Effect of Asymptomatic Common Carotid Artery Dissection on the Prognosis of Patients With Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection can extend upwards to involve the common carotid artery. However, whether asymptomatic common carotid artery dissection (CCAD) requires surgical repair remains controversial. This study aimed to explore the effect of asymptomatic CCAD without surgical intervention on the prognosis of patients who underwent surgery for acute type A aortic dissection. METHODS AND RESULTS: Between January 2015 and December 2017, 485 patients with no neurological symptoms who underwent surgery for acute type A aortic dissection were enrolled in this retrospective cohort study. The patients were divided into 2 groups based on the exposure factor of CCAD. CCAD was detected in 111 patients (22.9%), and after adjusting baseline data (standardized mean difference <0.1), the 30-day mortality (17.1% versus 6.0%, P<0.001) and incidence of fatal stroke (7.7% versus 1.6%, P=0.001) were significantly higher in the group with CCAD. Univariable and multivariable Cox regression analyses found CCAD as an independent risk factor for 30-day mortality (hazard ratio [HR], 2.8 [95% CI, 1.5-5.2]; P=0.001). At a median follow-up of 6.2 years (interquartile range, 5.6-6.9 years), landmark analysis with a cutoff value of 1 month postoperatively showed a significant increase in mortality in the group with CCAD, especially in the first month (log-rank P=0.002) and no significant difference in survival after the first month postoperatively between the 2 groups (log-rank P=0.955). CONCLUSIONS: Asymptomatic CCAD increased the risk of early fatal stroke and death in patients with acute type A aortic dissection after surgery but did not affect midterm survival in patients who survived the early postoperative period.

A scoring model based on clinical factors to predict postoperative moderate to severe acute respiratory distress syndrome in Stanford type A aortic dissection.

BACKGROUND: Postoperative acute respiratory distress syndrome (ARDS) after type A aortic dissection is common and has high mortality. However, it is not clear which patients are at high risk of ARDS and an early prediction model is deficient. METHODS: From May 2015 to December 2017, 594 acute Stanford type A aortic dissection (ATAAD) patients who underwent aortic surgery in Anzhen Hospital were enrolled in our study. We compared the early survival of MS-ARDS within 24 h by Kaplan-Meier curves and log-rank tests. The data were divided into a training set and a test set at a ratio of 7:3. We established two prediction models and tested their efficiency. RESULTS: The oxygenation index decreased significantly immediately and 24 h after TAAD surgery. A total of 363 patients (61.1%) suffered from moderate and severe hypoxemia within 4 h, and 243 patients (40.9%) suffered from MS-ARDS within 24 h after surgery. Patients with MS-ARDS had higher 30-day mortality than others (log-rank test: p-value <0.001). There were 30 variables associated with MS-ARDS after surgery. The XGboost model consisted of 30 variables. The logistic regression model (LRM) consisted of 11 variables. The mean accuracy of the XGBoost model was 70.7%, and that of the LRM was 80.0%. The AUCs of XGBoost and LRM were 0.764 and 0.797, respectively. CONCLUSION: Postoperative MS-ARDS significantly increased early mortality after TAAD surgery. The LRM model has higher accuracy, and the XGBoost model has higher specificity.

Midterm outcomes of simultaneous carotid revascularization combined with coronary artery bypass grafting.

BACKGROUND: Simultaneous carotid endarterectomy (CEA) combined with coronary artery bypass grafting (CABG) has been widely used in patients with coronary heart disease complicated with severe carotid stenosis to reduce the risk of stroke and death. Carotid artery stenting (CAS) has been proven to be an alternative to CEA in recent years. We investigated the early and mid-term outcomes of simultaneous CEA or CAS combined with CABG in these patients. METHODS: From January 2011 to January 2021, 88 patients who underwent simultaneous carotid revascularization combined with CABG under the same anesthesia in Beijing Anzhen Hospital were retrospectively analyzed, and this study included 25 patients who underwent CAS-CABG and 63 patients who underwent CEA-CABG. The main outcomes included all-cause death, stroke, myocardial infarction and combined adverse events. The main outcomes of the two groups were compared at 30 days after the operation and the mid-term follow-up. Univariate and multivariate Cox proportional hazards regression analyses were performed to determine the independent risk factors affecting mid-term mortality. RESULTS: Within 30 days after the operation, there was no significant difference in combined adverse events between the two groups (P = 0.88). During the median follow-up period of 6.69 years (IQR, 5.82-7.57 years), 9 patients (14.30%) in the combined CEA-CABG group died, while 1 patient (4.00%) in the combined CAS-CABG group died. There were no significant differences in mid-term death (P = 0.20), stroke (P = 0.78), myocardial infarction (P = 0.88), or combined adverse events (P = 0.62) between the two groups. Univariate and multivariate Cox proportional hazards regression showed that NYHA grade IV (HR 5.01, 95% CI 1.16-21.64, P = 0.03) and previous myocardial infarction (HR 5.43, 95% CI 1.01-29.29, p = 0.04) were independent risk factors for mid-term mortality. We also found that combined CEA-CABG surgery may be associated with a higher risk of death (HR, 13.15; 95% CI 1.10-157.69, p = 0.04). CONCLUSIONS: Combined CAS-CABG is a safe and effective treatment for patients with coronary heart disease complicated with severe carotid stenosis. NYHA grade IV and previous MI were independent risk factors for mid-term mortality.

Silenced LINC01134 Enhances Oxaliplatin Sensitivity by Facilitating Ferroptosis Through GPX4 in Hepatocarcinoma.

Purpose: Recently, long noncoding RNA LINC01134 has been shown to reduce cell viability and apoptosis via the antioxidant stress pathway, thereby enhancing OXA resistance in hepatocellular carcinoma. However, the association of LINC01134 with ferroptosis and the underlying molecular mechanisms remain to be elucidated. Methods: Bioinformatics analysis was employed to screen lncRNAs positively correlated with GPX4 and poor clinical prognosis. And Western blot and RT-PCR analysis in HCC cells confirmed the effect of LINC01134 on GPX4 expression. In addition, LINC01134 siRNA was transfected in HCC cells to detect the changes in cell viability, ROS, lipid peroxidation, MDA levels and GSH/GSSG levels. CCK-8, colony formation and apoptosis assays were performed to determine the effect of LINC01134 on cell death. The effect of LINC01134 and OXA on Nrf2 transcriptional binding to GPX4 was analyzed using dual luciferase reporter assay and CHIP. The expression of GPX4 and Nrf2 in HCC tissues was detected by FISH and IHC. Results: LINC01134 is a novel lncRNA positively correlated with GPx4 and associated with poor clinical prognosis. Silenced LINC01134 conferred OXA sensitivity by enhancing total ROS, lipid ROS, MDA levels and decreasing GSH/GSSG ratio. Mechanistically, LINC01134 and OXA could promote Nrf2 recruitment to the GPX4 promoter region to exert transcriptional regulation of GPX4. Clinically, LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of HCC. Conclusions: We identified LINC01134/Nrf2/GPX4 as a novel and critical axis to regulate HCC growth and progression. Targeting GPX4, knocking down LINC01134 or Nrf2 could be a potential therapeutic strategy for HCC.

INK4 cyclin-dependent kinase inhibitors as potential prognostic biomarkers and therapeutic targets in hepatocellular carcinoma.

The INK4 family is an important family of cyclin-dependent kinase inhibitors (CDKIs) and consists of CDKN2A, CDKN2B, CDKN2, and CDKN2D. Abnormal expression of CDKN2A has been reported in hepatocellular carcinoma (HCC) and is associated with the prognosis of patients and infiltration of immune cells. However, there is a lack of systematic research on the roles of the other INK4 family members in the diagnosis, prognosis, and immune regulation of HCC. Using online public databases and clinical samples, we comprehensively analyzed the INK4 family in HCC. All four INK4 proteins were overexpressed in HCC and correlated with advanced cancer stage and poor prognosis. INK4 expression accurately distinguished tumor from normal tissue, particularly CDKN2A and CDKN2C. The INK4 family participated in cell-cycle regulation and the DNA damage repair pathway, which inhibited genotoxic-induced apoptosis in tumorigenesis. INK4 proteins were positively correlated with the infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) and immune checkpoints (CTLA-4, PD1, and PD-L1). CDKN2D had the highest correlation (correlation coefficient >0.3) with all the above-mentioned infiltrating immune cells and immune checkpoints, indicating that it may be useful as an immunotherapy target. The INK4 family was valuable for diagnosis and predicting the prognosis of HCC and participated in the occurrence, progression, and immune regulation of HCC, demonstrating its potential as a diagnostic and prognostic biomarker and therapeutic target in HCC.

Effect of left ventricular ejection fraction (LVEF) on mortality of total arch replacement in subacute/chronic type A aortic dissection.

Background: Preoperative reduced left ventricular ejection fraction (LVEF) is a prognostic factor for postoperative mortality following cardiovascular surgery. We investigated the relationship between the LVEF and the outcome of total arch replacement (TAR) in patients with subacute/chronic type A aortic dissection (TAAD). Methods: A total of 136 patients with subacute/chronic TAAD who received a TAR at Beijing Anzhen hospital from January 2015 to January 2018 were included in the analysis. Univariable and multivariable Cox proportional hazards regression analyses were performed to assess the relationship between the LVEF and the surgical outcome in this subset of patients. Results: The in-hospital mortality rate 4.4%, and 6.6% of patients experienced neurologic complications. During the median follow-up period of 3.97 years [interquartile range (IQR) 3.20-4.67 years], the all-cause mortality was 10.3% (14/136). The multivariable Cox proportional hazards analysis demonstrated that reduced LVEF was an independent predictor of mid-term mortality (hazards ratio =0.93, 95% CI: 0.86-0.99, P=0.03). The Kaplan-Meier survival analysis showed that patients with a LVEF <55% had a significantly worse prognosis than those with a LVEF ≥55%. Conclusions: During the mid-term follow-up period, subacute/chronic TAAD patients had a satisfactory surgical survival rate following TAR. Patients with a reduced LVEF had higher postoperative mortality following TAR. Thus, subacute/chronic TAAD patients with LVEF <55% should be carefully evaluated to determine their suitability for elective repair with TAR.

Mid-term Patency of the Great Saphenous Bypass to Aorta vs. Non-aortic Arteries in Stanford Type A Aortic Dissection Surgery With Concomitant CABG.

Background: Stanford type A aortic dissection (STAAD) is often associated with coronary artery problems requiring coronary artery bypass grafting (CABG). However, the prognosis of different proximal graft locations remains unclear. Methods: From May 2015 to April 2020, 62 patients with acute STAAD who underwent aortic surgery concomitant with CABG were enrolled in our study. Aortic bypass was defined as connecting the proximal end of the vein bridge to the artificial aorta (SVG-AO); non-aortic bypass was defined as connecting the proximal end of the vein bridge to a non-aorta vessel, including left subclavian artery, left common carotid artery, and right brachiocephalic artery (non-SVG-AO). We compared early- and mid-term results between patients in the above two groups. Early results included death and bleeding, and mid-term results graft patency, aortic-related events, and bleeding. Grafts were evaluated by post-operative coronary computed tomography angiography. According to the Fitzgibbon classification, grade A (graft stenosis <50%) is considered a patent graft. Univariate and multivariate analyses were performed to assess differences between aortic and non-aortic bypass in STAAD. Results: SVG-AO and non-SVG-AO were performed in 15 and 47 patients, respectively. There was no significant difference in death (log-rank test, p = 0.426) or bleeding (p = 0.766) between the two groups in the short term. One year of follow-up was completed in 37 patients (eight in the SVG-AO group and 29 in the non-SVG-AO group), among which 14/15 (93.3%) grafts were patent in the SVG-AO group and 32/33 (97.0%) grafts in the non-SVG-AO at 1 week, without a significant difference (p = 0.532). At 3 months, 12/13 (92.3%) grafts were patent in the SVG-AO group and 16/32 (50.0%) grafts in the non-SVG-AO, with a significant difference (p = 0.015), and 12/13 (92.3%) grafts in the SVG-AO group and 15/32 (46.9%) grafts in the non-SVG-AO group were patents, with a significant difference. Multivariate analysis showed proximal aortic bypass and dual anticoagulation to be protective factors for the 1-year patency of grafts. Conclusion: In patients requiring aortic dissection surgery with concomitant CABG, no differencess' between SVG-AO and SVG-non-AO in early outcomes were detected, but SVG-AO may have higher mid-term patency.

STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis.

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.