Carotid Artery Thrombus Research Articles

Intraluminal Carotid Artery Thrombus in COVID-19: Another Danger of Cytokine Storm?

Coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Inflammation affects atherosclerotic plaque vulnerability and promotes a thrombogenic environment. We report a series of 6 patients with COVID-19 with acute ischemic stroke due to intraluminal carotid artery thrombus presenting during an 8-day period. Six patients were included (5 men) with a mean age of 65.8 years (range, 55-78 years). COVID-19 was diagnosed by detection of Severe Acute Respiratory Syndrome coronavirus 2 in 5 patients and was presumed due to typical clinical and imaging findings in 1 patient. All patients had vascular risk factors including diabetes (83%), hyperlipidemia (100%), and smoking (17%). Four patients presented with large infarcts with initial NIHSS scores of 24-30. During their hospitalization, all patients had elevated D-dimer and C-reactive protein levels, 5 patients had elevated lactate dehydrogenase and ferritin levels, 3 had elevated interleukin-6 levels, and 2 had elevated troponin levels. Inflammation related to COVID-19 may result in rupture of vulnerable atherosclerotic plaques, resulting in thrombosis and acute ischemic stroke.

Novel potent antiplatelet thrombotic agent derived from biguanide for ischemic stroke

Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia. Here, twenty-three biguanide derivatives were designed and synthesized based on the principles of bioisosteres. These derivatives were evaluated for the activity of antiplatelet thrombosis in vivo. We found that N-trifluoromethanesulfonyl biguanide derivative, compound b10, uniquely prevented cerebral infarction as well as neuronal function injury, and significantly decrease the mortality rate of ischemic stroke in the middle cerebral artery occlusion mice without significant side effects. We verified that b10 directly inhibited platelets thrombus formation and decreased the compactness of stroke thrombi. Particularly, b10 exhibited good potency to inhibit human platelet activation including platelet aggregation, adhesion, pseudopodia formation, integrin GPIIb/IIIa activation, CD62P expression and clot retraction. Meanwhile, the pharmacokinetics assessment showed that b10 had satisfying pharmacological characteristics including a longer duration and a higher oral absorption ratio than its parent compound. In addition, b10 remarkably ameliorated not only stroke related to platelet thrombosis but also carotid artery thrombus formation. It is concluded that the novel potent antiplatelet thrombotic agent derived from biguanide is a promising candidate for stroke treatment.

P1731 Multiple floating thrombi in aortic arch leading to acute stroke: A case report and systematic review of literature

Abstract Introduction Around 10-15% of acute cerebrovascular events occur in young adults with age less than 40 years. Trans-oesophageal echocardiogram (TOE) is routinely performed to rule out any cardio-embolic source in patients with ischemic stroke. TOE has shown to significantly change management strategy in up to 16.7% of stroke cases. We report a rare case of recurrent stroke in a young female who was found to have multiple mobile thrombi in aortic arch on TOE. We also report systematic review of literature of similar cases to highlight the management strategies. Case Presentation A 38-year-old female presented with one-week history of right upper and lower extremity paresthesia along with headache. Physical examination was unremarkable for any focal neurological deficits at time of initial evaluation. She had pertinent history of acute stroke two years ago associated with non-occlusive left common carotid artery thrombus for which she was previously on anticoagulation with rivaroxaban. The anticoagulation, however, was stopped five months ago after repeat imaging revealed complete resolution of thrombus. Electrocardiogram showed normal sinus rhythm without any other significant abnormality. CT head showed no acute bleeding or infarct. MRI brain showed scattered infarcts in right cerebral hemisphere and left cerebellar hemisphere. CT angiography of head and neck showed multiple small nodular and linear pedunculated thrombi in distal arch of aorta (see Figure 2). TOE was then performed which confirmed two pedunculated and mobile echogenic masses, largest measuring 0.9 x 0.6 cm, in the distal aortic arch (see Figure 1). TOE did not show intracardiac source of embolism. Laboratory testing for thrombophilia was negative for Factor V and Prothrombin gene mutation and heterozygous positive for Methylenetetrahydrofolate reductase (MTHFR)-677T gene. She was also found to have elevated homocysteine levels. She was restarted on anticoagulation with rivaroxaban. Discussion and Conclusion Young patients with stroke should undergo detailed investigation to rule out hypercoagulable pathology and cardiovascular embolic source. This should also include multimodality imaging including TOE in the selected patients. During TOE examination, a particular attention should be paid for evaluation of aortic source of thombo-embolism. Our patient was heterozygous for MTHFR-66T gene which is associated with decreassed activity of MTHFR by 35 % with elevated homocysteine levels. Treatment of floating aortic thrombus is still controversial. Anticoagulation is suggested as primary modality by multiple authors who reported complete resolution of thrombus. Other option includes surgical thrombectomy. Our patient was treated with anticoagulation alone due to hypercoagulable state and small size of thrombi. Abstract P1731 Figure.

Factor XIII deficiency does not prevent FeCl3‐induced carotid artery thrombus formation in mice

BackgroundThe compositions of venous (red blood cell–rich) and arterial (platelet‐rich) thrombi are mediated by distinct pathophysiologic processes; however, fibrin is a major structural component of both. The transglutaminase factor XIII (FXIII) stabilizes fibrin against mechanical and biochemical disruption and promotes red blood cell retention in contracted venous thrombi. Previous studies have shown factor XIII (FXIII) inhibition decreases whole blood clot mass and therefore, may be a therapeutic target for reducing venous thrombosis. The role of FXIII in arterial thrombogenesis is less studied, and the particular contribution of platelet FXIII remains unresolved. ObjectiveTo determine whether FXIII reduction prevents experimental arterial thrombogenesis. MethodsUsing wild‐type mice and mice with genetically imposed deficiency in FXIII, we measured thrombus formation and stability following ferric chloride–induced arterial thrombosis. We also determined the impact of FXIII on the mass of contracted platelet‐rich plasma clots. ResultsFollowing vessel injury, F13a+/+, F13a+/−, and F13a−/− mice developed occlusive arterial thrombi. FXIII deficiency did not significantly reduce the incidence or prolong the time to occlusion. FXIII deficiency also did not alter the timing of reflow events or decrease platelet‐rich clot mass. ConclusionsFXIII does not significantly alter the underlying pathophysiology of experimental arterial thrombus formation.

2182Sirtuin 5 regulates arterial thrombosis by modulating endothelial plasminogen activator inhibitor-1

Abstract Introduction Arterial thrombosis as a result of plaque rupture or erosion is a crucial event in myocardial infarction and stroke. Oxidative stress and inflammation promote endothelial dysfunction and play a pivotal role in destabilization of the atherosclerotic plaque. Sirtuin 5 (SIRT5) is a member of the sirtuin protein family with function as a NAD+-dependent protein desuccinylase and demalonylase. Being implicated in the regulation of different pathophysiological processes among which production of reactive oxygen species and transcription of inflammatory mediators, SIRT5 plays a role in the development of several cardiovascular diseases such as myocardial infarction and stroke. To date, the possible involvement of SIRT5 as a mediator of arterial thrombosis remains to be investigated. Purpose In this study we investigate the putative role of this protein in arterial thrombosis by using an established in vivo mouse model. The translational value of animal findings as well as the molecular mechanism underlying the observed effect will be investigated also in primary human aortic endothelial cells (HAECs). Methods SIRT5 knockout (KO) as well as SIRT5 transgenic (TG) animals were used for in vivo experiments. HAECs treated with SIRT5 silencing RNA (si-SIRT5) and stimulated with tumor necrosis factor (TNF)-α were used for in vitro assays. Results When compared to WT animals, SIRT5 KO mice display blunted carotid artery thrombus formation as underlined by delayed time to occlusion in a photochemical injury model. Oppositely, in SIRT5 TG mice the formation of an occlusive thrombus is accelerated (Fig 1). Mechanistically, SIRT5 KO and WT animals show no difference in terms of vascular tissue factor (TF) activity, TF concentration in plasma and expression of TF pathway inhibitor (TFPI) in the aorta. In line with the observed reduced thrombogenicity, SIRT5 KO animal express reduced level of the pro-thrombotic plasminogen activator-1 (PAI-1), as assessed by western blot in aorta lysate. Of interest, SIRT5 genetic deletion does not affect platelet aggregation, as assessed by ex-vivo collagen-induced aggregometry. In HAECs, SIRT5-silencing inhibits PAI-1 expression in response to TNF-α. Real-time polymerase chain reaction revealed that inhibition of PAI-1 expression occurs at the mRNA level. This effect is mediated by reduced activation of the MAP kinase Erk 1/2, but not JNK (Fig 1). Conclusions SIRT5 mediates arterial thrombosis by increasing endothelial PAI-1 expression. Hence, SIRT5 may be an effective therapeutic target in the context of atherothrombosis.

Anemia; an unusual cause of freefloating thrombus of carotid artery

The article's abstract is no available.

The antithrombotic activity of the active fractions from the fruits of Celastrus orbiculatus Thunb through the anti-coagulation, anti-platelet activation and anti-fibrinolysis pathways

Ethnopharmacological relevanceTraditional Chinese medicine Celastrus orbiculatus Thunb (C. orbiculatus) with peel and seeds is mainly composed of flavonoids, sesquiterpenes and tripenes. According to the Traditional Chinese medicine standard of Liaoning province (2009), it has been long used to invigorate blood circulation. Aim of the studyTo identify the antithrombus fraction and components of C. orbiculatus, and to investigate the underlying mechanisms. Materials and methodsThe antithrombus effects of C. orbiculatus fractions were evaluated in vitro by plasma recalcification time (PRT). The antithrombus effect of NST-50, the most effective fraction, was further investigated in acute pulmonary embolism (APE) mice and FeCl3-induced carotid arterial thrombus rats. Bleeding assessment was also carried out to assess the side effects of NST-50. In addition, the content of total flavonoids and active components of NST-50 was also quantified. ResultsNine flavonoids were detected in NST-50 as main components with the content of 44.70%. Next, NST-50 was found with significant anticoagulation activity by prolonging the plasma recalcification time (PRT), activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) and decreasing the content of fibrinogen (FIB). Furthermore, NST-50 administration markedly suppressed the level of TXB2 and PAI-1, while significantly up-regulated the level of 6-keto-PGF1a and t-PA (p < 0.05). ConclusionThe results demonstrated that NST-50 could be valuable in clinical application against acute coronary syndrome, venous thromboembolisms and cerebrovascular thrombosis. It was possible that the anticoagulation action of NST-50 could be related to the regulation of TXA2 - PGI2 and t-PA - PAI-1 pairs.

Symptomatic Extracranial Carotid Artery Thrombus: An Indian Experience

Introduction:Symptomatic intraluminal carotid artery thrombus (ICT) is an uncommon finding, whose incidence increases with the percentage of stenosis. The optimal treatment modality to address carotid artery thrombus is not well established. We present our data of medical management of carotid artery thrombus with antiplatelet and anticoagulation.Methods:We reviewed our data from January 1, 2016 to December 31, 2017. Patients with extracranial carotid artery thrombus underwent a catheter digital subtraction angiogram to confirm the presence of thrombus. Medical management was done with dual antiplatelets along with low-molecular-weight heparin, and a check angiogram was done after 14 days. Factors contributing to the persistence of thrombus were analyzed.Results:A total of 21 patients diagnosed with acute ischemic stroke and extracranial carotid artery thrombus. Three patients opted for endarterectomy. Eighteen patients underwent medical management. Nine (50%) had a resolution of thrombus. Those with persistent thrombus were significantly older (average age 64 vs. 43 years, P = 0.008). They also had significantly higher proportions of hypertension (100% vs. 44%, P = 0.029), diabetes mellitus (89% vs. 11%, P = 0.003), and underlying carotid stenosis (100% vs. 33%, P = 0.009).Conclusion:Our regimen of dual antiplatelets plus short-term anticoagulation is safe and effective in the management of ICT. Large-scale studies are warranted to determine the optimal regimen and duration of medical treatment.

Tick-borne meningitis complicated by a cardioembolic intraluminal carotid artery thrombus and stroke

Intraluminal carotid thrombus (ILCT) is present in less than 2% of patients presenting with acute ischaemic stroke, and 75–81% of ILCT cases are associated with atherosclerosis [1,2]. We present a rare case of acute stroke with ILCT on bare carotid artery without a plaque.

Antithrombotic effects and related mechanisms of Salvia deserta Schang root EtOAc extracts

Salvia deserta Schang (SDS) belongs to the same family as Salvia miltiorrhiza bunge, one of the antithrombotic Chinese herbal medicines. In our study, EtOAc root extracts were analyzed for their effects on adenosine diphosphate (ADP)-induced platelet aggregation in rabbits and FeCl3-induced rat common carotid artery thrombosis as well as on rat blood plasma concentrations of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1α), antithrombin-III (AT-III), protein C (PC), plasminogen (PLG), plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA). EtOAc extracts from SDS roots had significant inhibitory effects on ADP-induced maximum platelet aggregation rate (10.2 ± 2.6 vs control 35.7 ± 5.2; P < 0.05), reduced the FeCl3-induced rat common carotid artery thrombus weight and thrombus area ratio (P < 0.05), significantly decreased plasma TXB2, vWF and PAI-1 levels and increased 6-keto-PGF1α and t-PA levels in a dose dependent manner (all P < 0.05). Thus, the ratio of TXB2/6-keto-PGF1α was significantly decreased (P < 0.05), while the ratio of t-PA/PAI-1 was significantly increased (P < 0.05). In addition, enhanced AT-III and PC activities indicated coagulation inactivation effects of EtOAc SDS root extracts. EtOAc extraction from SDS showed antithrombotic effects, which are likely due to platelet adhesion and aggregation inhibition as well as anticoagulant activities.

Isolation and Characterization of Poecistasin, an Anti-Thrombotic Antistasin-Type Serine Protease Inhibitor from Leech Poecilobdella manillensis.

Antistasin, first identified as a potent inhibitor of the blood coagulation factor Xa, is a novel family of serine protease inhibitors. In this study, we purified a novel antistasin-type inhibitor from leech Poecilobdella manillensis called poecistasin. Amino acid sequencing of this 48-amino-acid protein revealed that poecistasin was an antistasin-type inhibitor known to consist of only one domain. Poecistasin inhibited factor XIIa, kallikrein, trypsin, and elastase, but had no inhibitory effect on factor Xa and thrombin. Poecistasin showed anticoagulant activities. It prolonged the activated partial thromboplastin time and inhibited FeCl3-induced carotid artery thrombus formation, implying its potent function in helping Poecilobdella manillensis to take a blood meal from the host by inhibiting coagulation. Poecistasin also suppressed ischemic stroke symptoms in transient middle cerebral artery occlusion mice model. Our results suggest that poecistasin from the leech Poecilobdella manillensis plays a crucial role in blood-sucking and may be an excellent candidate for the development of clinical anti-thrombosis and anti-ischemic stroke medicines.

Targeted thrombolysis by using c-RGD-modified N,N,N-Trimethyl Chitosan nanoparticles loaded with lumbrokinase

Lumbrokinase (LK) has strong fibrinolytic and thrombolytic activities, but it has a short half-life, can be easily inactivated, and may cause hemorrhage as a side effect. This study develops a potential thrombolytic therapy by fabricating N,N,N-Trimethyl Chitosan (TMC) nanoparticles modified with the cyclic Arg-Gly-Asp-Phe-Lys peptide (c-RGD) and loaded with LK (i.e. c-RGD-LK-NPs). The binding of c-RGD to platelet membrane GPIIb/IIIa receptors is expected to enable targeted delivery of the c-RGD-conjugated TMC to the thrombus. The synthesized c-RGD-LK-NPs had a mean particle size of 232.0 nm, zeta potential of 19.8 mV, entrapment efficiency of 52.7% ± 2.5%, and loading efficiency of 17.4% ± 0.65%. Transmission electron microscopy showed that they were generally spherical. The c-RGD-LK-NPs gave a cumulative in vitro LK release of 80.6% over 8 h, and the activity of LK was close to 80%, indicating that the nanoparticles protected the activity of LK. In vitro blood clot lysis assays were carried out and in vivo thrombolysis effect was tested in Sprague-Dawley rats carotid artery thrombus model. In all cases, the c-RGD-LK-NPs showed superior performance compared with the free LK and the unmodified TMC nanoparticles loaded with LK. The c-RGD-LK-NPs reagent is expected to be potentially useful in treating thromboembolic diseases.

SUBCLINICAL POLYCYTHEMIA VERA PRESENTING AS EXTENSIVE THROMBOSIS DUE TO MASSIVE TRANSFUSION

SESSION TITLE: Critical Care 1 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/09/2018 03:45 PM - 04:45 PM INTRODUCTION: Massive Transfusion Protocol (MTP) is used in patients with hemorrhagic shock. Iatrogenic polycythemia secondary to massive transfusion is exceedingly rare. We present first reported case of undiagnosed subclinical polycythemia vera (PV) which became manifest with extensive thrombosis, after massive transfusion. CASE PRESENTATION: 66-year-old male with history of hypertension and ischemic strokes, presented to the Emergency Department with hypovolemic shock due to lower gastrointestinal bleeding. Initial bloodwork showed a Hb of 6.2 gm/dL, Hct 19.1%, platelets-282 x 109/L, WBC 6.6 x 109/L, INR 2.7, aPTT 83.7s. He received 8 units of PRBC, 6 units of fresh frozen plasma, 6 units of platelets as well as human prothrombin complex concentrate to reverse coagulopathy. Patient was admitted to ICU and intubated for urgent endoscopy, which revealed an esophageal ulcer and gastritis. He was started on proton pump inhibitor and repeat labs showed Hb of 18 gm/dL, Hct 53.8%, platelets-546 x 109/L with INR of 1. On admission day 3, patient developed pulmonary infiltrate and BAL grew MRSA treated with vancomycin. Due to worsening ventilation, a CT scan was done which showed bilateral acute pulmonary embolism with right heart strain. Doppler venous ultrasound revealed deep vein thrombosis of both upper and lower extremities. He had Hb of 19.6 gm/dL, Hct 59.9%, platelets-450 x 109/L. Reviewing his history, he was noted to have baseline Hb of 14 to 16 gm/dL, Hct 40%, with one instance of Hb of 18 gm/dL, Hct 56. The previous cerebrovascular accident was found to be secondary to a carotid artery thrombus. Hematology was emergently consulted and anticoagulation with low intensity heparin was initiated inspite of GI bleeding. He underwent multiple bedside phlebotomies until his Hct was below 50%. CT abdomen showed mild splenomegaly. Serum erythropoietin initially was normal, but was low on repeat testing. Janus kinase 2 (JAK2) V617F mutation was present, confirming diagnosis of primary polycythemia. Upon discharge, he is to receive ASA, hydroxyurea and anticoagulation for the venous thrombosis. DISCUSSION: PV is a chronic myeloproliferative neoplasm that is associated with a JAK2 mutation in most cases. An elevation of hemoglobin/hematocrit>16.5/49 in men and 16/48 in women, a subnormal serum EPO level, and a JAK2 V617F mutation constitute the diagnostic criteria for PV. Thrombotic complications are a major cause of morbidity and mortality in polycythemia vera with a reported incidence of 12–39%1. CONCLUSIONS: Sustained elevation of Hb/Hct >16.5/49 after massive transfusion should raise the possibility of PV, prompting workup and a heightened concern for thrombosis. Recognition of subclinical polycythemia is extremely important in critical care setting as they share the same vascular risk as overt PV including risk of arterial and venous thrombosis. Reference #1: Cerquozzi S, Barraco D, Lasho T, Finke C, Hanson CA, Ketterling RP, Pardanani A, Gangat N, Tefferi A. Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017 Dec 27;7(12):662 DISCLOSURES: No relevant relationships by Paula Adamson, source=Web Response No relevant relationships by Shahla Bari, source=Web Response No relevant relationships by Donnie Carter, source=Web Response No relevant relationships by Marilyn Foreman, source=Web Response No relevant relationships by Swathi Sree Nutakki, source=Web Response

Endovascular aspiration of a symptomatic free-floating common carotid artery thrombus

Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of ischemic stroke. To date, only a few reports have been described in the academic literature. Revascularization is indicated due to the risk of thromboembolic disease and hemodynamic-related stroke syndromes. Medical treatment typically includes anticoagulation and, in some circumstances, open surgical thrombectomy is an additional option. Although rarely described in the literature, endovascular thrombectomy is a viable treatment alternative in these patients.

Free-floating thrombus of the carotid artery on MR vessel wall imaging: a case report

Free-floating thrombus of the carotid artery on MR vessel wall imaging: a case report

Chemokine CC-motif ligand 2 participates in platelet function and arterial thrombosis by regulating PKCα-P38MAPK-HSP27 pathway

BackgroundStudies indicate that chemokine CC-motif ligand 2 (CCL2) is involved in inflammation and atherosclerosis. However, the roles and mechanisms of CCL2 on platelet function and arterial thrombosis are unknown. MethodsThe expressions of CCL2 or CCR2 in the plasma, platelets and coronary thrombus of ST-elevated myocardial infarction (STEMI) patients were examined by ELISA, Western blot, immunohistochemistry and immunofluorescence. The roles of CCL2 on platelet aggregation, activation and secretion were examined by light transmission aggregometry, flow cytometry and ELISA. ResultsThe expressions of CCL2 or CCR2 in the plasma or platelets of STEMI patients with platelet high response were higher than those with platelet normal response; In vitro, exogenous recombinant human CCL2 markedly increased platelet aggregation, activation and granule secretion, which were abolished by CCL2 neutralizing antibody or CCR2 inhibiter. CCL2 increased the phosphorylation levels of PKCα (Thr638), P38MAPK (Thr180/Tyr182) and HSP27 (S78/S82) in human platelets, which were abrogated by PKCα inhibitor (RO 318220) or P38MAPK inhibitor (SB 203580). RO 318220 or SB 203580 diminished CCL2-induced platelet function. In CCL2−/− mice, platelet aggregation and secretion were attenuated; the phosphorylation of PKCα, P38MAPK and HSP27 were decreased. In a carotid arterial thrombus mouse model, CCL2−/− mice displayed a significantly extended carotid artery occlusion time compared with wild type. ConclusionsCCL2 played important roles in regulating platelet function and arterial thrombosis through the PKCα-P38MAPK-HSP27 pathway, which might provide theoretical basis for searching new antiplatelet drugs and the treatment for cardiovascular diseases.

Extending Carotid Artery Thrombus Associated with Thrombocytosis.

Extending Carotid Artery Thrombus Associated with Thrombocytosis.

Protection from Psoriasis-Related Thrombosis after Inhibition of IL-23 or IL-17A

Psoriasis patients experience chronic systemic skin inflammation and develop cardiovascular comorbidities that shorten their lifespan. Whether cardiovascular disease is improved by treatment with current biologics that target disease-specific pathways is unclear. KC-Tie2 mice develop psoriasiform skin inflammation with increases in IL-23 and IL-17A and proinflammatory monocytosis and neutrophilia that precedes development of carotid artery thrombus formation. To examine whether targeted blockade of IL-23 or IL-17A in KC-Tie2 psoriasis mice improves cardiovascular outcomes, mice were treated systemically for 6 weeks with antibodies targeting IL-17A, IL-17RA, IL-12/23p40, or IL-23p19. Skin inflammation; thrombosis clotting times; and percentage of splenic monocytes, neutrophils, and CD4 T cells were examined. Skin inflammation significantly improved in KC-Tie2 mice treated with each of the antibodies targeting IL-23, IL-17A, or IL-17RA, consistent with clinical efficacy observed in psoriasis patients. The time to occlusive thrombus formation lengthened in these mice and correlated with attenuated acanthosis. This decrease in skin inflammation paralleled decreases in splenic neutrophils (CD11b+Ly6G+) but not monocytes (CD11b+Ly6Chigh) or T cells (CD4+). Our data show that targeted inhibition of IL-23 or IL-17A improves psoriasis-like skin disease and also improves cardiovascular disease in mice.

The Thrombolytic Effect of Diagnostic Ultrasound-Induced Microbubble Cavitation in Acute Carotid Thromboembolism.

Acute ischemic stroke is often due to thromboembolism forming over ruptured atherosclerotic plaque in the carotid artery (CA). The presence of intraluminal CA thrombus is associated with a high risk of thromboembolic cerebral ischemic events. The cavitation induced by diagnostic ultrasound high mechanical index (MI) impulses applied locally during a commercially available intravenous microbubble infusion has dissolved intravascular thrombi, especially when using longer pulse durations. The beneficial effects of this in acute carotid thromboembolism is not known. An oversized balloon injury was created in the distal extracranial common CA of 38 porcine carotid arteries. After this, a 70% to 80% stenosis was created in the mid common CA proximal to the injury site using partial balloon inflation. Acute thrombotic CA occlusions were created just distal to the balloon catheter by injecting fresh autologous arterial thrombi. After angiographic documentation of occlusion, the common carotid thrombosis was treated with either diagnostic low MI imaging alone (0.2 MI; Philips S5-1) applied through a tissue mimicking phantom (TMP) or intermittent diagnostic high MI stable cavitation (SC)-inducing impulses with a longer pulse duration (0.8 MI; 20 microseconds' pulse duration) or inertial cavitation (IC) impulses (1.2 MI; 20 microseconds' pulse duration). All treatment times were for 30 minutes. Intravenous ultrasound contrast (2% Definity; Lantheus Medical) was infused during the treatment period. Angiographic recanalization in 4 intracranial and extracranial vessels downstream from the CA occlusion (auricular, ascending pharyngeal, buccinator, and maxillary) was assessed with both magnetic resonance 3-dimensional time-of-flight and phase contrast angiography. All magnetic resonance images were interpreted by an independent neuroradiologist using the thrombolysis in cerebral infarction (TICI) scoring system. By phase contrast angiography, at least mild recanalization (TICI 2a or higher) was seen in 64% of downstream vessels treated with SC impulses compared with 33% of IC treated and 29% of low MI alone treated downstream vessels (P = 0.001), whereas moderate or complete recanalization (TICI 2b or higher) was seen in 39% of SC treated vessels compared with 10% IC treated and 21% of low MI alone treated vessels (P = 0.001). High MI 20-microsecond pulse duration impulses during a commercial microbubble infusion can be used to recanalize acutely thrombosed carotid arteries and restore downstream flow without anticoagulants. However, this effect is only seen with SC-inducing impulses and not at higher mechanical indices, when a paradoxical reversal of the thrombolytic effect is observed. Diagnostic ultrasound-induced SC can be a nonsurgical method of dissolving CA thrombi and preventing thromboembolization.

Emergent vs. elective stenting of carotid stenosis with intraluminal carotid thrombus

Background and purposeCarotid stenosis (CS) with intraluminal carotid artery thrombus (ICAT) is rare but ominous finding. The optimal treatment modality is unclear. The aim of this study was to analyze the feasibility and outcome of acute endovascular intervention and delayed elective endovascular therapy after initial anticoagulation in these delicate cases. Moreover, both treatment points were compared and several parameters discussed to facilitate the determination of the optimal time modality in future cases. Materials and methodsA series of 11 consecutive cases with acute symptomatic CS with ICAT that received endovascular treatment was retrospectively analyzed. General patient data, pre and post-interventional symptoms and imaging were evaluated in an overall mean follow-up of 84 weeks. ResultsUrgent stenting and mechanical thrombectomy was performed in 6 patients. In the remaining 5 cases, elective endovascular treatment was planned after initial anticoagulation therapy with thrombus resolution. One case received secondary urgent treatment due to clinical deterioration. Overall outcome at three months follow-up was excellent (Modified Ranking Scale [mRS] 0–1) in 5 cases, good (mRS 2) in 4 and unfavorable in the remaining 2. Important differences between the two treatment arms were seen in 3 parameters (stenosis degree, thrombus length, and NIHSS score). ConclusionsThis is one of the largest studies analysing endovascular treatment in patients with acute symptomatic CS and additional ICAT only. Both endovascular treatment strategies seem feasible. Parameters such as size of intraluminal thrombus and clinical symptoms should be included in the decision-making process regarding the optimal individual treatment time.