Genomics reaches the clinic: from basic discoveries to clinical impact.

Today, more than ever, basic science research provides significant opportunities to advance our understanding about the genetic basis of human disease. Close interactions among laboratory, computational, and clinical research communities will be crucial to ensure that genomic discoveries advance medical science and, ultimately, improve human health.

Surgical shortening of lengthened iliac arteries in endurance athletes: Short-term and long-term satisfaction.

OBJECTIVE: Endurance athletes are prone to develop flow limitations in iliac arteries (FLIA). Especially in cyclists and ice speed skaters, excessive hemodynamic loading coupled with hip hyperflexion may cause kinking in lengthened iliac arteries necessitating surgical correction. This study investigated the short-term (≤1.5 years) and long-term (≥5 years) satisfaction of operative shortening of the iliac artery in endurance athletes. METHODS: All patients who were diagnosed and operated for FLIA owing to lengthened and kinked iliac arteries between 1997 and 2015 in one center were analyzed. Short-term follow-up consisted of an incremental maximal cycling test, ankle-brachial index with flexed hips, echo-Doppler examination with peak systolic velocity measurements and contrast-enhanced magnetic resonance angiography before and 6 to 18 months after surgery. Both short- and long-term satisfaction were assessed using questionnaires. RESULTS: A total of 83 patients (90 operated legs; 96.7% males; median age of 34 years at the time of surgery; interquartile range [IQR], 29-47) were analyzed. In the short-term, 87.5% reported symptom reduction with an 86.4% overall satisfaction rate. Symptom-free cycling improved from 272 ± 84 W to 384 ± 101 W (P < .001), whereas the maximal workload increased from 419 ± 72 W to 428 ± 67 W (P = .01). The ankle-brachial index with flexed hips increased from 0.55 (IQR, 0.45-0.65) to 0.62 (IQR, 0.52-0.74; P = .008), and the peak systolic velocity measured with hips flexed decreased from 2.50 m/s (IQR, 1.77-3.13 m/s) to 1.57 m/s (IQR, 1.20-2.04 m/s; P < .001). After a median of 12 years (IQR, 9.0-15.4 years), symptoms were still decreased in 84.1% of patients with an 81.2% overall satisfaction rate (79.5% response rate). Three patients needed a reintervention (recurrent FLIA, n = 2; failure, n = 1). CONCLUSIONS: Operative shortening of a lengthened and kinked iliac artery causing FLIA is successful both in the short- and long-term.

Short- and long-term outcomes after endarterectomy with autologous patching in endurance athletes with iliac artery endofibrosis.

OBJECTIVE: Endurance athletes such as cyclists may develop intermittent claudication owing to iliac artery endofibrosis after long-lasting extreme hemodynamic challenges. This study investigated short-term (<1.5 years) and long-term (>5 years) satisfaction and safety after a surgical endarterectomy and autologous patching. METHODS: Data of endurance athletes who underwent an endarterectomy for flow limitation of the iliac artery owing to endofibrosis between 1997 and 2015 in one center were studied. Maximal cycling exercise tests, ankle-brachial index with flexed hips, echo-Doppler examination (peak systolic velocity), and contrast-enhanced magnetic resonance angiography were performed before and 6 to 18 months after surgery. Short-term and long-term satisfaction were evaluated using questionnaires. Potential patch dilatation was assessed using echo-Doppler. RESULTS: Analysis of 68 patients (79 legs; 55.7% males, median age at the time of surgery, 34 years; interquartile range, 26-41 years) demonstrated that cycling workload at symptom onset improved from 226 ± 97 to 333 ± 101 (P < .001) Watts. Peak workload increased from 326 ± 111 to 352 ± 93 Watts (P < .001). Ankle-brachial index with flexed hips increased from 0.34 (interquartile range [IQR], 0.00-0.47) to 0.59 (IQR, 0.51-0.69; P < .001). Peak systolic velocity with extended and flexed hip decreased from 2.04 m·sec-1 (IQR, 1.52-2.56 m·3sec-1) to 1.25 m·sec-1 (IQR, 0.92-1.62 m·sec-1; P < .001) and 2.40 m·sec-1 (IQR, 1.81-2.81 m·sec-1) to 1.15 m·sec-1 (IQR, 0.97-1.60 m·sec-1; P < .001), respectively. Thirty-day major complication rate was 5.1% (hematoma requiring evacuation nLegs = 2, septic bleeding from deep infection nLegs = 1, and iliac occlusion requiring thrombectomy nLegs = 1). In the short term, 91.2% of patients reported symptom reduction with a 93.7% overall satisfaction rate. After a median of 11.1 years (IQR, 7.8-17.6 years), the overall satisfaction was 91.7%; 94.5% of patients reported persistent symptom reduction. Patch dilatation of >20 mm was observed in two patients. Linear mixed model analysis revealed no alarming patch dilatation in the long term. CONCLUSIONS: Endarterectomy with an autologous patch for intermittent claudication owing to iliac artery endofibrosis in endurance athletes shows high rates of patient satisfaction and symptom reduction in both the short and long term. The risk of surgical complications or patch dilatation is mild. A surgical intervention for flow limitation of the iliac artery owing to endofibrosis is safe and successful.

Analysis of 18F-Sodium Fluoride Positron Emission Tomography Signal Sources in Atherosclerotic Minipigs Shows Specific Binding of 18F-Sodium Fluoride to Plaque Calcifications.

Objective: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging is thought to visualize active atherosclerotic plaque calcification. This is supported by the binding of 18F-NaF to plaque calcification ex vivo, but no prior studies have examined binding of 18F-NaF to human-like plaque in vivo. Our aim was to validate the specificity of 18F-NaF PET for plaque calcifications in atherosclerotic minipigs. Approach and Results: Gain-of-function PCSK9D374Y (proprotein convertase/subtilisin kexin type 9) transgenic Yucatan minipigs (n=4) were fed high-fat diet for 2.5 years to develop atherosclerosis and then subjected to 18F-NaF PET/computed tomography imaging. The heart, aorta, and iliac arteries were immediately re-scanned ex vivo after surgical extraction. Lesions from the abdominal aorta, iliac arteries, and coronary arteries were cryo-sectioned for autoradiography. Histological plaque characteristics, PET/computed tomography signal, and autoradiography were linked through regression and co-localization analysis. Arterial 18F-NaF PET signal had intensities comparable to clinical scans and colocalized moderately with calcification detected by computed tomography. Histological analysis showed calcification spanning from microcalcifications near lipid pools and necrotic core to more homogenous macrocalcifications. Comparison with arteries from autopsy cases confirmed the resemblance in localization and appearance with early human plaque calcification. Regression analysis in the abdominal aorta showed correlations with calcified plaque but could not rule out contributions from noncalcified plaque. This was resolved by autoradiography, which showed specific accumulation in plaque calcifications in all examined arteries. In the context of porcine abdominal aorta, 18F-NaF PET imaging was, however, less accurate than computed tomography for detecting small calcifications. Conclusions: 18F-NaF accumulates specifically in calcifications of atherosclerotic plaques in vivo.

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report.

BACKGROUND: Endometrial carcinoma (EC) is a common malignant tumor of the female reproductive system, often accompanied by lymph node metastasis. Artificial vascular implantation is a common surgical treatment for mediastinal tumors and abdominal aortic aneurysms but is rarely used in gynecological surgery. CASE PRESENTATION: A 54-year-old female patient was first admitted to the hospital in January 2018 due to "irregular vaginal bleeding over 3 months". CT showed a mass in the uterine cavity, and several swollen lymph nodes in the retroperitoneum and pelvic cavity. The initial diagnosis was an endometrial malignant tumor. We performed radical endometrial cancer surgery with parallel resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, bilateral external iliac arteries, and artificial vessel replacement, which was successful, with good postoperative recovery and no lesion progression at 3 years postoperative follow-up. CONCLUSION: This is an early case of gynecological clinical use of prostheses. Through multidisciplinary cooperation, the surgical resection rate of patients with EC in radical surgery was improved without serious fatal complications and achieved a high long-term postoperative survival rate.

Distribution and Dynamic Changes in Matrix Metalloproteinase (MMP)-2, MMP-9, and Collagen in an In Stent Restenosis Process.

OBJECTIVE: The aim of this study was to observe the spatial distribution and dynamic changes of matrix metalloproteinase (MMP)-2, MMP-9, and collagen in in stent restenosis (ISR) and to explore their influence on ISR. METHODS: Sixty Z type stents were implanted into the common iliac arteries of minipigs, which were divided into 10 groups (six in each group) according to euthanasia time (6 hours, and 1, 3, 7, 14, 28, 56, 84, 168, and 336 days). After the samples were harvested, haematoxylin and eosin staining, immunohistochemical staining, Western blotting, and Picrosirius red staining were performed for all groups. RESULTS: ISR occurred in all six minipigs in the 56 day group (percentage diameter stenosis range 71.6%-79.2%, mean ± standard deviation 75.6% ± 2.5%). The percentage diameter stenosis decreased to 38.3% ± 2.7% at 336 days (p < .001). Immunohistochemical staining showed that MMP-2 and MMP-9 were strongly stained near the internal elastic lamina or in the damaged parts of the intima, around the struts and neointimal lumen surface in the ISR process. The expression of MMP-2 and MMP-9 at 56 days was significantly lower compared with their peaks (seven days and one day [p < .001; p = .002], respectively). At 56 days, the collagen content reached its maximum (mean integrated optical density range 0.73-0.92, mean ± standard deviation 0.82 ± 0.09). From the 14 day group to the 336 day group, mature collagen in neointima was correlated negatively with MMP-2 (γ(36) = -0.816; p < .001) and MMP-9 expression (γ(36) = -0.853; p < .001). During the neointimal regression period, new collagen in neointima was positively correlated with MMP-2 (γ(24) = 0.683; p < .001) and MMP-9 (γ(24) = 0.873; p < .001). CONCLUSION: This study has demonstrated the spatial distribution of and dynamic changes in MMP-2, MMP-9, and collagen in ISR by simulating the process of neointima from generation to regression after stent implantation. When ISR occurred, MMP-2 and MMP-9 expression decreased and collagen content reached its maximum, which might contribute to ISR.

Exercise induced leg pain due to endofibrosis of external iliac artery.

Due to monotonous movement patterns, muscular hypertrophy, and increased cardiac output peripheral vasculature of athletes are subject to extreme stresses during athletic performance. Individuals suffering from exercise induced non-traumatic lower leg pain may display underlying vascular pathology such as external iliac artery endofibrosis. Therefore, it is essential in the course of to discriminate vascular from non-vascular findings and prime the correct diagnostic path within the course of clinical examination. In this regard, interdisciplinary thinking and profound knowledge in exercise-associated pathologies of the musculoskeletal, nervous and vascular system is indispensable. Consequently, provocation testing displays an indispensable diagnostic tool and has to be continued until symptoms occur, or complete exhaustion is attained. Finally, selective assessment of conservative and surgical treatment options, as well as its ethical evaluation, are of major importance in order to protect, preserve and promote the health and physical integrity of our patients who are keen to perform.

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia.

(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC-derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC-derived MVs through the femoral artery. Doppler flowmetry and real-time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24-h behavior study and transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC-derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC-derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC-derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.

Novel bypass risk predictive tool is superior to the 5-Factor Modified Frailty Index in predicting postoperative outcomes.

OBJECTIVE: This study aimed to develop risk predictive models of 30-day mortality, morbidity, and major adverse limb events (MALE) after bypass surgery for aortoiliac occlusive disease (AIOD) and to compare their performances with a 5-Factor Frailty Index. METHODS: The American College of Surgeons National Surgical Quality Improvement Program 2012-2017 Procedure Targeted Aortoiliac (Open) Participant Use Data Files were queried to identify all patients who had elective bypass for AIOD: femorofemoral bypass, aortofemoral bypass, and axillofemoral bypass (AXB). Outcomes assessed included mortality, major morbidity, and MALE within 30 days postoperatively. Major morbidity was defined as pneumonia, unplanned intubation, ventilator support for >48 hours, progressive or acute renal failure, cerebrovascular accident, cardiac arrest, or myocardial infarction. Demographics, comorbidities, procedure type, and laboratory values were considered for inclusion in the risk predictive models. Logistic regression models for mortality, major morbidity and MALE were developed. The discriminative ability of these models (C-indices) were compared with that of the 5-Factor Modified Frailty Index (mFI-5): a general frailty tool determined from diabetes, functional status, history of chronic obstructive pulmonary disease, history of congestive heart failure, and hypertension. Calculators were derived using the most significant variables for each of the three risk predictive models. RESULTS: A total of 2612 cases (mean age 65.0, 60% male) were identified, of which 1149 (44.0%) were femorofemoral bypass, 1138 (43.6%) were aortofemoral bypass, and 325 (12.4%) were axillofemoral bypass. Overall, the rates of mortality, major morbidity, and MALE were 2.0%, 8.5%, and 4.9%, respectively. Twenty preoperative risk factors were considered for incorporation in the risk tools. Apart from procedure type, age was the most statistically significant predictor of both mortality and morbidity. Preoperative anemia and critical limb ischemia were the most significant predictors of MALE. All three constructed models demonstrated significantly better discriminative ability (P < .001) on the outcomes of interest as compared with the mFI-5. CONCLUSIONS: Our models outperformed the mFI-5 in predicting 30-day mortality, major morbidity, and adverse limb events in patients with AIOD undergoing elective bypass surgery. Calculators were created using the most statistically significant variables to help calculate individual patient's postoperative risks and allow for better informed consent and risk-adjusted comparison of provider outcomes.

Novel, vessel anatomy adjusting drug-coated balloon-Preclinical evaluation in peripheral porcine arteries.

BACKGROUND: The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). METHODS: Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry. RESULTS: HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm2 vs. 3.26 ± 0.72 mm2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed. CONCLUSIONS: HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.

Long-term performance and biocompatibility of a novel bioresorbable scaffold for peripheral arteries: A three-year pilot study in Yucatan miniswine.

AIMS: Peripheral arteries are constantly exposed to deformation (elongation, twisting, shortening, compression) making bioresorbable scaffolds (BRS) a potentially attractive therapeutic alternative to metallic stents. We conducted a long-term pilot preclinical study of a novel sirolimus-eluting BRS in peripheral arteries. METHODS AND RESULTS: Fourteen BRS were deployed in iliofemoral arteries of seven healthy Yucatan miniswine and examined with imaging, pharmacokinetic, histopathologic, and polymer degradation techniques at 0, 30, 90, 180 days, 1, 2, and 3.3 years. Angiographic late luminal loss remained unchanged at 30 and 180 days but significantly decreased from 1 to 3.3 years. optical coherence tomography (OCT) showed late increase in lumen area (1 year: 14.70 ± 3.58 mm2 , 2 years 22.04 ± 3.81 mm2 , and 3.3 years 23.45 ± 7.07 mm2 ; p < .05) primarily due to scaffold area enlargement between 1 and 3.3 years, while there was no difference in the percent area stenosis at all time points. Histologic evidence of scaffold degradation was observed starting at 2 years, with minimal inflammatory reaction. At 3.3 years, BRS struts were rarely discernible by OCT, confirmed by a nearly complete polymer degradation by molecular weight analysis. CONCLUSIONS: In this pilot study, novel sirolimus-eluting BRS showed promising acute and chronic performance in the iliofemoral arteries of Yucatan miniswine.

Monopolar Radiofrequency Energy Delivered by a Conductive Endovascular Basket or Guidewire Leads to Thermal Occlusion in a Swine Model.

PURPOSE: To assess the feasibility of inducing vascular occlusion by application of radiofrequency (RF) energy via conductive endovascular wires or baskets. MATERIALS AND METHODS: A retrievable nitinol basket and stainless steel guidewire with a platinum tip were evaluated as conductors for endovascular application of RF energy. Tissue-mimicking thermochromic gel phantoms that change color with heating were cast with 2-, 5-, and 7-mm-diameter lumens and filled with 37 oC saline. After ablation, the phantoms were sectioned, and the thermal footprints were evaluated. Six castrated male domestic swine underwent endovascular ablation using the basket in iliac arteries and guidewires in renal arteries. Post-procedural angiography was performed, and postmortem arterial segments were resected for histopathologic analysis. RESULTS: In the phantom, the depth of thermal change in the 5- and 7-mm lumens averaged 6.3 and 6.0 mm along the basket, respectively, and in the 2- and 5-mm lumens, the depth of thermal change averaged 1.9 and 0.5 mm along the wire, respectively. In the swine, RF energy delivery led to angiographic occlusion at 12 of 13 sites. Thermal injury and occlusion were similar at the proximal, middle, and distal basket treatment zone, whereas injury and occlusion decreased from the proximal to the distal end of the 5-cm wire treatment zone. CONCLUSIONS: Endovascular delivery of RF energy via a conductive basket in medium-sized arteries or a guidewire in small arteries led to acute angiographic and histologic occlusion. The potential to induce stasis might be useful in settings where rapid occlusion is desirable.

Evaluation of a Novel Spun Polytetrafluoroethylene Stent Graft in an Ovine External Iliac Artery Model.

PURPOSE: To evaluate the patency, cellular response, and thrombogenicity of a novel vascular stent graft. MATERIALS AND METHODS: Test stent grafts, incorporating luminal spun polytetrafluoroethylene and a nonpermeable fluoropolymer layer, and control stent grafts, constructed of permeable expanded polytetrafluoroethylene, were implanted in the external iliac arteries of 14 adult sheep with a median weight of 73.4 kg ranging from 60.6-86.8 kg for 30 (n = 4), 90 (n = 4), and 180 (n = 6) days. Angiographic patency and percent diameter stenosis (%DS) were assessed at termination. Excised stent grafts were fixed and stained for histopathologic analysis, including neointimal coverage (NC) assessment. RESULTS: Test and control device migration occurred in 1 animal, resulting in test device thrombosis. Both devices were excluded from analysis. Mean %DS in test and control implants was 4.6% and 8.2% (P = .563), 2.0% and 10.9% (P = .363), and 2.1% and 10.3% (P = .009) at 30, 90, and 180 days, respectively. Median NC scores at 30, 90, and 180 days were significantly lower in middle test device sections (P < .05). Proximal and distal test and control sections exhibited similar median NC scores at all time periods (P > .05). When present, test and control devices exhibited no neointimal detachment from the graft surface. Except for the migrated test device, no thrombus was observed. Transgraft cellular migration was absent in test devices but present in control devices with tissue accumulation around the stent struts. CONCLUSIONS: Test and control devices demonstrated excellent patency in an ovine model. Compared to the control, test devices exhibited significantly lower %DS values at 180 days and significantly lower mid-device NC scores at 30, 90, and 180 days.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

The Efficacy of a Protocol of Iliac Artery and Limb Treatment During EVAR in Minimising Early and Late Iliac Occlusion.

OBJECTIVE: Iliac limb occlusion (ILO) is a complication of endovascular aortic repair (EVAR) and requires re-intervention in most cases. Attention to any intra-operative defect of iliac limbs and arteries may prevent ILO. The study aimed to analyse the long term effect of an intra-operative protocol of iliac limb treatment during EVAR on ILO. METHODS: Patients treated from 2012 to 2017 for abdominal aortic aneurysm (AAA) with standard EVAR were collected prospectively. Pre-operative computed tomography angiography anatomical characteristics were evaluated. The protocol for intra-operative iliac limb management was: a. pre-EVAR angioplasty of common/external iliac artery stenosis; b. precise contralateral iliac limb deployment at the same level of the flow divider; c. iliac limb kissing ballooning with high pressure non-compliant balloons; d. iliac limb stenting for residual tortuosity/kink and adjunctive external iliac stenting for residual stenosis/dissection after EVAR. ILO was evaluated at 30 days and at follow up, which was performed by duplex ultrasonography before discharge, at three, six, and 12 months and yearly thereafter. Kaplan-Meier and Cox linear regression were used. RESULTS: Four hundred and forty-two patients and 884 iliac limbs were included in the study. Severe iliac tortuosity and calcification were present in 15% (132/884) and 8% (70/884), respectively. External iliac angioplasty and stenting of iliac limb were performed in 2% (18/884) and 9.5% (84/884) of limbs. The thirty day mortality was 1.6%, with no ILO. At a mean follow up of 33 ± 12 months, ILO occurred in 7/884 (0.8%) limbs of six patients. Five ILO were treated by endovascular relining, two surgically: one by femorofemoral bypass and one by surgical explant. On univariable analysis, sac shrinkage was significantly associated with ILO (HR 1, 95% CI 0.8-2.5, p = .043). CONCLUSION: A protocol of aggressive iliac limb treatment in EVAR leads to a very low rate of late ILO. The role of sac shrinkage in ILO should be investigated further.

Histological variation of early stage atherosclerotic lesions in baboons after prolonged challenge with high-cholesterol, high-fat diet.

INTRODUCTION: The baboon is a well-characterized model of human early stage atherosclerosis. However, histological and morphological changes involved in atherogenesis in baboons are not known. Previously, we challenged baboons with a high-cholesterol, high-fat diet for two years and observed fatty streak and plaque lesions in iliac arteries (RCIA). METHODS: We evaluated histological and morphological changes of baboon arterial lesions and control arteries. In addition, we evaluated the vascular expression of CD68 and SMαA markers with progression of atherosclerosis. RESULTS: We observed changes that correlated with extent of atherosclerosis, including increased maximum intimal thickness. We demonstrated at molecular level the infiltration of smooth muscle cells and macrophages into the intimal layer. Further, we observed histological and morphological discordancy between the affected and adjacent areas of the same RCIA. CONCLUSION: Atherogenesis in baboons is accompanied by histological, morphological, and molecular changes, as in humans, providing insights to evaluate the mechanisms underlying early stage atherosclerosis in target tissues.

Comparative Analysis of the Paclitaxel-Eluting Peripheral Igaki-Tamai Stent and the Drug-Free Igaki-Tamai Stent Using Optical Coherence Tomography and Histological Analysis in a Porcine Iliac Artery Model.

BACKGROUND: The combination of a bioresorbable scaffold and antiproliferative drugs is a promising treatment for peripheral artery disease. The novel paclitaxel-eluting peripheral Igaki-Tamai stent (PTX-ITS) has the same backbone design as the drug-free peripheral Igaki-Tamai stent and a paclitaxel coating. Arterial responses to the PTX-ITS and ITS using optical coherence tomography (OCT) and histological analysis in a porcine iliac artery model were compared.Methods and Results:In total, 6 PTX-ITSs and 6 ITSs implanted in porcine iliac arteries were evaluated. Quantitative measurements of the scaffold, lumen, neointimal areas, and percent area stenosis were performed using OCT at 1 and 3 months. Histological evaluations (PTX-ITS [n=5], ITS [n=4]) were performed following euthanasia at 3 months. Injury, inflammation, endothelialization, and fibrin scores were measured. Baseline angiographic characteristics were similar in both groups. The ITS group showed significantly smaller scaffold areas than the PTX-ITS group at 1 month (18.50±3.62 mm2vs. 23.54±3.64 mm2; P=0.037) and 3 months (15.82±2.57 mm2vs. 21.67±3.57 mm2; P=0.009). Percent area stenosis was significantly lower in the PTX-ITS group at 3 months (28.70±7.24% vs. 40.36±7.07%; P=0.018). Histological evaluations revealed similar low-grade inflammatory reactions for both scaffolds. CONCLUSIONS: PTX-ITSs showed significantly better suppression of late scaffold shrinkage and lower in-scaffold stenosis for up to 3 months. Additionally, PTX-ITSs exhibited high biocompatibility, which is comparable to ITSs.

Two-Year Results of a Multicenter Prospective Observational Study of the Zenith Spiral-Z Limb Deployed in the External Iliac Artery During Endovascular Aneurysm Repair.

BACKGROUND: Limited data is available on the use of a polyester graft limb with a helical stent configuration deployed in the external iliac artery (EIA) during endovascular aneurysm repair (EVAR), so we prospectively analyzed the efficacy of the Zenith Spiral-Z limb deployed in the EIA.Methods and Results:Patients undergoing EVAR using a Zenith stent-graft and Spiral-Z limb deployed in the EIA were prospectively registered in 24 Japanese institutions from June 2017 to November 2017. In total, 65 patients (74 limbs) (mean age: 77.1±8.0 years, 87.7% men, mean abdominal aortic aneurysm (AAA) diameter: 51.9±7.2 mm, mean iliac artery aneurysm (IAA) diameter: 38.3±10.0 mm) were registered and followed up. The most common reason for deployment in the EIA was a common IAA (43 limbs, 58.1%), and 8 limbs (10.8%) had a bare nitinol stent placed at the Spiral-Z limb. A total of 61 patients (70 limbs) completed a 24-month follow-up. There were 2 Spiral-Z limb stenoses and 1 occlusion, leading to a primary patency of 95.5% and a secondary patency of 100%, at 24 months. Buttock claudication occurred in 24.3% of the limbs treated at 1 month but decreased to 4.3% at 24 months. CONCLUSIONS: Our multicenter prospective study showed that Spiral-Z limb deployed in the EIA was associated with satisfactory results and seems to be a durable option, even in the era of iliac branch devices.

Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.

Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.

EVAR with Aortic Placement of a Single JOTEC E-iliac Stent-graft System in a Patient with Poliomyelitis Aortoiliac Deformities.

Small-sized vessels can represent a contraindication to standard endovascular aortic repair (EVAR), and more specifically, aortoiliac deformities resulting from poliomyelitis may add an adjunctive challenge for total endovascular repair. Herein we report a case of a 62-year-old man with a 55 mm abdominal aortic aneurysm (AAA) and a history of poliomyelitis. More specifically, a computed tomography angiogram (CTA) showed a very narrow infrarenal aortic neck, measuring 13 mm in maximum diameter, and severely atrophic external iliac and common femoral arteries. A total endovascular repair was planned and realized with a single aortic JOTEC iliac branch and contralateral VBX placement. All prosthetic materials were delivered from the nonatrophic side. At the 1-year CTA, the aneurysm was successfully excluded and both iliofemoral axes were patent.