Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models.

Coherent fluorescence imaging with two objective lenses (4Pi detection) enables single-molecule localization microscopy with sub-10 nm spatial resolution in three dimensions. Despite its outstanding sensitivity, wider application of this technique has been hindered by complex instrumentation and the challenging nature of the data analysis. Here we report the development of a 4Pi-STORM microscope, which obtains optimal resolution and accuracy by modeling the 4Pi point spread function (PSF) dynamically while also using a simpler optical design. Dynamic spline PSF models incorporate fluctuations in the modulation phase of the experimentally determined PSF, capturing the temporal evolution of the optical system. Our method reaches the theoretical limits for precision and minimizes phase-wrapping artifacts by making full use of the information content of the data. 4Pi-STORM achieves a near-isotropic three-dimensional localization precision of 2-3 nm, and we demonstrate its capabilities by investigating protein and nucleic acid organization in primary neurons and mammalian mitochondria.

Super-resolution fluorescence microscopy.

Achieving a spatial resolution that is not limited by the diffraction of light, recent developments of super-resolution fluorescence microscopy techniques allow the observation of many biological structures not resolvable in conventional fluorescence microscopy. New advances in these techniques now give them the ability to image three-dimensional (3D) structures, measure interactions by multicolor colocalization, and record dynamic processes in living cells at the nanometer scale. It is anticipated that super-resolution fluorescence microscopy will become a widely used tool for cell and tissue imaging to provide previously unobserved details of biological structures and processes.

Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder.

BACKGROUND: Depression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder. METHODS: This phase 2, open-label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25-mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist-to-patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability. RESULTS: Thirty participants completed the study. No psilocybin-related serious adverse events occurred; treatment-related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to -16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks. CONCLUSIONS: Psilocybin-assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group-oriented format, compact delivery time, community cancer center setting, and one-to-one therapist-to-patient ratio could also add to therapeutic gains and efficiency of administration. TRIAL REGISTRATION: NCT04593563. PLAIN LANGUAGE SUMMARY: Depression is common in patients with cancer and associated with lower treatment adherence, reduced quality of life, and limited response to antidepressants and psychotherapy. We conducted a phase 2 trial to study a single dose of psilocybin administered in a group therapy setting with one-to-one therapist-to-participant psychological support to patients with curable and noncurable cancer and major depressive disorder. Findings of the study showed safety (no treatment-related serious adverse events or suicidality) with psilocybin and suggested efficacy, with a significant reduction in depression severity scores from baseline to posttreatment. Further investigation is warranted.

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

Effect of parachute delivery on red blood cell (RBC) and plasma quality measures of blood for transfusion.

BACKGROUND: Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS: Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS: Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2 . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION: Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.

FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.

BACKGROUND: ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours. METHODS: In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting. Endogenous FKBPL protein levels were evaluated using tissue microarrays (TMA). RESULTS: ALM201 reduced CSCs in cell lines and primary samples by inducing differentiation. ALM201 treatment of highly vascularised Kuramochi xenografts resulted in tumour growth delay by disruption of angiogenesis and a ten-fold decrease in the CSC population. In contrast, ALM201 failed to elicit a strong antitumour response in non-vascularised OVCAR3 xenografts, due to high levels of IL-6 and vasculogenic mimicry. High endogenous tumour expression of FKBPL was associated with an increased progression-free interval, supporting the protective role of FKBPL in HGSOC. CONCLUSION: FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6.

A rare cause of stroke after transcatheter aortic valve replacement: Retained foreign body.

The field of transcatheter aortic valve replacement (TAVR) has matured significantly with the outcome and durability data now supporting use in lower-risk patients. We present a preventable complication from early in our experience (5 years ago) that illustrates the importance of heart team communication and cautious multidiscipline cross-pollination during the formative years of a program. An 87-year old female developed confusion, slurred speech and left upper extremity weakness 1 day following TAVR with inconclusive findings on carotid artery duplex and transthoracic echocardiography. Subsequent CT-scan disclosed a linear, ring-like, structure in the ascending aorta. The foreign body (FB) was radiolucent and successfully snared via tactile sensation and anatomic landmarks informed by the CT. The extricated FB was the valvuloplasty balloon guard (BG) that was inadvertently introduced into the patient via ascending aortic large sheath access. The failure mode was traced back to the first time use of a new balloon system and unrecognized BG by the surgical physician and technician components of the Heart Team who took the lead role in device insertion due to the open chest access. Subsequently, the heart team made changes to mitigate similar future complications by sharing multidiscipline responsibility for all procedural steps and ensuring the use of all new adjuvant devices are preceded by a procedural pause and team consensus regarding device preparation and use. Additionally, the manufacturer addition of a radiopaque marker or flair on the valvuloplasty BG may be warranted.

Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study.

BACKGROUND: Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension. METHODS: CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897. FINDINGS: Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13-34/6-18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14-29/7-16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1). INTERPRETATION: In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further. FUNDING: Vascular Dynamics.

Endovascular Baroreflex Amplification for Resistant Hypertension.

PURPOSE OF REVIEW: Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors play a pivotal role in maintaining adrenergic balance via a direct feedback interface and would be an exceptional target for intervention. The purpose of this review is to define the role of the baroreceptor in hypertension, to examine device-based therapies targeting the baroreflex and to explore future promises of endovascular baroreflex amplification (EBA). RECENT FINDINGS: In the last two decades, two therapeutic strategies targeting the carotid baroreceptor have evolved: baroreflex activation therapy (BAT) and EBA. Both therapies enhance baroreceptor activity, either directly by electrical stimulation or indirectly by changing the geometric shape of the carotid sinus and increasing pulsatile wall strain. By showing a significant, sympathetic inhibition-mediated effect on blood pressure, BAT has laid the foundation for baroreflex-targeting therapies for resistant hypertension. EBA is a less invasive therapy with promising first-in-man study results. Ongoing randomized sham-controlled trials are needed to better understand efficacy, durability, and long-term safety and define phenotypes that may most benefit from this treatment.

Appropriate Use of Venous Imaging and Analysis of the D-Dimer/Clinical Probability Testing Paradigm in the Diagnosis and Location of Deep Venous Thrombosis.

BACKGROUND: The D-dimer (DD) level combined with the pretest Wells criteria probability (WCP) score can safely exclude deep venous thrombosis (DVT). The objective of this study was to examine the correlation between DD results alongside WCP score with findings on venous duplex ultrasound (VDU). The hypothesis is that VDU remains overutilized in low-risk patients with negative DD and that higher DD levels may correlate with thrombus burden and location. METHODS: Patients who presented to a high-volume tertiary care center with lower limb swelling with or without associated pain were retrospectively examined through June and July for 4 consecutive years (2012 to 2015). After calculating WCP, patients were divided into low-, moderate-, and high-risk categories. Electronic DD results utilizing enzyme linked immunosorbent assay, WCP data, and VDU analysis data were merged and analyzed based on receiver operator characteristic curve to determine the DD cutoff point for each WCP. Abnormal DD with an average value ≥ 0.6 mg/L fibrinogen equivalent units (FEUs) was correlated to positive DVT to differentiate proximal DVT (above popliteal vein) from distal DVT (below popliteal vein). RESULTS: Data of 1,909 patients were analyzed, and 239 (12.5%) patients were excluded secondary to serial repeat visits or follow-ups, surveillance screens, and if they had a previous history of DVT. The average age was 62.1 ± 16.3 years with more women (55.7%) and the majority presented with limb pain and edema (87%). DD studies were ordered and completed in 202 patients and correlated with all positive and negative DVT patients (100% sensitivity and negative predictive value, with specificity and positive predictive value of 14.9% and 15.9%, respectively). Twenty-six of 202 patients had DD that were in the normal range 0.1-0.59 mg/L (FEU), all of which were negative for DVT (100% sensitive). Fifty one of 202 patients had DD values of 0.6-1.2 mg/L FEU, of which only 3 DVTs were recorded, and all of them were distal DVTs. In addition, 685 patients with WCP <1 and negative DD were sent for VDU. Thus, 762 patients had an unnecessary immediate VDU (Wells ≤1 and -DD) study during their initial presentation. Potential charge savings for VDU for all patients are 762 × $1,557 = $1,186,434 and DD for all patients are 762 × $182 = $138,684, with total potential savings of $1,047,750 (USD 2016). CONCLUSIONS: This study suggests that DD is still underutilized, and DD in conjunction with WCP could significantly reduce the number of unnecessary immediate VDUs. Higher value of DD (>1.2 mg/L FEU) may raise concern for proximal DVT. Concern on cost-effectiveness exists and raises the demand for a proposed algorithm to be followed.

Fluorescent Photoswitchable Diarylethenes for Biolabeling and Single-Molecule Localization Microscopies with Optical Superresolution.

A modular assembly of water-soluble diarylethenes (DAEs), applicable as biomarkers for optical nanoscopy, is reported. Reversibly photoswitchable 1,2-bis(2-alkyl-6-phenyl-1-benzothiophene-1,1-dioxide-3-yl)perfluorocyclopentenes possessing a fluorescent "closed" form were decorated with one or two methoxy group(s) attached to the para-position(s) of phenyl ring(s) and two, four, or eight carboxylic acid groups. Antibody conjugates of these DAEs feature low aggregation, efficient photoswitching in aqueous buffers, specific staining of cellular structures, and photophysical properties (high emission efficiencies and low cycloreversion quantum yields) enabling their application in superresolution microscopy. Images of tubulin, vimentin, and nuclear pore complexes are presented. The superresolution images can also be acquired by using solely 488 nm light without additional photoactivation with UV light. These DAEs exhibit reversible photoswitching without requiring any additives to the imaging media and open new paths toward the modular design of fluorescent dyes for bioimaging with optical superresolution.

Validation of subclavian duplex velocity criteria to grade severity of subclavian artery stenosis.

BACKGROUND: Validation of subclavian duplex ultrasound velocity criteria (SDUS VC) to grade the severity of subclavian artery stenosis has not been established or systematically studied. Currently, there is a paucity of published literature and lack of practitioner consensus for how subclavian duplex velocity findings should be interpreted in patients with subclavian artery stenosis. OBJECTIVE: The objective of the present study was to validate SDUS measurements using subclavian conventional or computed tomography angiogram (subclavian angiogram [SA])-derived measurements. Secondary objectives included measuring the correlation between SDUS peak systolic velocities and SA measurements, and to determine the optimal cutoff value for predicting significant stenosis (>70%). METHODS: This is a retrospective review of all patients with suspected subclavian artery stenosis and a convenience sample of carotid artery patients who underwent SDUS and SA from May 1999 to July 2013. SA reference vessel and intralesion minimal lumen diameters were measured and compared with SDUS velocities obtained within 3 months of the imaging study. Percent stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial method for detecting stenosis in a sufficiently large cohort. Receiver operating characteristic curves was generated for SDUS VC to predict >70% stenosis. Velocity cutoff points were determined with equal weighting of sensitivity and specificity. RESULTS: We examined 268 arteries for 177 patients. The majority of the arteries were for female patients (52.5%) with a mean age of 66.7 ± 11.1 years. Twenty-three arteries had retrograde vertebral artery flow and excluded from further analysis. For the remaining 245 arteries, the average peak systolic velocity was 212.6 ± 110.7 cm/s, with a range of 45-626 cm/s. Average stenosis was 25.8% ± 28.2%, with a range of 0% to 100%. Following receiver operating characteristic analysis, we found a cutoff value of >240 cm/s to be most predictive of >70%. Area under the curve was 0.94 with 95% confidence intervals of 0.91 to 0.97. The sensitivity and specificity for predicting >70% stenosis was 90.9 and 82.5%, respectively. CONCLUSIONS: In patients with known or suspected disease involving the great vessels, a subclavian artery flow velocity exceeding 240 cm/s seems to be predictive of significant subclavian stenosis. Thus, we propose new SDUS VC, for predicting subclavian artery stenosis. However, because of the use of a convenience sample, it is possible that the current proposed cutoff point might need to be adjusted for other populations.

Evidence-based medicine and contemporary certification: Analysis of the American Board of Vascular Medicine endovascular board examination.

Since 2005, the American Board of Vascular Medicine (ABVM) endovascular examination has been used to certify vascular practitioners. Annual rigorous review has confirmed it is psychometrically valid and reliable. However, the evidence basis underlying the examination items has not been studied systematically. The aim of this study was to adjudicate class of recommendation (COR) and level of evidence (LOE) for the 2015 ABVM endovascular examination and establish an additional feedback mechanism for examination improvement based on contemporary evidence-based guidelines. We performed a pooled consensus process to classify each of the 110 items in the 2015 ABVM endovascular examination by COR and LOE as detailed in the current guideline statements. We added additional categories for items that were not eligible for assignment using traditional current evidence-based metrics: 'COR X', cannot be determined, not applicable, or simple recognition; and 'LOE X', cannot be determined or not applicable. COR classifications were assigned in the following proportion: Class I=15%, Class II=40%, Class III=3%, COR X=42%. LOE classifications were assigned in the following proportion: Level A=12%, Level B=34%, Level C=32%, LOE X=22%. Our analysis showed that nearly half of the 2015 ABVM endovascular examination items were supported by strong scientific evidence or fact-based knowledge. COR and LOE analysis yielded notably different results. Use of alternate classification schema may be powerful tools for improving certification exams in healthcare.

Clinical Outcome of Carotid Artery Stenting According to Provider Specialty and Volume.

BACKGROUND: Several studies have demonstrated better outcomes for carotid endarterectomy with high-volume hospitals and providers. However, only a few studies have reported on the impact of operator specialty/volume on the perioperative outcome of carotid artery stenting (CAS). This study will analyze the correlation of CAS outcomes and provider specialty and volume. METHODS: Prospectively collected data of CAS procedures done at our institution during a 10-year period were analyzed. Major adverse events (MAEs; 30-day stroke, myocardial infarction, and death) were compared according to provider specialty (vascular surgeons [VSs], interventional cardiologists [ICs], interventional radiologists [IRs], interventional vascular medicine [IVM]), and volume (≥5 CAS/year vs. <5 CAS/year). RESULTS: Four hundred fourteen CAS procedures (44% for symptomatic indications) were analyzed. Demographics/clinical characteristics were somewhat similar between specialties. MAE rates were not significantly different between various specialties: 3.1% for IC, 6.3% for VS, 7.1% for IR, 6.7% for IVM (P = 0.3121; 6.3% for VS and 3.8% for others combined, P = 0.2469). When physicians with <5 CAS/year were excluded: the MAE rates were 3.1% for IC, 4.7% for VS, and 6.7% for IVM (P = 0.5633). When VS alone were compared with others, and physicians with <5 CAS/year were excluded, the MAE rates were 4.7% for VS vs. 3.6% for non-VS (P = 0.5958). The MAE rates for low-volume providers, regardless of their specialty, were 9.5% vs. 4% for high-volume providers (P = 0.1002). Logistic regression analysis showed that the odds ratio of MAE was 0.4 (0.15-1.1, P = 0.0674) for high-volume providers, while the odds ratio for VS was 1.3 (0.45-3.954, P = 0.5969). CONCLUSIONS: Perioperative MAE rates for CAS were similar between various providers, regardless of specialties, particularly for vascular surgeons with similar volume to nonvascular surgeons. Low-volume providers had higher MAE rates.

Issues related to renal artery angioplasty and stenting.

Renal artery stenosis may play a significant role in the pathogenesis of secondary hypertension, renal dysfunction, and flash pulmonary edema. Currently correction of renal arterial inflow stenosis is reserved for resistant hypertension patients who have failed maximal medical therapy, have worsening renal function and/or unexplained proximal congestive failure. With the recent advances in minimally invasive percutaneous stent placement techniques, open surgical revascularization has been largely replaced by renal artery stenting. The potential benefit of revascularization seemed intuitive; however, the initial enthusiasm and rise in the number of percutaneous interventions have been tempered by many subsequent negative randomized clinical trials that failed to prove the proposed benefits of the percutaneous intervention. The negative randomized trial results have fallen under scrutiny due to trial design concerns and inconsistent outcomes of these studies compared to pivotal trials undertaken under US Food and Drug Administration scrutiny. Treatment of atherosclerotic renal artery occlusive disease has become one of the most debatable topics in the field of vascular disease. The results from recent randomized clinical trials of renal artery stenting have basically limited the utilization of the procedure in many centers, but not every clinical scenario was covered in those trials. There are potential areas for improvement focusing mainly on procedural details and patient selection with respect to catheter based treatment of atherosclerotic renal artery stenosis. We believe, limiting patient selection, enrollment criteria and outcomes measured functioned to reduce the benefit of renal artery stenosis stenting by not enrolling patients likely to benefit. Future studies incorporating potential procedural improvements and that include patients more likely to benefit from renal stenting than were included in ASTRAL and CORAL are needed to more carefully examine specific patient subgroups so that "the baby is not thrown out with the bath water." We also discuss several other concerns related to renal artery stenting which include diagnostic, procedure, indication, and reimbursement issues.

Measuring image resolution in optical nanoscopy.

Resolution in optical nanoscopy (or super-resolution microscopy) depends on the localization uncertainty and density of single fluorescent labels and on the sample's spatial structure. Currently there is no integral, practical resolution measure that accounts for all factors. We introduce a measure based on Fourier ring correlation (FRC) that can be computed directly from an image. We demonstrate its validity and benefits on two-dimensional (2D) and 3D localization microscopy images of tubulin and actin filaments. Our FRC resolution method makes it possible to compare achieved resolutions in images taken with different nanoscopy methods, to optimize and rank different emitter localization and labeling strategies, to define a stopping criterion for data acquisition, to describe image anisotropy and heterogeneity, and even to estimate the average number of localizations per emitter. Our findings challenge the current focus on obtaining the best localization precision, showing instead how the best image resolution can be achieved as fast as possible.

Avoiding collateral damage in the war on hypertension.

When performed by experienced clinicians, renal nerve denervation (RND) can be done with very low risk of complication and/or acute renal injury Renal function seems to remain unchanged in this small series over 3 years More studies are needed to establish the role of renal biomarkers in assessment of acute renal injury in this setting and larger series of RND in azotemic patients should be done before the procedure indications can be expanded.

Update on intervention versus medical therapy for atherosclerotic renal artery stenosis.

Atherosclerotic renal artery stenosis is known to be one of the most common causes of secondary hypertension, and early nonrandomized studies suggested that renal artery stenting (RASt) improved outcomes. The vascular community embraced this less invasive treatment alternative to surgery, and RASt increased in popularity during the late 1990s. However, recent randomized studies have failed to show a benefit regarding blood pressure or renal function when RASt was compared with best medical therapy, creating significant concerns about procedural efficacy. In the wake of these randomized trial results, hypertension and renal disease experts along with vascular interventional specialists now struggle with how to best manage atherosclerotic renal artery stenosis. This review objectively analyzes the current literature and highlights each trial's design weaknesses and strengths. We have provided our recommendations for contemporary treatment guidelines based on our interpretation of the available empirical data.

Anatomic and clinical predictors of reintervention after subclavian artery stenting.

OBJECTIVE: This study was conducted to determine long-term predictors of target lesion reintervention (TLR) after subclavian artery stenting (SAS). METHODS: This was a single-center retrospective review of patients with symptomatic atherosclerotic subclavian artery disease who underwent SAS between January 1999 and December 2013. Repeat intervention was only performed in patients with recurrent symptoms and ≥70% in-stent restenosis (ISR). TLR was defined as need for a repeat percutaneous intervention involving a previously stented area. Freedom from events (ISR and TLR) was analyzed using Kaplan-Meier curves. Cox regression analysis was used to determine the significant predictors of TLR and ISR. RESULTS: Index procedures were performed on 139 arteries in 138 patients (69.6% female). Patients were an average age of 64.5 years, with major comorbidities of hypertension (80.4%), hyperlipidemia (72.5%), and tobacco use (60.1%). Also performed during the study period were 24 TLR procedures, resulting 166 SAS interventions attempted for patients with subclavian atherosclerotic disease during a 15-year span. Of 166 procedures, 163 (98.2%) were treated successfully. Stents were placed in all but two index arteries. The main indications for SAS were subclavian steal syndrome (48.9%), arm claudication (21.6%), and coronary steal syndrome (28.8%). The average preprocedure stenosis was 87.2% ± 11.2%. For index procedures (139 arteries), duplex follow-up was available for 134 arteries (96.4%), with an overall ISR rate of 18.7% (25 of 134). Primary patency for the index procedures was 84.7% at 10 years. The overall TLR rate for the index procedures was 12.7% (17 cases). Seven patients required more than one secondary procedure. For all cases, the freedom from ISR was 91%, 77%, and 68% at 1, 5, and 10 years, respectively, and freedom from TLR was 94%, 85%, and 82% at 1, 5, and 10 years, respectively. Multivariate analysis showed the significant predictors of ISR were smoking/chronic obstructive pulmonary disease (hazard ratio [HR], 3.2; P = .001), age by decade (HR, 0.5; P < .001), discharged with statin therapy (HR, 0.3; P = .001), vessel diameter ≤7 mm (HR, 2.3; P = .028), and right-sided intervention (HR, 0.3; P = .040). The sole significant predictor of TLR was age by decade (HR, 0.6; P = .008). CONCLUSIONS: SAS has a high primary success and durability with satisfactory outcomes well beyond 10 years. ISR was more likely to develop in patients who were smokers with chronic obstructive disease or had a baseline vessel size of ≤7 mm. Younger age could be an independent risk factor for secondary intervention.