Cardiac Myxoma and Cerebrovascular Events: A Retrospective Cohort Study

Background: Cardiac myxoma (CM) is the most frequent, cardiac benign tumor and is associated with enhanced risk for cerebrovascular events (CVE). Although surgical CM excision is the only curative treatment to prevent CVE recurrence, in recent reports conservative treatment with antiplatelet or anticoagulant agents in high-risk patients with CM-related CVE has been discussed.Methods: Case records at the University Hospital of Tübingen between 2005 and 2017 were screened to identify patients with CM-related CVE. Clinical features, brain and cardiac imaging findings, histological reports, applied treatments and long-term neurological outcomes were assessed.Results: 52 patients with CM were identified and among them, 13 patients with transient ischemic attack, ischemic stroke or retinal ischemia were included to the (to our knowledge) largest reported retrospective study of CM-related CVE. In all identified patients, CVE was the first manifestation of CM; 61% suffered ischemic stroke, 23% transient ischemic attack and 15% retinal ischemia. In 46% of the patients, CVE occurred under antiplatelet or anticoagulation treatment, while 23% of the patients developed recurrent CVE under bridging-antithrombotic-therapy prior to CM surgical excision. Prolonged time interval between CVE and CM-surgery was significantly associated with CVE recurrence (p = 0.021). One patient underwent i.v. thrombolysis, followed by thrombectomy, with good post-interventional outcome and no signs of hemorrhagic transformation.Discussion: Our results suggest that antiplatelet or anticoagulation treatment is no alternative to cardiac surgery in patients presenting with CM-related CVE. We found significantly prolonged time-intervals between CVE and CM surgery in patients with recurrent CVE. Therefore, we suggest that the waiting- or bridging-interval with antithrombotic therapy until curative CM excision should be kept as short as possible. Based on our data and review of the literature, we suggest that in patients with CM-related CVE, i.v. thrombolysis and/or endovascular interventions may present safe and efficacious acute treatments

Comparison of Risk Factors, Safety, and Efficacy Outcomes of Mechanical Thrombectomy in Posterior vs. Anterior Circulation Large Vessel Occlusion

Background and Purpose: It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO.Materials and Methods: We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles [including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times], recanalization success [Thrombolysis In Cerebral Infarction scale (TICI) 2b/3], symptomatic intracranial hemorrhage (sICH), and favorable functional outcome [modified Rankin Score (mRS) 0–2] and mortality at 90 days.Results: Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15–0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53–0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45–1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33–0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37–0.85) but higher mortality (OR 1.92, 95% CI 1.46–2.53).Conclusions: This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients

Differential response of human basophil activation markers: a multi-parameter flow cytometry approach

<p>Abstract</p> <p>Background</p> <p>Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions. </p> <p>Methods</p> <p>Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells. Basophil activation with fMLP, anti-IgE and calcium ionophore A23187 was evaluated by studying up-regulation of the indicated membrane markers with a two-laser six-color PFC protocol.</p> <p>Results</p> <p>Following stimulation, CD63, CD13, CD45 and the ectoenzyme CD203c up-regulated their membrane expression, while CD69 did not; CD63 expression occurred immediately (within 60 sec) but only in a minority of basophils, even at optimal agonist doses (in 33% and 14% of basophils, following fMLP and anti-IgE stimulation respectively). CD203c up-regulation occurred in the whole basophil population, even in CD63non expressing cells. Dose-dependence curves revealed CD203c as a more sensitive marker than CD63, in response to fMLP but not in response to anti-IgE and to calcium ionophore.</p> <p>Conclusion</p> <p>Use of polychromatic flow cytometry allowed efficient basophil electronic purification and identification of different behaviors of the major activation markers. The simultaneous use of two markers of activation and careful choice of activator are essential steps for reliable assessment of human basophil functions.</p

Identification and characterization of novel activation markers on basophilic granulocytes

Basophile und Mastzellen sind wichtige Effektorzellen entzündlicher Reaktionen. Im Unterschied zu Eosinophilen und Neutrophilen verfügen sie über hochaffine Immunglobulin (Ig) E-Rezeptoren, die durch Bindung von Allergenen an rezeptorgebundenes IgE vernetzt und dadurch aktiviert werden. Dies führt zur Ausschüttung verschiedener Mediatoren in den Extrazellulärraum. Zusätzlich kommt es zur Verschiebung von in Granula gespeicherten Membranproteinen wie CD63 und dem Ektoenzym CD203c an die Plasmamembran. Diese Aktivierungsmarker werden inzwischen routinemäßig in durchflußzytometrischen Basophilenaktivierungstests angewendet. Die Größe der durch die beiden Marker CD63 und CD203c erkannten Populationen unterscheidet sich deutlich. So zeigt nur eine Subpopulation der Zellen die auf Allergenstimulation CD203c hochregulieren auch eine gesteigerte Oberflächenexpression von CD63. Außerdem unterscheidet sich das kinetische Profil der Hochregulierung von CD63 sowie die Sensitivität gegenüber Inhibitoren und Aktivatoren der durch Fc&#61541;RI vermittelten Signaltransduktion gegenüber CD203c. Kürzlich wurde gezeigt, dass Tetradecanoylphorbolacetat (TPA), ein Aktivator der Proteinkinase C (PKC), zu einer beschleunigten und verstärkten Hochregulierung von CD203c, jedoch zu einer verzögerten Hochregulierung von CD63 führt. Im Gegensatz dazu unterdrückt der Inhibitor der Phosphoinositol-3-Kinase (PI3K) Wortmannin sowohl die Hochregulierung von CD203c als auch von CD63. Mittels doppelter Fluoreszenzmarkierung wurden >200 monoklonale Antikörper, die im Rahmen des 8. Internationalen Workshops humaner Leukozytendifferenzierungsantigene (HLDA8) zur Verfügung standen, auf ihre Reaktivität mit ruhenden und aktivierten CD203c+ Basophilen getestet. Vier Antikörper die nicht bzw. nur schwach mit ruhenden Basophilen reagierten zeigten eine erhöhte Reaktivität mit Basophilen die durch Vernetzung des hochaffinen IgE-Rezeptors (Fc&#61541;RI) mit einem IgE-Antikörper aktiviert wurden. Dabei handelte es sich um zwei Antikörper gegen CD164 (WS-80160, Klon N6B6 und WS-80162, Klon 67D2) sowie zwei Antikörper mit zunächst unbekannten Spezifitäten, die durch Immunpräzipitation und anschließende Massenspektrometrie als CD13 (WS-80274, Klon A8) und CD107a (WS80280, Klon E63-880) identifiziert werden konnten. Die Aktivierungsmuster folgten entweder dem Profil von CD203c oder dem von CD63. Das CD203c-Profil ist durch eine rasche Hochregulierung gekennzeichnet, mit einem Maximum 5- 15 Minuten nach der Stimulation. Hierzu gehören die Marker CD13, CD164 und CD203c. Der PI3K-Inhibitor Wortmannin unterdrückt die Hochregulierung dieser Marker, während TPA eine schnelle und Fc&#61541;RI-unabhängige Hochregulierung mit einem Maximum nach 1- 2 Minuten induzierte. Die Marker des CD63-Profils erreichen die maximale Hochregulierung erst nach 20- 40 Minuten, nach Stimulation mit TPA erst nach 60 Minuten. Hierzu gehören CD63 und CD107a. Zusammenfassend konnten in dieser Arbeit CD13, CD164 und CD107a als neue Aktivierungsmarker auf basophilen Granulozyten identifiziert werden. Die unterschiedlichen kinetischen Profile sowie die unterschiedliche Sensitivität gegenüber Inhibitoren und Aktivatoren der Signaltransduktion legen nahe, dass die Marker der „CD203c-Gruppe“ und der „CD63-Gruppe“ jeweils mit unterschiedlichen Mechanismen der Basophilenaktivierung verknüpft sind.Basophils and mast cells are important effector cells of inflammatory reactions. In contrast to eosinophils and neutrophils, they possess high-affinity immunoglobulin (Ig) E receptors (Fc&#61541;RI) that are cross-linked and thereby activated upon engagement of receptor-bound IgE with allergens, resulting in the release of several mediators to the extracellular space. In addition, membrane bound activation markers like the granuleassociated molecule CD63 and the ecto-enzyme CD203c are relocated to the plasma membrane. These markers are now routinely used for flow cytometry-based basophil activation tests. However, the population size of activated basophils as defined by the CD63 and CD203c tests differs significantly. Thus, only a subpopulation of basophils that is sensitive to allergen-induced CD203c upregulation shows also an upregulated expression of CD63. Moreover, the kinetic profile of CD63 upregulation and the sensitivity to inhibitors and activators of Fc&#61541;RI-mediated signalling differs from that of CD203c. In a recent report it was demonstrated that tetradecanoyl phorbol acetate (TPA), a stimulator of the protein kinase C (PKC) pathway, leads to an accelerated and enhanced CD203c upregulation, but a delayed CD63 upregulation. In contrast, the phosphoinositol- 3 kinase (PI3K) inhibitor wortmannin effectively inhibited CD203c as well as the CD63 upregulation Using two-colour flow cytometry >200 antibodies submitted to the 8th International Workshop of Human Leukocyte Differentiation Antigens (HLDA8) have been analyzed for their reactivity with resting and activated CD203c+ basophils. Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor (Fc&#61541;RI). These include antibodies against CD164 (WS-80160, clone N6B6 and WS-80162, clone 67D2), as well as two reagents with previously unknown specificities that were identified as CD13 (WS-80274, clone A8) and CD107a (WS-80280, clone E63-880) using immunoprecipitation and subsequent mass spectrometry. The activation patterns followed either the “CD203c-like” or “CD63-like” activation profile. The CD203c profile is characterized by a rapid upregulation (of CD13, CD164, and CD203c), reaching maximum levels after 5- 15 min of stimulation. The PI3K-specific inhibitor wortmannin inhibited the upregulation of these markers whereas TPA induced a rapid and Fc&#61541;RI-independent upregulation within 1-2 min. In the CD63 profile, maximum upregulation (of CD63 and CD107a) was detected only after 20-40 min, and upregulation by TPA reached maximum levels after 60 min. In summary, CD13, CD107a, and CD164 were identified as novel basophil-activation antigens. Based on time kinetics of upregulation and sensitivity to signalling inhibitors and activators, it can be hypothesized that molecules of the “CD203c group” and the “CD63 group” are linked to two different mechanisms of basophil activation

Triple platelet inhibition in intracranial thrombectomy with additional acute cervical stent angioplasty due to tandem lesion: a retrospective single-center analysis.

BACKGROUND Acute stroke treatment with intracranial thrombectomy and treatment of ipsilateral carotid artery stenosis/occlusion ("tandem lesion", TL) in one session is considered safe. However, the risk of stent restenosis after TL treatment is high, and antiplatelet therapy (APT) preventing restenosis must be well balanced to avoid intracranial hemorrhage. We investigated the safety and 90-day outcome of patients receiving TL treatment under triple-APT, focused on stent-patency and possible disadvantageous comorbidities. METHODS Patients receiving TL treatment in the setting of acute stroke between 2013 and 2022 were analyzed regarding peri-/postprocedural safety and stent patency after 90 days. All patients received intravenous eptifibatide and acetylsalicylic acid and one of the three drugs prasugrel, clopidogrel, or ticagrelor. Duplex imaging was performed 24 h after treatment, at discharge and 90 days, and digital subtraction angiography was performed if restenosis was suspected. RESULTS 176 patients were included. Periprocedural complications occurred in 2.3% of the patients at no periprocedural death, and in-hospital death in 13.6%. Discharge mRS score was maintained or improved at the 90-day follow-up in 86%, 4.54% had an in-stent restenosis requiring treatment at 90 days. No recorded comorbidity considered disadvantageous for stent patency showed statistical significance, the duration of the endovascular procedure had no significant effect on outcome. CONCLUSION In our data, TL treatment with triple APT resulted in a low restenosis rate, low rates of sICH and a comparably high number of patients with favorable outcome. Aggressive APT in the initial phase may therefore have the potential to prevent recurrent stroke better than restrained platelet inhibition. Comorbidities did not influence stent patency

Drug-Coated Balloons for Treatment of Internal Carotid Artery Restenosis After Stenting: A Single-Center Mid-Term Outcome Study.

PURPOSE Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. MATERIALS AND METHODS The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and-if there was agreement between the modalities-validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. RESULTS DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7-85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. CONCLUSION DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR