A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a ...marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.
A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD. The Asia-Pacific classification of BMI has a lower cutoff for ...overweight and obese categories compared to the World Health Organization (WHO) classification. The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific.
Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation. We enrolled 1,462 patients. Medical history including age, sex, St George's Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV
) were evaluated. Patients were categorized into different BMI groups according to the two BMI classification systems.
FEV
and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse "U"-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied. When Asia-Pacific cutoffs were applied, FEV
and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria. From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications. The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems.
The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms. Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification.
In patients with completely resected non‐small cell lung cancer (NSCLC), postoperative adjuvant chemotherapy has been associated with improvement in survival by minimizing the risk of recurrence. For ...years, systemic chemotherapy including platinum based regimen has been a mainstay treatment modality of adjuvant treatment after complete resection. ADAURA study showed that among completely resected IB to IIIA NSCLC, disease‐free survival was significantly better in patients under adjuvant osimertinib than a placebo group. After the advent of a variety of new treatment regimens, such as third generation TKI and immunotherapy, the landscape of postoperative adjuvant treatment has been changing. In this review, we discuss some key issues regarding choice of adjuvant treatment after complete resection in NSCLC, and provide further updates on recent advances in treatment modalities.
Notable trials on immunotherapy as adjuvant treatment after complete resection in patients with non‐small cell lung cancer.
A combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While ...previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet.
In this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment.
Between January 2012 and July 2016, 217 patients with stage IV NSCLC and MPE undergoing active anticancer treatment were selected for evaluation. If patients had both low LMR (< 2.47) and increased platelet (> 30.0 ×10(4) mm-3), they were assigned to COP-LMR group 2. Patients with one parameter were assigned to COP-LMR group 1. If none, patients were assigned to COP-LMR group 0.
Median overall survival (OS) (P < 0.001), progression free survival (PFS) (P < 0.001) and histological feature (P = 0.003) showed significant differences among COP-LMR groups. For COP-LMR groups 0, 1 and 2, median survival times were 35.9, 14.7 and 7.4 months, respectively, while median progression free times were 19.2, 13.3 and 7.4 months, respectively. Older age, male, low albumin, high CRP and high COP-LMR (0 vs 1, P = 0.021, hazard ratio (HR): 1.822, 95% confidence interval (CI): 1.096-3.027 and 0 vs 2, P = 0.003, HR: 2.464, 95% CI: 1.373-4.421) were independent predictive factors for shorter OS. Age, sex, histology, albumin, or CRP had no significant influence on PFS. High COP-LMR was the significant factor in predicting shorter PFS (0 vs 1, P = 0.116 and 0 vs 2, P = 0.007, HR: 1.902, 95% CI: 1.194-3.028).
A combination of pretreatment LMR and platelet levels can be used to predict short survival in stage IV NSCLC patients who underwent active anticancer treatment.
Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with ...autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF).
ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study.
Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002-1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955-0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366-3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192-0.984 (IPAF vs IPF), respectively) showed significant association.
Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.
The selective cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) to cancer cells but not to normal cells makes it an attractive candidate for cancer therapeutics. ...However, the disadvantages of TRAIL such as physicochemical instability and short half-life limit its further clinical applications. In this study, TRAIL was encapsulated into a novel anti-angiogenic nanocomplex for both improved drug distribution at the tumor site and enhanced anti-tumor efficacy. A nanocomplex was prepared firstly by entrapping TRAIL into PEG-low molecular weight heparin-taurocholate conjugate (LHT7), which is previously known as a potent angiogenesis inhibitor. Then, protamine was added to make a stable form of nanocomplex (PEG-LHT7/TRAIL/Protamine) by exerting electrostatic interactions. We found that entrapping TRAIL into the nanocomplex significantly improved both pharmacokinetic properties and tumor accumulation rate without affecting the tumor selective cytotoxicity of TRAIL. Furthermore, the anti-tumor efficacy of nanocomplex was highly augmented (73.77±4.86%) compared to treating with only TRAIL (18.49 ± 19.75%), PEG-LHT7/Protamine (47.84 ± 14.20%) and co-injection of TRAIL and PEG-LHT7/Protamine (56.26 ± 9.98%). Histological analysis revealed that treatment with the nanocomplex showed both anti-angiogenic efficacy and homogenously induced cancer cell apoptosis, which suggests that accumulated TRAIL and LHT7 in tumor tissue exerted their anti-tumor effects synergistically. Based on this study, we suggest that PEG-LHT7/Protamine complex is an effective nanocarrier of TRAIL for enhancing drug distribution as well as improving anti-tumor efficacy by exploiting the synergistic mechanism of anti-angiogenesis.
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Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in ...elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients.
The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown.
A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 71.0;82.0, 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio HR 0.58, 95% confidence interval CI 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05).
Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.
Background:
The efficacy of inhaled ciprofloxacin agents in the treatment of patients with bronchiectasis is controversial. The objective of the study was to review systematically the efficacy of ...inhaled ciprofloxacin agents in patients with bronchiectasis.
Methods:
We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) evaluating inhaled ciprofloxacin agents among patients with bronchiectasis. Data were pooled using a meta-analysis technique.
Results:
Two phase II and four phase III RCTs were included with a total of 1685 patients. Treatment durations of phase III studies were 48 weeks, while those of phase II studies were shorter. Pooled analysis of overall studies exhibited a statistically significant benefit of inhaled ciprofloxacin agents in three exacerbation outcome measures, including time to first exacerbation (hazard ratio 0.74, 95% confidence interval CI 0.63–0.86, I2 23%), exacerbation frequency (risk ratio RR 0.73, 95% CI 0.61–0.86, I2 42%), and exacerbation proportion (RR 0.85, 95% CI 0.76–0.96, I2 25%) without significant heterogeneity. Outcomes evaluating pulmonary function, quality of life, and adverse events were not significantly different between the two groups. Although eradication of respiratory pathogens was more frequently observed, the emergence of ciprofloxacin resistance was also significantly higher in the ciprofloxacin group.
Conclusions:
A meta-analysis of RCTs of inhaled ciprofloxacin agents showed clinical benefit in terms of pulmonary exacerbations in patients with bronchiectasis. Since a significant increase of resistance was also noticed, clinical trials with a longer study period are required for a conclusive assessment.
The reviews of this paper are available via the supplemental material section.
The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) ...activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma.
The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP
) receptors (IP
R) with treating lipopolysaccharide (LPS) and TIO.
Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (
< 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP
receptor levels. After TIO treatment, recovery of IP
R and improved PLCγ-1 levels were observed.
These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP
-IP
R mediated intracellular calcium ion pathway.
A higher platelet-to-lymphocyte ratio (PLR) has a clinical correlation with shorter survival in non-small cell lung cancer (NSCLC). The present study evaluated the association between the PLR and ...survival in patients with advanced NSCLC with malignant pleural effusion (MPE). Between January 2012 and July 2016, 237 patients with stage IV NSCLC were selected for evaluation. Receiver operating characteristic analysis was used to determine a cutoff for the PLR. Clinicopathological characteristics were compared between the high and low PLR groups, and the role of PLR as a predictive/prognostic maker was investigated. Among the 237 patients, 122 were assigned to the low PLR group and the other 115 to the high PLR group. According to multivariate analysis, male sex, not receiving active anticancer treatment, low hemoglobin level, low albumin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter overall survival (OS) (p = 0.010, <0.001, 0.011, 0.004, 0.003, and <0.001, respectively). In the subgroup multivariate analysis of driver mutation-negative NSCLC, high Eastern Cooperative Oncology Group score, not receiving active anticancer treatment, low hemoglobin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter OS (p = 0.047, <0.001, = 0.036, = 0.003, and <0.001, respectively). A high pretreatment PLR is independently associated with poor survival in stage IV NSCLC with MPE and in a subgroup of epidermal growth factor receptor and anaplastic lymphoma kinase wild-type NSCLC.
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