Construction and Validation of Two Hepatocellular Carcinoma-Progression Prognostic Scores Based on Gene Set Variation Analysis.

Background: Liver hepatocellular carcinoma (LIHC) remains a global health challenge with a low early diagnosis rate and high mortality. Therefore, finding new biomarkers for diagnosis and prognosis is still one of the current research priorities. Methods: Based on the variation of gene expression patterns in different stages, the LIHC-development genes (LDGs) were identified by differential expression analysis. Then, prognosis-related LDGs were screened out to construct the LIHC-unfavorable gene set (LUGs) and LIHC-favorable gene set (LFGs). Gene set variation analysis (GSVA) was conducted to build prognostic scoring models based on the LUGs and LFGs. ROC curve analysis and univariate and multivariate Cox regression analysis were carried out to verify the diagnostic and prognostic utility of the two GSVA scores in two independent datasets. Additionally, the key LCGs were identified by the intersection analysis of the PPI network and univariate Cox regression and further evaluated their performance in expression level and prognosis prediction. Single-sample GSEA (ssGSEA) was performed to understand the correlation between the two GSVA enrichment scores and immune activity. Result: With the development of LIHC, 83 LDGs were gradually upregulated and 247 LDGs were gradually downregulated. Combining with LIHC survival analysis, 31 LUGs and 32 LFGs were identified and used to establish the LIHC-unfavorable GSVA score (LUG score) and LIHC-favorable GSVA score (LFG score). ROC curve analysis and univariate/multivariate Cox regression analysis suggested the LUG score and LFG score could be great indicators for the early diagnosis and prognosis prediction. Four genes (ESR1, EHHADH, CYP3A4, and ACADL) were considered as the key LCGs and closely related to good prognosis. The frequency of TP53 mutation and copy number variation (CNV) were high in some LCGs. Low-LFG score patients have active metabolic activity and a more robust immune response. The high-LFG score patients characterized immune activation with the higher infiltration abundance of type I T helper cells, DC, eosinophils, and neutrophils, while the high-LUG score patients characterized immunosuppression with the higher infiltration abundance of type II T helper cells, TRegs, and iDC. The high- and low-LFG score groups differed significantly in immunotherapy response scores, immune checkpoints expression, and IC50 values of common drugs. Conclusion: Overall, the LIHC-progression characteristic genes can be great diagnostic and prognostic signatures and the two GSVA score systems may become promising indices for guiding the tumor treatment of LIHC patients.

Comparison of catheter-directed thrombolysis with and without percutaneous mechanical thrombectomy for subacute iliofemoral deep vein thrombosis.

OBJECTIVE: To evaluate and compare the treatment efficacy and safety between catheter-directed thrombolysis monotherapy and catheter-directed thrombolysis combined with percutaneous mechanical thrombectomy for patients with subacute iliofemoral deep vein thrombosis. METHODS: We conducted a retrospective analysis of a total of 74 subacute iliofemoral deep vein thrombosis patients who underwent catheter-directed thrombolysis with and without percutaneous mechanical thrombectomy. Patients treated with catheter-directed thrombolysis combined with percutaneous mechanical thrombectomy (percutaneous mechanical thrombectomy group, n = 30) or catheter-directed thrombolysis monotherapy (catheter-directed thrombolysis group, n = 44) were included. The primary endpoints were the clinical efficacy rate of thrombolysis, primary patency, and the incidence of post-thrombotic syndrome (at 12 months diagnosed according to the original Villalta score criteria. Secondary endpoints were the total urokinase dose, the thrombolysis time, the detumescence rate and complications. RESULTS: The percentage of successful thrombolysis for percutaneous mechanical thrombectomy group was higher than that for catheter-directed thrombolysis group (P = 0.045). At the 12-month follow-up, there was no difference in the primary patency (P > 0.05) or the incidence of post-thrombotic syndrome (P = 0.36). Percutaneous mechanical thrombectomy group had significant advantages in reducing urokinase doses and thrombolysis times compared with catheter-directed thrombolysis group for patients with thrombus clearance levels II and III (P < 0.05). CONCLUSION: Catheter-directed thrombolysis combined with percutaneous mechanical thrombectomy performs better in removing vein thrombi, reducing urokinase doses, and shortening thrombolysis times.

Modified one-session endovascular treatment for deep venous thrombosis with high risk of pulmonary embolism: Short-term outcomes.

OBJECTIVES: To evaluate the safety and short-term outcomes of the modified one-session endovascular treatment with inferior vena cava filter placement and retrieval in one stage for the treatment of acute lower extremity deep vein thrombosis. METHOD: Twenty-three patients with unilateral acute lower extremity deep vein thrombosis underwent modified one-session endovascular treatments, which were performed in one stage. Inferior vena cava filter placement without detachment, thrombectomy, and inferior vena cava filter retrieval were performed in one stage. Angioplasty and stent implantation were performed for patients with iliac vein stenosis. Venography was performed to identify the clearance of the thrombus. Color Doppler ultrasound and/or venography were conducted during the follow-up. RESULTS: A total of 20/23 (87%) patients with thrombus removal rate >90% successfully underwent modified one-session endovascular treatment. inferior vena cava filters were detached in 3/23 (13%) patients achieving 50%-90% thrombus removal rate. Twenty-one iliac vein stents were implanted in 21/23 (91%) patients with iliac vein stenosis. After treatment, the differences in the circumferences of the affected limb and the healthy limb both significantly decreased. No procedure-related death, symptomatic pulmonary embolism, or major bleeding occurred. During the 12-25 months of follow-up, iliac vein stents and lower extremity veins maintained patent. CONCLUSIONS: The modified one-session endovascular treatment with one-stage inferior vena cava filter placement and retrieval might be safe for the treatment of acute lower extremity deep vein thrombosis, and the early clinical outcomes are satisfactory. Placing and retrieving an inferior vena cava filter in one session could safeguard the endovascular interventions as well as reduce the filter-related complications associated with long dwelling times.

Balloon-assisted catheter-directed thrombolysis: A novel approach for acute deep vein thrombosis in the lower extremities.

BACKGROUND: Deep vein thrombosis (DVT) is a common cardiovascular emergency that may have life-threatening complications, including pulmonary embolism (PE) and post-thrombotic syndrome (PTS). Conventional anticoagulant medication does not completely dissolve the clots and does not decrease the risk of DVT complications. Invasive catheter-directed thrombolysis (CDT) is an approach that has been reported to reduce the reoccurrence of PTS during acute DVT. We compared balloon-assisted CDT with routine CDT in the treatment of acute DVT and evaluated the clinical efficacy and safety of balloon-assisted CDT. METHODS: This retrospective cohort study included 94 patients diagnosed with a first episode of DVT in the lower extremities and treated from September 2008 to February 2018. The patients underwent routine CDT (group A, n â€‹= â€‹50) or balloon-assisted CDT (group B, n â€‹= â€‹44) based on their enrollment date. We obtained the circumference difference between the limbs, the degree of clot lysis, and the lysis rate as parameters for evaluating the two approaches. The PE incidence and bleeding amount were recorded. We also compared the total urokinase dose, treatment duration, and retrieval rate of optional filters. RESULTS: Swelling was significantly alleviated in both groups, as indicated by a reduction in the limb circumference. Patients who underwent balloon-assisted CDT exhibited significantly lower thrombus scores compared with the routine group (S â€‹= â€‹1403.50, Z â€‹= â€‹-5.7702, P â€‹< â€‹0.0001). Additionally, the duration of balloon-assisted CDT was significantly shorter (6 vs. 10 days [S â€‹= â€‹1039.0, Z â€‹= â€‹-8.0358, P â€‹< â€‹0.0001]). The mean urokinase usage per patient was decreased in the balloon-assisted group (P â€‹< â€‹0.0001). Bleeding occurred in both groups, with no statistical significance. The filter retrieval rate in the balloon-assisted group was significantly higher than that in the routine CDT group (Χ 2 â€‹= â€‹4.829, P â€‹= â€‹0.028). CONCLUSIONS: Balloon-assisted CDT is an effective, cost-efficient, and safe method for the treatment of acute DVT. It exhibited advantages over routine CDT, including less lysis medication, decreased procedure duration, and higher patency rates. Inferior vena cava filtration is mandatory in balloon-assisted CDT. After thrombus removal, the risk of symptomatic PE did not increase in this approach.