Novel Self-expanding Shape-Memory Bioresorbable Peripheral Stent Displays Efficient Delivery, Accelerated Resorption, and Low Luminal Loss in a Porcine Model.

OBJECTIVE AND DESIGN: The search for improved stenting technologies to treat peripheral artery disease is trending toward biodegradable self-expanding shape-memory stents that, as of now, still suffer from the acute trade-off between deliverability and luminal stability: Higher deliverability leads to lower lumen stability, vessel recoil, and stent breakage. This study was aimed at the development and testing of a self-expanding bioresorbable poly(l,l-lactide-co-ε-caprolactone) stent that was designed to produce confident self-expansion after efficient crimping, as well as quick bioresorption, and sufficient radial force. MATERIALS AND METHODS: Bench tests were employed to measure shape-memory properties, radial force, and hydrolytic degradation of the stent. The porcine model was employed to study deliverability, lumen stability, biocompatibility, and stent integrity. A total of 32 stents were implanted in the iliac arteries of 16 pigs with 15 to 180 day follow-up periods. The stented vessels were studied by angiography and histological evaluation. RESULTS: Recovery of the diameter of the stent due to shape-memory effect was equal to 90.6% after 6Fr crimping and storage in refrigeration for 1 week. Radial force measured after storage was equal to 0.7 N/mm. Technical success of implantation in pigs (after the delivery implemented by pusher) was 94%. At 180 days, no implanted stents were found to be fragmented: All of the devices remained at the site of implantation with no stent migration and all stents retained their luminal support. Only moderate inflammation and neoepithelialization were detected by histological assessment at 60, 90, 120, and 180 days. Lumen loss at 180 days was less than 25% of the vessel diameter. CONCLUSIONS: The stent with the mechanical and chemical properties described in this study may present the optimal solution of the trade-off between deliverability and luminal stability that is necessary for designing the next generation stent for endovascular therapy of peripheral arterial disease.

Surgical Tray Optimization: a Quality Improvement Initiative that Reduces Operating Room Costs.

Surgical trays contain unused instruments which generate wasted resources from unnecessary reprocessing/replacement costs. We implemented a quality improvement initiative to optimize surgical trays for common otolaryngology procedures, and examined the impact on costs, operating room (OR) efficiency, and patient safety.We studied five common otolaryngology procedures over a 10-month period at a single community hospital. We compared pre- and post-intervention outcome measures including instrument utilization, tray set up time, tray rebuilding time, and balancing measures (operative time, instrument recall, patient safety). We estimated cost-savings from an institutional perspective over 1- and 10-year time horizons. Costs were expressed in 2017 Canadian dollars and modeled as a function of surgical volume, labor costs, instrument depreciation, and indirect costs.A total of 238 procedures by six surgeons were observed. At baseline, only 35% of instruments were utilized. We achieved an average instrument reduction of 26%, yielding 1-year cost savings of $9,010 CDN and 10-year cost savings of $69,576 CDN. Tray optimization reduced average OR tray setup time by 2.5 ± 0.4 min (p = 0.03) and average tray rebuilding time by 1.4 ± 0.2 min (p = 0.06). There was minimal impact on balancing measures such as OR time, stakeholder perception of patient safety and trainee education, and only a single case of instrument recall.Surgical tray optimization is a simple, effective, and scalable strategy for reducing costs and improving OR efficiency without compromising patient safety.

Impact of Renal Pelvic Denervation on Systemic Hemodynamics and Neurohumoral Changes in a Porcine Model.

INTRODUCTION: The blood pressure (BP) response to arterial renal denervation (RDN) is variable. METHODS: This study examined the effectiveness of renal pelvic denervation (RPD) on BP, heart rate (HR), norepinephrine (NE), and histopathology in 42 swine. NE levels were measured immediately, 7, 14, 30, and 90 days after RPD. Intra-arterial BP and HR were measured throughout RPD and after 14 days in 5 swine. RESULTS: During the procedure, RPD immediately reduced systolic BP (-20.6 ± 18.3 mm Hg), diastolic BP (-6.0 ± 8.3 mm Hg), and HR (-5.4 ± 5.6 bpm), which remained decreased at follow-up. The porcine kidneys had a mean NE reduction of 76% directly post procedure and 60% after 7 days, 64% after 14 days, 57% after 30 days, and 65% after 90 days. Histopathological examination confirmed nerve ablation. CONCLUSIONS: These preliminary findings suggest that the renal pelvis nerve ablation is an encouraging target for RDN. Clinical trials are required to test the feasibility of RPD in human hypertension.

Patient Perspectives on Removing Adult Tonsillectomy and Septoplasty from the Government Health Insurance Plan in a Publicly Funded Health Care System.

In several publicly funded health care systems, including Ontario, Canada, adult tonsillectomies and septoplasties have been suggested to be removed or "delisted" from the government health insurance plan. Thus, the objective of this study was to explore patient perspectives regarding out of pocket (OOP) payment for these procedures. An anonymous survey was administered to patients consented to undergo a tonsillectomy or septoplasty at a community otolaryngology-head and neck surgery (OHNS) practice. The survey asked patients if they would pay the projected cost for their surgery OOP and the maximum amount of time they would wait for their surgery. The survey also contained questions on socioeconomic status and disease severity. Seventy-one patients were included. Overall, 21% of patients were willing to pay OOP for their surgery. Forty-nine percent of patients reported that the maximum amount of time they would be willing to wait for their surgery was 2 to 6 months. There was no significant correlation found between any of the demographic variables or disease severity and willingness to pay OOP for these surgeries. In this study, a small percentage of patients who met the clinical indications for a tonsillectomy or a septoplasty would pay for their surgery in the event that it was not covered by the government health insurance plan. These surgeries are common operations and delisting them could potentially decrease the provision of these services and have a significant impact on Canadian OHNS practices.

Safety of catheter-based radiofrequency renal denervation on branch renal arteries in a porcine model.

OBJECTIVES: We aimed to investigate the safety of radiofrequency (RF)-renal denervation (RDN) on branch renal arteries (RAs) in a porcine model. BACKGROUND: The efficacy of RF-RDN was enhanced by treatment of the branch RA, in addition to the main RA. However, there are concerns regarding the safety of RF-RDN on branch RA because of their smaller diameter and proximity to the kidney. METHODS: RF was delivered to 24 RA from 12 swine. A total of 8 RA from 4 swine were untreated. Treated RA were examined by angiography and histopathology at 7, 30, and 90 days. Serum creatinine concentration, biophysical parameters during RF delivery, and renal norepinephrine concentration were also assessed. RESULTS: Angiography revealed minimal late lumen loss and diameter stenosis in the main and branch RA at any time point. There was no change in serum creatinine after RF-RDN. Histopathologically, no augmentation of medial damage or neointimal formation was found in branch RA compared with main RA. No or minimal damage to surrounding tissues including the kidneys, ureters, lymph nodes, and muscles was observed at any time point in both the main and branch RA. Equivalent electrode temperature in the main and branch RA was achieved by automatic adjustment of output power by the generator. The renal norepinephrine concentration was significantly lower in the treated group compared with the untreated group. CONCLUSIONS: RF-RDN on branch RA was safe in a porcine model, with stenosis-free healing of treated arteries and negligible kidney damage at 7, 30, and 90 days.

Procedural and anatomical predictors of renal denervation efficacy using two radiofrequency renal denervation catheters in a porcine model.

INTRODUCTION: Several renal denervation (RDN) systems are currently under investigation for treatment of hypertension by ablation of renal sympathetic nerves. The procedural efficacy of devices, however, is variable and incompletely understood. This study aimed at investigating procedural and anatomical predictors of RDN efficacy by comparing two radiofrequency catheter systems in a porcine model. METHODS: Domestic swine were assigned into two treatment groups (n = 10) and one sham group (n = 3). Bilateral RDN in main and in branch segments of renal arteries was performed using two different multielectrode catheter systems [Symplicity Spyral (SPY) and IberisBloom (IBB)]. After 7 days, measurement of norepinephrine (NEPI) tissue concentrations and histological analyses have been performed. RESULTS: Renal NEPI tissue concentration following RDN was significantly reduced when compared with Sham (SPY: -95 ±â€Š3% vs. Sham, P < 0.001; IBB: -88 ±â€Š11% vs. Sham, P < 0.001). Histological evaluation showed comparable lesion depth and lesion area (lesion depth: SPY-main 6.26 ±â€Š1.62 mm vs. SPY-branch 3.49 ±â€Š1.11 mm; IBB-main 5.93 ±â€Š1.88 mm vs. IBB-branch: 3.26 ±â€Š1.26 mm, P < 0.001; lesion area: SPY-main 43.5 ±â€Š29.5 mm vs. SYP-branch 45.0 ±â€Š38.0 mm; IBB-main 52.3 ±â€Š34.8 mm vs. IBB-branch 44.0 ±â€Š42.6 mm, P = 0.77; intergroup SPY vs. IBB, P = 0.73). Histological investigations documented a significant correlation between number of ablations per millimeter length of renal artery and reduction in NEPI tissue concentration. CONCLUSION: The two devices under investigation demonstrated similar histopathological lesion characteristics and similar reduction of renal NEPI levels. An increase in number of ablations per millmeter length of renal artery resulted in improved efficacy and reduced variability in treatment effects.

Neuromatous regeneration as a nerve response after catheter-based renal denervation therapy in a large animal model: immunohistochemical study.

BACKGROUND: Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN. METHODS AND RESULTS: Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thickened perineurium of severed nerves were observed. At 90 days, some TH expression was observed together with prominent S100+ and growth-associated protein 43+ neuromatous tangles with disorganized architecture. The potential for regenerative activity is unlikely based on the disrupted architecture of these neuromatous tangles at the radiofrequency lesion sites. CONCLUSIONS: This study is the first documentation that a progressive regenerative response occurs as early as 7 days after RDN, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of a regeneration after RDN.

A novel non-vascular system to treat resistant hypertension.

AIMS: To evaluate in a preclinical model the utility of a monopolar electrode catheter delivering radiofrequency (RF) energy placed into the renal pelvis in order to treat resistant hypertension (RH). METHODS AND RESULTS: Sixteen female domestic swine weighing 60-65 kg underwent renal pelvic denervation via ureteral access. Three animals were euthanised immediately after delivery of RF energy; five animals were allowed to survive for seven days, six animals were allowed to survive for 14 days and two animals were allowed to survive for 30 days. Renal cortical norepinephrine levels were measured in all groups of animals. Histopathology of the treated zone was performed to confirm nerve damage. Renal cortical tissue was harvested for determination of tissue norepinephrine by HPLC. The kidneys were then profusion-fixed and harvested for histopathologic analysis. Mean reduction of norepinephrine levels was 60.4% compared to control. Histopathology confirmed nerve ablation in the treated zone. CONCLUSIONS: In this small, preclinical study, we introduce a new non-vascular system to treat resistant hypertension. If the current clinical experience confirms efficacy and safety, this approach may be one way to treat patients who cannot be treated with the standard percutaneous arterial devices.

A portable, low-cost system for posturography: a platform for longitudinal balance telemetry.

OBJECTIVE: The Nintendo Wii Balance Board (WBB) is a low-cost, commercially available gaming device that shares many characteristics with a laboratory-grade forceplate. This study evaluates the WBB and explores its potential application as a low-cost posturography system. METHODS: Custom software was written to interface with the WBB and measure the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB). Centre of pressure (COP) path length was the primary outcome measure. Healthy patients without a history of vestibular problems were recruited to undertake testing on the WBB and underwent matched testing on an AMTI forceplate. RESULTS: Evaluation of the WBB transducers demonstrated excellent linearity (r = .994, p < .0001). Bland-Altman plots did not demonstrate any relationship between the mean and the difference for the four tested conditions. CONCLUSIONS: The WBB can be used as part of a portable, low-cost posturography system offering new options for longitudinal telemetry and in-home testing.

In vitro and in vivo characterization of novel biodegradable polymers for application as drug-eluting stent coatings.

We have used a series of in vitro and in vivo tests to assess the suitability of two new degradable polymers for application as coatings for drug-eluting stents. The first is a family of urethane-linked multi-block copolymers (MBCP) that comprise blocks of lactide, glycolide, epsilon-caprolactone and/or poly(ethylene glycol) chain-extended with 1,4-butanediisocyanate (SynBiosys polymers). The second is a family of maltodextrin (MD) modified with fatty acid sidechains to yield a hydrophobic polymer (Eureka() SOLO polymers). We coated stainless-steel stents with two representative urethane-linked MBCPs and one hydrophobic MD polymer alone or in combination with the anti-restenotic drug sirolimus. Urethane-linked MBCPs formed uniform coatings on the stent substrates, withstood crimping and expansion on balloon catheters, completely released sirolimus from the coating within 30 days, and degraded within 30-60 days in PBS. The hydrophobic MD polymer formed uniform coatings, exhibited somewhat slower release of sirolimus (approx. 85% within 30 days), degraded within 60 days in PBS when sirolimus was incorporated in the coating, but showed very slow degradation in the absence of drug. We implanted stents coated with urethane-linked MBCPs or hydrophobic MD polymers in a porcine coronary artery model and used histological analysis at 28- and 90-day end-points to assess the biological response to the materials. Measures of stenosis and inflammation for urethane-linked MBCP and hydrophobic MD polymer coatings were not statistically different from bare metal controls at 28 and 90 days, suggesting that the polymers show good vascular biocompatibility. Endothelialization was nearly complete at 28 days and complete at 90 days for all formulations. Urethane-linked MBCP polymer-only and drug-eluting coatings and hydrophobic MD drug-eluting coatings were nearly completely degraded within 90 days in vivo whereas roughly half of hydrophobic MD polymer-only coatings remained after 90 days. Taken together, our in vitro and in vivo results suggest that SynBiosys urethane-linked MBCP and Eureka SOLO hydrophobic MD polymer families possess the physical and chemical properties and vascular biocompatibility necessary for further investigation for use in the next generation of drug-eluting stents.