The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study.

BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Recanalization of superficial femoral artery chronic total occlusion through retrograde popliteal approach recanalization of superficial femoral artery chronic total occlusion.

Purpose: This retrospective study aims to evaluate the safety, practicality, and efficacy of the independent retrograde popliteal approach for recanalization superficial femoral artery (SFA) occlusions when the bilateral common femoral artery approach is unavailable, such as after endovascular aneurysm repair or common iliac artery stenting. Methods: This treatment was considered for patients with contralateral iliac artery occlusion, severe iliac tortuosity, or those who had previously undergone endovascular aneurysm repair or common iliac stenting. Patients with SFA lesions extending into the P1-P2 segment of the popliteal artery or with calcification in the P3 segment were excluded. Angioplasty and stenting were conducted via the popliteal artery approach, with hemostasis at the puncture site achieved using an EXOSEAL vascular closure device. Patients were routinely followed up at 3, 6, and 12 months, and annually thereafter. Results: Forty-eight consecutive patients with SFA occlusion who underwent endovascular treatment via the retrograde popliteal artery approach were included in this study. Retrograde puncture of the popliteal artery was successful in all cases. Six-French sheaths were utilized in all procedures. The EXOSEAL vascular closure device was successfully applied in all 48 cases. No instances of pseudoaneurysms, arteriovenous fistulas, major bleeding, or embolic complications were observed. The technical success rate for SFA recanalization was 100 %. All patients experienced clinical improvement. The ankle-brachial index significantly increased from an initial 0.33 ± 0.11 at admission to 0.81 ± 0.19 at discharge (P < 0.001). The mean follow-up period was 25.1 ± 11.7 months. Kaplan-Meier analysis revealed primary patency rates of 82.5 % at 12 months and 71.8 % at 24 months. No patients required major amputation during the follow-up period. Conclusion: The endovascular treatment of SFA occlusions via the independent retrograde popliteal approach is a viable alternative, demonstrating a low incidence of puncture-related complications and a high success rate of recanalization.

Effectiveness of iliac vein stenting combined with endovenous laser treatment of recurrent varicose veins associated with iliac vein compression.

Background: Iliac vein compression syndrome (IVCS) is an underlying cause of varicose vein (VV) recurrence after venous surgery. However, the management of recurrent varicose veins (RVVs) combined with IVCS has rarely been reported. This study aimed to investigate the outcomes of a one-stop procedure to correct outflow obstruction and superficial reflux for patients with RVVs and IVCS. Methods: A retrospective analysis was conducted of 102 consecutive patients diagnosed with RVVs. Computed tomography venography (CTV) was performed to confirm IVCS. The cases were divided into 2 groups: the IRVVs group, including patients with RVVs and IVCS (n=48), and the RVVs group, including patients with RVVs only (n=54). The characteristics, vein reflux, and clinical, etiological, anatomical, and pathophysiological (CEAP) distribution were investigated. Then, the IRVVs group patients who underwent endovenous laser ablation (EVLA) (n=39) were divided into a further 2 groups: the EVLA + S group (n=19), who received EVLA and stenting of iliac vein, and the EVLA group (n=20), who received EVLA treatment alone. The great/small saphenous vein (GSV/SSV) trunk occlusion, VV recurrence, visual analogue scale (VAS), and venous clinical severity score (VCSS) were investigated. Results: The prevalence rate of femoral vein reflux was 81.2% in IRVVs group and 50% in RVVs group (P<0.05). In the IRVVs group, 72.9% of patients manifested as CEAP clinical class >3, which was higher than that in RVVs group (48.1%) (P<0.05). The 12-month GSV/SSV occlusion rate in the EVLA + S and EVLA groups were 94.7% and 90.0%, respectively. Totals of 9 patients in EVLA + S group and 6 patients in EVLA group had active venous ulcers, and the ulcer healing time in EVLA + S group was significantly shorter (27.22±7.12 vs. 46.67±9.83 days, P<0.05). The reductions in the VAS and VCSS values between baseline, 1 month, and 12 months in the EVLA + S group were more obvious than those in EVLA group (P<0.05). Conclusions: The one-stop combination treatment of iliac venous stenting and EVLA in patients with RVVs and IVCS is safe and effective and provides prominent symptom relief, improved quality of life, and a more satisfactory ulcer healing than EVLA alone.

Comparison of angiography and ultrasound for femoropopliteal angioplasty: decision-making and 12-month outcomes.

BACKGROUND: This study aimed to investigate whether intravascular ultrasound (IVUS) combined with angiography during percutaneous transluminal angioplasty impacts treatment strategies and the 12-month patency of the femoropopliteal artery, compared to angiography alone. METHODS: This retrospective, single-center study enrolled 137 patients who underwent a femoropopliteal endovascular intervention between February 2020 and May 2021. Among these interventions, 43 were guided by IVUS combined with angiography and the remaining 94 were guided by angiography only. Treatment strategies and 12-month patency were analyzed in both groups. Multivariable analysis was performed to clarify the predictors of restenosis within 12 months. RESULTS: Primary patency at 12 months was significantly higher in the IVUS group than in the angiography group (56.4% vs. 76.7%, P=0.047). The reference diameter on IVUS images was greater than that on angiography images. Therefore, the IVUS group presented a higher balloon-to-vessel ratio [1.0 (0.97, 1.01) vs. 1.06 (1.0.1.25)]. More adjunctive stents were required in the angiography group. However, more dissections were performed in the IVUS group, with no difference in flow-limiting dissections between groups. Target disease length (odds ratio 1.02, P=0.021) and balloon-to-vessel ratio (odds ratio 0.01, P=0.021) were independent predictors of restenosis. CONCLUSIONS: Compared with angiography guidance alone, IVUS guidance for femoropopliteal artery-related treatment can significantly increase primary patency. This finding may be explained by the selection of larger balloons in IVUS and the resulting sufficient plaque compression and elastic membrane stretch. Moreover, IVUS was shown to detect more non-flow-limiting dissections than angiography.

Impact of plaque and luminal morphology in balloon angioplasty of the femoropopliteal artery: an intravascular ultrasound analysis.

Objective: To assess the effect of plaque and luminal morphologies in balloon angioplasty of femoropopliteal lesions using intravascular ultrasound (IVUS). Methods: This retrospective, observational study analyzed 836 cross-sectional images using IVUS, from 35 femoropopliteal arteries of patients who underwent endovascular treatment between September 2020 and February 2022. Pre- and post-balloon angioplasty images were matched per 5 mm. Post-balloon angioplasty images were grouped into successful (n = 345) and unsuccessful (n = 491) groups. Plaque and luminal morphologies (such as severity of calcification, vascular remodeling, and plaque eccentricity) were extracted before the balloon angioplasty procedure to identify the predictors of unsuccessful balloon angioplasty. Additionally, 103 images with severe dissection were analyzed using IVUS and angiography. Results: In univariate analyses, the predictive factors for unsuccessful balloon angioplasty were vascular remodeling (p < .001), plaque burden (p < .001), lumen eccentricity (p < .001), and balloon/vessel ratio (p = .01). Predictive factors for severe dissections were the guidewire route (p < .001) and balloon/vessel ratio (p = .04). In multivariate analysis, the predictive factors for unsuccessful balloon angioplasty included lumen eccentricity (odds ratio [OR]: 3.99, 95% confidence interval [CI]: 1.28-12.68, p = .02) and plaque burden (OR: 1.03, 95% CI: 1.02-1.04; p < .001). For severe dissections, the independent risk factor was an eccentric guidewire route (OR: 2.10, 95% CI: 1.22-3.65, p = .01). Conclusion: High plaque burden and luminal eccentricity were risk factors for failed femoropopliteal artery balloon angioplasty. Additionally, eccentric guidewire routes predicted severe dissection.

WIfI Classification Based Analysis of Risk Factors for Outcomes in Patients with Chronic Limb Threatening Ischaemia after Endovascular Revascularisation Therapy.

OBJECTIVE: The evaluation of limb status with the Wound, Ischaemia, and foot Infection (WIfI) classification and the assessment of patient risks combined with systemic factors, are recommended in patients with chronic limb threatening ischaemia (CLTI). However, there is little evidence of the application of the WIfI classification in the Chinese population. This study aimed to verify the use of the WIfI classification in a Chinese patient population, and to further identify local and systemic independent predictors of adverse CLTI outcomes. METHODS: A total of 474 patients who underwent endovascular therapy (EVT) for CLTI in a tertiary hospital between July 2017 and September 2020 were included in this retrospective study. The outcomes included one year major adverse limb events (MALEs), one year all cause mortality, and one year amputation free survival (AFS). Cox regression was used to analyse the association between risk factors and adverse outcomes. RESULTS: In total, 104 (21.9%) all cause deaths were recorded. The rate of MALEs was 17.5%, while the AFS was 71.9%. Multivariable analysis revealed that a body mass index (BMI) < 18.5 kg/m2 (p = .002), a left ventricular ejection fraction (LVEF) < 50% (p < .001), and WIfI wound grade (p < .001) were independent risk factors for MALEs, while age ≥ 77 years (p = .031), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .040), and WIfI clinical stages (p = .021) were independent risk factors for death in patients with CLTI. Age ≥ 77 years (p = .003), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .012), LVEF < 50% (p < .001), WIfI wound grade (p = .004), and WIfI clinical stages (p = .044) were independently associated with a decreased AFS rate. CONCLUSIONS: This study has confirmed the predictive ability of the WIfI classification for Chinese patients with CLTI who underwent EVT. Wound grade was the most sensitive and important risk factor of the three components of WIfI. In addition, systemic factors should be considered to ensure a more accurate prognosis prediction and appropriate clinical decision making in patients with CLTI.

Peptide-Targeted High-Density Lipoprotein Nanoparticles for Combinatorial Treatment against Metastatic Breast Cancer.

The sonic hedgehog (SHH) signaling pathway exhibits aberrant activation in triple-negative breast cancer (TNBC), wherein it regulates several malignant phenotypes related to tumor metastasis. GANT61, an inhibitor of the SHH signaling pathway, may offer promise when administered in combination with conventional chemotherapy to treat metastatic TNBC. However, poor bioavailability and substantial off-target toxicity limit its clinical application. To address these limitations, we designed a peptide-functionalized dual-targeting delivery system encapsulating paclitaxel and GANT61 in tLyP-1 peptide-modified reconstituted high-density lipoprotein nanoparticle (tLyP-1-rHDL-PTX/GANT61 NP) for metastatic TNBC treatment. The apolipoprotein A-1 and tLyP-1 peptide modified on the surface of nanoparticles enable the delivery system to target tumor cells by binding to the overexpressed scavenger receptor B type I and neuropilin-1 receptor. Moreover, the tLyP-1 peptide also enables the deep tumor penetration of nanoparticles further facilitating paclitaxel and GANT61 delivery. Increased cellular uptake of the nanoparticles was observed in both MDA-MB-231, BT-549 tumor cells, and their 3D tumor spheroids. A series of in vitro experiments reveal that GANT61 was able to suppress key metastasis-related tumor cell activities including angiogenesis, migration, invasion, and stemness. Owing to more effective drug administration, the metastasis suppression efficiency of GANT61 was significantly enhanced by the dual-targeting tLyP-1-rHDL delivery system. Meanwhile, the codelivery of paclitaxel and GANT61 by dual-targeting tLyP-1-rHDL nanoparticles demonstrated superior efficiency of disrupting proliferation and inducing apoptosis in tumor cells compared with drug solutions. In a spontaneous metastasis breast cancer NCG mice model, the tLyP-1-rHDL-PTX/GANT61 nanoparticles exhibited highly tumor-specific distribution and result in significant inhibition of the primary tumor growth and dramatic reduction of lung metastasis without obvious side effects. The present work suggests that a combination of the SHH signaling pathway suppression and chemotherapy assisted by peptide-functionalized targeting tLyP-1-rHDL nanoparticles may provide a promising strategy for metastatic TNBC treatment.

Four-year outcomes following endovascular repair in patients with traumatic isolated popliteal artery injuries.

OBJECTIVE: The effectiveness of endovascular treatment for popliteal arterial injury has not been well-documented. This study was aimed to investigate the midterm outcomes of endovascular repair of traumatic isolated popliteal arterial injury. METHODS: Medical records of the patients who underwent endovascular repair for traumatic popliteal arterial injuries from January 2012 to February 2020 were reviewed retrospectively. Clinical data including patient demographics, Injury Severity Score, type of injury, classification of acute limb ischemia, concomitant extremity fracture, runoff vessel status, complications, time of endovascular procedure, time interval from injury to blood flow restoration, length of hospital stay, reintervention, and follow-up were collected and analyzed. RESULTS: Endovascular repair was performed in 46 patients with traumatic popliteal arterial injuries. The mean Injury Severity Score was 15.8 ± 6.2. The overall limb salvage rate was 89.1%. There were 10 penetrating and 36 blunt injuries (78.3%). The initial angiographic findings revealed occlusion in 34 patients (73.9%), pseudoaneurysm in 2 (4.4%), active extravasation in 9 (19.5%), and arteriovenous fistulas in 1 (2.2%). Technical success was achieved in all 46 patients, via antegrade access in 24 patients (52.2%) and concurrent retrograde access in 22 (47.8%). The mean time interval from popliteal artery injury to blood flow restoration was 10.6 ± 4.9 hours and mean operative time was of 54.9 ± 10.0 minutes. The mean follow-up was 36.1 ± 14.5 months. The primary patency rate was 75.3% at 12 months, 61.9% at 24 months, and 55.7% at 48 months. The secondary patency rate was 92.2% at 12 and 24 months and 85.2% at 48 months. A Cox multivariate analysis revealed that single vessel runoff was an independent risk factor for primary patency loss. CONCLUSIONS: Endovascular repair of an isolated popliteal artery injury may be a safe and effective alternative treatment in select patients, with acceptable midterm outcomes. Single vessel runoff was an independent risk factor for primary patency loss.

Midterm outcome of pharmacomechanical catheter-directed thrombolysis combined with stenting for treatment of iliac vein compression syndrome with acute iliofemoral deep venous thrombosis.

OBJECTIVE: This study assessed the effectiveness and safety of percutaneous mechanical thrombectomy and catheter-directed thrombolysis combined with stent placement in the management of iliac vein compression syndrome with acute iliofemoral deep venous thrombosis (DVT). METHODS: From December 2014 to April 2016, there were 46 patients with DVT who underwent percutaneous mechanical thrombectomy and catheter-directed thrombolysis and stenting for acute proximal DVT with computed tomography-verified iliofemoral stenosis. The Venous Registry Index was used for evaluating the degree of patency after pharmacomechanical thrombolysis; the prevalence of post-thrombotic syndrome (PTS) in the follow-up was assessed according to the Villalta scale. For up to 24 months, conditions of the patients were assessed using periodic duplex ultrasound scans. RESULTS: For all patients, the technical success rate was 100%; no major bleeding or 30-day mortality was observed. Overall, the 6-, 12-, and 24-month primary patency rates were 97.8%, 95.7%, and 91.1%, respectively. There was a significant reduction in Venous Registry Index (9.82 ± 1.74 to 1.15 ± 1.02; P < .05) after the procedure. According to the Villalta score, only one patient developed mild PTS and none developed severe PTS. Symptomatic pulmonary embolism was not observed during the hospitalization. The mean hospital stay was 6.5 ± 1.7 days. CONCLUSIONS: This technique provides a safe and effective treatment option for patients with acute proximal DVT caused by vein compression syndrome.