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Background: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system., Objective: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients., Methods: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism., Results: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint., Conclusion: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients., Competing Interests: Disclosures Dr Beer reports grants from the Swiss National Foundation of Science, The Swiss Heart Foundation, and Bayer; and lecture fees from Sanofi Aventis and Amgen, to the institution outside the submitted work. Dr Blum has received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, all for work outside the submitted study. Dr Bonati has received an unrestricted research grant from AstraZeneca; consultancy or advisory board fees or speaker honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical; and travel grants from AstraZeneca and Bayer, outside the submitted work. Dr Conen received consultancy fees from Roche Diagnostics and Trimedics; and speaker fees from Servier and BMS/Pfizer, outside the submitted work. Dr Kühne received personal fees from Daiichi Sankyo and grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for CardioVascular Research Basel, Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo, outside the submitted work. Dr Krisai has speaker fees from BMS/Pfizer, outside the submitted work. Dr Müller reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, Zoll, and Bristol Myers Squibb; consultant fees from Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik, outside the submitted work. Dr Moschovitis has received advisory board and/or speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis, and Vifor, outside the submitted work. Dr Osswald received research grants from the Swiss National Science Foundation and Swiss Heart Foundation, Foundation for CardioVascular Research Basel, and F. Hoffmann-La Roche Ltd.; and educational and speaker grants from F. Hoffmann-La Roche Ltd., Bayer, Novartis, Sanofi, AstraZeneca, Daiichi-Sankyo, and Pfizer, outside the submitted work. Dr Reichlin has recieved research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support funds; speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Farapulse, Medtronic, Pfizer-,BMS and Roche; and support for his institution’s fellowship program from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic for work, outside the submitted study. Dr Zuern has received funding from the “Freiwillige Akademische Gesellschaft Basel”; and personal fees from Cardiomatics, outside the submitted work. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Neurological complexities resulting from surgery requiring cardiopulmonary bypass (CPB) remain a major concern, encompassing a spectrum of complications including thromboembolic stroke and various cognitive impairments. Surgical manipulation during CPB is considered the primary cause of these neurological complications. This study addresses the overall lack of knowledge concerning CPB hemodynamics within the aorta, employing a combined experimental-computational modeling approach, featuring computational fluid dynamics simulations validated with an in vitro CPB flow loop under steady conditions. Parametric studies were systematically performed, varying parameters associated with CPB techniques (pump flow rate and hemodiluted blood viscosity) and properties related to formed emboli (size and density). This represents the first comprehensive investigation into the individual and combined effects of these factors. Our findings reveal critical insights into the operating conditions of CPB, indicating a positive correlation between pump flow rate and emboli transport into the aortic branches, potentially increasing the risk of stroke. It was also found that larger emboli were more often transported into the aortic branches at higher pump flow rates, while smaller emboli preferred lower flow rates. Further, as blood is commonly diluted during CPB to decrease its viscosity, more emboli were found to enter the aortic branches with greater hemodilution. The combined effects of these parameters are captured using the non-dimensional Stokes number, which was found to positively correlate with emboli transport into the aortic branches. These findings contribute to our understanding of embolic stroke risk factors during CPB and shed light on the complex interplay between CPB parameters., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cerebral microvascular obstruction is critically involved in recurrent stroke and decreased cerebral blood flow with age. The obstruction must occur in the capillary with a greater resistance to perfusion pressure through the microvascular networks. However, little is known about the relationship between capillary size and embolism formation. This study aimed to determine whether the capillary lumen space contributes to the development of microcirculation embolism., Methods: To spatiotemporally manipulate capillary diameters in vivo, transgenic mice expressing the light-gated cation channel protein ChR2 (channelrhodopsin-2) in mural cells were used. The spatiotemporal changes in the regional cerebral blood flow in response to the photoactivation of ChR2 mural cells were first characterized using laser speckle flowgraphy. Capillary responses to optimized photostimulation were then examined in vivo using 2-photon microscopy. Finally, microcirculation embolism due to intravenously injected fluorescent microbeads was compared under conditions with or without photoactivation of ChR2 mural cells., Results: Following transcranial photostimulation, the stimulation intensity-dependent decrease in cerebral blood flow centered at the irradiation was observed (14%-49% decreases relative to the baseline). The cerebrovascular response to photostimulation showed significant constriction of the cerebral arteries and capillaries but not of the veins. As a result of vasoconstriction, a temporal stall of red blood cell flow occurred in the capillaries of the venous sides. The 2-photon excitation of a single ChR2 pericyte demonstrated the partial shrinkage of capillaries (7% relative to the baseline) around the stimulated cell. With the intravenous injection of microbeads, the occurrence of microcirculation embolism was significantly enhanced (11% increases compared to the control) with photostimulation., Conclusions: Capillary narrowing increases the risk of developing microcirculation embolism in the venous sides of the cerebral capillaries., Competing Interests: Disclosures None.

Case Presentation: A 30-year-old transgender woman who was HIV positive presented to the ED with progressive severe dyspnea and hemoptysis that started 1 day earlier. The patient was undergoing antiretroviral therapy with emtricitabine-rilpivirine-tenofovir with good compliance and feminizing hormone therapy with cyproterone acetate. She was otherwise healthy and was not taking any other medications., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.

The association of low-density lipoprotein cholesterol lowering with outcomes in embolic stroke of undetermined source (ESUS) patients is unclear. In these patients we aimed to assess the effect of statin on stroke recurrence, major adverse cardiovascular events (MACE) and death rates. Consecutive ESUS patients in the Athens Stroke Registry were prospectively followed-up to 10 years for stroke recurrence, MACE, and death. The Nelson-Aalen estimator was used to estimate the cumulative probability by statin allocation at discharge and cox-regression analyses to investigate whether statin at discharge was a predictor of outcomes. Among 264 ESUS patients who were discharged and followed for 4 years, 89 (33.7%) were treated with statin at discharge. Patients who were discharged on statin had lower rates of stroke recurrence (3.58 vs. 7.23/100 patient-years, HR: 0.48; 95% CI 0.26-0.90), MACE (4.98 vs. 9.89/100 patient-years, HR: 0.49; 95% CI 0.29-0.85), and death (3.93 vs. 8.21/100 patient-years, HR: 0.50; 95% CI: 0.28-0.89). In the multivariate analysis, statin treatment at discharge was an independent predictor of stroke recurrence (adjusted HR: 0.48; 95% CI 0.26-0.91), MACE (adjusted HR: 0.48; 95% CI 0.28-0.82), and death (adjusted HR: 0.50; 95% CI 0.27-0.93). Patients with ESUS discharged on statins have lower rates of stroke recurrence, MACE, and death compared to those not receiving statin therapy., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background and Purpose: Use of implantable cardiac monitors (ICMs) has increased diagnosis of atrial fibrillation (AF) in cryptogenic stroke (CS) patients. Identifying AF predictors may enhance the yield of AF detection. Recurrent strokes after CS are not well described. We aimed to assess the predictors for AF detection and the characteristics of recurrent strokes in patients after CS., Methods: We reviewed electronic medical records of CS patients who were admitted between February 2014 and September 2017 and underwent ICM placement with minimum one-year follow-up. Patient demographics, stroke characteristics, pre-defined risk factors as well as recurrent strokes were compared between patients with and without AF detection., Results: 389 patients with median follow-up of 548 days were studied. AF was detected in 102 patients (26.2%). Age (per decade increase, OR 2.10, CI 1.64-2.68, with vs. without AF) and left atrium diameter (per 5 mm increase, OR 1.91, CI 1.33-2.74) were identified as AF predictors. Intracranial large vessel stenosis >50% irrelevant to the index strokes was associated with AF detection within 30 days (OR 0.24, CI 0.09-0.69, >30 vs. <30 days). Recurrent strokes occurred in 14% patients with median follow-up about 2.5 years. Topography of these strokes resembled embolic pattern and was comparable between patients with and without AF. Among recurrent strokes in patients with AF, the median time to AF detection was much shorter (90 vs. 251 days), and the median time to first stroke recurrence was much longer (422 vs. 76 days) in patients whose strokes recurred after AF detection than those before AF detection., Conclusions: Older age and enlarged left atrium are predictors for AF detection in CS patients. Intracranial atherosclerosis is more prevalent in patients with early AF detection within 30 days. Recurrent strokes follow the embolic pattern, and early AF detection could delay the stroke recurrence., Competing Interests: Declaration of Competing Interest Dr. Xu receives speaker compensation from Portola Pharmaceuticals. Dr. Sethi receives speaker compensation, consulting fees and research support from Medtronic, as well as speaker compensation from Abbott Laboratories/St. Jude Medical, and W. L. Gore & Associates. Dr. Allred receives speaker compensation, consulting fees and research support from Medtronic and Janssen Pharmaceuticals. Ms. Biby and Ms. Seiler receive speaker compensation from Medtronic. Dr. Sabir reports no conflict., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk., Methods: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, nongated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures., Results: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 Embolic Stroke of Undetermined Source (ESUS), and 83 non-CE). In unadjusted models, there was an association between CE (versus non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, P < .001) and LAA density (4th quartile versus 1st quartile; OR 2.95, 95% CI 1.28-6.80, P = .011), but not with ESUS (versus non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, P = .010)., Conclusion: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is CE and anticoagulation can be tested for secondary stroke prevention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Compared with other causes of ischemic stroke, the mechanism of action of embolic stroke of undetermined source (ESUS) remains unclear, with previous literature suggesting that ESUS may be due to an undetected cardioembolic source. This study aimed to improve our understanding of the pathophysiology of ESUS through current knowledge of sleep disorders. Methods- Patients were included in this study if they sustained an ischemic stroke and completed either polysomnography or a home sleep apnea test. Strokes were classified into 1 of 6 mechanisms and were compared with the presence of sleep disorders (ie, obstructive sleep apnea, periodic limb movements, and abnormalities in sleep architecture). Results- There was a significant relationship between obstructive sleep apnea and cardioembolic stroke mechanism compared with the other stroke mechanisms ( P =0.018). There was no significant relationship between obstructive sleep apnea and ESUS ( P =0.585). Patients with ESUS were significantly more likely to have an elevated periodic limb movement index ( P =0.037) and prolonged sleep onset latency ( P =0.0166) compared with patients with other causes of stroke. Conclusions- ESUS was not associated with markers of cardioembolic stroke such as obstructive sleep apnea. There was a significant relationship between ESUS and elevated periodic limb movements and impaired sleep architecture, which suggests that ESUS may have a multifactorial underlying pathophysiology.

Background: This study was performed to summarize our experience in treating acute superior mesenteric artery embolism (SMAE) by percutaneous mechanical thrombectomy (PMT)., Methods: The clinical data of five patients with acute SMAE treated by PMT in our center from October 2015 to May 2018 were retrospectively analyzed. PMT was performed under local anesthesia. Access was established via the femoral artery or brachial artery. Thrombectomy was performed on the superior mesenteric artery using a 6F Rotarex catheter (Straub Medical, Wangs, Switzerland)., Results: Technical success of PMT was achieved in all five patients; emboli were completely removed in three patients and partially removed in two patients. No PMT-related complications were noted after surgery. Four patients were smoothly discharged from the hospital after their symptoms were relieved. One patient still had symptoms of intestinal ischemia after the operation, and massive small intestinal necrosis was found by exploratory laparotomy. Intestinal resection was performed, and the patient died 4 months later., Conclusions: PMT by the Rotarex system is a minimally invasive, safe, and effective technique in removing SMAE. Early application of PMT can avoid intestinal necrosis., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Early insight into the possible etiology of ischemic stroke allows for early initiation of mechanism-specific secondary stroke prevention. Initial systolic blood pressure during acute ischemic stroke may relate to stroke etiology. We sought to determine whether normotension at presentation with acute ischemic stroke predicts cardioembolic etiology. Methods and Results All patients presenting with acute ischemic stroke within 12 hours of symptom onset at a comprehensive stroke center from January 2015 to December 2017 were assessed. Normotension was defined as systolic blood pressure ≤130 mm Hg. The primary exposure was blood pressure on arrival at the hospital, and the primary outcome was cardioembolic etiology. Multivariable regression with stepwise selection was used to adjust for relevant covariates. We included 683 patients in our analysis, 303 (44%) of whom were diagnosed with cardioembolic etiology at 6 months. The probability of cardioembolic etiology was inversely associated with systolic blood pressure, and initial systolic blood pressure was significantly associated with cardioembolic etiology (odds ratio: 1.15; 95% CI, 1.05 to 1.26). Normotension was associated with 2.62-fold increased odds of cardioembolic etiology (95% CI, 1.46 to 4.72). Conclusions Normotension at presentation with acute ischemic stroke strongly predicts cardioembolic etiology. These patients may especially benefit from early and prolonged cardiac investigations.

Introduction: One cause of cerebral infarction during cryoballoon ablation is the entry of air into a sheath due to the use of inappropriate catheters. It is known that the left atrial pressure of patients with obstructive sleep apnea syndrome can be negative. However, the effects of catheter selection and negative pressure changes in the sheath on air intrusion are not yet well understood. The aim of this study was to evaluate how catheter selection and negative pressure changes affect air intrusion and to perform countermeasures for air intrusion., Methods and Results: This experiment used siphon principle to create negative pressure in the sheath. Noncryoablation catheters (not designed exclusively for cryoballoon ablation) and cryoballoon catheters were investigated. Catheters were inserted into the sheath and then removed. Thereafter, the amount of air in the sheath was measured. For catheters producing significantly larger amounts of air intrusion, the catheters were inserted via a long sheath in the sheath (sheath-in-sheath technique) and the same procedures were repeated. We found that the amount of air intrusion through most of the noncryoablation catheters was significantly larger than that through cryoablation catheters. An increase in the magnitude of negative pressure in the sheath resulted in a proportional increase in air intrusion, but the sheath-in-sheath technique significantly reduced air intrusion., Conclusion: The amount of air intrusion increased when using catheters with complicated tip shapes and thin outer diameters and when the magnitude of negative pressure in the sheath increased. The sheath-in-sheath technique may be an effective countermeasure., (© 2019 Wiley Periodicals, Inc.)

Purpose: There has been interest in recent work in using computational fluid dynamics with Lagrangian analysis to calculate the trajectory of emboli-like particles in the vasculature. While previous studies have provided an understanding of the hemodynamic factors determining the fates of such particles and their relationship to risk of stroke, most analyses have relied on a particle equation of motion that assumes the particle is "small" e.g., much less than the diameter of the vessel. This work quantifies the limit when a particle can no longer be considered "small"., Methods: The motion of embolus-like particles are simulated using an overset mesh technique. This allows the fluid stresses on the particle surface to be fully resolved. Consequently, the particles can be of arbitrary size or shape. The trajectory of resolved particles and "small" particles are simulated through a patient-specific carotid artery bifurcation model with particles 500, 1000, and 2000 μm in diameter. The proportions of particles entering the internal carotid artery are treated as the outcome of the particle fate, and statistical comparisons are made to ascertain the importance of non-small particle effects., Results: For the 2000 μm embolus, the proportion of particles traveling to the internal carotid artery is 74.7 ± 1.3% (mean ± 95% confidence margin) for the "small" particle model and is 85.7 ± 5.4% for a resolved particle model. The difference is statistically significant, [Formula: see text], based on the binomial test for the particle outcomes. No statistically discernible differences are found for the smaller diameter particles., Conclusions: Quantitative differences are observable for the 2000 μm trajectories between the "small" and resolved particle models which is a particle diameter 27% relative to the common carotid artery diameter. A fully resolved particle model ought to be considered for emboli trajectory simulations when the particle size ratio is ≳ 20%.

Background: Fenestrated/branched endografts for aortic repair (FB-EVAR) are valid options to treat thoracoabdominal aortic aneurysms (TAAAs). Successful repair requires manipulation of target visceral vessels (TVVs) with possible splanchnic ischemia. The aim of the study was to evaluate the clinical impact of splanchnic ischemia occurring in FB-EVAR for TAAA., Methods: Between 2010 and 2015, patients with TAAAs undergoing FB-EVAR were prospectively enrolled. Clinical, morphological, procedural, and 30-day data were evaluated. Splanchnic ischemia was defined as the presence of splanchnic ischemic lesions (SILs) visible at perioperative computed tomography angiography. Preoperative, postoperative, and 30-day hepatic/pancreatic/renal laboratory functions were analyzed. End points were incidence of SILs, laboratory splanchnic functions worsening (≥25% of baseline), and presence of related clinical/morphological and procedural risk factors., Results: Thirty-six patients (male: 78%; age: 73 ± 7 years) with 27 (75%) type I-III and 9 (25%) type IV TAAA who underwent FB-EVAR for a total of 127 TVV (branches: 47-60%; fenestrations: 53-67%). Fourteen SILs occurred in 12 (33%) patients: 4 (29%) in pancreas, 3 (21%) in spleen, 2 (14%) in bowel, 5 (36%) in kidney. The cause was embolic in 79% and thrombotic in 21%. No preoperative clinical/morphological data or procedural data were correlated with SIL. Pancreatic, hepatic, or renal function worsening occurred at 24 hr in 16 (44%), 16 (44%), and 9 (25%) cases, respectively. Overall, SILs were associated with increased values of C-reactive protein (CRP) (17.9 ± 0.4 vs. 9.9 ± 9.0 mg/dL; P = 0.03) and bilirubin (1.2 ± 2.3 vs. 1.0 ± 0.5 mg/dL; P = 0.02) at 24 hr. Specifically, SIL of the celiac trunk and superior mesenteric and renal arteries' parenchyma were associated with the significant laboratory function changes 24 hr. SIL of the superior mesenteric artery was associated with increased 30-day mortality (50% vs. 7 %; P = 0.002). Pancreatic, hepatic, or renal function worsening occurred at 30 days in 2 (6%), 0 (0%), and 4 (12%) cases, with similar laboratory tests in patients with and without SIL., Conclusions: SIL can be frequently detected after FB-EVAR for TAAA and appears mainly of embolic origin. No clinical, morphological, or procedural predictors could be identified in our series. Postoperative laboratory changes of CRP, bilirubin, activated partial thromboplastin time, and amylases are associated with SIL but disappear without clinical consequences within 30 days. However, SIL occurring in the superior mesenteric artery are associated with an increased 30-day mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Cardiogenic emboli account for 15% to 20% of acute ischemic stroke cases worldwide. However, the chance of such emboli, of varying sizes, causing a stroke under various flow types has not been evaluated. Methods- A patient-specific aortic arch model was fabricated from a medical image dataset of a 77-year-old male case, with atrial fibrillation and distal occlusion of the right M1 vessel. One hundred and eighty mammalian embolus analogs (EAs) were released one by one into the model under normal and atrial fibrillation flow conditions. A further 270 clots were fabricated using varying levels of thrombin (5-20 National Institutes of Health units thrombin). The effect of releasing several clots simultaneously was also examined by grouping EAs into 18 multiples of 5, 4, 3, and 2 clots, resulting in 504 EAs released. Results- EAs with a length of ≤10 mm were the most common geometry to travel through the common carotid arteries (44%); however, longer clots also traveled through these narrow vessels. Twenty two percent of EAs ranged from 10-20mm in length, 27% from 20-30mm and 7% were >30 mm in length. Higher density clots increased the propensity for clots to travel along the cerebral vessels ( P<0.05). Releasing more clots during each test, increased the probability of at least one clot traveling through an aortic arch branching vessel. Conclusions- Embolus trajectory through the branching vessels of the aortic arch is not exclusively dependent on embolus size. EAs tend to travel proportionally with outlet flow rates, with a greater chance of a stroke caused by multiple breakaway emboli.

The development of atherosclerotic plaques is a critical step that can result in an arterial embolism. Therefore, detection of these vulnerable plaques is of clinical significance for the diagnosis of atherosclerosis. However, there are few imaging systems able to detect such plaques easily. In this study, we designed a new platform for near-infrared fluorescence (NIRF) imaging of macrophages in atherosclerotic plaques, one using both a liposomal DDS and an activatable fluorescent probe, and evaluated the utility of this imaging for the diagnosis of atherosclerosis. We first synthesized a fluorescent switch-on probe, Peptide-ICG2, which is optically silent under normal conditions but activated in the presence of the lysosomal enzyme, cathepsin B. To achieve macrophage-specific fluorescence activation, we encapsulated Peptide-ICG2 into phosphatidylserine-containing liposome (P-ICG2-PS-Lip), since the accumulation of phosphatidylserine receptor-bearing macrophages is characteristic of embolism-vulnerable plaques. The experiments using macrophage-like RAW264 cells in culture showed that P-ICG2-PS-Lip was selectively taken up into the cells and that significant fluorescence of the probe was observed. For NIRF imaging of the atherosclerotic plaques, P-ICG2-PS-Lip was intravenously injected into ApoE-knockout atherosclerotic model mice or WHHL rabbits, and the fluorescence at the aortae was imaged. The results indicated that ICG fluorescence could be successfully observed at the plaques on the artery walls. The results of the present study thus suggest that NIRF imaging using P-ICG2-PS-Lip would be useful for detecting embolism-vulnerable atherosclerotic plaques., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The primary objective was to evaluate the safety of transfer, type of procedure, and factors associated with limb salvage in patients with acute limb ischemia (ALI) treated at a quaternary referral center., Methods: A retrospective review of all patients with ALI secondary to thrombotic or embolic occlusion at a quaternary referral hospital from 2013 to 2016 was conducted. Patients were transferred from throughout Washington and Alaska by ambulance, helicopter, or fixed-wing modes of transportation. Demographics, transport and operative timing, Rutherford classification, level of occlusion, procedural information, and fasciotomy characteristics were reviewed. Outcomes measured included limb salvage rates, discharge disposition, and mortality., Results: One hundred twelve patients with ALI were identified, with 82% due to thrombosis and 18% due to arterial embolization. Fifty-seven percent of patients were transferred from a referring hospital with low mean transfer times (1.9 hours for embolic, 2.7 hours for thrombotic). Although the initial operative strategy varied according to the etiology, with 50% of thrombotic occlusions treated with endovascular therapies and 80% of embolic occlusions treated with open thrombectomy, the rates of limb salvage did not vary based on operative approach (92% endovascular first, 90% open first). Further, limb salvage rates were identical between transferred and nontransferred patients (77%). Limb salvage was successful in 91% of patients with Rutherford class 1 and 2 disease, but only 8% in patients with Rutherford class 3 disease. In-hospital and 30-day mortality rates were not different based on ischemic etiology (5%), although patients with Rutherford class 3 disease had significantly higher mortality rates (15%) compared with patients with class 1 (6%), class 2a (6%), and class 2b (2%) disease. Fasciotomy was performed in 29% of patients, with 59% of fasciotomy wounds closed primarily. Predictors of amputation include multiple attempts at limb salvage, higher Rutherford class, multilevel occlusion, more proximal levels of occlusion, and nonviable muscle seen after fasciotomy, with ischemic times trending toward higher amputation rates without statistical significance. There was no difference in discharge disposition based on ischemic etiology., Conclusions: The modern treatment of patients with ALI is effective, with high rates of limb salvage and low mortality regardless of transfer status, etiology, or initial operation performed. In situations where compartment syndrome is unclear, fasciotomy should not be withheld because it provides valuable predictive information regarding limb salvage., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Coronary microembolization (CME) caused by physical obstruction in coronary microcirculation induces myocardial apoptosis and cardiac dysfunction, and it was reported that the inactivation of the Nrf2/HO-1 signaling was involved in this process. Astaxanthin (AST) is a reddish pigment that belongs to keto-carotenoids. It is also a potent antioxidant and has been reported to activate Nrf2/HO-1 signaling in vein endothelial cells. However, it is still unknown whether AST is able to activate Nrf2/HO-1 signaling pathway to protect cardiac functions from CME in vivo. To address this question, rats were orally administrated with AST or AST plus Zinc protoporphyrin IX (ZnPP, a HO-1 inhibitor), followed by CME modeling operation. Then, cardiac function was evaluated by echocardiographic measurement. Myocardial infarction was measured by HBFP staining, and apoptosis was assessed by TUNEL staining. The protein levels and mRNA expressions of Bax and Bcl-2 were measured by Western blot and qRT-PCR, respectively. ELISA was performed to measure the activity of enzymes related to oxidative stress. AST pretreatment dramatically attenuated CME-induced cardiac dysfunction, myocardial infarction, and cardiomyocyte apoptosis. Mechanistically, AST suppressed CME-induced oxidative stress by re-activating Nrf2/HO-1 signaling. HO-1 inhibitor ZnPP completely eliminated the benefits of AST in CEM, supporting the critical role of Nrf2/HO-1 signaling in mediating the cardioprotective function of AST in CME. Conclusion: AST suppresses oxidative stress via activating Nrf2/HO-1 pathway and thus prevents CME-induced cardiomyocyte apoptosis and ameliorates cardiac dysfunction in rats.

Purpose: To review preliminary efficacy and safety outcomes of mechanical thrombectomy using the Solitaire AB device combined with thromboaspiration for treatment of acute embolic occlusion of the superior mesenteric artery (SMA)., Materials and Methods: Between October 2015 and October 2017, 9 patients (average age, 77 y; range, 62-84 y) presenting with acute mesenteric ischemia attributable to embolic occlusion at the stem of the SMA were retrospectively evaluated for mechanical thrombectomy using the Solitaire AB device combined with manual thromboaspiration. Adjunctive stent implantation was performed to correct pre-existing atherosclerotic stenosis or as a rapid recanalization solution after unsuccessful thrombectomy. Technical success was defined as successful deployment of the Solitaire device across the thrombus and successful retrieval of the device. Clinical success was defined as successful embolus retrieval and SMA recanalization. Adjunctive procedures and periprocedural complications were noted. Technical success, clinical success, and follow-up outcomes were assessed., Results: Technical success was achieved in all patients. Clinical success was achieved in 7 (78%) patients. An adjunctive stent was required in 3 (33%) patients, including 1 unsuccessful thrombectomy. All patients had notable relief from abdominal pain after the procedure. No device-related complications or distal embolization events were noted during the procedures. Bowel resection was prevented in all patients. In-hospital mortality was 11% (1/9). During median follow-up of 6 months (range, 3-12 months), all surviving patients remained symptom-free, and stent patency was achieved in all patients., Conclusions: Preliminary outcomes suggest that mechanical thrombectomy using the Solitaire AB device with manual thromboaspiration is associated with rapid, effective, and safe recanalization for acute embolic occlusion at the stem of the SMA., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction and Study Aim: Embolic strokes of undetermined source (ESUS) represent a rather recent diagnostic entity under clinical research for relapse prevention in cryptogenic stroke patients. Despite strict diagnostic criteria, ESUS definition ignores major clinical and radiological aspects, so including heterogeneous cases and probably influencing trial results. This study researches clinically relevant phenotypes among ESUS patients., Patients and Methods: We evaluated ESUS patients admitted at Trento Stroke Unit over a 4-year period. Vascular risk factors (RFs), neurological deficit severity, presence of potential embolic sources, and ASCOD phenotype were recorded. Ischemic lesions were categorized considering their extension in 4 groups. Subgroup comparisons by predefined differences in age, amount of RFs, history of previous stroke, deficit severity, and stroke lesion extension were done., Results: ESUS cases were 86. Patients younger than 50 years old (n = 17) had a lower prevalence of RFs, left atrial enlargement, left ventricle diastolic dysfunction, a higher proportion of ASCOD score A0 (P < .05). Patients without RFs (n = 18) differed from those with greater than or equal to 3 RFs (n = 23) for a younger age and a lower prevalence of potential causes of embolism (P < .05). Patients without a previous stroke (n = 70) were younger, had a lower prevalence of RFs, left ventricle diastolic dysfunction, a higher prevalence of ASCOD score A0 (P < .05). No differences were observed comparing minor and major clinical and radiological strokes., Discussion and Conclusions: ESUS patients can be distinguished in 2 opposite phenotypes defined by a lower and a higher load of atherosclerotic pathology. They may suggest possible underlying pathogenic mechanisms and support interpretation of ongoing trials results., (Copyright © 2018. Published by Elsevier Inc.)

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

Acute renal artery embolism (RAE) is a rare condition associated with significant morbidity and mortality. The treatment strategy for RAE includes anticoagulation with or without thrombolysis or surgical or endovascular embolectomy. We describe here a case presentation of acute RAE secondary to atrial fibrillation treated successfully with Penumbra Indigo Aspiration System, a novel device in peripheral endovascular interventions. Our patient had ongoing symptoms and acute renal failure on presentation with contraindication to thrombolysis given hypertensive emergency. A 6F Penumbra Aspiration catheter was used to aspirate large amounts of thrombus from segmental renal arteries with restoration of flow. Patient's symptoms and renal function returned to baseline after intervention. Penumbra system is used routinely in cerebral endovascular intervention, yet here we describe its potential use in peripheral vascular interventions in addition to a literature review of all available evidence for the different treatment modalities of acute RAE.

A 42-year-old female patient was referred our clinic for investigation of a history of acute retinal artery occlusion. Transthoracic echocardiography showed a cyst-like, mobile formation on posterior mitral valve leaflet. 2D and real time 3D transesophageal echocardiography showed a flexible circular mobile structure which was attached to posterior mitral valve leaflet. Echocardiographic appearance and morphological characteristics were suggestive of accessory mitral valve tissue., (© 2018, Wiley Periodicals, Inc.)

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a method used for the treatment most severe cases of decompensated heart failure. The purpose of this study was to evaluate the risk of the formation of microembolisms during VA-ECMO-based therapy. Heart failure was induced with simultaneous detection of microembolisms and the measurement of blood flow rate in the common carotid artery (CCA) without VA-ECMO (0 l/min) and at the VA-ECMO blood flow rate of 1, 2, 3 and 4 l/min. If embolisms for VA-ECMO 0 l/min and the individual regimes for VA-ECMO 1, 2, 3, 4 l/min are compared, a higher VA-ECMO flow rate is accompanied by a higher number of microembolisms. The final microembolism value at 16 min was for the VA-ECMO flow rate of 0 l/min 0.0 (0, 1), VA-ECMO l/min 7.5 (4, 19), VA-ECMO 2 l/min 12.5 (4, 26), VA-ECMO 3 l/min, 21.0 (18, 57) and VA-ECMO 4 l/min, 27.5 (21, 64). Such a comparison is statistically significant if VA-ECMO 0 vs. 4 l/min p<0.0001, 0 vs. 3 l/min p<0.01 and 1 vs. 4 l/min p<0.01 are compared. The results confirm that high VA-ECMO flow rates pose a risk with regards to the formation of a significantly higher number of microemboli in the blood circulation and that an increase in blood flow rates in the CCA corresponds to changes in the VA-ECMO flow rates.

Objective: To assess whether clinical criteria can differentiate between presumed embolic strokes and non-embolic strokes before the full etiologic workup., Methods: Between January 1, 2014 to December 30, 2015, patients with a diagnosis of stroke or transient ischemic attack were first classified clinically (without access to a cardiac assessment) as: 1. presumed embolic stroke defined as a combination of definite cardioembolic stroke and likely to be embolic stroke (no evidence of large/small artery atherosclerosis); 2. non-embolic strokes; i.e. small/large artery diseases and stroke due to other causes. Stroke etiology was reassessed after investigations and concordances between the early diagnosis and final classifications were analyzed., Results: 77 patients with early diagnosis of presumed embolic strokes and 45 cases with non-embolic stroke (selected randomly) were enrolled. We were able to differentiate between presumed embolic strokes and non-embolic strokes with a high level of accuracy (sensitivity 81.40%, 95% CI: 71.55%-88.98%; specificity 80.56%, 95% CI: 63.98%-91.81%). A moderate level of agreement between initial and final diagnosis of embolic/non-embolic strokes (kappa 0.58, SE 0.08, p≤0.01) was observed. The results of carotid imaging improved the specificity and positive likelihood ratio of correct differentiation., Conclusions: Those at high risk of embolism can be diagnosed clinically even before the completion of tests. This is a practical approach to distinguish patients at risk and help balance early risks of recurrence with those of short-term anticoagulation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Blindness caused by soft tissue fillers is an extremely low-probability event, but it results in great concern because of its devastating consequences. Currently, the mechanism of an embolism is usually considered to be an accidental injection of fillers into the blood vessels of the face, such as a facial artery, and then retrograding into the ophthalmic artery system, which causes retinal ischemic necrosis. In addition, previous studies have shown that there are anastomoses between facial arteries and branches of the ophthalmic artery in cadavers. An in vivo study, however, has not yet been reported., Methods: This study was approved by the institutional review board of Xijing Hospital, Fourth Military Medical University. Under general anesthesia, we dissected the same side of the face and eyeball in rabbits to manifest the facial artery and retina separately. Later, a needle (27 g) connected to a syringe (10 ml) full of methylene blue was inserted into a rabbit facial artery. Then, after poking a tiny hole in the central retinal artery, methylene blue was injected into the facial artery as quickly as possible (0.5 ml per second). At the same time, we carefully observed whether the central retinal artery had dye spillover or staining in the sclera. If blue dye was observed in the eye ground and/or the sclera, then it was thought to have entered the ophthalmic artery system (a positive result). In contrast, if none of the blue dye was observed, it was considered a negative result. A Chi-square (χ 2 ) test with a fourfold table was used to compare the differences in the frequencies of blue dye observed between living and dead rabbits. A value of p < 0.05 was considered significant., Results: One of the 20 rabbits showed the appearance of blue dye in the ophthalmic artery system in vivo, and the remaining 19 living rabbits had negative results. All 20 of the dead rabbits showed dye appearance in the eye ground. A statistically significant difference existed between the living and dead rabbits (p < 0.05)., Conclusion: In vivo, fillers can retrogradely enter the ophthalmic artery if the fillers entered the facial artery. Although the possibility is much lower in vivo than it is in corpses, adequate attention should be paid because of the catastrophic complications., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Purpose: To evaluate the feasibility of intravoxel incoherent motion (IVIM) for the measurement of diffusion and perfusion parameters in hyperacute strokes., Materials and Methods: An embolic ischemic model was established with an autologous thrombus in 20 beagles. IVIM imaging was performed on a 3.0 Tesla platform at 4.5 h and 6 h after embolization. Ten b values from 0 to 900 s/mm 2 were fitted with a bi-exponential model to extract perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D*. Additionally, the apparent diffusion coefficient (ADC) was calculated using the mono-exponential model with all the b values. Statistical analysis was performed using the pairwise Student's t test and Pearson's correlation test., Results: A significant decrease in f and D was observed in the ischemic area when compared with those in the contralateral side at 4.5 h and 6 h after embolization (P < 0.01 for all). No significant difference was observed in D* between the two sides at either time point (P = 0.086 and 0.336, respectively). In the stroke area, f at 6 h was significantly lower than that at 4.5 h (P = 0.016). A significantly positive correlation was detected between ADC and D in both stroke and contralateral sides at 4.5 h and 6 h (P < 0.001 for both). Significant correlation between ADC and f was only observed in the contralateral side at 4.5 h and 6 h (P = 0.019 and 0.021, respectively)., Conclusion: IVIM imaging could simultaneously evaluate the diffusion and microvascular perfusion characteristics in hyperacute strokes., Level of Evidence: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:550-556., (© 2016 International Society for Magnetic Resonance in Medicine.)

Background: Echocardiographically estimated pulmonary artery systolic pressure (PASP) is a non-invasive widely available method that is used to estimate pulmonary arterial pressure. Although elevated PASP predicts mortality in patients with hypertrophic cardiomyopathy (HCM), the relationship between PASP and embolic events is unclear. This study aimed to determine whether elevated PASP is associated with stroke and systemic embolic events in a tertiary referral HCM cohort., Methods: This study included 374 clinically diagnosed patients with HCM. PASP was estimated from tricuspid regurgitant jet velocity using the modified Bernoulli equation., Results: The median (interquartile range) PASP was 33 (28-37) mm Hg, and elevated PASP (>40mmHg) was observed in 66 (17.6%) patients. Seventeen of the 66 (25.8%) patients with elevated PASP and 24 of the 308 (7.8%) patients without elevated PASP experienced stroke and systemic embolic events during the 10.3±7.4years of follow-up (log-rank P<0.001). Multivariable analysis showed that age at diagnosis, atrial fibrillation, and PASP >40mmHg (adjusted hazard ratio, 2.59; 95% confidence interval, 1.31-5.12; P=0.006) were independently associated with embolic events., Conclusions: In addition to age and atrial fibrillation, PASP estimated by Doppler echocardiography could help embolic risk stratification in patients with HCM., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To report the safety and efficacy of a new technique to prevent distal embolism during treatment of iliofemoral occlusions: reverse flow aspiration with proximal sheath blockage (ReFLAP)., Method: Between October 2013 and December 2014, 90 patients (mean age 74 years; 66 men) were prospectively enrolled in a study to evaluate the ReFLAP technique during treatment of 110 occlusions in the iliac artery (72, 65%) or superficial femoral artery (SFA; 38, 35%). The mean occlusion lengths of iliac and SFA lesions were 79 and 179 mm, respectively. The concept of ReFLAP is to aspirate debris after balloon dilation using reverse flow through collaterals without antegrade flow. The main endpoints were the incidence of distal embolization, amputation, complications, and the ReFLAP capture rate, which was visually estimated during aspiration using 4 prespecified grades (0, none; 1, foamy debris; 2, small particles; 3, massive particles)., Results: ReFLAP was successful in 105 (95.4%) of the 110 lesions attempted; the 5 failures were due to severe vessel tortuosity or calcification. The incidences of distal embolization and amputation were both 0. Minor complications unrelated to ReFLAP were observed in 8 patients. The ReFLAP procedure aspirated debris in 57 (54%) of the 105 lesions. Aspirated material, including marked clots (grades 2 and 3), was confirmed in 40 (38%) of the lesions. The distribution of aspiration grades was significantly different between iliac and SFA lesions (p=0.02)., Conclusion: Our results suggest that the ReFLAP endovascular technique to prevent distal embolization during iliofemoral occlusive disease treatment is simple, safe, and effective.

Vascular quadrilateral space syndrome (vQSS) is an underdiagnosed cause of extremity ischemia, pain, and paresthesia in overhand throwing athletes. The mechanism of vQSS is thought to result from repeated abduction and external rotation of the arm leading to a distraction injury of the posterior circumflex humoral artery (PCHA) as this courses through the quadrilateral space. This trauma may cause dissection and dissecting aneurysm formation. Thrombus from this arterial injury then embolizes down the arm resulting in the symptomatic presentation. Patients were often presented after multiple embolic events, which have resulted in obliteration of digital arteries. Later stages of presentation may include ischemic ulceration and gangrene. We report 3 cases of vQSS in overhand throwing athletes. All 3 underwent surgical correction and have returned to competition. We discuss presentation, diagnosis, imaging findings, management, outcomes, and review of the literature. Prompt recognition of this syndrome is essential to optimal treatment, which includes PCHA ligation and division with or without thrombolytic therapy. Increased awareness of vQSS is needed among coaches and athletic trainers who often identify the symptoms and initiate the treatment. When treated promptly, these athletes return to baseline functional status., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Distal embolization (DE) during peripheral arterial endovascular interventions is a well-known complication that is poorly studied. The goal of this study was to determine the incidence, risk factors, and effect of DE on the outcomes of lower extremity endovascular interventions (LEIs)., Methods: All LEIs between 2010 and 2014 in the Vascular Study Group of New England (VSGNE) database were reviewed. Patient characteristics were analyzed to determine predictors of DE. LEIs involving the superficial femoral artery (SFA) were reviewed to assess the effect of type of treatment on DE. The outcomes examined were loss of patency, limb loss, and mortality after LEI involving the SFA. A multivariable regression was used to determine predictors of DE., Results: There were 10,875 procedures. The incidence of DE was 17.3 per 1000 procedures, and 68% required treatment (57% endovascular, 11% open surgery). DE was more common in patients treated for critical limb ischemia compared with claudication (relative risk [RR], 2.06; 95% confidence interval [CI], 1.24-3.45; P = .006) and for emergency interventions compared with elective (RR, 2.98; 95% CI, 1.22-7.30; P = .017). DE increased with the number of arteries treated (P < .0001) and with the length of occlusion (P < .0001). The SFA was the most commonly treated artery (4751 [43.7%]). In comparison with atherectomy and balloon angioplasty, stenting alone (RR, 0.36; 95% CI, 0.17-0.73; P = .005), balloon angioplasty alone (RR, 0.23; 95% CI, 0.13-0.41; P < .0001), and combined stenting and balloon angioplasty (RR, 0.29; 95% CI, 0.17-0.49; P < .0001) were associated with a significantly lower risk of DE. DE was not significantly associated with loss of patency, major amputation, or mortality., Conclusions: The incidence of DE during LEIs is 1% to 2% in the VSGNE database, and most patients are treated with additional endovascular interventions. The incidence increases in patients with critical limb ischemia and with the use of atherectomy., (Copyright © 2017 Society for Vascular Surgery. All rights reserved.)

Inferior vena cava (IVC) filters are medical devices designed to provide a mechanical barrier to the passage of emboli from the deep veins of the legs to the heart and lungs. Despite decades of development and clinical use, IVC filters still fail to prevent the passage of all hazardous emboli. The objective of this study is to (1) develop a resolved two-way computational model of embolus transport, (2) provide verification and validation evidence for the model, and (3) demonstrate the ability of the model to predict the embolus-trapping efficiency of an IVC filter. Our model couples computational fluid dynamics simulations of blood flow to six-degree-of-freedom simulations of embolus transport and resolves the interactions between rigid, spherical emboli and the blood flow using an immersed boundary method. Following model development and numerical verification and validation of the computational approach against benchmark data from the literature, embolus transport simulations are performed in an idealized IVC geometry. Centered and tilted filter orientations are considered using a nonlinear finite element-based virtual filter placement procedure. A total of 2048 coupled CFD/6-DOF simulations are performed to predict the embolus-trapping statistics of the filter. The simulations predict that the embolus-trapping efficiency of the IVC filter increases with increasing embolus diameter and increasing embolus-to-blood density ratio. Tilted filter placement is found to decrease the embolus-trapping efficiency compared with centered filter placement. Multiple embolus-trapping locations are predicted for the IVC filter, and the trapping locations are predicted to shift upstream and toward the vessel wall with increasing embolus diameter. Simulations of the injection of successive emboli into the IVC are also performed and reveal that the embolus-trapping efficiency decreases with increasing thrombus load in the IVC filter. In future work, the computational tool could be used to investigate IVC filter design improvements, the effect of patient anatomy on embolus transport and IVC filter embolus-trapping efficiency, and, with further development and validation, optimal filter selection and placement on a patient-specific basis.

Incidental capture, or 'bycatch' in fishing gear is a major global threat to sea turtle populations. A recent study showed that underwater entrapment in fishing gear followed by rapid decompression may cause gas bubble formation within the blood stream (embolism) and tissues leading to organ injury, impairment, and even mortality in some bycaught individuals. We analyzed data from 128 capture events using logistic and ordinal regression to examine risk factors associated with gas embolism in sea turtles captured in trawls and gillnets. Likelihood of fatal decompression increases with increasing depth of gear deployment. A direct relationship was found between depth, risk and severity of embolism, which has not been previously demonstrated in any breath-hold diving species. For the trawl fishery in this study, an average trawl depth of 65 m was estimated to result in 50% mortality in by-caught turtles throughout the year. This finding is critical for a more accurate estimation of sea turtle mortality rates resulting from different fisheries and for devising efforts to avoid or minimize the harmful effects of capture.

Objectives: The purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion., Methods: This was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%., Results: The mean follow-up was 59.4 months (95% CI, 56.1-62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p < .001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p = .002) and lower for the occluded graft/stent group (43.3%, p < .001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p = .001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p = 0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p = .007)., Conclusion: Intra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

An anatomically detailed model consisting of a network of electric transmission lines is developed to simulate propagation of the pulse waves in humans. The simulations show that the real arterial tree geometry, together with the elastic and rheological parameters of particular segments, ensure an efficient protection of vital organs against pulse waves generated at peripheral locations. Because locomotive movements are the most obvious source of such disturbances, additional cyclic perturbations are applied to the model femoral arteries. It is shown that the impact of such peripherally generated pulse waves onto the pressure profiles at the ascending aorta and at other vital locations of the system is surprisingly weak independently of synchronization/desynchronization with the heart action period. This may witness to an intrinsically protective nature of the arterial tree anatomy in addition to its known functionality of the optimal blood supply at possibly low lumen volume. The extent of the protection is also studied in the presence of a complete arterial embolism at the left common carotid artery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The complexity of inertial particle dynamics through swirling chaotic flow structures characteristic of pulsatile large-artery hemodynamics renders significant challenges in predictive understanding of transport of such particles. This is specifically crucial for arterial embolisms, where knowledge of embolus transport to major vascular beds helps in disease diagnosis and surgical planning. Using a computational framework built upon image-based CFD and discrete particle dynamics modeling, a multi-parameter sampling-based study was conducted on embolic particle dynamics and transport. The results highlighted the strong influence of material properties, embolus size, release instance, and embolus source on embolus distribution to the cerebral, renal and mesenteric, and ilio-femoral vasculature beds. The study also isolated the importance of shear-gradient lift, and elastohydrodynamic contact, in affecting embolic particle transport. Near-wall particle re-suspension due to lift alters aortogenic embolic particle dynamics significantly as compared to cardiogenic. The observations collectively indicated the complex interplay of particle inertia, fluid-particle density ratio, and wall collisions, with chaotic flow structures, which render the overall motion of the particles to be non-trivially dispersive in nature., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied., Objective: To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections., Materials and Methods: The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2., Results: Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups., Conclusion: A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.

Purpose: We report a combined technique consisting of thrombectomy and thromboaspiration for the treatment of acute embolic occlusion of the superior mesenteric artery (SMA) at the origin., Case: A 90-year-old female with chronic atrial fibrillation had a sudden onset of abdominal pain and hematochezia due to acute embolic occlusion at the origin of the SMA. Computed tomographic findings showed reversible bowel wall ischemia. We performed mechanical thrombectomy using the Solitaire FR revascularization device, a self-expanding and fully retrievable stent-based thrombectomy system for acute intracranial large artery occlusion, combined with manual aspiration through a 6F guiding sheath placed at the SMA origin via a right brachial approach. Prompt and complete recanalization of the SMA was obtained without distal embolism, and intestinal necrosis was avoided., Conclusion: Combined endovascular procedures of mechanical thrombectomy using the Solitaire FR with thromboaspiration may allow prompt recanalization, clot removal, and prevention of distal embolism and therefore would be a new therapy for acute embolic occlusion at the origin of the SMA.

In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice. We observed cellular microembolism of precapillary pulmonary arteriolar bottlenecks by neutrophil-platelet aggregates. Blood from SCD patients was next studied under flow in an in vitro microfluidic system. Similar to the pulmonary circulation, circulating platelets nucleated around arrested neutrophils, translating to a greater number and duration of neutrophil-platelet interactions compared with normal human blood. Inhibition of platelet P-selectin with function-blocking antibody attenuated the neutrophil-platelet interactions in SCD patient blood in vitro and resolved pulmonary arteriole microembolism in SCD mice in vivo. These results establish the relevance of neutrophil-platelet aggregate formation in lung arterioles in promoting lung vaso-occlusion in SCD and highlight the therapeutic potential of targeting platelet adhesion molecules to prevent acute chest syndrome., Competing Interests: The authors have declared that no conflict of interest exists.

Objective: Conventional catheter manipulation in the arch and supra-aortic trunks carries a risk of cerebral embolization. This study proposes a platform for detailed quantitative analysis of contact forces (CF) exerted on the vasculature, in order to investigate the potential advantages of robotic navigation., Methods: An anthropomorphic phantom representing a type I bovine arch was mounted and coupled onto a force/torque sensor. Three-axis force readings provided an average root-mean-square modulus, indicating the total forces exerted on the phantom. Each of the left subclavian, left common carotid, and right common carotid arteries was cannulated within a simulated endovascular suite with conventional (n = 42) vs robotic techniques (n = 30) by two operator groups: experts and novices. The procedure path was divided into three phases, and performance metrics corresponding to mean and maximum forces, force impact over time, standard deviation of forces, and number of significant catheter contacts with the arterial wall were extracted., Results: Overall, median CF were reduced from 1.20 N (interquartile range [IQR], 0.98-1.56 N) to 0.31 N (IQR, 0.26-0.40 N; P < .001) for the right common carotid artery; 1.59 N (IQR, 1.11-1.85 N) to 0.33 N (IQR, 0.29-0.43 N; P < .001) for the left common carotid artery; and 0.84 N (IQR, 0.47-1.08 N) to 0.10 N (IQR, 0.07-0.17 N; P < .001) for the left subclavian artery. Robotic navigation resulted in significant reductions for the mean and maximum forces for each procedural phase. Significant improvements were also seen in other metrics, particularly at the target vessel ostium and for the more anatomically challenging procedural phases. Force reductions using robotic technology were evident for both novice and expert groups., Conclusions: Robotic navigation can potentially reduce CF and catheter-tissue contact points in an in vitro model, by enhancing catheter stability and control during endovascular manipulation., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)