Biosensitive and antibacterial coatings on metallic material for medical applications.

Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.

Carcinogenic hazard assessment of cobalt-containing alloys in medical devices: Review of in vivo studies.

Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.

Cost-effectiveness of lung volume reduction coil treatment in patients with severe emphysema: results from the 2-year follow-up crossover REVOLENS study (REVOLENS-2 study).

BACKGROUND: The REVOLENS study compared lung volume reduction coil treatment to usual care in patients with severe emphysema at 1 year, resulting in improved quality-adjusted life-year (QALY) and higher costs. Durability of the coil treatment benefit and its cost-effectiveness at 2 years are now assessed. METHODS: After one year, the REVOLENS trial's usual care group patients received coil treatment (second-line coil treatment group). Costs and QALYs were assessed in both arms at 2 years and an incremental cost-effectiveness ratio in cost per QALY gained was calculated. The uncertainty of the results was estimated by probabilistic bootstrapping. RESULTS: The average cost of coil treatment in both groups was estimated at €24,356. The average total cost at 2 years was €9655 higher in the first-line coil treatment group (p = 0.07) and the difference in QALY between the two groups was 0.127 (p = 0.12) in favor of first-line coil treatment group. The 2-year incremental cost-effectiveness ratio (ICER) was €75,978 / QALY. The scatter plot of the probabilistic bootstrapping had 92% of the replications in the top right-hand quadrant. CONCLUSION: First-line coil treatment was more expensive but also more effective than second-line coil treatment at 2 years, with a 2-year ICER of €75,978 / QALY. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01822795 .

3-Year follow-up of temporary implantable nitinol device implantation for the treatment of benign prostatic obstruction.

OBJECTIVES: To report 3-year follow-up results of the first implantations with a temporary implantable nitinol device (TIND® ; Medi-Tate Ltd., Or Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 32 patients with LUTS were enrolled in this prospective study. The study was approved by the local Ethics Committee. Inclusion criteria were: age >50 years, International Prostate Symptom Score (IPSS) ≥10, peak urinary flow (Qmax ) <12 mL/s, and prostate volume <60 mL. The TIND was implanted within the bladder neck and the prostatic urethra under light sedation, and removed 5 days later in an outpatient setting. Demographics, perioperative results, complications (according to Clavien-Dindo classification), functional results, and quality of life (QoL) were evaluated. Follow-up assessments were made at 3 and 6 weeks, and 3, 6, 12, 24 and 36 months after the implantation. The Student's t-test, one-way analysis of variance and Kruskal-Wallis tests were used for statistical analyses. RESULTS: At baseline, the mean (standard deviation, sd) patient age was 69.4 (8.2) years, prostate volume was 29.5 (7.4) mL, and Qmax was 7.6 (2.2) mL/s. The median (interquartile range, IQR) IPSS was 19 (14-23) and the QoL score was 3 (3-4). All the implantations were successful, with a mean total operative time of 5.8 min. No intraoperative complications were recorded. The change from baseline in IPSS, QoL score and Qmax was significant at every follow-up time point. After 36 months of follow-up, a 41% rise in Qmax was achieved (mean 10.1 mL/s), the median (IQR) IPSS was 12 (6-24) and the IPSS QoL was 2 (1-4). Four early complications (12.5%) were recorded, including one case of urinary retention (3.1%), one case of transient incontinence due to device displacement (3.1%), and two cases of infection (6.2%). No further complications were recorded during the 36-month follow-up. CONCLUSIONS: The extended follow-up period corroborated our previous findings and suggests that TIND implantation is safe, effective and well-tolerated, for at least 36 months after treatment.

NaK alloy-induced in vivo tumor ablation therapy.

PURPOSE: Alkali metal ablation is newly emerging as an effective, economic and minimally invasive ablation therapy. This study is dedicated to demonstrate the high efficiency of NaK alloy ablation on in vivo tumors with different stages in mice. MATERIAL AND METHODS: Panc02 tumor cells were injected into 21 female C57B/L mice, which were divided into three groups. Two experimental groups of mice received the same percutaneous NaK alloy injection for a week apart. The inner temperature response and surface temperature distribution were measured using a thermal couple and an infrared camera. After each ablation experiment, two mice in each group were chosen randomly to make pathological sections. The tumor volumes were measured once every two days. At the end, all tumors were cut off to calculate the tumor inhibition rates. RESULTS: The NaK alloy-induced ablation therapy produced an obvious temperature increase (85 °C) in the ablation region and the high temperature distribution was relatively concentrated. The histopathology sections showed that developing stage tumors received incomplete destruction of the malignant cells compared with early stage tumors. The tumor inhibition rate in the early and developing tumor treatment groups were 88.5% and 67.6%, respectively. CONCLUSIONS: This technology provides a nearly thorough ablation treatment for early stage tumors and also a palliative treatment for developing tumors.

Vascular response after Zilver PTX stent implantation for superficial femoral artery lesions: serial optical coherence tomography findings at 6 and 12 months.

PURPOSE: To compare the vascular response after paclitaxel-coated nitinol drug-eluting stent (Zilver PTX) implantation for superficial femoral artery lesions after 6 and 12 months using optical coherence tomography (OCT). METHODS: Serial OCT examinations were performed in 5 patients (4 men; mean age 78.4 ± 6.8 years) with 9 Zilver PTX stents at 6- and 12-month follow-up. Variables evaluated included neointimal thickness and apposition on each strut, the incidence of extrastent lumen (ESL), peristrut low-intensity area (PLIA), and neovascularization at 1-mm intervals. RESULTS: A total of 249 matched cross-section images were evaluated and included 4788 and 4826 struts at 6 and 12 months, respectively. Mean neointimal thickness significantly increased from 480 to 540 µm between 6 and 12 months (p < 0.001). The percentage of uncovered struts tended to decrease at 12 months (3% vs. 2.3%, p = 0.054), whereas the percentage of malapposed struts were similar at both examinations (0.2% vs. 0.2%, p > 0.99). Although the incidence of ESL in cross sections was not different (35% vs. 31%, p = 0.29), median ESL area significantly increased from 6 to 12 months [0.12 (0.04-0.36) vs. 0.31 (0.14-0.59) mm(2), p = 0.003)]. The presence of PLIA (29% vs. 44%, p < 0.001) and neovascularization (14% vs. 27%, p < 0.001) increased from 6 to 12 months. CONCLUSION: These findings suggest that delayed vascular healing and persistent peristent inflammation may be present even at 12 months after Zilver PTX implantation.

The new nitinol conformable self-expandable metal stents for malignant colonic obstruction: a pilot experience as bridge to surgery treatment.

INTRODUCTION: Self-expandable metal stents (SEMS) are a nonsurgical option for treatment of malignant colorectal obstruction also as a bridge to surgery approach. The new nitinol conformable stent has improved clinical outcomes in these kinds of patients. We report a pilot experience with nitinol conformable SEMS placement as bridge to surgery treatment in patients with colorectal obstruction. MATERIALS AND METHODS: Between April and August 2012, we collected data on colonic nitinol conformable SEMS placement in a cohort of consecutive symptomatic patients, with malignant colorectal obstruction, who were treated as a bridge to surgery. Technical success, clinical success, and adverse events were recorded. RESULTS: Ten patients (7 male (70%)), with a mean age of 69.2±10.1, were evaluated. The mean length of the stenosis was 3.6±0.6 cm. Five patients (50%) were treated on an emergency basis. The median time from stent placement to surgery was 16 days (interquartile range 7-21). Technical and clinical success was achieved in all patients with a significant early improvement of symptoms. No adverse events due to the SEMS placement were observed. CONCLUSION: This pilot study confirmed the important role of nitinol conformable SEMS as a bridge to surgery option in the treatment of symptomatic malignant colorectal obstruction.

A randomized controlled trial to assess the efficacy and cost-effectiveness of urinary catheters with silver alloy coating in spinal cord injured patients: trial protocol.

BACKGROUND: Patients with non-acute spinal cord injury that carry indwelling urinary catheters have an increased risk of urinary tract infection (UTIs). Antiseptic Silver Alloy-Coated Silicone Urinary Catheters seems to be a promising intervention to reduce UTIs; however, actual evidence cannot be extrapolated to spinal cord injured patients. The aim of this trial is to make a comparison between the use of antiseptic silver alloy-coated silicone urinary catheters and the use of standard urinary catheters in spinal cord injured patients to prevent UTIs. METHODS/DESIGN: The study will consist in an open, randomized, multicentre, and parallel clinical trial with blinded assessment. The study will include 742 spinal cord injured patients who require at least seven days of urethral catheterization as a method of bladder voiding. Participants will be online centrally randomized and allocated to one of the two study arms (silver alloy-coated or standard catheters). Catheters will be used for a maximum period of 30 days or removed earlier if the clinician considers it necessary. The main outcome will be the incidence of UTIs by the time of catheter removal or at day 30 after catheterization, the event that occurs first. Intention-to-treat analysis will be performed, as well as a primary analysis of all patients. DISCUSSION: The aim of this study is to assess whether silver alloy-coated silicone urinary catheters improve ITUs in spinal cord injured patients. ESCALE is intended to be the first study to evaluate the efficacy of the silver alloy-coated catheters in spinal cord injured patients. TRIAL REGISTRATION: NCT01803919.

Biological interactions and toxicity of nanomaterials in the respiratory tract and various approaches of aerosol generation for toxicity testing.

After deposition in the respiratory tract, nanoparticles exhibit acute, neutrophil-driven inflammatory and oxidative reactions, fibrotic responses and in chronic studies under overload conditions carcinogenic effects, more severely than the microscaled materials of the same chemistry. Besides these effects also known to be induced by microsized particles, nanoparticles principally can translocate from the site of exposure to circulation and become systemically available. This may either increase the toxic outcome (e.g. cardio-vascular effects and potential responses in remote organs) or facilitate an elimination of nanomaterials. For example, in combination with partial dissolution, a strong lung response after a short-term inhalative exposure may be followed by a rapid recovery effect. Mechanistically, in vitro and in vivo tests demonstrated that nanoparticles induce inflammation and oxidative stress after interaction with macrophages and lung epithelial cells; consequently, a cytotoxic and genotoxic potential may exist. The deposition, retention and clearance behaviour of inhaled nanomaterials and the toxic effects observed are decisively dependent on the particle agglomeration status of the aerosol. Two principally different experimental approaches are used for inhalative exposure to nanoparticles: either (1) a basic research-oriented approach using very small aerosol mass concentrations or particle formulations that result in at least partially nanoscaled aerosols; in this way, the potential hazard and the translocation potential for individual nanoparticles can be followed effectively; or (2) exposure scenarios mimicking the occupational situation (risk-oriented) with mostly agglomerated nanoparticles; consequently, the probable risk deriving from incidental/accidental exposure can be assessed more adequately.

Double Mesh Nitinol Stent Versus Self-expanding Stent-graft in Recurrent/Resistant Cephalic Vein Arch Stenoses in Dialysis Fistulae: A Comparative Study.

PURPOSE: To compare the double mesh nitinol stent (DNS) versus the self-expanding stent-graft (SES) in recurrent/resistant cephalic vein arch stenosis in dialysis fistulae. MATERIALS AND METHODS: 17 cases with recurrent/resistant stenosis of the cephalic vein arch treated with a DNS were compared retrospectively with 18 cases treated with an SES. Stenting was performed either for significant recoil post-angioplasty with high-pressure balloons or in recurrent stenoses. Patients were followed up with Doppler ultrasound in our vascular access surveillance programme. Primary and assisted primary patency rates at 3, 6 and 12 months were estimated by Kaplan-Meier analysis. RESULTS: Both stents showed 100% technical success immediately post-stenting, defined as residual stenosis < 30%. 3, 6 and 12 month primary patency of the DNS was 82.4%, 69.7% and 28.1% versus 88.9%, 77.8% and 72.2% for the SES. The DNS had a mean primary patency of 242.4 days compared to 896.3 days for the SES (p = 0.021). 12 month assisted primary patency was 88.2% (DNS) and 100% (SES). The DNS had a mean assisted primary patency of 812 days compared to 1390.3 days for the SES, though this did not reach statistical significance. No stent fractures were identified at 2 years in either group. CONCLUSION: Both stents had 100% technical success with no stent fractures. SES showed statistically significant higher primary patency. Assisted primary patency was also higher, though this did not reach statistical significance.

Colloidal Porous AuAg Alloyed Nanoparticles for Enhanced Photoacoustic Imaging.

Colloidal porous AuAg alloyed nanoparticles (pAuAgNPs) were synthesized by galvanic replacement reaction from Ag nanocubes. pAuAgNPs have a 50 nm exterior diameter and half of their inner space consists of voids that have a bimodal size distribution with peaks at 21 and 8.3 nm. pAuAgNPs showed a plasmonic peak at 750 nm, which was exploited for photoacoustic (PA) imaging. Gold nanorods (AuNRs) were prepared and used as the control; they have a strong plasmonic peak at 720 nm. In in vitro experiments at respective plasmonic peak excitations, pAuAgNPs gave stronger PA signals than AuNRs by 8.9 times per particle and 11.7 times per dosage by exogenous atom. The high surface area per volume as a result of the inner voids amplified the PA signals by efficient thermoacoustic conversion. In experiments of chicken-tissue phantoms, pAuAgNPs showed PA signals through 4.5 cm thick tissue, whereas AuNRs gave no detectable signal. In whole-body in vivo experiments, pAuAgNPs injected into the body showed 2.7 times stronger PA signals than AuNRs. Coating the pAuAgNPs with a silica layer additionally increased their PA signal by 1.8 times when compared to the uncoated ones.

Ability of adhesion and biofilm formation of pathogens of periprosthetic joint infections on titanium-niobium nitride (TiNbN) ceramic coatings.

BACKGROUND: Orthopedic metal implants are notoriously associated with release of metallic ions able to cause biological adverse reactions which might lead to implant loosening and failure. To limit any possible adverse reactions, ceramic coatings for orthopedic metal implants have been introduced. However, information regarding the interaction of these coatings with microbes responsible for periprosthetic joint infections (PJIs) is lacking. Hence, the aim of the present in vitro study is to assess the microbial affinity to a titanium-niobium nitride (TiNbN) coating. METHODS: Adhesion and biofilm formation of clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Cutibacterium acnes were assessed on TiNbN-coated titanium discs in comparison with uncoated titanium and cobalt-chrome alloys discs, with either smooth or rough surfaces. Bacterial adhesion was performed by counting adhered bacteria in the first hours of incubation, and the biofilm formation was performed by means of a spectrophotometric assay and by confocal laser scan microscopy after 72 hours of incubation. RESULTS: Overall, Staphylococcus aureus and Staphylococcus epidermidis, among the most common bacteria responsible for PJIs, displayed a significantly decreased attachment in the first hours of contact and, when cultured in presence of TiNbN coating, in comparison with CoCrMo. Biofilm formation of the four tested strains was comparable on all alloys. CONCLUSIONS: Although the onset of a PJI is more complex than in an in vitro scenario, these findings suggest that TiNbN-coated orthopedic implants do not increase PJIs risk while ameliorating tribological and surface properties could represent a valid choice to limit possible complications such as metal hypersensitivity.

A new pan-nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.

BACKGROUND: The Amplatzer ventricular septal defect (VSD) occluder has a fixed stainless steel pin bottom protruding out of the surface at the center of the discs on both sides. Theoretically, this protruding bottom may interfere with epithelialization or, in some cases, cause thrombosis. OBJECTIVE: To evaluate a new type of pan-nitinol VSD occluder without the protruding stainless steel pin bottom on both sides in a canine VSD model designed to ensure safety, effectiveness, and feasibility. METHODS AND RESULTS: VSDs were successfully created by transseptal ventricular septal puncture with a Brockenbrough needle and dilation with an 8-mm-diameter balloon via the right jugular vein in 9 out of 12 canines. The new type VSD occluder was successfully implanted in 8 of the 9 modeled canines. No procedure- or device-related complication was observed. Transthoracic echocardiography and MRI 2 months after device implantations showed that there was no device dislocation or heart valve dysfunction in 6 of the 8 tested canines. In addition, gross and pathological examinations 3-6 months after implantation showed no corrosion of the devices or serious inflammatory reactions in the modeled animals. Complete endothelialization was seen over the surface of the discs. CONCLUSIONS: The new pan-nitinol VSD device can be successfully implanted in a canine VSD model via a transcatheter approach featuring high success rate, low risk of procedure-related complications, and sound biocompatibility. The result suggests that this new VSD occluder could be used safely in future clinical trials for further test.

The Randomized Freeway Stent Study: Drug-Eluting Balloons Outperform Standard Balloon Angioplasty for Postdilatation of Nitinol Stents in the SFA and PI Segment.

PURPOSE: The prospective randomized multicenter Freeway study evaluated the possible hemodynamic and clinical benefits of primary stent insertion followed by percutaneous transluminal angioplasty (PTA) with drug-eluting balloons (DEB) over post-stent insertion PTA with standard balloons in the treatment of symptomatic femoropopliteal arteriosclerotic lesions. METHODS: In total, 204 patients in 13 centers in Germany and Austria were enrolled and randomized to primary stenting followed by either FREEWAY™ drug-eluting balloon or standard PTA balloon angioplasty. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) at 6 months; the secondary endpoints include TLR rate at 12 months and primary patency, shift in Rutherford classification, ankle-brachial index (ABI) and major adverse events (MAE) at 6 and 12 months. Lesion characteristics and vessel patency were analyzed by an independent and blinded corelab. RESULTS: At 6-month and 12-month follow-up, TLR rate was lower in the DEB arm compared to standard PTA but did not reach statistical significance (4.1% vs. 9.0% p = 0.234 and 7.9% vs. 17.7% p = 0.064, respectively). Primary patency was significantly better for patients treated with the DEB at 6 months (90.3% vs. 69.8% p = 0.001) and 12 months (77.4% vs. 61.0% p = 0.027). Improvement in Rutherford classifications was likewise significantly better for patients in the DEB group at 6 (94.9% vs. 84.3% p = 0.027) and 12 months (95.5% vs. 79.9% p = 0.003). The percentage of patients with an improved ABI of 1.0-1.2 was significantly higher in the DEB group compared to the PTA group at 6 months (55.3% vs. 35.3%; p = 0.015) but without significant difference at 12 months (48.2% vs. 32.9%; p = 0.055). At 6 months, rate of major adverse events (MAE) was 1% in both arms, and at 12 months 2.2% for the DEB and 3.8% for the PTA group. CONCLUSION: The Freeway Stent Study shows that the usage of DEB as a restenosis prophylaxis seems to be safe and feasible. The 12-month follow-up results give a clear sign in favor of the DEB group.

First-in-man experience of the Versi Retriever in acute ischemic stroke.

OBJECTIVE: To describe our initial experience with the Versi Retriever for mechanical thrombectomy in patients with acute ischemic stroke. METHODS: This study is a single-center, single-arm, first-in-man registry under institutional review board control to evaluate the efficacy and safety of the new stent retriever, the Versi Retriever. Patients with acute ischemic stroke were consecutively enrolled between September and November 2017. The clinical and procedural data were retrospectively analyzed. The angiographic result after the procedure was self-graded based on the Thrombolysis in Cerebral Infarction (TICI) scale by each operator. RESULTS: Eleven patients with a mean age of 69.4 years were treated with the Versi Retriever. Median National Institutes of Health Stroke Scale score on admission was 16 (IQR 10-34). The occluded vessel was located in the anterior circulation in 81.8%. Revascularization rates of TICI 2b-3 and TICI 3 at final angiogram were achieved in 100% and 63.6%, respectively. A favorable functional outcome (modified Rankin Scale 0-2) at 90 days was obtained in 72.7%. No symptomatic intracranial hemorrhage occurred and no procedure-related complication was observed. CONCLUSIONS: Our initial experience suggests that the Versi Retriever is a safe and effective stent retriever for mechanical thrombectomy in patients with acute ischemic stroke. CLINICAL TRIAL REGISTRATION: NCT03366818.

Hemocompatibility of biodegradable Zn-0.8 wt% (Cu, Mn, Li) alloys.

Zinc alloys have been explored as potential materials for biodegradable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. However, the performances of Zn alloys were not supported with enough toxicity or biological compatibility evaluation, particularly hemocompatibility for vascular scaffolding application. In this work, the hemocompatibility of three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) was evaluated with 316 L stainless steel and pure zinc as controls. The hemolysis ratios of 316 L stainless steel, pure Zn, Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li were 0.38 ±â€¯0.08%, 1.04 ±â€¯0.21%, 0.47 ±â€¯0.21%, 0.57 ±â€¯0.14% and 0.52 ±â€¯0.22%, respectively, for direct contact method. Platelets aggregation on the 316 L stainless steel was observed, while the adhered platelets on the Zn alloys exhibited round shape with few pseudopodia spreading. The number of adhered platelets on the three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) had no statistically difference compared with 316 L stainless steel, while significant fewer than the pure Zn group. None remarkable platelet activation, hematocyte aggregation, coagulation or complement activation was observed in any Zn alloy group. Furthermore, the Zn alloys prolonged prothrombin time and partial thromboplastin time, demonstrating a potential function of anticoagulation. The results demonstrated that Zn alloys presented in this work are indeed meeting the hemocompatible requirements of implant and showing the promise for perspective application as biodegradable stent.

Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST).

BACKGROUND: Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year. METHODS AND RESULTS: Two hundred forty-four patients (168 men; 66+/-9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) "crossed over" to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, -6.9%; 95% CI, -19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, -3.3%; 95% CI, -13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease. CONCLUSIONS: In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.

Evaluation of central venous catheters coated with a noble metal alloy-A randomized clinical pilot study of coating durability, performance and tolerability.

The use of Central Venous Catheters (CVCs) commonly results in complications. Coatings with silver or metal alloys can reduce the risk associated with the use of CVC. We have evaluated the durability of a noble metal coated CVC (the Bactiguard Infectious Protection, BIP CVC) and compared with an uncoated CVC for clinical tolerability (Adverse Events, AEs) and performance, in order to create a baseline for a large future study. Patients undergoing major surgery, randomised at a 2:1 ratio to BIP CVC (n = 22) or standard CVC (n = 12), were catheterized 9 - 12 days, respectively. Adverse events, microbial colonization and metal release were measured. FINDINGS: There were no AEs in the BIP CVC-group, but 5 AEs occurred in 4 patients (1 patient had 2 AEs) in the standard CVC-group, p = 0.011 (whereof 3 were catheter related). The BIP CVC showed an initial release of coating metals in blood (gold, silver and palladium), which rapidly decreased and were far below Permitted Paily Exposure (PDE) for chronical use. The levels of silver concentration were far below those needed to develop microbial resistance. The performance was equal, and there was no difference concerning microbial colonization, for the two CVCs. CONCLUSION: In this pilot study the BIP CVC had significantly lower AEs and showed a comparable performance to the standard CVC. The coating was durable throughout the study length (up to 16 days) and toxicological evaluation showed good safety margins. Larger studies are needed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2337-2344, 2018.

Contribution of cutlery and serving dishes to the human daily intake of silver An in vitro assessment.

Silver cutlery and serving dishes are a potential source of exposure of humans that was never quantified. Release of silver was assessed in vitro in an acidic solution mimicking food fluid in two conditions: i] the JRC guidelines for hot fill conditions with stable high temperature over a 2 hour-period of time, and ii] a more realistic condition with spontaneous progressive decline from 90̊C to ambient temperature over the same period of time. Massive silver 95% strips were exposed to a 5% citric acid solution: i) cooling down from 90̊C to ambient or ii) 70̊C maintained, during 2 hours. Spectrometry with optical emission was used to measure silver in solution. In the spontaneous cooling down study, the time-course of temperature was close to the Newton's law of cooling and the released quantities were detected but too low to be measured. The 70̊C exposition resulted in a non-linear release that became quantifiable after one hour of heating up to an apparent plateau at 120 min with a mean concentration [extreme] of 24.6 [22.3-26.8] µg/L. The results of the present study allow concluding that 95% silver used for cutlery and serving dishes may be released in foods. However, the extent of release depends on the condition of use. At a stable 70̊C temperature over a 2 h-period of time, silver is released in a non-linear model up to a mean concentration of 24.6 µg/L. In contrast, in conditions fitting with the routine recommendations of use, infinitesimal detectable amounts of silver were released.

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method.

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm3 of clinically relevant CoCrMo, Ti-6Al-4V or Si3N4 particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si3N4 particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues. STATEMENT OF SIGNIFICANCE: This research presents a novel method for the isolation of wear particles from tissue. Methodology outlined in this work would be a valuable resource for future researchers wishing to isolate particles from tissues, either as part of preclinical testing, or from explants from patients for diagnostic purposes. It is increasingly recognised that analysis of wear particles is critical to evaluating the safety of an orthopaedic device.