A Quantitative Analysis of Publication Trends in Vascular Surgery and a Comparative Analysis with Interventional Radiology.

BACKGROUND: Since its recognition as an independent surgical subspecialty, vascular surgery has experienced rapid growth in both surgical volume and research productivity. Trends in vascular surgery research have not been well characterized. Understanding how research in the field has evolved in comparison to interventional radiology can offer insights into evolving interests and discrepancies between the specialties. METHODS: Primary and secondary research publications indexed in the MEDLINE database from 1992 to 2023 were analyzed using a novel text mining algorithm. Eight high-impact vascular surgery journals and 6 interventional radiology journals were included. Articles were categorized based on treatment modalities, pathologies, and other subgroup analyses. Temporal trends were assessed using linear regression and correlation analysis. A comparative analysis was performed assessing publication trends by broad pathology groups between vascular surgery and interventional radiology journals. A further subgroup analysis was conducted comparing publication trends by endovascular treatment modality for peripheral arterial disease (PAD). RESULTS: 28,931 vascular surgery publications and 13,094 interventional radiology publications met the inclusion criteria. Publication volume grew exponentially, with over 50% emerging in the last decade. Publications exploring endovascular interventions have increasingly exceeded those focused on exclusively open interventions in research volume since 2006. Aortic pathology, carotid disease, PAD, and venous pathology represented the vast majority of vascular surgery research output, with PAD exhibiting the fastest growth. Comparative analysis revealed a number of key differences in research focus and treatment modalities between vascular surgery and interventional radiology, including a greater emphasis on venous pathology in interventional radiology journals and fewer relative publications on carotid artery pathology (P < 0.001). When comparing endovascular treatments for PAD, interventional radiology journals published more frequently on endovascular brachytherapy (8.73% vs 1.02%, P < 0.001) and less frequently on atherectomy (4.29% vs 6.50%, P = 0.035) as compared to the vascular surgery journals. CONCLUSIONS: Our findings demonstrate increasing emphasis on endovascular interventions and specific pathologies in vascular surgery research. Despite some key differences, there is notable overlap in interests between vascular surgery and interventional radiology, which may represent promising opportunities for collaboration in advancing endovascular procedures. Differences in research focus may stem from specialty perspectives and be perpetuated by differences in training.

Rapid single-photon color imaging of moving objects.

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

Risk factors for spinal cord injury and complications of cerebrospinal fluid drainage in patients undergoing fenestrated and branched endovascular aneurysm repair.

OBJECTIVE: Spinal cord injury (SCI) is one of the most devastating complications of thoracoabdominal aortic aneurysm (TAAA) repair. Cerebrospinal fluid drainage (CSFD) is routinely used to prevent and to treat SCI during open TAAA repair. However, the risks and benefits of CSFD during fenestrated-branched endovascular aneurysm repair (F/B-EVAR) are unclear. This study aimed to determine the risk of SCI after F/B-EVAR and to assess the risks and benefits of CSFD. METHODS: We analyzed 106 consecutive patients with TAAAs treated with F/B-EVAR from 2014 to 2019 in a prospective physician-sponsored investigational device exemption study (G130193). Data were collected prospectively and audited by an independent external monitor. All patients were treated with Cook manufactured patient-specific F/B-EVAR devices or the Cook t-Branch devices (Cook Medical, Bloomington, Ind). CSFD was used at the discretion of the principal investigator. Risk factors for SCI were identified, and CSFD complications were assessed. RESULTS: Prophylactic CSFD was used in 78 patients (73.6%), and 28 patients (26.4%) underwent F/B-EVAR without CSFD. Four patients (3.8%) with prophylactic CSFD developed SCI, including two patients (1.9%) with permanent paraplegia (Tarlov grade 1-2) and two patients (1.9%) with paraparesis (Tarlov grade 3). Multivariate analysis revealed that greater extent of thoracic aortic coverage (odds ratio, 1.06; 95% confidence interval, 1.00-1.11; P = .02) and intraoperative blood loss (odds ratio, 1.00; 95% confidence interval, 1.00-1.002; P = .04) were the significant risk factors for SCI. Six patients (7.6% [6/78]) experienced major CSFD-related complications, including subarachnoid hemorrhage in 2.6% (2), spinal hematoma in 2.6% (2), cerebellar hemorrhage in 1.3% (1), and spinal drain fracture requiring surgical laminectomy in 1.3% (1). Minor CSFD-related complications occurred in 20 patients (25.6% [20/78]), including paresthesia during CSFD insertion (10), minimal bloody cerebrospinal fluid (7), drain malfunction (2), and reflex hypotension (1). Technical difficulties during CSFD catheter placement were noted in seven patients (9.0%). Excluding four patients with SCI, intensive care unit stay was 3.3 ± 4.0 days in the CSFD group vs 1.2 ± 0.9 days in the no-CSFD group (P = .007). Total hospital length of stay was 6.0 ± 4.9 days in the CSFD group vs 3.5 ± 1.9 days in the no-CSFD group (P = .01). CONCLUSIONS: The incidence of SCI after F/B-EVAR with selective CSFD was low, and risk factors for SCI were greater with extent of thoracic aortic coverage and intraoperative blood loss. However, the incidence of major CSFD-related complications exceeded the incidence of SCI, and CSFD significantly increased both intensive care unit and total hospital length of stay. Therefore, routine prophylactic CSFD may not be justified, and a prospective randomized trial of CSFD in patients undergoing F/B-EVAR seems appropriate.

Retrograde Endovascular With Intimal Re-Entry Through Endarterectomy: The REWIRE Technique.

OBJECTIVE: Hybrid lower extremity revascularization has been well described, typically consisting of common femoral endarterectomy (CFE) followed by direct patch puncture and endovascular treatment of any distal disease. We describe a modified technique that obviates the need for endovascular re-entry and simplifies treatment at the proximal and distal endpoints. METHODS: The REWIRE technique begins with retrograde arterial access via a patent tibial, pedal or femoropopliteal vessel. The diseased segment is crossed in the subintimal plane. Once the wire reaches the common femoral artery (CFA), the vessel is surgically exposed. Arteriotomy is performed and the wire is externalized during standard CFE. With through-wire access achieved, a sheath is inserted and the distal disease is treated. The proximal extent of the endovascular revascularization is incorporated into a standard CFE with patch angioplasty. RESULTS: Seven patients with chronic limb-threatening ischemia were treated with this approach, all with long segment occlusions of the SFA and significant CFA disease. The SFA disease was stented and bovine pericardial patch was used for CFE in all. Technical success was achieved in all patients. There were no complications related to the retrograde puncture site, which was controlled with manual pressure (4) or excluded with a covered stent (3). Thirty-Day freedom from major adverse limb events was 100%. CONCLUSIONS: The REWIRE technique is an effective approach to hybrid revascularization involving the CFA. By crossing the occluded segment in a retrograde fashion and surgically externalizing the wire during CFE, the proximal and distal endpoints can be addressed with ease, the profunda femoris is protected under direct visualization, and the need for endovascular re-entry is eliminated.

Endovascular management of a large renal artery aneurysm: a case report and review of the literature.

BACKGROUND: A renal artery aneurysm is a rare clinical presentation that can be found incidentally on imaging or during workup for refractory hypertension. Its presentation can be similar to that of a renal artery pseudoaneurysm, but the etiologies of the two vascular lesions differ. We present a patient who had an incidental finding of a large renal artery aneurysm that was managed with endovascular embolization. We also describe the literature surrounding the etiology, presentation and management of both renal artery aneurysms and renal artery pseudoaneurysms. CASE PRESENTATION: A 62-year-old man was referred to a urologic oncologist for workup of a newly found renal mass. Initial imaging with computed tomography showed a homogenous, well-circumscribed mass arising from the right kidney. Further evaluation with Doppler ultrasonography demonstrated pulsatile flow within the renal mass that was concerning for a renal artery pseudoaneurysm. The patient initially underwent a diagnostic angiogram by interventional radiology and was found to have a true renal artery aneurysm. Interventional radiology considered placement of a covered stent or angioembolization, but treatment was deferred due to concern for compromising the patient's renal function. Patient was subsequently transferred to a neighboring hospital for management by vascular surgery. After considering both open surgical and endovascular approaches, the patient ultimately underwent angioembolization of the renal artery aneurysm. Short-term follow-up showed successful exclusion of the aneurysm with minimal adverse effects to the patient. CONCLUSIONS: Our case report documents a unique case of an incidentally found large renal artery aneurysm that was successfully managed with endovascular embolization. Renal artery aneurysms and renal artery pseudoaneurysms, which can present similarly on imaging, are important diagnostic considerations in a patient presenting with a new renal mass. While open surgical approaches can be used to repair aneurysms, endovascular approaches using stenting or angioembolization are safe and effective options for treating renal aneurysms and renal pseudoaneurysms.

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer.

BACKGROUND: Antiandrogens are effective therapies that block androgen receptor (AR) transactivation and signaling in over 50% of castration-resistant prostate cancer (CRPC) patients. However, an estimated 30% of responders will develop resistance to these therapies within 2 years. JNJ-pan-AR is a broad-spectrum AR antagonist that inhibits wild-type AR as well as several mutated versions of AR that have emerged in patients on chronic antiandrogen treatment. In this work, we aimed to identify the potential underlying mechanisms of resistance that may result from chronic JNJ-pan-AR treatment. METHODS: The LNCaP JNJR prostate cancer subline was developed by chronically exposing LNCaP parental cells to JNJ-pan-AR. Transcriptomic and proteomic profiling was performed to identify potential drivers and/or biomarkers of the resistant phenotype. RESULTS: Several enzymes critical to intratumoral androgen biosynthesis, Aldo-keto reductase family 1 member C3 (AKR1C3), UGT2B15, and UGT2B17 were identified as potential upstream regulators of the JNJ-pan-AR resistant cells. While we confirmed the overexpression of all three enzymes in the resistant cells only AKR1C3 expression played a functional role in driving JNJ-pan-AR resistance. We also discovered that AKR1C3 regulates UGT2B15 and UGT2B17 expression in JNJ-pan-AR resistant cells. CONCLUSIONS: This study supports the rationale to further investigate the benefits of AKR1C3 inhibition in combination with antiandrogens to prevent CRPC disease progression.

Pharmacologic Characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a Reversible, Selective, and Potent Monoacylglycerol Lipase Inhibitor.

The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. Inhibition of 2-AG degradation leads to elevation of 2-AG, the most abundant endogenous agonist of the cannabinoid receptors (CBs) CB1 and CB2. Activation of these receptors has demonstrated beneficial effects on mood, appetite, pain, and inflammation. Therefore, MAGL inhibitors have the potential to produce therapeutic effects in a vast array of complex human diseases. The present report describes the pharmacologic characterization of [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone (JNJ-42226314), a reversible and highly selective MAGL inhibitor. JNJ-42226314 inhibits MAGL in a competitive mode with respect to the 2-AG substrate. In rodent brain, the compound time- and dose-dependently bound to MAGL, indirectly led to CB1 occupancy by raising 2-AG levels, and raised norepinephrine levels in cortex. In vivo, the compound exhibited antinociceptive efficacy in both the rat complete Freund's adjuvant-induced radiant heat hypersensitivity and chronic constriction injury-induced cold hypersensitivity models of inflammatory and neuropathic pain, respectively. Though 30 mg/kg induced hippocampal synaptic depression, altered sleep onset, and decreased electroencephalogram gamma power, 3 mg/kg still provided approximately 80% enzyme occupancy, significantly increased 2-AG and norepinephrine levels, and produced neuropathic antinociception without synaptic depression or decreased gamma power. Thus, it is anticipated that the profile exhibited by this compound will allow for precise modulation of 2-AG levels in vivo, supporting potential therapeutic application in several central nervous system disorders. SIGNIFICANCE STATEMENT: Potentiation of endocannabinoid signaling activity via inhibition of the serine hydrolase monoacylglycerol lipase (MAGL) is an appealing strategy in the development of treatments for several disorders, including ones related to mood, pain, and inflammation. [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone is presented in this report to be a novel, potent, selective, and reversible noncovalent MAGL inhibitor that demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol as well as efficacy in models of neuropathic and inflammatory pain.

The discovery of diazetidinyl diamides as potent and reversible inhibitors of monoacylglycerol lipase (MAGL).

Monoacylglycerol lipase (MAGL) has emerged as an attractive drug target because of its important role in regulating the endocannabinoid 2-arachidonoylglycerol (2-AG) and its hydrolysis product arachidonic acid (AA) in the brain. Herein, we report the discovery of a novel series of diazetidinyl diamide compounds 6 and 10 as potent reversible MAGL inhibitors. In addition to demonstrating potent MAGL inhibitory activity in the enzyme assay, the thiazole substituted diazetidinyl diamides 6d-l and compounds 10 were also effective at increasing 2-AG levels in a brain 2-AG accumulation assay in homogenized rat brain. Furthermore, selected compounds have been shown to achieve good brain penetration after oral administration in an animal study.

The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors.

Monoacylglycerol lipase (MAGL) is the enzyme that is primarily responsible for hydrolyzing the endocannabinoid 2-arachidononylglycerol (2-AG) to arachidonic acid (AA). It has emerged in recent years as a potential drug target for a number of diseases. Herein, we report the discovery of compound 6g from a series of azetidine-piperazine di-amide compounds as a potent, selective, and reversible inhibitor of MAGL. Oral administration of compound 6g increased 2-AG levels in rat brain and produced full efficacy in the rat complete Freund's adjuvant (CFA) model of inflammatory pain.

Carbon Dioxide Angiography in the Treatment of Transplant Renal Artery Stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a serious complication associated with graft loss. Selective carbon dioxide angiography allows for effective diagnosis and therapy with the use of minimal to no contrast agent. This study sought to evaluate the efficacy of the adjunctive use of carbon dioxide angiography in the treatment of TRAS. METHODS: Patients undergoing endovascular therapy (percutaneous transluminal angioplasty with or without stent) for TRAS between the years 2012 and 2017 at a single tertiary care academic medical center were studied. Outcomes of interest included technical success, postoperative glomerular filtration rate, and renal ultrasound hemodynamic parameters. RESULTS: Of the 37 patients who underwent angiography for TRAS during the study period, 34 underwent a therapeutic intervention. Of those, 24 patients (70.6%) underwent adjunctive carbon dioxide angiography versus 10 patients (29.4%) who underwent standard contrast angiography. Baseline characteristics between the carbon dioxide angiography and traditional angiography groups were similar. Patients undergoing carbon dioxide angiography received significantly less contrast agent than patients undergoing traditional angiography [9.5 mL (IQR 2-19.5) versus 19.5 mL (IQR 15-30), P = 0.03)] and maintained equivalent technical success rates (92.2% vs. 91.7%, P = 0.9). CONCLUSIONS: The adjunctive use of carbon dioxide angiography allows for significantly less contrast administration compared with standard angiography while achieving an equivalent rate of technical success. Selective carbon dioxide angiography should be considered a first-line modality for patients with TRAS in need of endovascular therapy.

High concentration factor diffractive microlenses integrated with CMOS single-photon avalanche diode detector arrays for fill-factor improvement.

Large-format single-photon avalanche diode (SPAD) arrays often suffer from low fill-factors-the ratio of the active area to the overall pixel area. The detection efficiency of these detector arrays can be vastly increased with the integration of microlens arrays designed to concentrate incident light onto the active areas and may be refractive or diffractive in nature. The ability of diffractive optical elements (DOEs) to efficiently cover a square or rectangular pixel, combined with their capability of working as fast lenses (i.e., ∼f/3) makes them versatile and practical lens designs for use in sparse photon applications using microscale, large-format detector arrays. Binary-mask-based photolithography was employed to fabricate fast diffractive microlenses for two designs of 32×32 SPAD detector arrays, each design having a different pixel pitch and fill-factor. A spectral characterization of the lenses is performed, as well as analysis of performance under different illumination conditions from wide- to narrow-angle illumination (i.e., f/2 to f/22 optics). The performance of the microlenses presented exceeds previous designs in terms of both concentration factor (i.e., increase in light collection capability) and lens speed. Concentration factors greater than 33× are achieved for focal lengths in the substrate material as short as 190µm, representing a microlens f-number of 3.8 and providing a focal spot diameter of <4µm. These results were achieved while retaining an extremely high degree of performance uniformity across the 1024 devices in each case, which demonstrates the significant benefits to be gained by the implementation of DOEs as part of an integrated detector system using SPAD arrays with very small active areas.

Discovery and optimization of a series of small-molecule allosteric inhibitors of MALT1 protease.

We describe a series of potent and highly selective small-molecule MALT1 inhibitors, optimized from a High-Throughput Screening hit. Advanced analogues such as compound 40 show high potency (IC50: 0.01 µM) in a biochemical assay measuring MALT1 enzymatic activity, as well as in cellular assays: Jurkat T cell activation (0.05 µM) and IL6/10 secretion (IC50: 0.10/0.06 µM) in the TMD8 B-cell lymphoma line. Compound 40 also inhibited cleavage of the MALT1 substrate RelB (IC50: 0.10 µM). Mechanistic enzymology results suggest that these compounds bind to the known allosteric site of the protease.

Safety and Effectiveness of Percutaneous Axillary Artery Access for Complex Aortic Interventions.

BACKGROUND: The aim of this study is to evaluate the safety and effectiveness of percutaneous axillary artery access in patients requiring upper extremity large sheath access during complex aortic interventions. METHODS: Consecutive patients who had percutaneous axillary artery access with a large-bore sheath during endovascular thoracoabdominal aortic artery aneurysm repair within an Food and Drug Administration-approved, physician-sponsored investigational device exemption study or visceral artery interventions during other complex aortic interventions were included in the study. All patients had percutaneous axillary artery ultrasound-guided access and deployment of 2 Perclose ProGlide devices (Abbott Vascular, Santa Clara, CA) prior to introduction of a large sheath. Completion angiography was performed to assess technical success of percutaneous access site closure, which was defined as hemostatic arterial closure without evidence of axillary artery stenosis or occlusion requiring intervention. Follow-up computed tomography scans and patient records were also reviewed for access site associated complications. RESULTS: A total of 46 patients underwent percutaneous axillary artery access. Largest sheath profile was 16F in 1 (2%), 12F in 42 (91%), 10F in 1 (2%), 9F in 1 (2%), and 8F in 1 (2%) patient. Technical success was achieved in 41 of 46 patients (89%). Five patients required endovascular covered stent placement during the index operation to control persistent access site bleeding. Two of 46 patients (4%) suffered access-related complications; both patients experienced ipsilateral upper extremity paresthesias without motor weakness, with persistent digit numbness in one. There was no incidence of conversion to open axillary artery repair and no additional access site complications (stenosis, occlusion, or dissection) but neurologic complications were observed during follow-up. CONCLUSIONS: Percutaneous axillary artery access can be used to provide upper extremity arterial access during complex aortic interventions with high rates of safety and technical success. Overall complication rates are low and occurred mainly during the early experience, indicating that there is an associated learning curve effect. Elimination of surgical cutdown incisions and arterial conduits by using percutaneous axillary access may reduce operative times and wound-related complications during complex aortic interventions requiring large-bore upper extremity access.

Safety and Effectiveness of Retrograde Arterial Access for Endovascular Treatment of Critical Limb Ischemia.

BACKGROUND: Retrograde arterial access (RA) of the popliteal, tibial, or pedal arteries may facilitate endovascular treatment of complex infrainguinal lesions in patients with critical limb ischemia (CLI). Here, we assess the safety and efficacy of this technique. METHODS: A retrospective review of prospectively collected institutional data (consecutive M2S entries) was performed to identify patients with CLI undergoing peripheral vascular intervention from February 2012 through December 2017. Demographics, comorbidities, procedural characteristics, and outcomes were analyzed, and comparisons were made between outcomes of patients undergoing RA and those undergoing a standard antegrade access (SA) approach. RESULTS: Five hundred sixty-six patients were identified, of whom 26 (4.6%) underwent RA. Of these, 4 were accessed via the popliteal artery (15.4%), 13 via the tibial vessels above the ankle (50.0%), and 9 via pedal vessels (34.6%). RA facilitated procedural success in 96.2% of cases. There were no instances of distal embolization, perforation, or loss of distal target with RA. Primary, primary assisted, and secondary patency rates were consistently lower for RA patients than for SA patients, as was limb salvage and amputation-free survival. No difference was seen in overall survival. CONCLUSIONS: RA represents a viable and safe option for revascularization when SA fails. Although outcomes are poorer than SA, this technique can be useful in CLI patients, especially when open surgical revascularization is not an option.

Transradial interventions in contemporary vascular surgery practice.

OBJECTIVES: Upper extremity arterial access is often required for endovascular procedures, especially for antegrade access to the visceral aortic branches. Radial arterial access has been shown previously to have low complication rates, and patients tolerate the procedure well and are able to recover quickly. However, transradial access remains relatively uncommon amongst vascular surgeons. METHODS: The radial artery was evaluated by ultrasound to evaluate for adequate caliber, and to identify any aberrant anatomy or arterial loops. A modified Barbeau test was performed to ensure sufficient collateral circulation. A cocktail of nitroglycerin, verapamil and heparin was administered intra-arterially to combat vasospasm. Sheaths up to 6 French were utilized for interventions. On completion of the procedure, a compression band was used for hemostasis in all cases. RESULTS: Twenty-five interventions were performed in 24 patients. The left radial artery was used in 23/25 cases (92.0%). Procedures included visceral and renal artery interventions; stent graft repair of a renal artery aneurysm; embolization of splenic, pancreaticoduodenal and internal mammary aneurysms; embolization of bilateral hypogastric arteries following blunt pelvic trauma; interventions for peripheral arterial disease; delivery of a renal snorkel graft during endovascular aortic aneurysm repair, and access for diagnostic catheters during thoracic endovascular aortic aneurysm repair. Technical success was 92.0%. There was one post-operative radial artery occlusion (4.3%) which led to paresthesias but resolved with anticoagulation. There were no instances of arterial rupture, hematoma, or hand ischemia requiring intervention. CONCLUSIONS: Using the transradial approach, we have demonstrated a high technical success rate over a range of clinical contexts with minimal morbidity and no significant complications such as bleeding or hand ischemia. The safety profile compares favorably to historical complication rates from brachial access. Radial access is a safe and useful skill for vascular surgeons to master.

Analysis of the Learning Curve and Patient Outcomes of Endovascular Repair of Thoracoabdominal Aortic Aneurysms Using Fenestrated and Branched Stent Grafts: Prospective, Nonrandomized, Single-center Physician-sponsored Investigational Device Exemption Clinical Study.

OBJECTIVE: To evaluate the outcomes and learning curve of fenestrated and branched endovascular repair (F/BEVAR) of thoracoabdominal aneurysms. SUMMARY OF BACKGROUND DATA: Endovascular aneurysm repair has reduced morbidity and mortality compared with open surgical repair. However, application to thoracoabdominal aneurysm repair remains limited by procedural complexity and device availability. METHODS: Fifty patients treated in a prospective, nonrandomized, single-center Investigational Device Exemption (IDE) study between January 2014 and July 2017 were analyzed. Patients (mean age 75.6 ±â€Š7.5 years; mean aneurysm diameter 67.3 ±â€Š9.8 mm) underwent F/BEVAR of thoracoabdominal aneurysms (58% type IV; 42% type I-III) using custom-manufactured endografts. The experience was divided into 3 cohorts (Early: 1 to 17; Mid: 18 to 34; Late: 35 to 50) to evaluate learning curve effects on key process measures. RESULTS: F/BEVAR included 194 visceral arteries (average 3.9 per patient). Technical success was 99.5% (193/194 targeted arteries). Thirty-day major adverse events (MAEs) included 3 (6%) deaths, 1 (2%) new-onset dialysis, 3 (6%) paraparesis/paraplegia, and 2 (4%) strokes. One-year survival was 79 ±â€Š7%. Comparing the Early and Late groups revealed reductions in procedure time (452 ±â€Š74 vs 362 ±â€Š53 minutes; P = 0.0001), fluoroscopy time (130 ±â€Š40 vs 99 ±â€Š27 minutes; P = 0.016), contrast administration (157 ±â€Š73 vs 108 ±â€Š38 mL; P = 0.028), and estimated blood loss (EBL; 1003 ±â€Š933 vs 481 ±â€Š317 mL; P = 0.042). Intensive care unit (ICU) and total length of stay (LOS) decreased from 4 ±â€Š3 to 2 ±â€Š1 days and from 7 ±â€Š6 to 5 ±â€Š2 days, respectively, but was not statistically significant. CONCLUSIONS: Use of F/BEVAR for treatment of thoracoabdominal aneurysms is safe and effective. During this early experience, there was a significant improvement in key process measures reflecting improvements in technique and physician learning over time.

High-resolution depth profiling using a range-gated CMOS SPAD quanta image sensor.

A CMOS single-photon avalanche diode (SPAD) quanta image sensor is used to reconstruct depth and intensity profiles when operating in a range-gated mode used in conjunction with pulsed laser illumination. By designing the CMOS SPAD array to acquire photons within a pre-determined temporal gate, the need for timing circuitry was avoided and it was therefore possible to have an enhanced fill factor (61% in this case) and a frame rate (100,000 frames per second) that is more difficult to achieve in a SPAD array which uses time-correlated single-photon counting. When coupled with appropriate image reconstruction algorithms, millimeter resolution depth profiles were achieved by iterating through a sequence of temporal delay steps in synchronization with laser illumination pulses. For photon data with high signal-to-noise ratios, depth images with millimeter scale depth uncertainty can be estimated using a standard cross-correlation approach. To enhance the estimation of depth and intensity images in the sparse photon regime, we used a bespoke clustering-based image restoration strategy, taking into account the binomial statistics of the photon data and non-local spatial correlations within the scene. For sparse photon data with total exposure times of 75 ms or less, the bespoke algorithm can reconstruct depth images with millimeter scale depth uncertainty at a stand-off distance of approximately 2 meters. We demonstrate a new approach to single-photon depth and intensity profiling using different target scenes, taking full advantage of the high fill-factor, high frame rate and large array format of this range-gated CMOS SPAD array.

Design and synthesis of a series of bioavailable fatty acid synthase (FASN) KR domain inhibitors for cancer therapy.

We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC50 = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC50 = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect. Compound 34 is also active in many other cell types, including PC3M (IC50 = 25 nM) and LnCaP-Vancouver prostate cells (IC50 = 66 nM), and is highly bioavailable (F 61%) with good exposure after oral administration. In a pharmacodynamics study in H460 lung xenograft-bearing mice, oral treatment with compound 34 results in elevated tumor levels of malonyl-CoA and decreased tumor levels of palmitate, fully consistent with the desired target engagement.

Risk Factors for Suboptimal Utilization of Statins and Antiplatelet Therapy in Patients Undergoing Revascularization for Symptomatic Peripheral Arterial Disease.

BACKGROUND: The objective of this study was to identify risk factors for suboptimal medical therapy (defined as reported antiplatelet and statin use) among patients undergoing lower extremity bypass (LEB) and peripheral vascular interventions (PVIs) for symptomatic peripheral arterial disease (PAD). METHODS: The Vascular Study Group of Greater New York (VSGGNY) database was used to identify all patients undergoing PVI or LEB for PAD (2011-2013). Bivariate analyses were performed to identify characteristics of patients who were not prescribed statins and/or antiplatelet agents before revascularization. Multivariate relative risk regression models were developed to identify patients at risk for suboptimal therapy, with regards to antiplatelet and statin therapy. RESULTS: About 1,030 patients underwent endovascular therapy (n = 822; 80%) or surgical bypass (n = 208; 20%) for symptomatic PAD (57.2% claudication; 15% rest pain and 27.8% tissue loss). Overall, preoperative statin use was observed in 59%. Preoperative antiplatelet therapy was observed in 79% of patients. Bivariate analysis revealed comparatively reduced statin use among patients without other cardiovascular risk factors including hypertension (63% vs. 39.3%; P < 0.0001) and coronary artery disease (CAD) with or without prior cardiac revascularization (coronary artery bypass grafting [CABG]/percutaneous coronary intervention [PCI]; 75.2% vs. 47.4%; P < 0.0001). Multivariate relative risk regression confirmed higher rates of statin use among patients with other cardiovascular risk factors including hypertension (1.14 [1.02-1.27]; P = 0.02) and CAD with prior CABG/PCI (1.22 [1.13-1.31]; P < 0.0001). Reduced statin use was observed in patients over 80 years old. (0.92 [0.84-0.1.0]; P = 0.059). By multivariate regression, antiplatelet therapy use was associated with CAD and/or prior CABG/PCI (1.11 [1.04-1.17]; P = 0.0015) and prior peripheral revascularization (1.07 [1.01-1.13]; P = 0.03). CONCLUSIONS: Patients with symptomatic PAD, but without an antecedent cardiovascular history, are less likely to be optimally managed with statins and antiplatelet therapy preoperatively. Given the established role of these medications in the optimal medical management of patients with PAD, this presents an opportunity for improvement in the overall vascular care of patients undergoing intervention for symptomatic PAD at VSGGNY centers.

Impact of surgeon and hospital experience on outcomes of abdominal aortic aneurysm repair in New York State.

OBJECTIVE: This study aimed to assess the impact of the surgeon's and hospital's experience on the outcomes of open surgical repair (OSR) and endovascular aneurysm repair (EVAR) of intact and ruptured abdominal aortic aneurysms (AAAs) in New York State. METHODS: New York Statewide Planning and Research Cooperative System data were used to identify patients undergoing AAA repair from 2000 to 2011. Characteristics of the provider and hospital were determined by linkage to the New York Office of Professions and National Provider Identification databases. Distinct hierarchical logistic regression models for EVAR and OSR for intact and ruptured AAAs were created to adjust for the patient's comorbidities and to evaluate the impact of the surgeon's and hospital's experience on outcomes. The provider's years since medical school graduation as well as annual volume of the facility and provider are examined in tertiles. Adjusted odds ratios and 95% confidence intervals are presented. RESULTS: A total of 18,842 patients underwent AAA repair by a vascular surgeon. For intact AAAs (n = 17,118), 26.2% of patients underwent OSR and 73.8% underwent EVAR. For ruptured AAAs (n = 1724), 63.9% underwent OSR and 36.1% underwent EVAR. After intact AAA repair, OSR adjusted outcomes were significantly influenced by the surgeon's annual volume but not by the facility's volume or the surgeon's age. The lowest volume providers (1-4 OSRs) had higher in-hospital mortality rates than high-volume (>11 OSRs) surgeons (adjusted odds ratio, 1.87 [95% confidence interval, 1.1-3.17]). Low-volume providers also had higher odds of major complications (1.23 [1-1.51]). For patients with intact AAA undergoing EVAR, mortality was higher at low-volume facilities (2.6 [1.3-5.3] and 2.7 [1.5-4.8] for <33 EVARs and 34-81 EVARs, respectively). After OSR for ruptured AAA, treatment at a low-volume facility (<9 OSRs for ruptured AAA) was associated with greater mortality than at high-volume (>27 OSRs for ruptured AAA) centers (1.56 [1.02-2.39]), whereas low-volume physicians (<4 OSRs for ruptured AAA) had higher odds of major complications (1.58 [1.04-2.41]). In the case of EVAR for rupture, there were no characteristics of the hospital or surgeon significantly associated with poorer outcomes. CONCLUSIONS: For intact AAA, the surgeon's volume was an important factor for OSR outcomes, whereas low facility volume was associated with worse outcomes after EVAR. For ruptured AAA, low-volume surgeons and low-volume facilities had worse outcomes after OSR but not after EVAR. The interaction between the surgeon's volume and the hospital's volume is complex and varies on the basis of the acuity of presentation and treatment modality.