Objective: Both stent grafts (SG) and drug-coated balloons (DCBs) have shown to be effective treatments for long and complex femoropopliteal (FP) lesions. However, there has not been a clinical trial comparing the 2 treatments directly. This study aims to compare the primary patency (PP) and clinical outcomes of SG and DCB for endovascular treatment of complex FP Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions in patients. Methods: From July 2013 to May 2019, a retrospective study was conducted at 2 medical centers to compare the clinical outcomes of Viabahn SG and DCB angioplasty in patients with TASC C/D FP lesions. The study used overlap weighting to adjust for differences in baseline characteristics and to reduce the impact of confounding factors and selection bias between the 2 groups. The primary endpoint was PP through 24 months, and the secondary endpoints included freedom from clinical-driven target lesion revascularization (CD-TLR), all-cause of death rate, and major amputation rate. Results: A total of 161 limbs in 150 patients with TASC C/D FP lesions were treated either with Viabahn SGs (67 limbs, 65 patients) or DCBs (94 limbs, 85 patients). In the DCB group, 22 target vessels (23.4%) underwent directional atherectomy before DCB angioplasty and 37 target vessels (39.4%) underwent bail-out bare-metal stent implantation for early recoil or severe dissection. The SG group had significantly higher PP rates at both the 12 and 24 months than in the DCB group (75.8% vs 39.2%, p=0.02; 64.1% vs 31.9%, p=0.02), respectively. However, there were no significant differences between the 2 groups in terms of CD-TLR, death rate, and major amputation rate. According to the results of multivariate analysis, DCB angioplasty was the only independent predictor associated with restenosis (hazard ratio [HR]=0.264, 95% confidence interval [CI]=0.100-0.696, p=0.007). Conclusions: This study showed that SG was associated with a significantly higher PP rate in complex long FP lesions compared with DCB angioplasty. However, there was no significant difference in the freedom from CD-TLR and major amputation rate. It is important to follow the criteria for using SG strictly to avoid early restenosis, which can lead to acute thrombosis and severe limb ischemia. Closer monitoring is recommended for patients who undergo SG implantation. Clinical Impact: There has no head-to-head clinical trial that compares DCB and SG in complex long FP lesions. This study showed that SG following the criteria was associated with a significantly higher PP rate compared with DCB angioplasty. Closer monitoring is recommended for patients with SG to avoid acute thrombosis. Randomized controlled trials comparing SG and DCB are necessary.

Background: Circulating proteins play a critical role in rheumatoid arthritis (RA), yet few have been targeted therapeutically. This study aimed to identify novel protein targets for RA therapy. Methods: We conducted a comprehensive proteome-wide Mendelian Randomization (MR), colocalization analysis, and summary-data-based MR (SMR) to explore potential causal relationships between plasma proteins and RA, with an overall sample size of 1,148,608. The GWAS data on plasma proteins were obtained from the FinnGen study, the UK Biobank Pharma Proteomics Project and Iceland GWAS data. Then, validation of key molecules’ differential expression pattern was done using external transcriptomic data from RA patients, while the Drug Signatures Database (DsigDB) was used to identify potential therapeutic drugs. Drugs and target proteins interactions was evaluated with molecular docking and molecular dynamics simulations approaches. Potential side effects of plasma proteins associated with RA were elucidated by phenome-wide association study (Phe-WAS) approach. Results: Genetically predicted levels of 68 plasma proteins were associated with RA. After colocalization and SMR analysis, 6 plasma proteins (FCRL3, SUGP1, TNFAIP3, EHBP1, HAPLN4, and CILP2) have been passed all tests and identified as having potential as therapeutic targets for RA. Further Receiver operating characteristic curve (ROC) analysis indicated that three protiens (CILP2, TNFAIP3 and EHBP) have a good potential as biomarkers for RA. Differential gene analysis showed the downregulation of HAPLN4, FCRL3, EHBP1 and TNFAIP3 in RA, as well as the upregulation of CILP2 in RA. Further Phe-WAS suggested that targeting these proteins may have potential side effects. Conclusion: Our study investigated the causal relationships between plasma proteins and RA, deepening our understanding of the molecular mechanisms and facilitating the development of new therapeutic drugs.

Background: Thromboelastography (TEG) and coagulation tests can be used to detect hypercoagulability to assess thrombus formation. This study explored the association between TEG and coagulation in evaluating disease severity in elderly patients with lower extremity arteriosclerotic occlusive disease (LEASO), aimed to provide surgical treatment guideline.Methods: We retrospectively analyzed the clinical characteristics, laboratory biomarkers, TEG and coagulation parameters of 233 elderly LEASO patients treated between 2020 and 2023. Among them, 86 underwent surgical amputation, 51 received vascular intervention, and the remaining were treated conservatively. Differences in TEG and coagulation among the three groups were assessed using Spearman's correlation. Multivariate logistic regression and receiver operating characteristic curves analyzed the relationships among TEG, fibrinogen (FIB), and D‐dimer (D‐D) levels for surgical evaluation.Results: Inflammatory factors, platelet counts, and Fontaine stages III‐IV differed significantly between the surgery and conservative groups (p < 0.05). The surgery group had higher α‐angle, maximum amplitude (MA), coagulation comprehensive index (CI), FIB, and D‐D, whereas lower clotting time (K) compared to the conservative group (p < 0.05), correlated with a lower ankle brachial index (ABI), indicating more severe clinical presentation. Spearman's analysis identified positive associations between α‐angle, MA with FIB and D‐D levels in surgical patients. Area under curve analysis indicated that combining MA, α‐angle, FIB, and D‐D could enhance accuracy in evaluating surgical necessity in LEASO.Conclusion: In elderly LEASO patients, TEG and coagulation analysis revealed a positive association between thrombus intensity and disease severity. Increased MA, α‐angle, FIB, and D‐D levels serve as predictors for surgical treatment necessity in LEASO.