Management of anticoagulation in patients with infective endocarditis.

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team.

Cerebral Embolism as a Result of Facial Filler Injections: A Literature Review.

BACKGROUND: With the growth in the popularity of facial filler injections, increased numbers of severe adverse events, such as cerebral embolism, have been reported. OBJECTIVES: The aim of this article was to summarize the clinical manifestations and proposed mechanisms of filler-induced cerebral embolism (FICE). METHODS: A literature review was performed with the search keywords "filler injection," "hyaluronic acid," "fat graft," "cerebral infarction," "cerebral embolism," "stroke," "cerebrovascular infarction," "disorders of consciousness," and "hemiplegia." RESULTS: Among the 43 cases of FICE enrolled from 35 articles, 37 patients were female, and 6 were male. Twenty-nine of these patients had received fat grafting, and 12 hyaluronic acid injection. Most FICE patients had been injected in the glabella, followed by the temporal, forehead, and nasal areas. Among 30 patients injected under local anesthesia, 43.33% presented with neurologic symptoms during the procedure. The main symptoms were consciousness disorders and hemiplegia. Most of the embolization sites were in the middle cerebral artery, followed by frontal lobe infarction and anterior cerebral artery infarction. Three patients developed cerebral hemorrhage after embolism. Twenty-six patients presented with newly acquired vision loss. The management for FICE cases included embolectomy, thrombolysis, decompressive craniectomy, antiplatelet/anticoagulant therapy, and symptomatic and nutritional treatment. Nearly half of the patients recovered or exhibited improved neurologic manifestations but not visual loss. Five patients died. CONCLUSIONS: FICE is a severe complication following facial filler injection. Careful prevention, timely identification, and treatment are crucial to decreasing the morbidity and mortality of FICE.

Cerebral embolism during edoxaban administration for venous thromboembolism in a patient with lung adenocarcinoma: A case report.

RATIONALE: The efficacy of direct oral anticoagulants (DOACs) in the treatment and prophylaxis of cancer-related venous thromboembolism (VTE) is reportedly similar to that of heparin. However, the effect of DOACs on the prophylaxis of cancer-related arterial thromboembolism (ATE) remains unclear. To our knowledge, we present the 1st case where cerebral ATE was encountered during edoxaban administration for VTE in a patient with lung adenocarcinoma. PATIENT CONCERNS: In March 2017, a 63-year-old female was diagnosed with lung adenocarcinoma (cT2aN3M1b stage IVa) along with having asymptomatic VTE; thus, 60 mg/day edoxaban administration was initiated. In addition, 1st-line chemotherapy generated a partial antitumoral response. However, owing to lung cancer progression, a secondary treatment with pembrolizumab administration was initiated. The patient suddenly experienced aphasia 11 days after pembrolizumab administration. DIAGNOSIS: The patient was diagnosed as multiple cerebral ATE using brain magnetic resonance imaging. However, VTE recurrence was not observed. Based on the findings of lung cancer progression and increased coagulation, cerebral ATE was diagnosed as Trousseau syndrome. INTERVENTIONS: DOAC administration was switched to heparin administration. OUTCOMES: Coagulation profile normalized and aphasia improved without any further disease symptoms. LESSONS: We considered that DOACs are effective for the treatment and prophylaxis of VTE but may be insufficient for ATE prevention. Therefore, DOACs should be replaced with heparin to prevent ATE when cancer and coagulation become uncontrollable with DOAC.

Devastating cerebral Lipiodol® embolization related to therapeutic lymphangiography for refractory chylothorax in a patient with Behçet's disease.

Onset of neurological symptoms early after intranodal lymphangiography can occur due to Lipiodol droplet migration through intrapulmonary lymphovenous communication. Patients with Behçet's disease may be at higher risk of developing this devastating complication.

Early administration of pyrrolidine dithiocarbamate extends the therapeutic time window of tissue plasminogen activator in a male rat model of embolic stroke.

Tissue plasminogen activator (tPA) is used in fewer than 4% of patients after ischemic stroke because of its narrow therapeutic time window. We tested whether pyrrolidine dithiocarbamate (PDTC), a drug with multiple mechanisms to provide neuroprotection, can be used to extend the therapeutic time window of tPA. Three-month-old male Sprague-Dawley rats were subjected to embolic stroke in the area supplied by the right middle cerebral artery. tPA at 10 mg/kg was given intravenously 4 h after the onset of stroke. PDTC at 50 mg/kg was given via gastric gavage at 30 min or 4 h after the onset of stroke. Two days after the stroke, neurological outcome was evaluated and the right frontal cortex area 1 (Fr1), an ischemic penumbral region, was harvested for analysis. PDTC given at 30 min after the stroke reduced infarct volumes and improved neurological functions no matter whether the rats received tPA. PDTC also reduced tPA-increased hemorrhagic volumes. Consistent with these results, PDTC in the presence or absence of tPA treatment attenuated the increase of proinflammatory cytokines, oxidative stress and matrix metalloprotease 2 activity in the right Fr1. However, PDTC given at 4 h after the onset of stroke did not improve the neurological outcome of rats treated with or without tPA. Our results suggest that PDTC given at an early time point but not in a delayed phase provides neuroprotection against embolic stroke and may be used to extend the therapeutic time window of tPA.

Hyperbaric oxygen therapy for the prevention of arterial gas embolism in food grade hydrogen peroxide ingestion.

Food grade hydrogen peroxide ingestion is a relatively rare presentation to the emergency department. There are no defined guidelines at this time regarding the treatment of such exposures, and providers may not be familiar with the potential complications associated with high concentration hydrogen peroxide ingestions. In this case series, we describe four patients who consumed 35% hydrogen peroxide, presented to the emergency department, and were treated with hyperbaric oxygen therapy. Two of the four patients were critically ill requiring intubation. All four patients had evidence on CT or ultrasound of venous gas emboli and intubated patients were treated as if they had an arterial gas embolism since an exam could not be followed. After hyperbaric oxygen therapy each patient was discharged from the hospital neurologically intact with no other associated organ injuries related to vascular gas emboli. Hyperbaric oxygen therapy is an effective treatment for patients with vascular gas emboli after high concentration hydrogen peroxide ingestion. It is the treatment of choice for any impending, suspected, or diagnosed arterial gas embolism. Further research is needed to determine which patients with portal venous gas emboli should be treated with hyperbaric oxygen therapy.

Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis.

An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures.

Cerebral arterial gas embolism after pre-flight ingestion of hydrogen peroxide.

Cerebral arterial gas embolism (CAGE) is a feared complication of ambient depressurisation and can also be a complication of hydrogen peroxide ingestion. We present an unusual case of CAGE in a 57-year-old woman exposed to both of these risk factors. We describe her subsequent successful treatment with hyperbaric oxygen, despite a 72-hour delay in initial presentation and diagnosis, and discuss the safety of aero-medical transfer following hydrogen peroxide ingestions.

Variability in initial response to standard clopidogrel therapy, delayed conversion to clopidogrel hyper-response, and associated thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms.

BACKGROUND AND PURPOSE: Variability in response to clopidogrel therapy is increasingly being recognized as an important factor in thromboembolic and hemorrhagic complications encountered after neurointerventional procedures. This study aims to determine the variability in response to clopidogrel therapy and associated complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms. METHODS: We recorded baseline patient characteristics, co-administered medications, P2Y12 reaction units (PRU) values with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms at our institution during a 19 month period. RESULTS: 100 patients were included in the study, 76 women and 24 men, mean age 57.3 years. 15 patients exhibited an initial clopidogrel hypo-response (PRU >240) and 21 patients an initial clopidogrel hyper-response (PRU <60). 36 patients had a follow-up VerifyNow test performed without changes to the standard 75 mg daily clopidogrel dose, which demonstrated that 59% of patients who had initially been within the target 60-240 PRU range exhibited a delayed conversion to clopidogrel hyper-response. In our cohort, a clopidogrel hypo-response was associated with a significantly increased risk of thromboembolic complications in patients undergoing cerebral aneurysm treatment with stent assistance or the pipeline embolization device (60%, p=0.003), while a clopidogrel hyper-response was associated with a significantly increased risk of major hemorrhagic complications in all patients undergoing endovascular treatment of cerebral aneurysms (11%, p=0.016). CONCLUSIONS: We found wide and dynamic variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms, which was significantly associated with thromboembolic and major hemorrhagic complications in our cohort.

Cerebral lipiodol embolism after transarterial chemoembolization for hepatic carcinoma: a case report.

We report a case of cerebral lipiodol embolism (CLE) after transarterial chemoembolization (TACE) for unresectable hepatic carcinoma (HCC). A 54-year-old man with unresectable HCC underwent TACE via the right hepatic artery and right inferior phrenic artery using a mixture of 40 mg pirarubicin and 30 mL lipiodol. His level of consciousness deteriorated after TACE, and non-contrast computed tomography revealed a CLE. The cerebral conditions improved after supportive therapy. The complication might have been due to hepatic arterio-pulmonary vein shunt caused by direct invasion of the tumor. Even though CLE is an uncommon complication of TACE, we should be aware of these rare complications in patients with high risk factors.

Middle cerebral air embolism after foam sclerotherapy.

In the recent past, eight cases of transient ischaemic attack or cerebral vascular accident related to foam sclerotherapy have been reported. The following case is reported to add to the world clinical experience and raises the concern that foam sclerotherapy should continue to be evaluated and reported rigorously to establish the incidence of potentially devastating complications. While waiting for clinical studies to further establish best practice in this area of treatment, it may be in our patients' best interests to reserve the option of foaming sclerosants for selected rather than routine cases of venous insufficiency.

Cannabis-related myocardial infarction and cardioembolic stroke.

We report a 33-year-old man with a history of chronic cannabis use who sustained myocardial infarction followed by cerebral infarction after a recent significant increase in cannabis use. This is the first case of cannabis-associated stroke of probable cardioembolic origin.

Multiple ischemic strokes after transcatheter arterial chemoembolization for hepatocellular carcinoma with a radiographic and pathological correlate.

INTRODUCTION: Transcatheter arterial chemoembolization (TACE) is a widely used form of therapy in advanced hepatocellular carcinoma. We report the first pathological data from an autopsy case of multiple cerebral emboli occurring during TACE. METHODS: A Medline search for previous cases of cerebral embolism and TACE revealed 11 other cases. FINDINGS: Multiple microscopic subacute infarcts were found in the cerebrum, midbrain, and cerebellum of our patient on autopsy, but no embolic material was seen. Embolic material was noted in dilated vessels throughout the fibrotic right diaphragm and in the upper lobe of the right lung. Combining the literature search with our patient, the mortality of cerebral embolism after TACE is 25% (n = 12). Intracardiac shunts were seen in 20% of the cases (n = 10). Hyperdense lesions were seen on head CT in 80% of the patients evaluated (n = 10). Chest imaging revealed infiltrate or consolidation in 60% of the cases (n = 5). Pulmonary emboli were reported in 100% of the cases (n = 8). CONCLUSIONS: Cerebral embolism after TACE is devastating. Brain pathology supports embolization of ethiodized oil rather than DC beads as the mechanism of cerebral injury. Further pathological studies are needed to better understand the pathophysiology of this condition. Lung pathology confirmed the presence of embolic material in the distal lung, suggestive of a hepatopulmonary shunt undetectable by current modalities. Evaluation for such shunts with emerging modalities such as TCD with emboli detection may be an area of future research.

Xenon administration immediately after but not before or during cardiopulmonary bypass with cerebral air embolism impairs cerebral outcome in rats.

CONTEXT: The neuroprotective properties of xenon might improve cerebral outcome after cardiac surgery using cardiopulmonary bypass. However, in the presence of cerebral air emboli, xenon impaired cognitive and histological outcome in a rat cardiopulmonary bypass model, a result which is due to the property of xenon to expand air bubbles. OBJECTIVE: The current study was designed to assess whether cerebral outcome in the setting of cardiopulmonary bypass with cerebral air embolism could be altered by administration of xenon restricted to periods when the occurrence of cerebral air embolism is unlikely. DESIGN: With institutional review board approval, 40 rats were allocated randomly to one of four groups (n = 10) which determined the period of xenon inhalation: 'before', 'during' or 'after' cardiopulmonary bypass or 'none'. SETTING: Rats were subjected to 90  min of normothermic cardiopulmonary bypass combined with 10 small cerebral air emboli. Xenon was administered according to group assignment: the 'none' group received no xenon; in the other groups, the lungs were ventilated with 56% xenon before, during or after cardiopulmonary bypass and cerebral air embolism. MAIN OUTCOME MEASURES: Motor and cognitive outcomes were tested using the modified hole-board test. Cerebral infarction volumes were determined on postoperative day 21. RESULTS: Animals that received xenon after cardiopulmonary bypass and cerebral air embolism had impaired motor function scores [after: median 6.6 (range 0.25-8), before: 0.5 (0-3), during: 1.5 (0.25-2.75), none: 1 (0-1.75)] and cognitive performance [after: 9 (6.5-9), before: 0 (0-5.5), during: 1 (0-5.5), none: 1 (0-4)] compared with all other groups (P < 0.05). Administration of xenon after cardiopulmonary bypass and cerebral air embolism also led to larger cerebral infarction volumes [after: 74 µl (54-157), before: 45 µl (20-82), during: 33 µl (23-54), none: 22 µl (17-78)] compared with the groups that received xenon during cardiopulmonary bypass and cerebral air embolism or no xenon at all (P < 0.05). CONCLUSION: Xenon administered immediately after cardiopulmonary bypass and cerebral air embolism impaired motor, cognitive and histological outcome in rats. At no time did inhalation of xenon lead to any beneficial effects on cerebral outcome when compared with inhalation of nitrogen.

Injectable corticosteroid preparations: an embolic risk assessment by static and dynamic microscopic analysis.

BACKGROUND AND PURPOSE: Transforaminal CS injections have been associated with severe adverse CNS events, including brain and spinal cord infarction. Our purpose was to describe the static and dynamic microscopic appearances of CS preparations, with an emphasis on their potential to cause adverse central nervous system events by embolic mechanisms during transforaminal injection. MATERIALS AND METHODS: Pharmaceutical preparations of nondilute injectable CSs were used after appropriate mixing: MPA (40 mg/mL), TA (40 mg/mL), and DSP (8 mg/2 mL). For dynamic imaging, a novel methodology was devised to replicate the flow of crystals within spinal cord arterioles. In addition, CS preparations were mixed with plasma to assess for changes in crystal size, morphology, and tendency to aggregate. RESULTS: The CS preparations MPA and TA are composed of crystals of varying sizes. MPA crystal size range was 0.4-26 µm (mean, 6.94 µm), TA crystal size range 0.5-110 µm (mean, 17.4 µm), and DSP did not contain any significant crystals or particles. There was no change in the crystal morphology or propensity to aggregate after mixing with local anesthetic. After mixing with plasma, the crystals also were unchanged; however, there was a significant reduction in the size of aggregates. On dynamic imaging, these aggregates were proved to maintain their integrity and to act as potential embolization agents. CONCLUSIONS: MPA and TA have a substantial risk of causing infarction by embolization if inadvertently injected intra-arterially at the time of TFESI. DSP is completely soluble and microscopically has no potential to obstruct arterioles. When performing cervical TFESI procedures, the administration of insoluble CSs should be avoided.

[Cannabis and myocardial infarction without angiographic stenosis in young patient: guilty or not guilty? A case report]. / Cannabis et infarctus du myocarde du sujet jeune : association fortuite ? À propos d'une observation.

Cannabis is the most consumed drug in France, particularly in young adults. Few reports have suggested a causal role of cannabis in the development of cardiovascular events. We describe one case of 26-year-old man, cannabis and tobacco smoker, admitted with recurrent ischemic stroke cause by post-myocardial infarction left ventricular thrombus. Coronary arteries were angiographicaly normal and etiological tests were negative. We suggest the possible relationship between marijuana use with coronary heart disease.

A mouse model of hemorrhagic transformation by delayed tissue plasminogen activator administration after in situ thromboembolic stroke.

BACKGROUND AND PURPOSE: thrombolytic treatment with tissue plasminogen activator (tPA) improves outcome of patients with stroke who can be treated within 3 hours of symptom onset. However, delayed treatment with tPA leads to increased risk of hemorrhagic transformation and can result in enhanced brain injury. The purpose of this study is to validate a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA. METHODS: mice were anesthetized and thrombin was injected into the middle cerebral artery to induce the formation of a clot as described by Orset et al. To induce reperfusion, tPA (10 mg/kg) was intravenously administered 20 minutes or 3 hours after thrombin injection. RESULTS: thrombin produced a clot in 83.1% of the animals, which caused focal ischemia determined 24 hours after the injection. Different degrees of bleeding were found in the middle cerebral artery occlusion group, including hemorrhagic infarction type 1 (HI-1) in 46.2%, hemorrhagic infarction type 2 (HI-2) in 30.8% and parenchymal hemorrhage type 1 in 23.0%. Administration of tPA 20 minutes after the occlusion produced an effective reperfusion in 62.5% of the animals and reduced both infarct volume and appearance of severe hemorrhage (10% nonhemorrhage, 80% HI-1 and 10% HI-2). However, administration of tPA 3 hours after the occlusion led to effective reperfusion in 47.1% of the animals, did not reduce infarct volume, caused hemorrhagic transformation (25% HI-1, 37.5% HI-2, and 37.5% parenchymal hemorrhage type 1), and increased hemorrhage and brain swelling. CONCLUSIONS: we have set up a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA similar to that observed in humans.

[The role of platelets in atherosclerosis, diabetes mellitus, and chronic kidney disease. An attempt at explaining the TREAT study results]. / Die Rolle der Thrombozyten bei Atherosklerose, Diabetes mellitus und chronischer Niereninsuffizienz : Ein Versuch, die Resultate der TREAT-Studie zu erklären.

Erythropoiesis-stimulating agents (ESA) are used to treat renal anemia. The TREAT study (Trial to Reduce Cardiovascular Events with Aranesp Ther- apy) of diabetic patients with chronic kidney disease (CKD) found that the risk of stroke was significantly higher than in the control arm. This raises the question as to what causes this phenomenon. Platelets may play a crucial role in this context. Atherogenesis involves complex interactions between platelets and monocytes (platelet-monocyte crosstalk) and with endothelial cells. Platelets are activated in cases of diabetes mellitus, especially. During atherogenesis, partial functions of platelets other than those inhibited by aspirin, as a cyclooxygenase inhibitor, or by adenosine diphosphate receptor P2Y(12)antagonists, such as thienopyridines, are of relevance. During platelet-monocyte crosstalk, specifically, an important role is played by adhesion receptors such as selectins and integrins. In addition, ESA cause platelet activation by direct and indirect mechanisms. Antagonistic thereto is a renal bleeding tendency in cases of severe CKD, due to platelet dysfunction, which can be remedied with appropriate renal replacement therapy and administration of ESA in order to reach a hemoglobin (Hb) level of 10 g/dl. However, if the Hb level exceeds 10 g/dl, the even stronger platelet activation caused by ESA, combined with the activation caused by diabetes, leads to a prothrombotic state, which in patients with severe atherosclerosis can result in acute atherothrombotic complications, in the genesis of which platelets play a key role. This would be one hypothesis for explaining the increased incidence of strokes in the TREAT study.