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The clinical significance of bacteremia in patients with complicated pleural infection is still uncertain. We aimed to examine the incidence and clinical significance of bacteremia in patients with complicated pleural infection.

Introduction: Data on factors related to mortality in patients with bronchiectasis exacerbation are insufficient. Computed tomography (CT) can measure the pectoralis muscle area (PMA) and is a useful tool to diagnose sarcopenia. This study aimed to evaluate whether PMA can predict mortality in patients with bronchiectasis exacerbation. Methods: Patients hospitalized due to bronchiectasis exacerbation at a single center were retrospectively divided into survivors and non-survivors based on 1-year mortality. Thereafter, a comparison of the clinical and radiologic characteristics was conducted between the two groups. Results: A total of 66 (14%) patients died at 1 year. In the multivariate analysis, age, BMI <18.4 kg/m2, sex-specific PMA quartile, ≥3 exacerbations in the previous year, serum albumin <3.5 g/dL, cystic bronchiectasis, tuberculosis-destroyed lung, and diabetes mellitus were independent predictors for the 1-year mortality in patients hospitalized with bronchiectasis exacerbation. A lower PMA was associated with a lower overall survival rate in the survival analysis according to sex-specific quartiles of PMA. PMA had the highest area under the curve during assessment of prognostic performance in predicting the 1-year mortality. The lowest sex-specific PMA quartile group exhibited higher disease severity than the highest quartile group. Conclusions: CT-derived PMA was an independent predictor of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. Patients with lower PMA exhibited higher disease severity. These findings suggest that PMA might be a useful marker for providing additional information regarding prognosis of patients with bronchiectasis exacerbation. [ABSTRACT FROM AUTHOR]

Introduction: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. Results: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D′ = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30–0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15–0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29–0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10−5). Conclusion: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC. [ABSTRACT FROM AUTHOR]

Background: Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods: In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results: The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion: These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified. Materials and Methods: Here, we aimed to examine the clinical impact of miR‐135a, located in the 3p21 region, in lung cancer. miR‐135a expression was assessed using quantitative real‐time polymerase chain reaction. LOH was analyzed at microsatellite loci D3S1076 and D3S1478, and promoter methylation status was determined by pyrosequencing of resected samples of primary non‐small‐cell lung cancer (NSCLC). The regulation of telomerase reverse transcriptase (TERT) was evaluated in lung cancer cells H1299 by luciferase report assays after treatment with miR‐135a mimics. Results: miR‐135a was significantly downregulated in squamous cell cancer (SCC) tumor tissues compared to normal tissues (p = 0.001). Low miR‐135a expression was more frequent in patients with SCC (p = 2.9 × 10−4) and smokers (p = 0.01). LOH and hypermethylation were detected in 27.8% (37/133) and 17.3% (23/133) of the tumors, respectively. Overall, 36.8% (49/133) of the NSCLC cases harbored either miR‐135a LOH or promoter hypermethylation. The frequencies of LOH and hypermethylation were significantly associated with SCCs (p = 2 × 10−4) and late‐stage (p = 0.04), respectively. MiR‐135a inhibited the relative luciferase activity of psiCHECK2‐TERT‐3'UTR. Conclusion: These results suggest that miR‐135a may act as a tumor suppressor to play an important role in lung cancer carcinogenesis, which will provide a new insight into the translational value of miR‐135a. Further large‐scale studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. Methods: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. Results: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. Conclusion: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non‐small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first‐line paclitaxel‐cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02–3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62–0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first‐line paclitaxel‐cisplatin chemotherapy in NSCLC. [ABSTRACT FROM AUTHOR]

Hemoptysis is a common cause of emergency department (ED) visits. There is little data about the role of systemic hypertension as a cause of hemoptysis. The aim of this study was to evaluate the association between systemic blood pressure and the unknown etiology of hemoptysis. This retrospective study included consecutive patients who visited the ED owing to hemoptysis and underwent a chest computed tomography between January 2011 and June 2021. Details of the initial blood pressure at the ED visit were compared between two groups with identified and unidentified causes of hemoptysis. In total, 1105 adult patients were included. The etiology of hemoptysis was identified in 1042 patients (94.3%) and remained unidentified in 63 patients (5.7%). The percentage of patients with severe hypertension was significantly higher in patients with unidentified causes of hemoptysis than in those with identified causes (35% vs. 11%, p < 0.001). In multivariate analysis, age, ever-smoker, and initial systolic blood pressure were significantly associated with hemoptysis of unidentified causes. Although further studies are needed, our findings suggest a possible association between high blood pressure and cryptogenic hemoptysis. [ABSTRACT FROM AUTHOR]

Although anti-angiogenic agents have been of limited use in the treatment of non-small cell lung cancer (NSCLC) until recently, further roles for the use of angiogenesis inhibition have emerged in the era of targeted therapy and immune checkpoint blockade. Given the shared common downstream signals of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) with their complementary roles in tumorigenesis and tumor angiogenesis, the dual inhibition of EGFR and VEGF pathways represents a rational strategy to maximize clinical efficacy and overcome resistance in the treatment of EGFR-mutant NSCLC. VEGF-driven angiogenesis is a potent driver of immunosuppressive tumor microenvironment (TME), with the recruited immunosuppressive cells driving angiogenesis, highlighting the interplay between the tumor vasculature and the anticancer immunity. Anti-angiogenic therapy can normalize the tumor vasculature and reprogram the TME from immunosuppressive into immunosupportive. Intensive research is under way to utilize the anti-angiogenic combination therapy to its full potential in diverse clinical settings in urgent unmet needs for the treatment of NSCLC. In this review, we present an overview of tumor angiogenesis and summarize the scientific background and preclinical and clinical evidence of anti-angiogenic therapy in combination with target therapy and immunotherapy for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]