% vs. 0.7%; P=0.046), and pyrazinamide (9.5% vs. 0.7%; P=0.046). Further, MDR/XDR was observed more frequently in the previously treated elderly patients than that in the treatment-naïve elderly patients (14.3% vs. 1.4%; P=0.017). A relatively small number of drug-resistant cases (5.6%) were observed in young patients. CONCLUSIONS: Elderly EBTB patients with previous Anti-tuberculous medications had a significantly higher proportion of drug-resistant TB. These patients should be carefully assessed using DST analysis before treatment.

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.

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.

The impact of driving pressure on postoperative pulmonary complication in patients with different respiratory spirometry.

Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02-1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05-1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89-1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.

Impact of nutrition and physical activity on outcomes of hospital-acquired pneumonia.

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.

Differences in the clinical characteristics of chronic pulmonary aspergillosis according to spirometric impairment.

The clinical features by declining lung function remain uncharacterized in chronic pulmonary aspergillosis (CPA) patients. We investigated the clinical characteristics of CPA patients based on spirometric impairments (restrictive spirometric pattern [RSP] and obstructive spirometric pattern [OSP]) and their severity. We retrospectively analyzed medical records of CPA patients who underwent pulmonary function tests from March 2017 to February 2020. We used Global Lung Initiative 2012 equations with lower limit of normal. The clinical characteristics of patients with RSP were compared to those with OSP. Additionally, RSP patients' characteristics were analyzed according to forced vital capacity (FVC) tertile, and OSP patients' characteristics were analyzed according to forced expiratory volume in 1 second (FEV1) tertile. Among the 112 patients with CPA (52 [46%] with RSP and 60 [54%] with OSP), body mass index (BMI) was significantly lower in patients with RSP than in those with OSP (17.6 kg/m2 versus 20.3 kg/m2; P = 0.003), and non-tuberculous mycobacterial disease was more frequently observed in patients with RSP than in those with OSP (28.8% versus 11.7%; P = 0.004). Additionally, for patients with RSP, younger age and bilateral pulmonary lesions were more frequently observed in the first tertile group than in the other groups (P for trend: 0.025 and 0.001, respectively). For patients with OSP, low BMI, paracavitary infiltrates, and elevated WBC count were more frequently observed in the first tertile group than in the other groups (P for trend: < 0.001, 0.011, and 0.041, respectively). Differences in the clinical features of CPA patients were identified according to heterogeneous spirometric patterns and their severity. Further studies are needed to investigate the clinical significance of these findings.