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A cybersecurity approach for a large-scale user facility is presented—utilizing the National High Magnetic Field Laboratory (NHMFL) at Florida State University (FSU) as an example. The NHMFL provides access to the highest magnetic fields for scientific research teams from a range of disciplines. The unique challenges of cybersecurity at a widely accessible user facility are showcased, and relevant cybersecurity frameworks for the complex needs of a user facility with industrial-style equipment and hazards are discussed, along with the approach for risk identification and management, which determine cybersecurity requirements and priorities. Essential differences between information technology and research technology are identified, along with unique requirements and constraints. The need to plan for the introduction of new technology and manage legacy technologies with long usage lifecycles is identified in the context of implementing cybersecurity controls rooted in pragmatic decisions to avoid hindering research activities while enabling secure practices, which includes FAIR (findable, accessible, interoperable, and reusable) and open data management principles. The NHMFL’s approach to FAIR data management is presented. Critical success factors include obtaining resources to implement and maintain necessary security protocols, interdisciplinary and diverse skill sets, phased implementation, and shared allocation of NHMFL and FSU responsibilities.

Products containing cannabinoids such as cannabidiol (CBD) have proliferated since 2018, when the Agriculture Improvement Act removed hemp (ie, cannabis containing0.3% Δ9-tetrahydrocannabinol [THC]) from the US controlled substances list. Topical cannabinoid products can be purchased nationwide at retail stores and over the internet, yet research on these products is scarce.To evaluate the cannabinoid content (ie, CBD and THC) and label accuracy of topical cannabinoid products and to quantify their therapeutic and nontherapeutic claims.Product inclusion criteria included designation as hemp products, intended for topical or transdermal application, and purported to contain cannabinoids (eg, CBD). All unique products available at each retail store were purchased. Online products were identified via Google using relevant keywords (eg, hemp or CBD topical). Various products (eg, lotions and patches) were purchased from retail stores (eg, pharmacies, grocery stores, and cosmetic or beauty stores) in Baltimore, Maryland, and online. Data analysis was performed from March to June 2022.Labeled and actual total amounts of CBD and THC, measured via gas chromatography-mass spectrometry. Therapeutic and nontherapeutic claims and references to the US Food and Drug Administration were quantified.A total of 105 products were purchased, 45 from retail locations and 60 online. Of the 89 products that listed a total amount of CBD on the label, 18% (16 products) were overlabeled (ie, contained10% less CBD than advertised), 58% (52 products) were underlabeled (ie, contained10% more CBD than advertised), and 24% (21 products) were accurately labeled. The median (range) percentage deviation between the actual total amount of CBD and the labeled amount was 21% (-75% to 93%) for in-store products and 10% (-96% to 121%) for online products, indicating that products contained more CBD than advertised overall. THC was detected in 37 of 105 products (35%), although all contained less than 0.3% THC. Among the 37 THC-containing products, 4 (11%) were labeled as THC free, 14 (38%) indicated they contained less than 0.3% THC, and 19 (51%) did not reference THC on the label. Overall, 28% of products (29 products) made therapeutic claims, 14% (15 products) made cosmetic claims, and only 47% (49 products) noted that they were not Food and Drug Administration approved.In a case series of topical cannabinoid products purchased online and at popular retail stores, products were often inaccurately labeled for CBD and many contained THC. These findings suggest that clinical studies are needed to determine whether topical cannabinoid products with THC can produce psychoactive effects or positive drug tests for cannabis.

To evaluate the maximal load at failure, cyclic displacement, and stiffness of onlay subpectoral biceps tenodesis (BT) with an intramedullary unicortical metal button (MB) versus a unicortical all-suture button (ASB).Eighteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either ASB or MB using a high-strength suture. Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. The clamp was then adjusted to isolate the suture-anchor point interface and loaded to failure. Maximal load to failure, displacement, and stiffness were compared.There was no significant difference between groups in stiffness, displacement, or yield load. The maximal load to failure for the MB was greater than the ASB (347.6 ± 74.1N vs 266.5 ± 69.3N,This study demonstrates that the MB and ASB have similar biomechanical performance when used in subpectoral BT. Although the MB showed statistically significant greater maximal load to failure, there was no difference between the MB and ASB when the suture-tendon interface was eliminated. Suture pull-through was the most common mode of failure for both implants, underscoring the importance of the suture-tendon interface.Fixation techniques for the treatment of long head of the biceps brachii tenodesis continue to evolve. The use of an all-suture suspensory button has advantages, but it is important to understand if this implant is a biomechanically suitable alternative to a metal suspensory button.

Hemp products are readily available and are aggressively marketed for their health and medicinal benefits. Most consumers of these products are interested because of cannabidiol (CBD), which has taken the natural products industry by storm. The CBD and Δ9-tetrahydrocannabinol (Δ9-THC) concentrations in these products are often absent, and even where labeled, the accuracy of the label amounts is often questionable. In order to gain a better understanding of the CBD content, fifty hemp products were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) for CBD, Δ9-THC, tetrahydrocannabinolic acid (Δ9-THCAA), and cannabidiolic acid (CBDA). Δ9-THCAA and CBDA are the natural precursors of Δ9-THC and CBD in the plant material. Decarboxylation to Δ9-THC and CBD is essential to get the total benefit of the neutral cannabinoids. Therefore, analysis for the neutral and acid cannabinoids is important to get a complete picture of the chemical profile of the products. The GC-MS method used for the analysis of these products was developed and validated. A 10-m × 0.18-mm DB-1 (0.4 μ film) column was used for the analysis. The majority of the hemp products were oils, one of the products was hemp butter, one was a concentrated hemp powder capsule, and another was a hemp extract capsule. Most of the products contained less than 0.1% CBD and less than 0.01% Δ9-THC. Three products contained 0.1–1% CBD, and 2 products contained 0.1–0.9% Δ9-THC. All of the samples appeared to be decarboxylated since the CBDA and Δ9-THCAA results were less than 0.001%. The developed method is simple, sensitive, and reproducible for the detection of Δ9-THC, Δ9-THCAA, CBD, and CBDA in CBD oil/hemp products.

A 31-year-old US service member presented with a patellar tendon tear that was repaired acutely with 2 biocomposite suture anchors. He presented more than 2 years later with a stress fracture through a suture anchor drill hole and was treated with partially threaded screw fixation.Stress fracture through a suture anchor drill hole after patellar tendon repair is a previously unreported complication. Surgeons should have a high index of suspicion and low threshold to obtain advanced imaging in cases of unexplained pain after patellar tendon repair.

Tian Chen,1 Pamela Brewster,1 Katherine R Tuttle,2 Lance D Dworkin,1 William Henrich,3 Barbara A Greco,4 Michael Steffes,5 Sheldon Tobe,6 Kenneth Jamerson,7 Karol Pencina,8 Joseph M Massaro,8 Ralph B D’Agostino Sr,8 Donald E Cutlip,9 Timothy P Murphy,10 Christopher J Cooper,1 Joseph I Shapiro11 1University of Toledo, Toledo, OH, USA; 2Providence Health Care, University of Washington, Spokane, WA, USA; 3University of Texas Health Science Center, San Antonio, TX, USA; 4Baystate Health, Springfield, MA, USA; 5University of Minnesota, Minneapolis, MN, USA; 6University of Toronto, Toronto, ON, Canada; 7University of Michigan, Ann Arbor, MI, USA; 8Harvard Clinical Research Institute, Boston University, Boston, MA, USA; 9Beth Israel Deaconess Medical Center, Boston, MA, USA; 10Brown University, Providence, RI, USA; 11Marshall University, Huntington, WV, USA Background: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study. Methods: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R. Results: The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models. Conclusion: Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome. Clinical Trial Registration: ClinicalTrials.gov, NCT00081731 Keywords: chronic kidney disease, cardiovascular disease, glomerular filtration rate, hypertension, ischemic renal disease, renal artery stenosis

Products containing cannabidiol (CBD) are now available throughout the United States, but their quality is oftentimes questionable. The CBD and Δ9-tetrahydrocannabinol (THC) content of 25 commercia...

After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT.The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups.Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P .0001) and 6 months (8.8; P .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups.Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Purpose To perform a post-hoc analysis of the Nephropathy Ischemic Therapy (NITER) trial, which enrolled patients with atherosclerotic renal artery stenosis, to evaluate whether medical therapy plus stent placement is superior to medical therapy alone in patients without elevated albuminuria. Materials and Methods Data from 51 patients were analyzed and stratified into 2 cohorts by median urinary albumin (UAlb) levels: cohort 1 (“low albuminuria,” UAlb ≤0.04 g/24h) and cohort 2 (“high albuminuria,” UAlb >0.04g/24h). Interaction effect between treatment arms and UAlb cohorts was calculated using Cox regression analysis. Survival analysis was followed by test for effect size, power analysis, and construction of a Kaplan-Meier survival table. Results At study completion, 13 patients had an outcome event: 6 (23%) from cohort 1 and 7 (28%) from cohort 2. Patients in cohort 1 had event-free survival of 83% at 3.9 ± 0.3 years from the primary endpoints of all-cause mortality, dialysis, and cardiovascular events when treated with interventional therapy, compared to 45% when treated with medical therapy alone (P = .501), which showed a 62% treatment effect for stent placement. In cohort 2, event-free survival rates were 64% for medical therapy versus 52% for medical plus interventional therapy (P = .64). Using Cox regression analysis, the interaction effect between treatment arms and UAlb cohorts was not significant (P = .32). The power of the study to detect an interaction effect, if one existed, was only 15%. Conclusions Inference cannot be drawn for similar populations because of inadequate sample size, but, in this sample, patients treated with stent placement who had low albuminuria had better outcomes than patients treated with medical therapy alone.

Objectives: Shoulder instability is a common cause of shoulder pain and dysfunction, particularly in young and active individuals. While anterior instability remains the most common type, recent literature shows that posterior instability occurs more frequently than previously thought. As opposed to its anterior counterpart, posterior instability most often presents with pain, particularly in active individuals involved in dynamic posterior loading of the shoulder resulting in repetitive microtrauma of the posterior capsulolabral structures. While arthroscopic stabilization for posterior glenohumeral instability has shown excellent success preventing recurrent instability and allowing return to sport, eventual progression to glenohumeral arthritis remains a concern in these patients. However, the rate of and risk factors for arthritis post-surgery in young and high demand populations have not been described in the literature and may be important in guiding decision making when treating the young patient with posterior shoulder instability. The purpose of this study was to evaluate the rate of progression to glenohumeral arthritis and identify potential risk factors after arthroscopic posterior stabilization in a young and high demand population. Methods: This study included 110 active duty servicemembers identified in the Military Heath System (MHS) with ICD-9/ICD-10 posterior shoulder instability who underwent primary arthroscopic surgical stabilization and had postoperative imaging or medical records available over a twelve-year period between January 2004 and September 2016. All procedures were performed at a single institution. Patients were excluded if the they had previously undergone a stabilization procedure on the shoulder of interest, if no pre-operative imaging was available, if they did not have a minimum follow-up of four years, or if operative information regarding the number of anchors used was unavailable. Presence of arthritis (yes/no) was defined over follow-up using radiographic parameters as described by Samielson and Prieto identifying patients with at least ‘mild arthritis’. Kaplan-Meier survival curves were estimated for development of arthritis and compared by patient characteristics using log-rank tests. Cox proportional hazard models were used to calculate Hazard Ratios (HR) with 95% confidence intervals (95% CI) associated with patient characteristics as predictors of the development of glenohumeral arthritis. Results: Among the 110 patients with posterior shoulder instability requiring surgical fixation, 12% (13/110) developed glenohumeral arthritis. The mean age of all patients was 23.9 years (SD 6.71). The median time to diagnosis of arthritis was 7 years and the median follow-up time was 8 years (IQR 5;11). Kaplan-Meier curves showed differences in time to arthritis among patient groups stratified by age and index surgery anchor number (log rank p for each Conclusions: No previous study has reported the incidence and risk factors for glenohumeral arthritis after arthroscopic surgical stabilization for posterior shoulder instability. In the current study, generally young and high demand patient population, the rate of progression to glenohumeral arthritis after posterior stabilization surgery was 12%. Within this cohort, older age and higher number of anchors used were associated with progression to arthritis. The incidence of arthritis over follow up post surgery was lower than incidences previously described in older populations, a finding which may advocate for early surgical intervention for a young patient presenting with posterior shoulder instability.

Background Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results Patients enrolled in the medical therapy–only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy–only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11–2.85]; P=0.02), age (odds ratio, 1.04 [1.00–1.07]; P, See Editorial Beige

The objective of the study was to determine if time to positive (TTP), defined as the time from the start of (99m)Tc-labeled RBC scanning to the appearance of a radionuclide blush (considered to be a positive finding for acute lower gastrointestinal bleeding [LGIB]), and lag time (LT), defined as the time from the appearance of a radionuclide blush to the start of catheter angiography (CA), affected the yield of CA for the detection of acute LGIB.TTP and LT were retrospectively evaluated in 120 patients who had positive findings for acute LGIB on (99m)Tc-labeled RBC scanning and subsequently underwent CA for the diagnosis and localization of gastrointestinal bleeding. Two nuclear medicine fellowship-trained radiologists independently reviewed the (99m)Tc-labeled RBC scans. Two fellowship-trained interventional radiologists independently reviewed the angiograms. All data were analyzed using SAS software.When a TTP threshold of ≤ 9 minutes was used, the sensitivity, specificity, positive predictive value, and negative predictive value for a positive CA study were 92%, 35%, 27%, and 94%, respectively. In addition, the odds of detecting bleeding on CA increased 6.1-fold with a TTP of ≤ 9 minutes relative to a TTP of9 minutes (p = 0.020). A significant inverse relationship was found between LT and a positive CA study (p = 0.041).TTP and LT impact the rate of positive CA studies. A TTP threshold of ≤ 9 minutes allows the detection of almost all patients who would benefit from CA for treatment and allows a reduction in unnecessary negative CA studies. The likelihood of positive findings on CA decreases with a delay in the performance of CA.

Background Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. Objectives The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. Methods Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. Results There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. Conclusions Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the trans-stenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731 )

Purpose To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). Materials and Methods In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years. Results The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was 0% (n = 126) through 1 year and 2.4% (n = 85) through the second year of follow-up, with 2 new nonfatal cases at 581 and 624 days that were adjudicated as not related to the procedure or device. Two patients (1.6%) developed symptomatic caval thrombosis during the first month and underwent successful interventions without recurrence. No other filter-related symptomatic complications occurred through 2 years. There was no filter tilting, migration, embolization, fracture, or caval perforation and no filter-related deaths through 2 years. Filter bioconversion was successful for 95.7% (110/115) of patients at 6 months, 96.4% (106/110) of patients at 12 months, and 96.5% (82/85) of patients at 24 months. Through 24 months of follow-up, there was no evidence of late-stage IVC obstruction or thrombosis after filter bioconversion or of thrombogenicity associated with retracted filter arms. Conclusions The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 2 years of follow-up.

We have demonstrated a high resolution (10 micron) X-ray scintillator plate as part of an indirect X-ray detection system. Scintillator plates are typically integrated with a 2-dimensional array of photodiodes based upon amorphous Si. This paper describes an alternative digital capture system that leverages low cost CCD/CMOS cameras. Our detector has a broad set of potential applications, however the initial target application is mammography. Full-field mammography mandates an imaging area of 180mm x 240mm or larger. Very large CCD/CMOS sensors have recently been developed for high resolution cameras, such as the 250-pixel Canon camera which has sensor dimensions of 202mm x 205mm, and could conceivably be matched to our high-resolution scintillator plate without any intervening optics for magnification. However, such large format CCD/CMOS sensors have limited availability because of low production yields and high cost considerations. On the other hand, small form (36mm x 24mm) and medium format (44mm x 33mm) CCD/CMOS-based photodiodes have become widely available at low cost due to their applications in the large markets of mobile devices and consumer cameras. We have therefore developed a simple optical scheme for utilizing four small or medium format CCD/CMOS cameras to capture a larger, high-resolution image. Current systems employed in screening mammography resolve tissue features of 75-100 microns. Suspicious features found during preliminary mammographic screenings are further investigated during diagnostic mammographic tests which use a high-resolution detector that is focused over the suspicious lesion. Typically, an area less than 100mm x 80mm, the current maximum size of our high-resolution scintillation plate, is interrogated. We show that diagnostic mammography, over an area of 100mm x 80mm, could be performed using our system with a feature resolution down to 7 microns.

In digital X-ray imaging, a crucial factor determining image resolution of all indirect detection systems is the spread of light in the X-ray scintillator. Currently deployed clinical x-ray detectors, with a resolution between 75 and 300 microns, are affected by such spread of light. This work demonstrates the significantly improved the resolution of an indirect X-ray scintillation detector using a new structuring approach The new structured scintillator consists of three main components: a high optical quality ‘channel plate’, a reflective material within the capillaries of the channel plate, and a polymer-based scintillating material that is incorporated in the capillaries. Channel plates, which are utilized for a variety of optical applications, are produced from bundles of hollow drawn borosilicate glass fibers, with repeated bundling and drawing reducing the diameter of the core and capillary pores down to values as low as 5 microns. These bundles are then cut to make high quality plates (‘channel plates’) with a thickness around 1 mm. Channel plates contain geometrically ordered capillary channels (about 5 million channels per square cm). The channel walls were coated with a 70 nm thick coating of Al2O3:W using atomic layer deposition (ALD) to optically confine the photoemission within the channel. The optical channel plates were infiltrated with a new bismuth-based scintillating polymer developed at Lawrence Livermore National Laboratory, with a photon yield of > 30,600 photons/keV for X-ray energies of 20-30 keV, a range of interest for mammography. The new scintillator plate was used to experimentally demonstrate an X-ray resolution of 10 microns (or 50 linepairs/ mm), an approximately 7 times improvement over existing scintillating detectors. A structured scintillator plate, coupled with a digital detection system may be used to improve the spatial resolution in applications such as mammography, radiography, and computed tomography.

Improving symptoms, functions, and quality-of-life (ie, health status) is one of the important goals in treatment of patients with peripheral artery disease (PAD).1 However, it is unknown whether health status responses differ by race (black versus white) with alternative PAD treatment modalities. Such differences may exist given the disproportionate burden of PAD in minority populations, and rapid disease progression as compared with white,2 as well as differences in psychosocial and economic factors and possibly differences in exercise level, which is known to improve outcomes in patients with PAD.3,4 Understanding whether black and white respond differently to treatments can help us better support targeted therapy to improve quality of care. This is relevant because until now, supervised exercise (SE) programs for PAD were not available in the United States, and recently, the Centers for Medicare and Medicaid Services agreed to reimburse for SE therapy.5 If there is heterogeneity in response to SE, knowing this difference is important to provide patient-centered care and to get maximum treatment benefit for each unique patient population. The CLEVER trial (Claudication: Exercise Versus Endoluminal Revascularization) randomized patients with claudication from aortoiliac disease to SE, stent therapy (ST), or optimal medical care (OMC). Short-term results indicated superior treadmill walking performance (ie, peak walking time and claudication onset time) with SE than either ST or OMC. Conversely, benefit in PAD-specific health status (Peripheral Artery Questionnaire [PAQ] summary score)6 was more favorable for ST than either SE or OMC.3 Similarly, general quality-of-life benefit as assessed with Short Form-12 Physical Component Summary (SF-12 PCS)7 was similar for ST and SE when compared with OMC.3 Long-term results, however, showed similar and sustained benefits for both ST and SE over OMC in treadmill walking performance, but PAQ summary score was more favorable …

The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up.Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups.Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

BACKGROUND The aim of this study was to examine the relationship of albuminuria to cardiovascular disease outcomes in diabetic patients undergoing treatment for stable coronary artery disease. METHODS AND RESULTS We analyzed data from 2176 participants of the Bypass Angioplasty Revascularization Investigation in type-2 diabetes (BARI-2D) trial, a randomized clinical trial comparing Percutaneous coronary intervention/Coronary artery bypass grafting (PCI/CABG) to medical therapy for people with diabetes. The population was stratified by baseline spot urine albumin-creatinine ratio (uACR) into normal (uACR

Background Treatment for claudication that is due to aortoiliac peripheral artery disease (PAD) often relies on stent revascularization (ST). However, supervised exercise (SE) is known to provide comparable short-term (6-month) improvements in functional status and quality of life. Longer-term outcomes are not known. Objectives The goal of this study was to report the longer-term (18-month) efficacy of SE compared with ST and optimal medical care (OMC). Methods Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of SE and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. Results Peak walking time improved from baseline to 18 months for both SE (5.0 ± 5.4 min) and ST (3.2 ± 4.7 min) significantly more than for OMC (0.2 ± 2.1 min; p Conclusions Both SE and ST had better 18-month outcomes than OMC. SE and ST provided comparable durable improvement in functional status and in quality of life up to 18 months. The durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment. (Claudication: Exercise Versus Endoluminal Revascularization [CLEVER]; NCT00132743 )

In an earlier study, we developed two sensitive and reliable procedures for gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of methylhexaneamine (MHA) in P. graveolens plant materials and volatile oils. None of the analyzed plant materials or oils showed any detectable levels of MHA which was further substantiated by high resolution liquid chromatography-quantum time of flight-mass spectrometry (LC-QTOF-MS) analysis with a limit of detection of 10 ppb. However, other laboratories (two studies) reported the presence of MHA in some samples of P. graveolens and pelargonium oil acquired by the investigators from China. Because of the controversy of whether Pelargonium species or pelargonium oil contains MHA, it was recommended that splits of multiple samples be analyzed by different laboratories. In this investigation, multiple plant materials and oil samples were collected from around the world. These samples were submitted to four different sites for analysis. All sites adopted a similar extraction method. All the analysis sites used LC-MS/MS or LC-QTOF-MS and detection limit was set close to the 10 ng/mL as previously reported. A total of 18 plant samples belonging to 6 different Pelargonium species and 9 oils from different locations around the world were split among 4 different analytical laboratories for analysis (each lab received the same samples). None of the laboratories detected MHA in any of the samples at or around the 10 ppb detection level of the procedure used. Copyright © 2014 John Wiley & Sons, Ltd.

Renal artery fibromuscular dysplasia (FMD) may be underdiagnosed. We evaluated the prevalence of FMD in CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) renal artery stent trial participants, in which FMD was an exclusion criterion for inclusion. We also evaluated the prevalence of FMD in a relatively healthy population of patients undergoing computed tomographic angiographic (CTA) screening for renal donor evaluation. All renal donor CTAs performed at our institution from January 2003 through November 2011 were retrospectively reviewed for the presence of FMD along with patient sex and age. These results were compared to angiographic core lab (ACL) findings for the CORAL trial. The CORAL ACL database contained 997 patients (mean age 69.3 years; 50% female). Fifty-eight (5.8%) CORAL trial patients (mean age 71.8 years; 75.9% female) demonstrated incidental FMD. The renal donor cohort included 220 patients (mean age 40.5 years; 64.5% female). Five (2.3%) demonstrated FMD (mean age 48.6 years; all female). The odds of FMD in the CORAL cohort were 2.65 times that seen in the renal donor cohort (95% CI: 1.12, 7.57). In conclusion, the 5.8% prevalence of renal artery FMD in the CORAL trial population, the presence of which was biased against, suggests underdiagnosis.

Purpose To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study. Materials and Methods The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y ± 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months. Results Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2–4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly more endpoints reported by site in subjects with bilateral renal artery stenosis ( P = .01) and prior history of stroke ( P = .03). Conclusions In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly.

BACKGROUND Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. METHODS We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). RESULTS Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P = 0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P = 0.03). CONCLUSIONS Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.) abstr act

We present this preliminary investigation into the safety and feasibility of endovascular therapy for morbid obesity in a swine model. A flow-limiting, balloon-expandable covered stent was placed in the superior mesenteric artery of three Yorkshire swine after femoral arterial cutdown. The pigs were monitored for between 15 and 51 days after the procedure and then killed, with weights obtained at 2-week increments. In the two pigs in which the stent was flow limiting, a reduced rate of weight gain (0.42 and 0.53 kg/day) was observed relative to the third pig (0.69 kg/day), associated with temporary food aversion and signs of mesenteric ischemia in one pig.

Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease– or kidney disease–related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P =0.02), cardiovascular disease–related death (93% versus 85%; P ≤ 0.01), progressive renal insufficiency (91% versus 77%; P =0.03), and overall survival (89% versus 76%; P ≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00081731.

Background and objectives Atherosclerotic renal artery stenosis may cause kidney function loss, but effects of stenting on eGFR and clinical events associated with CKD are uncertain. Our study objectives were to determine effects of stenting on eGFR and predictors of clinical events. Design, setting, participants, & measurements Participants (n=931) in the Cardiovascular Outcomes in Renal Artery Stenosis Trial (from May of 2005 to September of 2012) had >60% atherosclerotic renal artery stenosis and systolic hypertension on two or more antihypertensive drugs and/or stage ≥3 CKD. The intervention was stenting versus no stenting on a background of risk factor management: renin-angiotensin system inhibition, statin, antiplatelet therapy, and smoking cessation education. The effect of stenting on eGFR by the serum creatinine-cystatin C Chronic Kidney Disease Epidemiology Collaboration equation was the prespecified analysis of kidney function. Predictors of eGFR and CKD outcomes (≥30% eGFR loss, ESRD, and death) and cardiovascular disease outcomes (stroke, myocardial infarction, heart failure, and death) controlling for eGFR and albuminuria were also determined. Results eGFR was 59±24 ml/min per 1.73 m2 (mean±SD) at baseline. Over 3 years, eGFR change, assessed by generalized estimating equations, was −1.5±7.0 ml/min per 1.73 m2 per year in the stent group versus −2.3±6.3 ml/min per 1.73 m2 per year in the medical therapy only group (P=0.18). eGFR predictors (multiple variable generalized estimating equations) were age, albuminuria, systolic BP, and diabetes (inverse associations) as well as men, total cholesterol, and HDL cholesterol (positive associations). CKD outcomes events occurred in 19% (175 of 931), and predictors (Cox proportional hazards models) included albuminuria (positive association), systolic BP (positive association), and HDL cholesterol (inverse association). Cardiovascular disease outcomes events occurred in 22% (207 of 931), and predictors included age, albuminuria, total cholesterol, prior cardiovascular disease, and bilateral atherosclerotic renal artery stenosis (positive associations). Conclusions Stenting did not influence eGFR in participants with atherosclerotic renal artery stenosis receiving renin-angiotensin system inhibition–based therapy. Predictors of clinical events were traditional risk factors for CKD and cardiovascular disease.

Transluminal ablation of renal artery sympathetic nerves has been shown to provide a significant and durable reduction in blood pressure with very low complication rates. Additional publications have documented improvement in insulin sensitivity, obstructive sleep apnea indices, and frequency and severity of congestive heart failure in subgroups undergoing the procedure. This technology may provide effective management of other diseases in which there is autonomic imbalance. Available data are reviewed with the intent to provoke interest within the interventional radiology community in this novel technology, which may allow minimally invasive treatment of many important chronic medical conditions.

Methylhexaneamine (MHA) has been marketed in dietary supplements based on arguments that it is a constituent of geranium (Pelargonium graveolens) leaves, stems, roots or oil, and therefore qualifies as a dietary ingredient. The purpose of this study is to determine whether P. graveolens plant material (authenticated) or its oil contains detectable quantities of MHA. Two analytical methods were developed for the analysis of MHA in P. graveolens using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. The results were further confirmed using liquid chromatography-high-resolution mass spectrometry. Twenty commercial volatile oils, three authenticated volatile oils and authenticated P. graveolens leaves and stems (young and mature, and fresh and dried) were analyzed for MHA content. In addition, three dietary supplements containing MHA that alleged P. graveolens as the source are analyzed for their MHA content. The data show that none of the authenticated P. graveolens essential oils or plant material, nor any commercial volatile oil of Pelargonium (geranium oil) contain MHA at detectable levels (limit of detection: 10 ppb). The dietary supplements that contained MHA as one of their ingredients (allegedly from geranium or geranium stems) contained large amounts of MHA. The amounts of MHA measured are incompatible with the use of reasonable amounts of P. graveolens extract or concentrate, suggesting that MHA was of synthetic origin.

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1 . Unique identifier: NCT00132743.

Robert C. Hendel, MD, FACC, FAHA, Chair; Biykem Bozkurt, MD, PhD, FACC, FAHA; Gregg C. Fonarow, MD, FACC, FAHA; Jeffrey P. Jacobs, MD, FACC; Pamela N. Peterson, MD, FACC; Veronique L. Roger, MD, MPH, FACC, FAHA[∥∥∥][1]; Eric E. Smith, MD, MPH, FAHA; James E. Tcheng, MD, FACC, FSCAI; Tracy

Because of the structural and functional homology to the hair cells of the mammalian inner ear, the neurons that innervate the Drosophila external sense organs provide an excellent model system for the study of mechanosensation. This protocol describes a simple touch behavior in fruit flies which can be used to identify mutations that interfere with mechanosensation. The tactile stimulation of a macrochaete bristle on the thorax of flies elicits a grooming reflex from either the first or third leg. Mutations that interfere with mechanotransduction (such as NOMPC), or with other aspects of the reflex arc, can inhibit the grooming response. A traditional screen of adult behaviors would have missed mutants that have essential roles during development. Instead, this protocol combines the touch screen with mosaic analysis with a repressible cell marker (MARCM) to allow for only limited regions of homozygous mutant cells to be generated and marked by the expression of green fluorescent protein (GFP). By testing MARCM clones for abnormal behavioral responses, it is possible to screen a collection of lethal p-element mutations to search for new genes involved in mechanosensation that would have been missed by more traditional methods.

Introduction: In current guidelines congestive heart failure (CHF) is an indication for renal artery stenting, however there is no data on the utility of stenting for the prevention of CHF. We sought to determine the effect of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) without a history of CHF. Hypothesis: In ARAS renal artery stenting does not prevent incident CHF in patients with no history of CHF. Design and method: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial is a prospective, international, multicenter clinical trial that randomized participants with ARAS, who received optimal medical therapy plus stenting versus no stenting. Optimal medical therapy included treating blood pressure and diabetes to goal, use of an angiotensin receptor-blocking drug, statin, and anti-platelet therapy. Glomerular filtration (eGFR) was estimated using the MDRD-GFR equation. Patients were followed for a median of 43 months (IQR, 31 to 55). Results: At enrollment, there were 795 out of 931 patients without a history of CHF, 395 were in the medical therapy group and 400 were in the medical therapy plus stenting group. In this group 117/795 had global renal ischemia. The rate of CHF admission (7% vs. 6%. p=0.74) and the pulmonary edema rate within those admitted for CHF were not different (82% vs. 64%, p=0.21). The rate of incident CHF was not different in patients with global renal ischemia and renal stenting did not prevent CHF events in this subgroup. Neither the composite event rate (35% vs. 34%, p=0.72), nor the rate of cardiovascular death (8% vs. 8%, p=0.96) differed between the two groups. At 3-year follow-up no differences were observed between medical therapy and medical therapy plus stenting for systolic blood pressure (SBP) (135±19 vs. 134±21 mmHg, p=0.74) or eGFR (56±22 vs. 55±23 ml/min, p=0.50). Conclusions: Renal artery stenting and optimal medical therapy, when compared to optimal medical therapy only, did not reduce the risk of CHF, or other cardio-renal events in patients that were enrolled without history of CHF in the CORAL trial.

The recent escalation in lower extremity revascularization procedures suggests a concomitant increase in peripheral arterial disease (PAD) screening. We hypothesized that self-referring physicians would show the greatest growth in noninvasive physiologic testing for PAD and similar trends for revascularization procedures. We compared utilization rates for self-referring specialties (vascular surgery, interventional radiology, and cardiology) with the utilization rate for a referral-based specialty (diagnostic radiology), assuming the latter to be "basal"--that is, responsive only to changes in demographics and medical knowledge.We analyzed 100% procedure-specific claims for services provided to Medicare Part B beneficiaries during 6 years over an 8-year span (2000-2007). We extracted all Current Procedural Terminology codes for lower extremity vascular noninvasive physiologic studies, peripheral arterial stent placement, and transluminal angioplasty. Utilization volumes were adjusted per 100,000 beneficiaries. Compound annual growth rates were calculated.Utilization of both noninvasive physiologic and revascularization services increased steadily over the study period. Growth rates of diagnostic services provided by interventional radiologists (7%) and vascular surgeons (8%) were slightly higher than the basal rate (7%), with cardiologists (14%) at the top of the list. For revascularization procedures, vascular surgery showed the greatest growth (28%), a rate more than twice that of cardiology (13%); radiology experienced a decrease in volumes (-2%).Self-referring specialists are screening large volumes of Medicare beneficiaries for lower extremity PAD at an accelerated rate compared with testing done by those who do not self-refer. Similar trends exist for endovascular interventions.

Purpose To prospectively assess the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). Materials and Methods At 23 sites, 129 patients with documented deep vein thrombosis (DVT) or PE, or at temporary risk of developing DVT or PE, unable to use anticoagulation were enrolled. The primary end point was clinical success, including successful filter deployment, freedom from new symptomatic PE through 60 days before filter bioconversion, and 6-month freedom from filter-related complications. Patients were monitored by means of radiography, computerized tomography (CT), and CT venography to assess filtering configuration through 60 days, filter bioconversion, and incidence of PE and filter-related complications through 12 months. Results Clinical success was achieved in 111 of 114 evaluable patients (97.4%, 95% confidence interval [CI] 92.5%–99.1%). The rate of freedom from new symptomatic PE through 60 days was 100% (n = 129, 95% CI 97.1%–100.0%), and there were no cases of PE through 12 months for either therapeutic or prophylactic indications. Two patients (1.6%) developed symptomatic caval thrombosis during the first month; neither experienced recurrence after successful interventions. There was no filter tilting, migration, embolization, fracture, or caval perforation by the filter, and no filter-related death through 12 months. Filter bioconversion was successful for 95.7% (110/115) at 6 months and for 96.4% (106/110) at 12 months. Conclusions The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 12 months of imaging-intense follow-up.