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.).

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.

Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis.

BACKGROUND: Epidemiological observations have demonstrated that ambient fine particulate matter with dp < 2.5 µm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM2.5 with lung carcinogenesis and to compare PM2.5 with smoking carcinogens. METHODS: To study whether PM2.5 can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM2.5 and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model. RESULTS: We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs. CONCLUSION: Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2.

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.

Novel method for rapid identification of micropapillary or solid components in early-stage lung adenocarcinoma.

OBJECTIVE: Sublobar resection may be insufficient for early-stage lung adenocarcinoma with micropapillary or solid components because of the associated higher incidence of locoregional recurrence. This study sought to establish a novel method for rapidly identifying their presence to facilitate decision making for sublobar resection. METHODS: Antibody arrays of adhesion and apoptosis molecules were applied for adenocarcinomas with or without micropapillary/solid components to identify differentially expressed proteins. A semi-dry dot-blot system that visualizes the presence of target proteins was used to determine the presence of micropapillary or solid components in a prospective cohort of patients with clinical stage I who underwent operation. Sensitivity and specificity were calculated by comparing semi-dry dot-blot results with pathologic examinations. RESULTS: Insulin-like growth factor-binding protein 2 and P-cadherin were found more frequently in the micropapillary or solid positive group, and these were used as the target proteins in the semi-dry dot-blot system for detection of micropapillary or solid components. A total of 68 nodules with a mean size of 2.3 ± 0.7 cm, including 13 (19.1%) with a micropapillary and 20 (29.4%) with a solid pattern, were recruited. Micropapillary or solid (+) lesions were more likely to have lymph node upstaging, greater diameter, and higher maximum standardized uptake value. The specificity and sensitivity for detecting the minor presence of micropapillary or solid component using the semi-dry dot-blot method were 94.4% (95% confidence interval, 81.3-99.3) and 65.6% (95% confidence interval, 46.8-81.4), respectively. The average test duration was 26.9 ± 2.5 minutes. CONCLUSIONS: Detecting insulin-like growth factor-binding protein 2 and P-cadherin via the semi-dry dot-blot method could identify micropapillary or solid components in early-stage lung adenocarcinoma in a short processing time.

Redo tricuspid valve operation in patients with 1st-generation mitral prostheses.

Background In patients with remarkably enlarged cardiac chambers and history of implantation of older types of mitral valve prosthesis, the considerations for reoperative tricuspid valve surgery are not limited to the risks of sternal reentry but also include the dilemma of whether to carry out prophylactic replacement of the normal functioning but outdated prosthesis or leave it in situ. Methods We reviewed our surgical strategy and postoperative 5-year follow-up findings in two patients who underwent redo tricuspid surgery 3 to 4 decades after mechanical mitral valve replacement. Both patients presented with significant symptoms of progressive right heart failure due to severe tricuspid regurgitation, despite optimal medical therapy. Results We found the beating-heart approach to be an effective and safe method for redo tricuspid surgery. Both first-generation mitral mechanical prostheses were not replaced and have remained well functional upon the patients' postoperative 5-year follow-up, respectively. Conclusion For patients with normal functioning first-generation mechanical mitral prostheses, whether to prophylactically replace the prosthesis should be based on an individualized risk-benefit analysis.

Video-assisted thoracic surgery for tiny pulmonary nodules with real-time image guidance in the hybrid theatre: the initial experience.

BACKGROUND: Localization of tiny lung nodules during video-assisted thoracic surgery (VATS) resection can be challenging. Real-time image-guided hookwire localization of the target lesions immediately followed by VATS lung resection in the hybrid operating theatre setting is an emerging approach. METHODS: We retrospectively reviewed our experience with this form of hybrid operating theatre image-guided VATS (iVATS) for lung nodules 1.5 cm or less, or soft in consistency. These patients were compared with matched cohort who received standard hookwire localization in the radiology department. RESULTS: From February 2014 to September 2017, lung nodules of indeterminate nature in 32 consecutive patients with mean size 9.1±4.6 mm underwent iVATS. All were accurately localized by hookwire and successfully resected. There was no postoperative mortality. There were 21 (66%) malignant lesions, all with adequate resection margins. Major outcomes were compared with a comparable cohort of 8 patients who received standard hookwire localization and VATS (sVATS) performed at separate departments operation suites. sVATS groups has significantly longer 'at-risk' period for pneumothorax progression and hookwire dislodgement (109.5±57.1 minutes for sVATS vs. 41.1±15.0 minutes for iVATS, P=0.011), and a higher risk of hookwire dislodgement (25% for sVATS vs. 0 for iVATS, P=0.036). CONCLUSIONS: Real-time image-guided hookwire localization in the hybrid theatre setting is an effective facilitator of VATS resection of tiny lung nodules in selected patients, and may have added advantages in terms of safety and localization accuracy over the conventional sVATS method.

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.

Endovascular Fenestration for Distal Aortic Sealing After Frozen Elephant Trunk With Thoraflex.

We describe a case of total arch replacement with frozen elephant trunk for chronic type B aortic dissecting aneurysm, which resulted in inadvertent landing of the frozen elephant trunk into the false lumen. A radiofrequency puncture system-assisted controlled endovascular fenestration of the dissection flap was performed at the upper abdominal aorta and subsequent thoracic endovascular stenting, successfully redirecting the blood flow from the false to the true lumen. Our case illustrated a possible way to seal distal reentry in chronic type B aortic dissection.

Functional Implication of Mitral Annular Disjunction in Mitral Valve Prolapse: A Quantitative Dynamic 3D Echocardiographic Study.

OBJECTIVES: This study aimed to assess the hypothesis that mitral annular disjunction (MAD) is associated with abnormal annular dynamics due to decoupling of annular-ventricular function. BACKGROUND: MAD, defined as a separation between the atrial wall-mitral valve (MV) junction and left ventricular (LV) attachment, is a structural abnormality occurring in MV prolapse (MVP). Few data exist on the 3-dimensional (3D) geometry of MAD and its functional implication. METHODS: A total of 156 subjects including 101 MVP patients (58 ± 11 years), 30 subjects with normal MV (57 ± 15 years), and 25 heart failure patients with functional mitral regurgitation (66 ± 10 years) were studied using real-time 3D transesophageal echocardiography. The spatial relation between atrial wall, MV, and LV attachment was examined for MAD. The 3D extent of MAD and annular dynamics were quantitatively assessed. The LV global longitudinal strain and basal circumferential strains were measured by speckle tracking echocardiography. RESULTS: MAD was evident in 42 MVP patients (42%), measuring 8.9 mm (6.3 to 10.7 mm), circumferentially spanning 87 ± 41°. Dynamically, normal and nondisjunctive annulus contracted and increased in a saddle shape during systole. In heart failure patients with functional mitral regurgitation, mitral annulus was dilated and relatively adynamic, probably related to poor LV function. In contrast, disjunctive annulus displayed paradoxical systolic expansion and flattening (p < 0.0001), despite preserved and comparable LV strains with normal patients. The 3D extent of MAD correlated significantly with abnormal annular dynamics and larger regurgitant orifice (p < 0.0001). In MVP patients without MAD, the LV global longitudinal strain correlated inversely with change in height (r = -0.61; p < 0.0001), whereas LV basal circumferential strain correlated with change in area (r = 0.61; p < 0.0001), but not in patients with MAD (p > 0.05). CONCLUSIONS: MAD is a common anatomic abnormality in MVP. The disjunctive annulus is decoupled functionally from the ventricle, leading to paradoxical annular dynamics with systolic expansion and flattening, and may thus require specific intervention.

Comparison of Segmentectomy and Lobectomy in Stage IA Adenocarcinomas.

INTRODUCTION: Recent studies have suggested that segmentectomy may be an acceptable alternative treatment to lobectomy for surgical management of smaller lung adenocarcinomas. The objective of this study was to compare survival after lobectomy and segmentectomy among patients with pathological stage IA adenocarcinoma categorized as stage T1b (>0 to ≤20 mm) according to the new eighth edition of the TNM system. METHODS: In total, 7989 patients were identified from the Surveillance, Epidemiology, and End Results registry. Propensity scores generated from logistic regression on preoperative characteristics were used to balance the selection bias of undergoing segmentectomy. Overall and lung cancer-specific survival rates of patients undergoing segmentectomy and lobectomy were compared in propensity score-matched groups. RESULTS: Overall, 564 patients (7.1%) underwent segmentectomy. Lobectomy led to better overall and lung cancer-specific survival than segmentectomy for the entire cohort (log-rank p < 0.01). After 1:2 propensity score matching, segmentectomy (n = 552) was no longer associated with significantly worse overall survival (5-year survival = 74.45% versus 76.67%, hazard ratio = 1.09, 95% confidence interval: 0.90-1.33) or lung cancer-specific survival (5-year survival = 83.89% versus 86.11%, hazard ratio = 1.12, 95% confidence interval: 0.86-1.46) compared with lobectomy (n = 1085) after adjustment for age, sex, lymph node quantity, and histological subtype. Similar negative findings were identified when patients were stratified according to sex, age, histological subtype, and number of evaluated lymph nodes. CONCLUSIONS: Patients who underwent segmentectomy may have survival outcomes no different than those of some patients who received lobectomy for pathological stage IA adenocarcinomas at least 10 but no larger than 20 mm in size. These results should be further confirmed through prospective randomized trials.

Preemptive Aneurysm Sac Embolization for Thoracic Endovascular Aortic Repair With Inadequate Proximal Landing Zone.

Thoracic endovascular aortic repair (TEVAR) offers a less invasive treatment for aortic arch aneurysms. Clinical challenges arise when there is inadequate proximal landing for zone 1 TEVAR, such that a median sternotomy with total aortic debranching is required before stent deployment. The chimney technique was reported as an alternative approach to stent the arch branches and avoid sternotomy, but it was still associated with considerable chance of a type IA endoleak. We report a case of aortic arch aneurysm with an inadequate proximal landing for zone 1 TEVAR that was treated with debranching of head and neck vessels followed by TEVAR and preemptive and targeted coil embolization of the arch aneurysmal sac. Postoperative computed tomography showed no significant endoleak, and the patient had an unremarkable recovery.

Penetrating thoracic injury with retained foreign body: can video-assisted thoracic surgery take up the leading role in acute management?

Video-assisted thoracic surgery (VATS) is widely adopted in acute management of patient with thoracic trauma, but its use in penetrating thoracic injuries with retained foreign bodies were rarely reported. We described three of such cases using VATS as the first line approach. Identification of injuries, control of bleeders, clot evacuation, resection of damaged lung parenchyma and safe retrieval of foreign bodies were all performed via complete VATS within short operative time. Patient were uneventfully discharged during early post-operative period. We suggest that, for haemodynamically stable patients, VATS offers a safe and minimally-invasive alternative to conventional thoracotomy for penetrating thoracic injury with retained foreign bodies.

Mycotic aortic arch aneurysm coexistent with constrictive pericarditis: is surgery a dangerous resort?

An elderly man presented with fever and evidence of Salmonella infection, and was diagnosed to have coexisting constrictive pericarditis and mycotic aneurysm of the aortic arch. Pericardiectomy was performed under cardiopulmonary bypass with good result. To avoid deep hypothermic circulatory arrest, an aorto-brachiocephalic bypass, instead of total arch replacement, was performed. This was followed by a staged carotid-carotid bypass, thoracic endovascular stent graft placement. He was subsequently treated with prolonged antibiotics, and inflammatory marker normalized afterwards. He was last seen well 2 years after the operation. Follow-up computer tomography (CT) scan at 18 months post-op showed no evidence of endoleak or fistulation. Our case demonstrated that a hybrid treatment of open pericardiectomy and aortic debranching followed by thoracic endovascular stent graft placement is feasible and associated with satisfactory mid-term outcome.

Hypoxemia associated with right-side cardiac tumor: right atrial lymphoma with patent foramen ovale.

A 66-year-old man presented with acute type I respiratory failure, and was diagnosed to have a huge mass occupying the right atrium (RA) of the heart, with no evidence of pulmonary embolism. Intra-operative transesophageal echocardiogram identified a patent foramen ovale (PFO) with right-to-left shunt apart from a huge right atrial tumor arising from the atrioventricular groove. The tumor was debulked, and the patent foramen was closed. Patient had an uneventful recovery and WAS discharged on post-operative day 7. Pathology revealed diffuse large B-cell lymphoma (DLBCL). The patient was further treated with adjuvant chemotherapy and remained well 1 year after surgery. This case illustrates the importance of meticulous echocardiographic examination to look for any intracardiac shunts in the case of hypoxemia associated with a right-sided cardiac tumor. We advocate surgery as the most important initial management to maximize survival, as it allows correction of any hemodynamic sequelae, and simultaneous attainment of definite histological diagnosis for guidance of adjuvant therapy.

Coil Embolization of Diverticulum of Kommerell: A Targeted Hybrid Endovascular Technique.

A 57-year-old man was incidentally found to have a dissected diverticulum of Kommerell originating from aberrant origin of right subclavian artery during follow-up for treated colon cancer. A right carotid-axillary bypass was followed by embolization of aberrant artery and the diverticulum by deployment of multiple detachable coils using the Penumbra Ruby System (Penumbra, Alameda, CA). Angiography after embolization showed exclusion of flow to the aberrant artery and a patent right carotid-axillary bypass. The patient recovered uneventfully and remained well for 12 weeks after the operation, without any complications. We believe this targeted endovascular approach can avoid complications related to the coverage of thoracic aorta and reduce the risk of access vessel trauma.

Tumorigenesis of smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is related to its ability to stimulate thromboxane synthase and enhance stemness of non-small cell lung cancer stem cells.

Lung cancer stem cells (LCSCs) play a critical role in lung cancer development, however, it is unknown whether thromboxane synthase (TXS) plays a role in the maintenance of LCSCs stemness. This study aimed to determine the in vivo role of TXS in lung cancer induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a smoking carcinogen. Results showed that ozagrel, a TXS blocker, suppressed NNK-induced lung tumors in mice. The expressions of CD133 and ALDH1A1 were positively associated with TXS. Similar results were observed in human NSCLC tumor samples. NNK significantly stimulated TXS and enhanced the generation of LCSCs, evident by the upregulation of CD133 and ALDH1A1 expression, and the increase in the number and size of tumor spheres. NNK also promoted the expression of LCSC-related molecules including ß-catenin and Nanog. All these NNK-mediated effects could be offset by ozagrel. In the colony formation assay, NNK increased whereas ozagrel decreased the number of colonies. Collectively, LCSCs and TXS participate in NNK-induced lung cancer. Our data suggest that TXS is a promising therapeutic target as it is a key molecular in NNK-mediated stemness of LCSCs.