1-Year Results of the ZEPHYR Registry (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery) Predictors of Restenosis

AbstractObjectivesThis study sought to assess the rate and predictors of 1-year restenosis after drug-eluting stent implantation for femoropopliteal (FP) lesions in patients with peripheral arterial disease.BackgroundZilver PTX, a paclitaxel-eluting stent for FP lesions, provides superior outcomes to angioplasty and bare-metal stents in clinical trials. However, its real-world outcomes and the associated features remain unclear.MethodsThis was a prospective multicenter study enrolling 831 FP lesions (797 limbs, 690 patients) treated by Zilver PTX implantation. The primary endpoint was 1-year restenosis. Secondary endpoints included major adverse limb event and stent thrombosis.ResultsMean lesion length was 17 ± 10 cm. One-year restenosis, major adverse limb event, and stent thrombosis rates were 37%, 22%, and 2%, respectively. The generalized linear mixed model showed that lesion length ≥16 cm assessed by angiography and distal external elastic membrane area ≤27 mm2 and minimum stent area ≤12 mm2 assessed by intravascular ultrasound were independent risk factors for restenosis. One-year restenosis rates were 15% in cases with none of these risk factors and 50% in those with ≥2 risk factors.ConclusionsThe current study demonstrated 1-year real-world outcomes after drug-eluting stent treatment for FP lesions, including challenging ones in clinical practice. Lesion length, external elastic membrane area, and minimum stent area were independent predictors for restenosis. (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery—Prospective Multicenter Registry [ZEPHYR]; UMIN000008433

TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling

The mammalian target of rapamycin (mTOR) pathway is commonly activated in human cancers. The activity of mTOR complex 1 (mTORC1) signaling is supported by the intracellular positioning of cellular compartments and vesicle trafficking, regulated by Rab GTPases. Here we showed that tuftelin 1 (TUFT1) was involved in the activation of mTORC1 through modulating the Rab GTPase-regulated process. TUFT1 promoted tumor growth and metastasis. Consistently, the expression of TUFT1 correlated with poor prognosis in lung, breast and gastric cancers. Mechanistically, TUFT1 physically interacted with RABGAP1, thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promoted mTORC1 signaling. In addition, expression of TUFT1 predicted sensitivity to perifosine, an alkylphospholipid that alters the composition of lipid rafts. Perifosine treatment altered the positioning and trafficking of cellular compartments to inhibit mTORC1. Our observations indicate that TUFT1 is a key regulator of the mTORC1 pathway and suggest that it is a promising therapeutic target or a biomarker for tumor progression.UTokyo FOCUS Articles掲載「がんの増殖・転移を促進する新規因子の同定 小胞輸送を標的とする新しいがん治療戦略への可能性」 https://www.u-tokyo.ac.jp/focus/ja/articles/z0508_00119.htmlUTokyo FOCUS Articles "Possible target for future cancer treatment : Deregulation of system to move molecules in the cell may promote tumor growth, metastasis" https://www.u-tokyo.ac.jp/focus/en/articles/z0508_00120.htm

Sodium-glucose co-transporter 2 inhibitor use in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease

Abstract Background This study aimed to reveal the prevalence of sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment and its association with restenosis risk in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease. Methods We used the database of a multicenter prospective study registering patients with symptomatic peripheral artery disease undergoing femoropopliteal drug-coated balloon treatment in Japan. The current analysis included 1058 patients with diabetes mellitus free from end-stage renal disease. The association of clinical characteristics with SGLT2 inhibitor use was investigated using the logistic regression model. The propensity score matching was adopted to compare the primary patency, i.e., freedom from restenosis, after endovascular therapy between patients treated with and without a SGLT2 inhibitor. Results The proportion of SGLT2 inhibitor treatment at revascularization was 14.8% (95% confidence interval, 12.8–17.1%). Younger age, increased body mass index, and increased hemoglobin A1c levels were independently associated with SGLT2 inhibitor use (all P < 0.05). The proportion of SGLT2 inhibitor reached 38.2% (95% confidence interval, 25.4–52.3%) in patients with the three associated factors. The propensity score-matching analysis demonstrated that primary patency was not different between patients treated with a SGLT2 inhibitor and those without it (72.0% [95% confidence interval, 64.1–80.9%] versus 67.8% [62.7–73.3%] at 2 years; P = 0.45). Conclusions SGLT2 inhibitors were not rarely used in patients with diabetes mellitus who underwent femoropopliteal endovascular therapy using a drug coated balloon for symptomatic peripheral artery disease in real-world settings. SGLT2 inhibitor treatment was not associated with an increased risk of restenosis

Clinical efficacy of endovascular therapy for patients with critical limb ischemia attributable to pure isolated infrapopliteal lesions

BackgroundPrognosis of endovascular therapy (EVT) for isolated infrapopliteal lesions has not been adequately studied. We investigated and risk-stratified long-term prognosis after EVT for critical limb ischemia (CLI) attributable to isolated infrapopliteal lesions.MethodsBetween March 2004 and October 2010, 884 patients (1057 limbs) with CLI attributable to isolated infrapopliteal lesions who underwent EVT with angioplasty alone were enrolled. Outcome measures were freedom from major adverse limb events with perioperative death (MALE+POD) and amputation-free survival. Cox proportional hazards models were used to assess independent predictors for these outcomes.ResultsFreedom from MALE+POD was 82 ± 1% and 74 ± 2% at 1 and 5 years, respectively. Risk factors associated with MALE+POD were age ≥80 years (adjusted hazard ratio [HR], 0.4; P < .001), nonambulatory status (HR, 2.0; P < .001), albumin <3.0 g/dL (HR, 1.4; P < .0001), Rutherford 6 (HR, 2.2; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 2.1; P < .001), and below-the-ankle disease (HR, 2.0; P < .001). One- and 5-year amputation-free survival was 71 ± 2% and 38 ± 3%, respectively. Risk factors associated with major amputation/mortality were nonambulatory status (adjusted HR, 2.1; P < .001), body mass index <18.5 kg/m2 (HR, 1.4; P = .02), albumin <3.0 g/dL (HR, 1.8; P < .0001), end-stage renal disease (HR, 1.4; P = .004), ejection fraction <50% (HR, 1.6; P < .001), Rutherford 6 (HR, 1.9; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 1.7; P < .0001), and below-the-ankle disease (HR, 1.8; P < .001). In patients with more than four risk factors, both end points at 1 year were below the 71% suggested efficacy objective performance goal.ConclusionsLong-term clinical outcomes were acceptable after EVT for patients with CLI due to pure isolated infrapopliteal lesion. Risk stratification by baseline characteristics is useful in estimating long-term prognosis