High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

FOXP3 promotes tumor growth and metastasis by activating Wnt/ß-catenin signaling pathway and EMT in non-small cell lung cancer.

BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. RESULTS: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/ß-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with ß-catenin and TCF4 to enhance the functions of ß-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. CONCLUSIONS: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.

Antineoplastic effects of 15(S)-hydroxyeicosatetraenoic acid and 13-S-hydroxyoctadecadienoic acid in non-small cell lung cancer.

BACKGROUND: Previous studies have shown that the levels of 15-lipoxygenase 1 (15-LOX-1) and 15-LOX-2 as well as their metabolites 13-S-hydroxyoctadecadienoic acid (13(S)-HODE) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) are significantly reduced in smokers with non-small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen-induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC. METHODS: NSCLC cells were treated with exogenous 13(S)-HODE and 15(S)-HETE, and then the ways in which they affected cell function were examined. 15-LOX-1 and 15-LOX-2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)-HODE and 15(S)-HETE before cell function was assessed. RESULTS: The application of exogenous 13(S)-HODE and 15(S)-HETE significantly enhanced the activity of peroxisome proliferator-activated receptor γ (PPARγ), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15-LOX-1 and 15-LOX-2 obviously promoted the endogenous levels of 13(S)-HODE and 15(S)-HETE, which were demonstrated to be more effective in the inhibition of NSCLC. CONCLUSIONS: This study has demonstrated that exogenous or endogenous 13(S)-HODE and 15(S)-HETE can functionally inhibit NSCLC, likely by activating PPARγ. The restoration of 15-LOX activity to increase the production of endogenous 15(S)-HETE and 13(S)-HODE may offer a novel research direction for molecular targeting treatment of smoking-related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPARγ ligands.

A randomized controlled trial of adaptive support ventilation mode to wean patients after fast-track cardiac valvular surgery.

BACKGROUND: Adaptive support ventilation can speed weaning after coronary artery surgery compared with protocolized weaning using other modes. There are no data to support this mode of weaning after cardiac valvular surgery. Furthermore, control group weaning times have been long, suggesting that the results may reflect control group protocols that delay weaning rather than a real advantage of adaptive support ventilation. METHODS: Randomized (computer-generated sequence and sealed opaque envelopes), parallel-arm, unblinded trial of adaptive support ventilation versus physician-directed weaning after adult fast-track cardiac valvular surgery. The primary outcome was duration of mechanical ventilation. Patients aged 18 to 80 yr without significant renal, liver, or lung disease or severe impairment of left ventricular function undergoing uncomplicated elective valve surgery were eligible. Care was standardized, except postoperative ventilation. In the adaptive support ventilation group, target minute ventilation and inspired oxygen concentration were adjusted according to blood gases. A spontaneous breathing trial was carried out when the total inspiratory pressure of 15 cm H2O or less with positive end-expiratory pressure of 5 cm H2O. In the control group, the duty physician made all ventilatory decisions. RESULTS: Median duration of ventilation was statistically significantly shorter (P = 0.013) in the adaptive support ventilation group (205 [141 to 295] min, n = 30) than that in controls (342 [214 to 491] min, n = 31). Manual ventilator changes and alarms were less common in the adaptive support ventilation group, and arterial blood gas estimations were more common. CONCLUSION: Adaptive support ventilation reduces ventilation time by more than 2 h in patients who have undergone fast-track cardiac valvular surgery while reducing the number of manual ventilator changes and alarms.

Quantitative analysis of mitral valve morphology in mitral valve prolapse with real-time 3-dimensional echocardiography: importance of annular saddle shape in the pathogenesis of mitral regurgitation.

BACKGROUND: Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse. METHODS AND RESULTS: Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR- group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR- groups, the MR+ group had more dilated mitral annulus (P<0.0001), a reduced annular height to commissural width ratio (AHCWR) (P<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (P<0.0001), greater leaflet billow volume (P<0.0001) and billow height (P<0.0001), longer lengths from papillary muscles to coaptation (P<0.0001), and more frequent chordal rupture (P<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%-20%, and <15%, respectively; P=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (r(2)=0.66, P<0.0001). MR severity correlated strongly with leaflet billow volume (r(2)=0.74, P<0.0001) and inversely with AHCWR (r(2)=0.44, P<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P=0.0004) was strongly associated with significant MR in mitral valve prolapse. CONCLUSION: Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.

Quantification of mitral valve morphology with three-dimensional echocardiography--can measurement lead to better management?

The mitral valve (MV) has complex 3-dimensional (3D) morphology and motion. Advance in real-time 3D echocardiography (RT3DE) has revolutionized clinical imaging of the MV by providing clinicians with realistic visualization of the valve. Thus far, RT3DE of the MV structure and dynamics has adopted an approach that depends largely on subjective and qualitative interpretation of the 3D images of the valve, rather than objective and reproducible measurement. RT3DE combined with image-processing computer techniques provides precise segmentation and reliable quantification of the complex 3D morphology and rapid motion of the MV. This new approach to imaging may provide additional quantitative descriptions that are useful in diagnostic and therapeutic decision-making. Quantitative analysis of the MV using RT3DE has increased our understanding of the pathologic mechanism of degenerative, ischemic, functional, and rheumatic MV disease. Most recently, 3D morphologic quantification has entered into clinical use to provide more accurate diagnosis of MV disease and for planning surgery and transcatheter interventions. Current limitations of this quantitative approach to MV imaging include labor-intensiveness during image segmentation and lack of a clear definition of the clinical significance of many of the morphologic parameters. This review summarizes the current development and applications of quantitative analysis of the MV morphology using RT3DE.

Cannula malposition during antegrade cerebral perfusion for aortic surgery: role of cerebral oximetry.

PURPOSE: To describe the use of cerebral oximetry to detect a lack of right cerebral perfusion resulting from a malpositioned catheter used for antegrade cerebral perfusion during deep hypothermic circulatory arrest (DHCA). The simple corrective surgical adjustment that followed averted a potentially serious complication. CLINICAL FEATURES: A 57-yr-old male with a type-A aortic dissection undergoing DHCA required antegrade cerebral perfusion for cerebral protection. Catheters were placed accordingly in the left common carotid and brachiocephalic arteries. Whereas frontal cerebral oximetry immediately improved on the left, it did not improve on the right. It was immediately suspected that the tip of the brachiocephalic cannula had advanced into the right subclavian artery, thus depriving the right common carotid artery of blood flow. The problem resolved upon slight withdrawal of the cannula. CONCLUSION: Vigilance in anesthesia should not stop during DHCA or cardiopulmonary bypass. Cerebral oximetry may provide important information leading to actions that improve brain protection. Vigilances proved important in this case where the cannula tip used for antegrade cerebral perfusion was advanced too far into the right subclavian artery.

Calcium-activated potassium channels in vasculature in response to ischemia-reperfusion.

Based on the genetic relationship, single-channel conductance, and gating mechanisms, calcium-activated potassium (KCa) channels identified in vasculature can be divided into 3 groups including large-conductance KCa, small, and intermediate conductance KCa. KCa channels in smooth muscle and endothelial cells are essential for the regulation of vascular tone. Vascular dysfunction under ischemia-reperfusion (I-R) or hypoxia-reoxygenation (H-R) conditions is associated with modulations of KCa channels that are attributable to multiple mechanisms. Most studies in this regard relied on the change of relaxation components sensitive to certain channel blockers to indicate the alteration of KCa channels under I-R conditions, which however provided conflicting results for the effect of I-R. The possible mechanisms involved in KCa channel modulation under I-R/H-R include overproduction of reactive oxygen species such as superoxide anion, hydrogen peroxide, and peroxynitrite, increase of intracellular H ion, and lactate accumulation, etc. However, more studies are necessary to further understand the discrepancies in the sensitivity of KCa channels to I-R injury in different vascular beds.

Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB.

Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

Spontaneous haemopneumothorax: current management.

Spontaneous haemopneumothorax (SHP) can be life threatening and is an important cause for unexplained signs of significant hypovolaemia. There is still some debate relating to patient selection and timing of surgery, particularly in those who become stable following chest tube insertion without further blood loss. Review of the literature over the past decade in the management of SHP are presented and discussed. Surgery should be considered early in the management of SHP to reduce morbidity associated with continued haemorrhage and inadequate drainage. Lower postoperative complications and shorter hospital stay following video assisted thoracic surgery compared with thoracotomy have led to its increased acceptance as an alternative approach for SHP patients who are haemodynamically stable.

PPARgamma activation extinguishes smoking carcinogen by inhibiting NNK-mediated proliferation.

Among the carcinogenic chemicals of cigarette smoking, 4-(methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is the most potent. The activation of peroxisome proliferator-activated receptor (PPAR)gamma can arrest the growth of lung cancer. We hypothesized that PPARgamma activation inhibits NNK-mediated proliferation of lung cancer cells. PPARgamma expression was increased in 94.7% human lung cancer tumor tissues, compared with their paired corresponding nontumor tissues. PPARgamma was also found to be abundant in all the lung cancer cell lines tested. Troglitazone dose-dependently inhibited the NNK-mediated proliferation of lung cancer cells that expressed PPARgamma. Troglitazone blocked NNK-induced up-regulation of HO-1, Bcl-2, and c-IAP2, and recovered Bad activity that was suppressed by NNK. NNK promoted the nuclear p21, whereas troglitazone increased cytosolic p21. Troglitazone increased PPARgamma transcriptional activity in NNK-treated cells and a PPARgamma dominant-negative inhibitor completely suppressed the action of troglitazone, indicating that troglitazone against NNK was PPARgamma-dependent. The findings reveal a novel molecular pathway of PPARgamma activation against cigarette smoking-related lung cancer.

Roles of peroxisome proliferator-activated receptor-alpha and -gamma in the development of non-small cell lung cancer.

Peroxisome proliferator-activated receptor (PPAR)-α and PPARγ participate in cell proliferation and apoptosis. Few studies have simultaneously investigated both PPARα and PPARγ in lung cancers in vivo. The roles of PPARα and -γ were investigated in the development of pulmonary tumors induced in the adult A/J mouse by treatment with 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK). Compared with the normal lung tissues, PPARγ expression was much higher in the NNK-induced lung tumor tissues. However, PPARγ transcriptional activity, and the levels of two major endogenous PPARγ ligands, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, were significantly lower in the NNK-treated lung tissues. The ligand changes in mice were confirmed in human lung cancer tissues. Along with the alteration of PPARγ and its endogenous ligands, the level of PPARα and its activity were increased in the NNK-induced mouse lung tumors. Treatment of mice with the synthetic PPARγ ligand, pioglitazone, significantly inhibited the formation of mouse lung tumors induced by NNK. Our study demonstrated that the reduction of endogenous PPARγ ligands and increased PPARα occurred before the formation of lung tumors, indicating that the molecular changes play a role in lung carcinogenesis. The results suggest that the enhancement of PPARγ activity with its ligands, and the suppression of PPARα with its inhibitors, may prevent the formation of lung tumors, as well as accelerate the therapy of lung cancer. Our findings may also reveal the possibility of using the level of endogenous PPARγ ligands and the activities of PPARγ or PPARα as tumor markers for lung cancer.

15-Lipoxygenases and its metabolites 15(S)-HETE and 13(S)-HODE in the development of non-small cell lung cancer.

BACKGROUND: 15-S-Hydroxyeicosatetraenoic acid (15(S)-HETE) and 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), both of which are metabolites of 15-lipoxygenases (15-LOXs), are endogenous ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). The activation of PPARgamma inhibits cell growth and induces apoptosis in some cancers. The role of 15(S)-HETE) and 13(S)-HODE in the development of lung cancer is not clear. METHODS: 15-LOXs, 15(S)-HETE and 13(S)-HODE were monitored during the development of mouse lung tumours induced by the tobacco smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the levels of these markers were determined in 54 human non-small cell lung cancers. RESULTS: 15-LOXs, 15(S)-HETE and 13(S)-HODE levels were significantly reduced in human lung cancer tissue compared with non-tumour lung tissue (p=0.011 and p=0.022, respectively). In mouse experiments, 15(S)-HETE and 13(S)-HODE started to reduce at 26 and 30 weeks, respectively, after NNK treatment. The time frame of 15(S)-HETE reduction was in line with the decrease in 12/15-LOX mRNA and protein. A significant difference in the number of tumours in NNK-treated mice and controls was not observed until week 34 (p<0.05) and week 38 (p<0.01). The reduction in 12/15-LOX and 15(S)-HETE therefore predated the appearance of lung tumour. Furthermore, PPARgamma activity was decreased in NNK-treated mouse lungs compared with the control, and the decreased PPARgamma activity occurred at the same time points as the reduction in 12/15-LOX and 15(S)-HETE. CONCLUSION: These findings indicate that the reduction in 15-LOX, 15(S)-HETE and 13(S)-HODE results in the decreased PPARgamma activity seen in lung tumours and contributes to the development of lung tumours induced by tobacco smoking.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27.

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB(2)) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB(2) but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Recent advances in video-assisted thoracoscopic approach to posterior mediastinal tumours.

Minimal invasive video-assisted thoracic surgery can be a safe alternative technique in the assessment, diagnosis and surgical resection of posterior mediastinal tumours. Video-assisted thoracic surgery may be particularly suited for the management of posterior mediastinal tumours as most are benign. Surgical technique continues to evolve from the classic 3-port access in order to tackle more complex tumours positioned at the apical and inferior recesses of the posterior mediastinum. The preoperative identification of dumbbell tumours is important to facilitate arrangements for a single-stage combined resection for both the intra-thoracic and intraspinal tumour. Results from Video-assisted thoracic surgery posterior mediastinal tumour resection are comparable with conventional surgical techniques in terms of symptomatic improvement, recurrence and survival. Video-assisted thoracic surgery approach has been shown to result in less post-operative pain, improved cosmesis, shorter hospital stay, and more rapid recovery and return to normal activities. In over a decade, video-assisted thoracic surgery has gradually matured and is now a promising therapeutic alternative to open approach. In certain selected patients, video-assisted thoracic surgery may be considered the standard of care for conditions of the posterior mediastinum. Recent developments in robotic surgery for the management of mediastinal tumours are promising, however, long-term results are pending.

Management of acute type A intramural hematoma: upfront surgery or individualized approach? A retrospective analysis and meta-analysis.

BACKGROUND: Management of acute type A intramural hematoma (IMH) is a controversial topic. In our study, we aim to analyze the survival outcomes in local patients with acute type A IMH and a meta-analysis on survival in type A IMH treated medically versus surgically was performed. METHODS: From 2014 to 2019, 65 patients with acute type A IMH were selected for analysis. Primary outcome of interest was 1 year all cause survival. The rate of aortic-related events in the medical group was evaluated. PubMed and Embase were searched for meta-analysis. RESULTS: The mean age of our cohort was 61.7±9.7 years. Of the 65 patients, 40% had emergency operation. Overall 1-year survival was 96.9%. The 1-year survival was 94.9% for the medical group. 46.2% of the medical group required aortic intervention at a mean duration of 191±168 days. Maximal aortic diameter (MAD) ≥45 mm was predictive of aortic-related events in the medical group (OR: 7.0; 95% CI, 1.7-29.4; P=0.008). For the meta-analysis, 21 studies were identified, and 900 patients were included. Emergent surgery was associated with improved survival in type A IMH (OR: 0.76; 95% CI, 0.29-1.97, P=0.58; I2=27%). CONCLUSIONS: The 1-year survival after type A IMH was promising, regardless of approach. The conservative-first approach was found to be safe & feasible, and upfront surgery remained the management of choice in general. Patients with MAD ≥45 mm was associated with subsequent aortic intervention in the medical-first group.

10-year outcomes post coronary artery bypass grafting in Asian patients with ischemic cardiomyopathy: a comprehensive analysis of survival and cardiac performance.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard of care for patients with ischemic cardiomyopathy (ICM). Despite recent evidence supporting the role of CABG, long term outcomes for patients with ICM remain poor and 10-year results post CABG in ICM patients are under-reported, especially among Asians. Uncertainty on whether CABG improves cardiac performance and survival in the long term remains. In this study, we aim to analyze 10-year results concerning cardiac performance and survival post CABG in Asian patients with left ventricular ejection fraction (LVEF) ≤35% and predominant heart failure symptoms, and identify perioperative risk factors affecting long term survival and cardiac function. METHODS: Thirty-six patients with LVEF <35% who had CABG performed between the year 2006-2009 were selected from local hospital records for retrospective analysis. Outcomes of interest included post-operative cardiac symptoms, LVEF & 10-year all-cause and cardiac-event free survival. Survival analysis was performed using Kaplan Meier analysis, and predictive factors were identified with log- rank test and logistic regression analysis. RESULTS: The mean age of the cohort was 62.9±9.9 years. Operative mortality within 30 days was 5.6%. The 10-year all-cause mortality rate was 55.6%. The mean duration of survival was 105.9±8.3 months. Of the patients who did not survive till 10 years, 65.0% died of cardiac-related causes, with non-ST elevation myocardial infarction being the commonest cause. CABG improved LVEF (24.9% to 32.2%; P<0.001) and 66.7% of patients remained with impaired LVEF ≤35% post CABG. Post op NYHA class 3-4 symptoms (OR: 6.3; P=0.012) was the only predictive factor for 10 year all-cause mortality and post op LVEF improvement ≥5% (OR: 5.8; 95% CI, 1.1-29.9; P=0.036) was associated with improvement in NYHA class. Completeness of revascularization and viability of myocardium were not predictive of survival or changes in LVEF or NYHA class. CONCLUSIONS: The 10-year survival rates of Asian patients with ICM were similarly disappointing as its counterparts in the west. A majority of patients still suffered from cardiac-event related deaths. Post CABG NYHA class was found to be important in determining success and adequacy of treatment in patients with ICM and improvement in LVEF ≥5% was predictive of improvement of symptoms. Neither completeness of revascularization or presence of myocardial viability had any impact on survival in our patient cohort.

EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancer.

BACKGROUND: Early data showed that FOXP3 could induce epithelial-mesenchymal transition by stimulating the Wnt/ß-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, how the expression of FOXP3 is regulated in NSCLC remains unknown. We thus explored the impacts of the long noncoding RNA EGFR antisense RNA 1 (EGFR-AS1) and hypoxia-inducible factor-2A (HIF2A) on FOXP3 expression and the cancer stemness of NSCLC. METHODS: Lung tissues samples from 87 patients with NSCLC and two NSCLC cell lines were used in this study. The regulation of FOXP3 and lung cancer cell stemness by EGFR-AS1 and HIF2A was determined at molecular levels in NSCLC tissue samples and cultured cells in the presence/absence of the smoking carcinogen, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (also known as nicotine-derived nitrosamine ketone). The results were confirmed in tumor xenograft models. RESULTS: We found that NNK decreased the expression of EGFR-AS1 in the long term, but increased the expression of HIF2A and FOXP3 to stimulate lung cancer cell stemness. EGFR-AS1 significantly inhibited FOXP3 expression and NSCLC cell stemness, whereas HIF2A obviously promoted both. The enhancement of lung cancer stemness by FOXP3 was, at least partially, via stimulating Notch1, as the inhibition of Notch1 could markedly diminish the effect of FOXP3. CONCLUSIONS: FOXP3, the expression of which is under the fine control of EGFR-AS1, is a critical molecule that promotes NSCLC cancer cell stemness through stimulating the Notch1 pathway.