Diabetes mellitus and femoropopliteal in-stent restenosis.

Background: The influence of diabetes mellitus (DM) on recurrent in-stent restenosis (ISR) of femoropopliteal arteries remains understudied. We investigated whether DM has an impact on recurrent restenosis after femoropopliteal stenting in patients included in the dRug-coatEd balloon angioPlasty for femoropopliteAl In-stent Restenosis (REPAIR) cooperation. Patients and methods: The REPAIR cooperation pooled the patient-level data from 3 randomized trials in which patients with ISR of femoropopliteal arteries received either drug-coated balloon (DCB) or plain balloon angioplasty. For this analysis, patients were divided in two groups based on whether they had or had not a DM diagnosis at the time of enrollment. The primary outcome was target lesion revascularization (TLR). The main secondary outcome was recurrent ISR. Other outcomes of interest were death, Rutherford class improvement and ankle-brachial index at follow-up. Results: 256 patients (DM, n=99 vs. non-DM, n=157) with 12-month follow-up were included in the analysis. Compared to non-DM patients, DM patients displayed no difference in terms of TLR [adjusted hazard ratio (95% Confidence intervals): 0.96 (0.55, 1.69), p=0.89] and recurrent ISR [1.04 (0.61, 1.77), p=0.88], whilst mortality was higher [9.38 (1.06, 83.11), p=0.044]. There were no differences between groups with respect to other secondary outcomes. The percutaneous treatment with DCB as compared to plain balloon angioplasty significantly reduced the risk of TLR and recurrent ISR without an excess risk of death irrespective of DM (p for interaction ≥0.70). Conclusions: In patients with femoropopliteal ISR, diabetes has a neutral effect on the risk of recurrence, but increases mortality at 12-month follow-up. DCB as compared to plain balloon angioplasty is associated with superior efficacy without trade-off in safety, regardless of diabetes.

The Current Use of Drug-Eluting Balloons and Stents in Peripheral Arterial Disease: An Online Survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).

PURPOSE: To assess the current use of drug-eluting devices for peripheral arterial disease (PAD) among interventional radiologists following the controversy caused by the 2018 meta-analysis suggesting an increased mortality risk for paclitaxel-eluting devices. METHODS: An anonymous survey was sent to 7035 CIRSE members via email; only complete responses were included and statistically analysed. RESULTS: Three hundred and seven members (4.4%) completed the survey. Among these, 95.8% indicated that they personally perform peripheral vascular procedures. Thirty-eight percentage of respondents did not see any change of practice since 2018, while 47% reported that the use of drug-eluting devices decreased; for 13%, the use stopped altogether, while it increased in 3% of responses. 45.6% of respondents also felt the impact of the controversy in terms of pricing, availability or directives from hospital administration. A large majority of respondents (83.7%) who perform peripheral vascular procedures consider the use of these devices as safe, 12.9% were undecided and 3.4% did not consider them as safe. Among the respondents who do not perform endovascular procedures, 77% considered these devices as safe and 23% were undecided. CONCLUSION: Although the 2018 meta-analysis had a disruptive impact on the use of drug-eluting devices in PAD, with the increasing body of evidence available, a majority of respondents continue to believe in the safety of these devices for use in femoropopliteal disease.

Oligo(glycerol) methacrylate macromonomers.

Linear, protected ω-methoxy oligo(glycerol) methacrylate (OGly(P)MA) macromonomers are synthesized via anionic ring-opening polymerization of ethoxyethyl glycidyl ether (EEGE) followed by termination with methacrylic acid anhydride (DP(n) = 3-11, PDI < 1.30). The covalently bound methacrylate moiety allows the homopolymerization of OGly(P)MA as well as copolymerization with low molecular weight comonomers. In homopolymerizations, macromonomers are polymerized by atom transfer radical polymerization (ATRP) yielding well-defined graft polymers (M(n) = 20,000-30,000 g mol(-1)). Acidic hydrolysis of the protecting groups releases water-soluble polyhydroxy-functional structures. First results on the copolymerization with 2-hydroxyethyl methacrylate (HEMA) are given in the final part of this work.

Drug coated balloons in the superficial femoral artery.

Despite the progress in endovascular treatment of patients with peripheral arterial disease, restenosis remains the major drawback, especially in patients with femoropopliteal lesions. To reduce neointimal proliferation and subsequent restenosis the use of antiproliferative drug eluting devices was implemented in the endovascular treatment of femoropopliteal disease. Aiming to use the favorable effects of these antiproliferative agents and to reduce foreign body exposure in affected arteries, drug coated balloons (DCB) have been developed. Up to now, several randomized controlled trials have consistently demonstrated the superiority of DCB over uncoated balloon angioplasty in the treatment of femoropopliteal lesions. Similarly, DCB appear to have favorable effects on vessel patency in the treatment of femoropopliteal in-stent restenosis. However, there still is a need for further studies, especially addressing different lesion characteristics as well as the combinations of particular treatment modalities.

Drug-Coated Balloon Angioplasty for Femoropopliteal In-Stent Restenosis.

BACKGROUND: The optimal revascularization therapy for in-stent restenosis (ISR) of femoropopliteal arteries represents a matter of debate. We investigated the outcomes of patients treated with drug-coated balloon (DCB) angioplasty for ISR of femoropopliteal arteries. METHODS AND RESULTS: Patient-level data from 3 randomized trials of DCB angioplasty for ISR of femoropopliteal arteries were pooled. The primary outcome was target lesion revascularization. The main secondary outcome was recurrent ISR. Other outcomes of interest were ipsilateral amputation, death, Rutherford class improvement, and ankle-brachial index at follow-up. A total of 263 patients randomly assigned to DCB (n=133) or plain balloon angioplasty (n=130) were included in the analysis. After a follow-up of 12 months, patients treated with DCB angioplasty displayed a lower risk for target lesion revascularization (hazard ratio [95% CIs]: 0.25 [0.14-0.46]; P<0.001) and recurrent ISR (0.19 [0.10-0.35]; P<0.001) as compared with those treated with plain balloon angioplasty. There was no significant interaction between the treatment effect for target lesion revascularization and high-risk subgroups of patients such as those with diabetes mellitus, longer lesions, small vessels, moderate to severe underlying calcification, and occlusive pattern of ISR. DCB and plain balloon angioplasty were comparable with respect to other secondary outcomes. CONCLUSIONS: In case of femoropopliteal ISR, the percutaneous treatment with DCB angioplasty is associated with superior clinical and antirestenotic efficacy as compared with plain balloon angioplasty at 1-year follow-up, without attrition of efficacy in high-risk subgroups of patients. The long-term durability of DCB angioplasty in this setting remains to be further investigated.

Paclitaxel-Eluting Balloon Versus Standard Balloon Angioplasty in In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Artery: 1-Year Results of the PACUBA Trial.

OBJECTIVES: The hypothesis that paclitaxel-eluting balloon angioplasty provides higher 1-year patency rates in femoropopliteal artery in-stent restenosis compared with standard percutaneous transluminal angioplasty (PTA) was tested. BACKGROUND: Several trials have demonstrated that paclitaxel-eluting balloon angioplasty reduces late luminal loss in comparison with PTA. METHOD: In a prospective, randomized, single-blind, dual-center study, 74 patients with symptomatic peripheral artery disease due to in-stent restenosis were treated with either paclitaxel-based drug-eluting balloon (DEB) angioplasty (n = 35) or standard PTA (n = 39). Clinical outcomes and patency rates were assessed at 1, 6, and 12 months. RESULTS: The mean lesion length was 17.3 ± 11.3 cm in the DEB group and 18.4 ± 8.8 cm in the PTA group. A single major complication (bleeding) was observed once (1.4%). The mean ankle-brachial index before endovascular treatment was 0.65 ± 0.16 in both groups and 0.79 ± 0.2 versus 0.84 ± 0.3 (p = 0.70, Student t test) in the DEB versus PTA group at 12 months. The 12-month primary patency rates were 40.7% (95% confidence interval [CI]: 0.26 to 0.64) versus 13.4% (95% CI: 0.05 to 0.36) (log-rank p = 0.02) in the DEB versus PTA group. The odds ratio for PTA over DEB angioplasty for experiencing an event was estimated at 2.8 (95% CI: 1.2 to 6.6). Freedom from clinically driven target lesion revascularization was 49.0% (95% CI: 0.32 to 0.75) versus 22.1% (95% CI: 0.10 to 0.48) (log-rank p = 0.11) in the DEB versus PTA group. Clinical improvement by ≥1 Rutherford-Becker category was 68.8% versus 54.5% (p = 0.87) in the DEB versus PTA group at 12 months. CONCLUSIONS: When treating peripheral artery disease in patients with in-stent restenosis in the femoropopliteal artery, paclitaxel-eluting balloon angioplasty provides significantly higher patency rates than standard PTA. (Paclitaxel Balloon Versus Standard Balloon in In-Stent Restenoses of the Superficial Femoral Artery [PACUBA I Trial] [PACUBA 1]; NCT01247402).

Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results.

OBJECTIVES: This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). BACKGROUND: Drug-eluting BVS has shown promise in coronary arteries. METHODS: The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. RESULTS: Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 ± 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 ± 0.14 improved from pre-procedure to 0.96 ± 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. CONCLUSIONS: The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974).

Sustained benefit at 2 years for covered stents versus bare-metal stents in long SFA lesions: the VIASTAR trial.

PURPOSE: The hypothesis that covered stents are superior to bare-metal stents (BMS) in long femoropopliteal artery disease was tested. The one-year results of the VIASTAR trial revealed a patency benefit of covered stents in the treatment-per-protocol (TPP) analysis only. METHODS: A prospective, randomized, single-blind, multicenter study evaluated 141 patients with symptomatic peripheral arterial disease (PAD) after treatment with heparin-bonded covered stents (VIABAHN(®) Endoprosthesis) or BMS. Clinical outcomes and patency rates were assessed at 1, 6, 12, and 24 months. Mean lesion length was 19.0 ± 6.3 cm in the VIABAHN(®) versus 17.3 ± 6.6 cm in the BMS group. RESULTS: The 24-month primary patency rates in the VIABAHN(®) and BMS group were: intention-to-treat 63.1 (95 % CI 0.52-0.76) versus 41.2 % (95 % CI 0.29-0.57; log rank p = 0.04) and TPP 69.4 (95 % CI 0.58-0.83) versus 40.0 % (95 % CI 0.28-0.56; log rank p = 0.004). Freedom from target-lesion-revascularization (TLR) was 79.4 (95 % CI 0.70-0.90) versus 73.0 % (95 % CI 0.63-0.85) for VIABAHN(®) versus BMS (log rank p = 0.37). For the TPP group in lesions ≥20 cm, the 24-month patency rates were 65.2 (95 % CI 0.50-0.85) versus 26.7 % (95 % CI 0.12-0.59; log rank p = 0.004) for VIABAHN(®) versus BMS, and freedom from TLR was 80.0 (95 % CI 0.68-0.94) versus 61.9 % (95 % CI 0.44-0.87; log rank p = 0.13). The ankle brachial index was 0.89 ± 0.18 versus 0.91 ± 0.17 (p = 0.76) at 24-month in the VIABAHN(®) versus the BMS group, respectively. CONCLUSION: At 24-month, this trial in PAD patients with long femoropopliteal lesions demonstrated a significantly improved primary patency rate for heparin-bonded covered stents compared to BMS, however, without a significant impact on clinical outcomes and TLR rate (Reg. Nr. ISRCTN48164244).

Cementless total hip arthroplasty with a tapered, rectangular titanium stem and a threaded cup: a minimum ten-year follow-up.

BACKGROUND: We report the results of cementless total hip arthroplasty with a tapered, rectangular titanium stem that was introduced in 1979 and continues to be used today with only minor changes. The aim of the design is to achieve primary stability to resist rotational and axial forces through precision rasping and press-fit implantation of a tapered, rectangular femoral component. METHODS: Between October 1986 and November 1987, 208 total hip arthroplasties with insertion of a tapered, rectangular titanium stem and a threaded cup without cement were performed in 200 consecutive patients (average age, sixty-one years; range, twenty-two to eighty-four years). RESULTS: At the time of the latest follow-up, fifty-one patients (fifty-two hips) had died and sixteen patients had been lost to follow-up, leaving 133 patients. Twelve hips had been revised, two in patients who subsequently died, leaving 123 living patients without revision. The median follow-up time was 120.7 months. Five cups needed revision surgery because of aseptic loosening; two, because of massive polyethylene wear; one, because of posttraumatic migration; and one, because of breakage. Three femoral stems were revised: one because of malpositioning (the reoperation was done five days after implantation); one, because of infection; and the third, after multiple failed acetabular revisions. The mean Harris hip score for the patients who did not have revision was 85.4 points (range, 46 to 100 points) at the time of the latest follow-up. Four patients (3%) complained of thigh pain that was not associated with another disorder. According to the criteria of Engh et al., all femoral implants were graded as stable bone-ingrown. The probability of survival of both the femoral and the acetabular component at ten years, with any revision as the end point, was 0.92 (95% confidence interval, 0.88 to 0.97). The probability of survival of the cup was 0.93 (95% confidence interval, 0.89 to 0.97), and that of the stem was 0.99 (95% confidence interval, 0.97 to 1.00). CONCLUSIONS: The results of arthroplasty with a tapered, rectangular titanium stem combined with a conical threaded cup inserted without cement were excellent at a minimum of ten years. Our data suggest that femoral stem fixation continues to be secure, while the threaded cup is prone to aseptic loosening.

Can dual-energy CT improve the assessment of tumor margins in oral cancer?

OBJECTIVES: The aim was to investigate the image quality of dual-energy computed-tomography (DECT) compared to single-energy images at 80 kV and 140 kV in oral tumors. MATERIALS AND METHODS: Forty patients underwent a contrast-enhanced DECT scan on a definition flash-CT. Four reconstructions (80 kV, 140 kV, mixed (M), and optimum-contrast (OC)) were assessed by four blinded readers for subjective image quality (10-point scale/10=best). For objective quality assessment, linear attenuation measurements (line density profiles (LDP)) were positioned at the tumor margin, and the difference between minimum and maximum was calculated. Signal-to-noise ratios (SNR) were measured in the tongue. RESULTS: The mean image quality for all readers was 5.1±0.3, 8.4±0.3, 8.1±0.2, and 8.3±0.2 for the 140 kV, 80 kV, M, and OC, respectively (P<001 between 140 kV and all others). The mean difference between the minimum and maximum within the LDP was 139.4±59.0, 65.7±29.5, 105.1±46.5, and 118.7±59.4 for the 80 kV, 140 kV, M, and OC, respectively (P<001). The SNR for the tongue was 3.8±2.1, 3.8±2.1, 4.2±2.4, and 4.1±2.3 for the 80 kV, 140 kV, M, and OC, respectively. DISCUSSION: DECT of oral tumors offers high image quality, with subjectively rated image quality and attenuation contrast at the tumor margin similar to that of 80 kV; DECT, however, provides a significantly higher SNR compared to 80 kV.

Heparin-bonded covered stents versus bare-metal stents for complex femoropopliteal artery lesions: the randomized VIASTAR trial (Viabahn endoprosthesis with PROPATEN bioactive surface [VIA] versus bare nitinol stent in the treatment of long lesions in superficial femoral artery occlusive disease).

OBJECTIVES: The hypothesis that endovascular treatment with covered stents has equal risks but higher efficacy than bare-metal stents (BMS) in long femoropopliteal artery disease was tested. BACKGROUND: Although endovascular treatment of short superficial femoral artery lesions revealed excellent results, efficacy in long lesions remains unsatisfactory. METHODS: In a prospective, randomized, single-blind, multicenter study, 141 patients with symptomatic peripheral arterial disease were assigned to treatment with heparin-bonded, covered stents (Viabahn 72 patients) or BMS (69 patients). Clinical outcomes and patency rates were assessed at 1, 6, and 12 months. RESULTS: Mean ± SD lesion length was 19.0 ± 6.3 cm in the Viabahn group and 17.3 ± 6.6 cm in the BMS group. Major complications within 30 days were observed in 1.4%. The 12-month primary patency rates in the Viabahn and BMS groups were: intention-to-treat (ITT) 70.9% (95% confidence interval [CI]: 0.58 to 0.80) and 55.1% (95% CI: 0.41 to 0.67) (log-rank test p = 0.11); treatment per-protocol (TPP) 78.1% (95% CI: 0.65 to 0.86) and 53.5% (95% CI: 0.39 to 0.65) (hazard ratio: 2.23 [95% CI: 1.14 to 4.34) (log-rank test p = 0.009). In lesions ≥20 cm, (TransAtlantic Inter-Society Consensus class D), the 12-month patency rate was significantly longer in VIA patients in the ITT analysis (VIA 71.3% vs. BMS 36.8%; p = 0.01) and the TPP analysis (VIA 73.3% vs. BMS 33.3%; p = 0.004). Freedom from target lesion revascularization was 84.6% for Viabahn (95% CI: 0.72 to 0.91) versus 77.0% for BMS (95% CI: 0.63 to 0.85; p = 0.37). The ankle-brachial index in the Viabahn group significantly increased to 0.94 ± 0.23 compared with the BMS group (0.85 ± 0.23; p < 0.05) at 12 months. CONCLUSIONS: This randomized trial in symptomatic patients with peripheral arterial disease who underwent endovascular treatment for long femoropopliteal lesions demonstrated significant clinical and patency benefits for heparin-bonded covered stents compared with BMS in lesions ≥20 cm and for all lesions in the TPP analysis. In the ITT analysis for all lesions, which was flawed by major protocol deviations in 8.5% of the patients, the difference was not significant. (GORE VIABAHN® endoprosthesis with bioactive propaten surface versus bare nitinol stent in the treatment of TASC B, C and D lesions in superficial femoral artery occlusive disease; ISRCTN48164244).

P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: polylactide stereochemistry controls micellization, cellular uptake kinetics, intracellular localization and drug efficiency.

In order to explore the influence of polymer microstructure and stereochemistry in biological settings, the synthesis, micellization, cellular fate and the use in paclitaxel formulations of poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(L-lactide) (P(HPMA)-block-P(LLA)) and poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(DL-lactide) block copolymers (P(HPMA)-block-P(DLLA)) were studied. To this end, P(HPMA)-block-P(lactide) block copolymers and their fluorescently labeled analogues were synthesized. The polymers exhibited molecular weights M(n) around 20,000 g/mol with dispersities (D=M(w)/M(n)) below 1.3. In addition, the solution conformation of this new type of partially degradable amphiphilic block copolymers was studied with and without paclitaxel loading in PBS buffer (pH 7.2), employing fluorescence correlation spectroscopy (FCS). We observed polymeric micelles with a hydrodynamic diameter of 17.0 nm for a fluorescently labeled P(HPMA)-block-P(LLA) block copolymer (P2*) and 20.4 nm for a P(HPMA)-block-P(DLLA) block copolymer (P3*). For the corresponding loaded block copolymers aggregates with a diameter of 40.0 nm (P2*) and 41.4 nm (P3*) in formulations containing 17 wt.% paclitaxel were observed, respectively. While the block copolymer itself showed non-toxic behavior up to a concentration of 3 mg/mL in HeLa (human cervix adenocarcinoma) cells, the paclitaxel containing formulations showed IC 50 values in the range of 10-100 nM. The P(HPMA)-block-P(DLLA) polymer (P3*) enters the cells more efficiently than stereo regular polymer (P2*) via an energy-dependent uptake mechanism. Thus, differences in the IC(50) value are--most likely--attributed to significant changes in cellular uptake. Polymer tacticity and stereoregularity appear to represent a key feature determining cellular uptake and efficiency for the PLA block copolymer drug formulations. This work demonstrates the importance of the microstructure of polymers used in drug delivery systems (DDS).

Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate.

We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700 micron) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed. Cumulative survival rates were calculated. No patient died during embolization or within the first 24 hours. Severe procedure-related complications were observed in 2 patients. At the time of analysis, 38 of 46 patients were alive. The 180-, 360-, 520-, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days. TAE with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. Bland embolization with the use of microspheres can be used in patients for whom chemoembolization is not desired.