Optimal timing for video assisted thoracic surgery decortication for improved survival in chronic empyema.

BACKGROUND: Video-assisted thoracic surgery decortication for phase 3 thoracic empyema is widely accepted, but its optimal timing has not been established. We aim to investigate and assess this timing, in terms of overall survival, for chronic empyema. METHODS: Two hundred four patients with pneumonia-caused phase 3 empyema were treated with video-assisted thoracic surgery decortication over 10-years at Changhua Christian Hospital. The 90-day post-operative survival status was analyzed, and we compared the survivor group versus the non-survivor group. A receiver operating characteristic curve was used to identify the optimal decortication timing. RESULTS: A comparison between survivors and non-survivors showed statistical differences among age (p=0.004), presence of cardiovascular disease (p=0.018), presence of end-stage renal disease (p=0.002), duration to surgery (p=0.013), length of intensive care unit stay (p=0.010), and overall length of hospital stay (p=0.015). ROC curve analysis determined the cut-off for video-assisted thoracic surgery decortication, based on optimal 90-day post-operative survival, to be 7.5 days after hospitalization; mortality increases threefold thereafter (14.2% vs 44.6%, p<0.001). Multivariate analysis revealed that age, end-stage renal disease, pleural effusion pH≦7.2 and duration to surgery >7.5 days negatively impacted 90-day post-operative survival. CONCLUSIONS: Patients receiving decortication surgery within 7.5 days of hospital admission had better overall survival.

Prognostic factors in clinical stage IIIA small cell lung cancer: An analysis of a population-based cancer registry in Taiwan.

Lung cancer stands as the primary cause of cancer-related death across the globe. The standard therapeutic approach for lung cancer involves concurrent chemoradiotherapy, with consideration of prophylactic cranial irradiation for younger or well-performing patients. In this study, we aimed to investigate prognostic factors and the impacts of different treatment methods on overall survival for stage IIIA small cell lung cancer in Taiwan. We obtained data from the Taiwan Cancer Registry, which included clinical and pathology data of 579 stage IIIA small cell lung cancer patients from January 2010 to December 2018, for this retrospective study. The enrolled patients had data on age, sex, Charlson Comorbidity Index score, histologic grading, clinical T, clinical N, clinical stage, treatment modality, and overall survival time. We compared overall survival among different subgroups to assess the impacts of these prognostic factors. The five-year survival rate for all patients was 20.57%, with a median survival time of 15.79 months. The data suggest that Charlson Comorbidity Index score, histologic grade, and clinical stage subgroups did not reach statistically significant differences. During the multivariate analysis, age over 70 years, sex, and treatment method were determined to be statistically significant independent prognostic factors. Patients who underwent surgical intervention exhibited significantly better outcomes compared to those who did not undergo operation.. In conclusion, stage IIIA small cell lung cancer is a highly heterogeneous disease. Operation should be considered as one of the alternative treatments in stage IIIA Small cell lung cancer patients.

Seasonal variations of empyema in Taiwan: A 10-year analysis.

BACKGROUND: Empyema is a serious infection in pleural space. Finding out seasonal variations of empyema and its pathogens can help in providing preventive measures, and implicating future researches. METHODS: This study is a 10-year observational study in a single center. Patients with empyema thoracis receiving thoracoscopic decortication between January 2012 and December 2021 were included in the study. RESULTS: There were 1082 empyema patients enrolled in this study. No seasonal variation was noted (spring = 25.7 %, summer =25.5 %, autumn = 24.8 %, winter = 24.0 %). However, we observed seasonal variations in pathogens. Streptococcus species had slightly higher prevalence in winter and spring than summer and autumn (54.3 % vs. 45.7 %) without significant difference (p = 0.251). On the contrary, Staphylococcus species occurred more often in summer and autumn than winter and spring (61.5 % vs. 38.5 %) (p = 0.035). Klebsiella species were more likely found in autumn (34.9 %) (p = 0.050), and Pseudomonas species showed no peak prevalence in any season (p = 0.423). The incidence of Streptococcus species increased over the years. CONCLUSIONS: Although no seasonal variation was found in severe empyema patients requiring surgery, there were seasonal variations for the pathogens in Taiwan. The medical community should focus on Streptococcus species in winter and spring and Staphylococcus species in summer and autumn.

A Lactobacillus Combination Ameliorates Lung Inflammation in an Elastase/LPS-induced Mouse Model of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the world's leading lung disease and lacks effective and specific clinical strategies. Probiotics are increasingly used to support the improvement of the course of inflammatory diseases. In this study, we evaluated the potential of a lactic acid bacteria (LAB) combination containing Limosilactobacillus reuteri GMNL-89 and Lacticaseibacillus paracasei GMNL-133 to decrease lung inflammation and emphysema in a COPD mouse model. This model was induced by intranasal stimulation with elastase and LPS for 4 weeks, followed by 2 weeks of oral LAB administration. The results showed that the LAB combination decreased lung emphysema and reduced inflammatory cytokines (IL-1ß, IL-6, TNF-α) in the lung tissue of COPD mice. Microbiome analysis revealed that Bifidobacterium and Akkermansia muciniphila, reduced in the gut of COPD mice, could be restored after LAB treatment. Microbial α-diversity in the lungs decreased in COPD mice but was reversed after LAB administration, which also increased the relative abundance of Candidatus arthromitus in the gut and decreased Burkholderia in the lungs. Furthermore, LAB-treated COPD mice exhibited increased levels of short-chain fatty acids, specifically acetic acid and propionic acid, in the cecum. Additionally, pulmonary emphysema and inflammation negatively correlated with C. arthromitus and Adlercreutzia levels. In conclusion, the combination of L. reuteri GMNL-89 and L. paracasei GMNL-133 demonstrates beneficial effects on pulmonary emphysema and inflammation in experimental COPD mice, correlating with changes in gut and lung microbiota, and providing a potential strategy for future adjuvant therapy.

The Prognostic Value of Positron Emission Tomography/Computed Tomography in Clinical Stage I Lung Cancer Patients: A Propensity-Match Analysis.

Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT.

Adjuvant chemotherapy in pathological node-negative non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is associated with a poor survival rate, even for patients with early-stage cancer. Identifying patients with pathological N0 NSCLC who may benefit from adjuvant chemotherapy treatment after surgery is essential. We conducted a retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database and included 26,380 patients with pathological N0 NSCLC after surgery between January 2018, and December 2019. Among 26,380 patients, 24,273 patients received surgery alone and the other 2107 patients received surgery plus adjuvant chemotherapy. After 1:1 propensity score matching, both groups contained 2107 patients. Adjuvant chemotherapy did not show significantly better 24-month survival in T2aN0 NSCLC patients (83.41% vs. 82.91%, p = 0.067), although it did for T2bN0 patients (86.36% vs. 81.70%, p = 0.028). Poorly-differentiated NSCLC remained a high-risk factor for pT2N0, and adjuvant chemotherapy provided better 24-month survival after matching (86.36% vs. 81.70%, p = 0.029). In conclusion, when treating pN0 NSCLC, adjuvant chemotherapy had a beneficial effect when the tumor size was larger than 4 cm. The effect when the tumor size was between 3 and 4 cm was not remarkable. Poorly-differentiated NSCLC was a high-risk factor in the pT2N0 stage.

Inhibition of Na+/H+ exchanger (NHE) 7 by 5-(N-ethyl-N-isopropyl)-Amiloride displays anti-cancer activity in non-small cell lung cancer by disrupting cancer stem cell activity and downregulating PD-L1 expression.

The alkaline intracellular environment of cancer cells is critical for cell proliferation and controlled by various plasma membrane transporters including Na+/H+ exchangers (NHEs). NHEs can also mediate cell behavior by regulating signaling transduction. In this study, we investigated the role of NHE7 in cancer stem cell (CSC) activity in non-small cell lung cancer (NSCLC) cells and the potential therapeutic implications of targeting NHE7 and the associated immune checkpoint molecule PD-L1. By analyzing the database from The Cancer Genome Atlas, we found a positive correlation between SLC9A7 mRNA levels (the gene encoding NHE7) and poor overall survival in lung adenocarcinoma patients. Using 5-(N-ethyl-N-isopropyl)-Amiloride (EIPA) to inhibit NHE7 activity, we observed disrupted cell cycle progression and suppressed NSCLC cell proliferation without inducing apoptosis. Furthermore, EIPA demonstrated a suppressive effect on CSC activity, evidenced by decreased tumorsphere numbers and inhibition of CSC markers such as ALDH1A2, ABCG2, CD44, and CD133. Flow cytometric analysis revealed that EIPA treatment or NHE7 knockdown in NSCLC cells led to downregulated PD-L1 expression, associated with inhibited STAT3 activity. Interestingly, EIPA's CSC-targeting activity was preferentially observed in NSCLC cells overexpressing BMI1, while increased PD-L1 expression was detected in BMI1-overexpressing NSCLC cells. Our findings suggest that targeting NHE7 with inhibitors like EIPA may have therapeutic potential in NSCLC treatment by disrupting cell cycle progression and suppressing CSC activity. The observed increase in PD-L1 expression in BMI1-overexpressing NSCLC cells upon EIPA treatment highlights the potential benefit of combining NHE7 inhibitors with anti-PD-L1 agents as a promising new therapeutic strategy for NSCLC.

An integrated analysis of dysregulated SCD1 in human cancers and functional verification of miR-181a-5p/SCD1 axis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC), one of the most lethal cancers, has become a global health issue. Stearoyl-coA desaturase 1 (SCD1) has been demonstrated to play a crucial role in human cancers. However, pan-cancer analysis has revealed little evidence to date. In the current study, we systematically inspected the expression patterns and potential clinical outcomes of SCD1 in multiple human cancers. SCD1 was dysregulated in several types of cancers, and its aberrant expression acted as a diagnostic biomarker, indicating that SCD1 may play a role in tumorigenesis. We used ESCC as an example to demonstrate that SCD1 was dramatically upregulated in tumor tissues of ESCC and was associated with clinicopathological characteristics in ESCC patients. Furthermore, Kaplan-Meier analysis showed that high SCD1 expression was correlated with poor progression-free survival (PFS) and disease-free survival (DFS) in ESCC patients. The protein-protein interaction (PPI) network and module analysis by PINA database and Gephi were performed to identify the hub targets. Meanwhile, the functional annotation analysis of these hubs was constructed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Functionally, the gain-of-function of SCD1 in ESCC cells promoted cell proliferation, migration, and invasion; in contrast, loss-of-function of SCD1 in ESCC cells had opposite effects. Bioinformatic, QPCR, Western blotting and luciferase assays indicated that SCD1 was a direct target of miR-181a-5p in ESCC cells. In addition, gain-of-function of miR-181a-5p in ESCC cells reduced the cell growth, migratory, and invasive abilities. Conversely, inhibition of miR-181a-5p expression by its inhibitor in ESCC cells had opposite biological effects. Importantly, reinforced SCD1 in miR-181a-5p mimic ESCC transfectants reversed miR-181a-5p mimic-prevented malignant phenotypes of ESCC cells. Taken together, these results indicate that SCD1 expression influences tumor progression in a variety of cancers, and the miR-181a-5p/SCD1 axis may be a potential therapeutic target for ESCC treatment.

Prediction of Surgical Outcome by Tumor Volume Doubling Time via Stereo Imaging Software in Early Non-Small Cell Lung Cancer.

BACKGROUND: Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We proposed to investigate the surgical outcomes according to VDT. METHODS: We retrospectively studied 96 cases post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating the VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days and VDT ≥ 133 days. Univariable and multivariable analyses were performed for comparative purposes. RESULTS: Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The five year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9%, and the five year DFS rates were 95.9% and 61.5%. CONCLUSION: As VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested.

Comparison of three-dimensional and two-dimensional thoracoscopic segmentectomy in lung cancer.

BACKGROUND: Thoracoscopic segmentectomy is considered to be a safe and effective procedure for early lung cancer. A three-dimensional (3D) thoracoscope can provide high resolution and accurate images. We compared the outcomes from using two-dimensional (2D) and 3D video systems in thoracoscopic segmentectomy for lung cancer. METHODS: The data of consecutive patients diagnosed with lung cancer that underwent 2D or 3D thoracoscopic segmentectomy in Changhua Christian Hospital from January 2014 to December 2020 were retrospectively analyzed. Tumor characteristics and perioperative short-term outcomes (operative time, blood loss, incision numbers, length of stay and complication) were compared between 2D and 3D thoracoscopic segmentectomy. RESULTS: Among the 192 patients, 68 patients underwent segmentectomy with a 2D thoracoscopic system and 124 patients had 3D thoracoscopic surgery. Patients undergoing 3D thoracoscopic segmentectomy had a shorter operative time (174.19 ± 64.63 min vs. 207.06 ± 72.99 min, p = 0.002), less blood loss (34.40 ± 43.58 ml vs. 50.81 ± 57.61 ml, p = 0.028), fewer incisions (1.50 ± 0.716 vs. 2.19 ± .058, p < 0.001) and a shorter length of stay (5.67 ± 3.44 days vs. 8.18 ± 11.862 days, p = 0.029). The postoperative complications were similar between the two groups. Surgical mortality was not found in any patient. CONCLUSION: Our finding suggests that the incorporation of a 3D endoscopic system could facilitate thoracoscopic segmentectomy in lung cancer patients.

The prognosis of clinical stage IIIa non-small cell lung cancer in Taiwan.

Lung cancer is the leading cause of cancer death. The treatment of stage IIIa remained the most controversial of all stages of non-small cell lung cancer (NSCLC). We reported on the heterogenicity and current treatment strategies of stage IIIa NSCLC in Taiwan. This study is a retrospective analysis using data from the Taiwan Society of Cancer Registry between January 2010 and December 2018. 4232 patients with stage IIIa NSCLC were included. Based on cell type, the best 5-year OS (40.40%) occurred among adenocarcinoma victims. The heterogenicity of T1N2 had the best 5-year OS (47.62%), followed by T4N0 (39.82%), and the others. Patients who underwent operations had better 5-year OS (over 50%) than those who did not (less than 30%). Segmentectomy (75.28%) and lobectomy (54.06%) showed better 5-year OS than other surgical methods (less than 50%). In multivariable analysis, young age, female, lower Charlson Comorbidity Index score, adenocarcinoma cell type, well differentiated, T1N2/T4N0 heterogenicity, treatment with operation, and segmentectomy/lobectomy/bilobectomy were significant factors. In conclusions, the heterogenicity of T1N2 had the best outcomes followed by T4N0. Patients received surgical treatment revealed much better outcomes than those did not. As always, multimodal therapies with individualized treatment tend to provide better survival outcomes.

Culture-Positive and Culture-Negative Empyema After Thoracoscopic Decortication: A Comparison of Short-term and Long-term Outcomes.

Background: Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods: This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results: A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P < .001), longer ventilator usage (24.70 vs 14.01 days, P = .002), and longer postoperative hospital stays (40.83 vs 28.37 days, P < .001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P = .913). The 2-year survival was not significantly different between the 2 groups (P = .236). Conclusions: Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia.

The impact of the duration of the integrated disease management program on COPD-related outcomes.

BACKGROUND: The aim of this study is to assess the impact of the duration of the integrated disease management (IDM) program on COPD-related outcomes in real-world setting. METHODS: A retrospective cohort study among 3771 patients with COPD who had regularly completed 4 visits of IDM program within 1 year between April 1, 2017 and December 31, 2018. CAT score as the primary outcome used to investigate the association between IDM intervention duration and improvement in CAT score. Change in CAT score from baseline to each follow-up visit determined by using least-squares means (LSMeans) approach. The cut-off value of IDM duration for improving the CAT score was determined by the Youden index. Logistic regression was used to analyze the relationship between IDM intervention duration and MCID (the minimal clinically important difference) improvement in CAT score and the factor associated CAT improvement. Risks of COPD exacerbation events (COPD-related ED visit and COPD-related hospitalization) were estimated by using the cumulative incidence curve and Cox proportional hazards models. RESULT: Among 3771 enrolled COPD patients, the majority of the study cohort were males (91.51%) and 42.7% of patients had CAT score of ≥ 10 at baseline. The mean of age was 71.47 years and the mean CAT at baseline were 10.49. The mean change from baseline in CAT score was - 0.87, - 1.19, - 1.23 and - 1.40 at 3-, 6-, 9- and 12 month follow-up (p < 0.0001 for all visits), respectively. Statistically significantly lower likelihood of achieving MCID improvement in CAT were observed at 3- and 6 month compared to 9 month (at 3 month: OR: 0.720, 95% CI 0.655-0.791; at 6 month: OR: 0.905, 95% CI 0.825-0.922). And only a modest increase likelihood of achieving MCID improvement in CAT at 12 month (OR: 1.097, 95% CI 1.001-1.201) compared with 9-month follow-up. In logistic regression on the entire cohort, CAT MCID improvement was most associated with baseline CAT scores ≥ 10, followed by frequent exacerbation in previous year (> 2 episodes/year), wheezing, and GOLD B or D at baseline. In baseline CAT ≥ 10 group, patients were more likely to achieve CAT MCID improvement and had greater decreases from baseline in CAT score observed at 3-, 6-, 9-, and 12 month compared with baseline CAT score < 10 group (all p < 0.0001). Moreover, in CAT ≥ 10 groups, patients who achieved CAT MCID improvement had lower risk of subsequent COPD exacerbation events (COPD-related ED visit: aHR: 1.196, 95% CI 0.985-1.453, p = 0.0713; COPD-related hospitalization: aHR: 1.529, 95% CI 1.215-1.924, p = 0.0003) when compared to those without. CONCLUSION: This is the first real-world study indicating the association between COPD IDM intervention duration and COPD-related outcomes. From 3 to 12 month follow-up results showed that continued improvement over time in COPD-specific health status, particularly in patients with baseline CAT score of ≥ 10. Furthermore, a reduction of the risk of subsequent COPD exacerbations were observed in patients with CAT MCID improvement.

The outcomes of thoracoscopic decortication between fungal empyema and bacterial empyema.

BACKGROUND: Fungal empyema is an uncommon disease and is associated with a high mortality rate. Surgical intervention is suggested in stage II and III empyema. However, there were no studies that reported the outcomes of surgery for fungal empyema. METHODS: This study is a retrospective analysis in a single institute. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. We separated the patients into a fungal empyema group and a bacterial empyema group according to culture results. We used 1:3 propensity score matching to reduce selection bias. RESULTS: There were 1197 empyema patients who received surgery. Of these, 575 patients showed positive culture results and were enrolled. Twenty-eight patients were allocated to the fungal empyema group, and the other 547 patients were placed in the bacterial empyema group. Fungal empyema showed significantly longer intensive care unit stay (16 days vs. 3 days, p = 0.002), longer median ventilator usage duration (20.5 days vs. 3 days, p = 0.002), longer hospital stay duration (40 days vs. 17.5 days, p < 0.001) and a higher 30-day mortality rate (21.4% vs. 5.9%, p < 0.001). Fungal empyema revealed significantly poorer 1-year survival rate than bacterial empyema before matching (p < 0.001) but without significant difference after matching. CONCLUSIONS: The fungal empyema patients had much worse surgical outcomes than the bacterial empyema patients. Advanced age and high Charlson Comorbidity Index score are independent predictors for poor prognosis. Prompt surgical intervention combined with the use of antifungal agents was the treatment choice for fungal empyema.

Survival Comparison Between Open and Thoracoscopic Upfront Esophagectomy in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear. OBJECTIVE: The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT). METHODS: The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors. RESULTS: After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching. CONCLUSION: This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.

miR-145-5p Targets Sp1 in Non-Small Cell Lung Cancer Cells and Links to BMI1 Induced Pemetrexed Resistance and Epithelial-Mesenchymal Transition.

Pemetrexed is a folic acid inhibitor used as a second-line chemotherapeutic agent for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancers. However, prolonged treatment with pemetrexed may cause cancer cells to develop resistance. In this study, we found increased expressions of BMI1 (B Lymphoma Mo-MLV insertion region 1 homolog) and Sp1 and a decreased expression of miR-145-5p was found in pemetrexed-resistant A400 cells than in A549 cells. Direct Sp1 targeting activity of miR-145-5p was demonstrated by a luciferase based Sp1 3'-UTR reporter. Changed expression of miR-145-5p in A400 or A549 cells by transfection of miR-145-5p mimic or inhibitor affected the sensitivity of the cells to pemetrexed. On the other hand, the overexpression of Sp1 in A549 cells caused the decreased sensitivity to pemetrexed, induced cell migratory capability, and epithelial-mesenchymal transition (EMT) related transcription factors such as Snail Family Transcriptional Repressor 1 and Zinc Finger E-Box Binding Homeobox 1. In addition, the overexpression of BMI1 in the A549 cells resulted in an increase in Sp1 and a decrease in miR-145-5p accompanied by the elevations of cell proliferation and EMT transcription factors, which could be reduced by the overexpression of miR-145-5p or by treatment with the Sp1 inhibitor of mithramycin A. In conclusion, the results of this study suggest that the downregulation of miR-145-5p by BMI1 overexpression could lead to the enhanced expression of Sp1 to induce the EMT process in pemetrexed-resistant NSCLC cells. These results suggest that increasing miR-145-5p expression by delivering RNA drugs may serve as a sensitizing agent for pemetrexed-resistant NSCLC patients.

Blood monocyte levels predict the risk of acute exacerbations of chronic obstructive pulmonary disease: a retrospective case-control study.

Monocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case-control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies.

The perioperative outcomes of uniport versus two-port and three-port video-assisted thoracoscopic surgery in lung cancer: a systematic review and meta-analysis.

BACKGROUND: Uniport video-assisted thoracoscopic surgery (VATS) has been applied widely for the treatment of lung cancer in recent years. Some studies have reported that uniport VATS might provide better outcomes than multiport VATS. However, the perioperative outcomes of uniport VATS compared with two-port and three-port VATS, respectively, have yet to be studied at a comprehensive scale. This meta-analysis study compares the perioperative efficacy among uniport, two-port, and three-port VATS. METHODS: We searched studies published before October 1, 2019, by using Web of Science databases, Ovid Medline, Embase, and PubMed. Studies that compared uniport VATS with two-port or three-port VATS for patients with lung cancer were included. Operative time, perioperative blood loss, number of lymph nodes retrieved, conversion rate, duration of postoperative chest tube drainage, length of hospital stay (LoS), visual analogue pain scores on postoperative day (POD) 1 and POD 3, and overall morbidity were evaluated. RESULTS: Sixteen studies that compared uniport VATS with two-port or three-port VATS in the treatment of lung cancer were included. Uniport VATS showed less blood loss, a shorter duration of postoperative drainage and a lower visual analogue pain score on POD 3 than two-port VATS; it showed a shorter duration of postoperative drainage, a shorter LoS, and lower visual analogue pain scores on POD 1 and POD 3 than three-port VATS. There were no significant differences in the number of lymph nodes retrieved, operative time, conversion rate, and overall morbidity rate when comparing uniport VATS with two-port VATS or three-port VATS. CONCLUSIONS: Uniport VATS might provide better perioperative outcomes than either two-port or three-port VATS in lung cancer treatment.