Spontaneous regression of multiple flow-related aneurysms following treatment of an associated brain arteriovenous malformation: A case report.

INTRODUCTION There is no consensus in the treatment strategy of intracranial aneurysms (IAs) associated with brain arteriovenous malformation (BAVM). In particular, it is unknown if a more aggressive approach should be considered in patients harboring a BAVM, in whom multiple aneurysms or a history of aneurysmal subarachnoid hemorrhage (aSAH) is present. CASE PRESENTATION We report on an elderly woman harboring multiple aneurysms with a history of SAH due to rupture of an unrelated IA. On evaluation, she was also found to harbor a contralateral, left parietal convexity BAVM. Following resection of the latter, spontaneous regression of two large flow-related aneurysms was encountered. DISCUSSION We discuss the therapeutic decision-making, risk stratification, and functional outcome in this patient with regard to the pertinent literature on the risk of hemorrhage in IAs associated with BAVM

Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data

Symptomatic patients with ischemic stroke due to internal carotid artery (ICA) occlusion often present with compromised brain hemodynamic status involving substantially larger parts of the affected vascular territory than the ischemic core itself (1-3). Despite the fact that the “Extracranial-Intracranial” (EC-IC) Bypass Study Group and the “Carotid Occlusion Surgery Study” (COSS) failed to demonstrate a benefit of bypass in comparison to medical therapy (4,5), several studies showed a significant improvement in hemodynamic parameters after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery was performed in carefully selected patients (6-9) and even a reduction in stroke recurrence (6). Analysis showed that the failure of the COSS trial (5) to show a benefit regarding ipsilateral 2-year stroke recurrence in patients undergoing cerebral bypass revascularization was likely caused by a failure of the semiquantitative, hemispheric oxygen extraction fraction (OEF) ratio method used in the trial than by the selection of the patients for bypass based on hemodynamic compromise (10). Therefore, alternative and especially quantitative imaging techniques are needed to assess hemodynamic status in patients with ischemic stroke due to ICA occlusion

Single-antiplatelet regimen in ruptured cerebral blood blister and dissecting aneurysms treated with flow-diverter stent reconstruction

BackgroundFlow diversion treatment of ruptured cerebral aneurysms remains challenging due to the need for double-antiplatelet therapy. We report our experience with flow-diverter stent (FDS) reconstruction with single-antiplatelet therapy of ruptured cerebral blood blister and dissecting aneurysms.MethodsIn this case series we performed a retrospective analysis of all patients with ruptured cerebral aneurysms who were treated with a phosphoryl-bonded FDS between 2019 and 2022 in a single center. Periprocedurally, all patients received weight-adapted eptifibatide IV and heparin IV. After 6–24 hours, eptifibatide was switched to oral prasugrel as monotherapy. We analyzed the rate of bleeding complications, thromboembolic events, occlusion rate and clinical outcome.ResultsNine patients with subarachnoid hemorrhage were treated, eight within 24 hours of symptom onset. Seven patients were treated with one FDS and two patients received two FDS in a telescopic fashion. Two aneurysms were additionally coil embolized. Fatal re-rupture occurred in one case; eight patients survived and had no adverse events associated with the FDS. Six patients showed complete occlusion of the aneurysm after 3 months (n=2) and 1 year (n=4), respectively. Two patients showed subtotal occlusion of the aneurysm at the last follow-up after 3 months and 6 months, respectively. Favorable clinical outcome was achieved in five patients.ConclusionsPeri-interventional single-antiplatelet therapy with eptifibatide followed by prasugrel was sufficient to prevent thromboembolic events and reduce re-bleeding using an anti-thrombogenic FDS. FDS with single-antiplatelet therapy might be a viable option for ruptured blood blister and dissecting cerebral aneurysms

Challenges in Coagulation Management in Neurosurgical Diseases: A Scoping Review, Development, and Implementation of Coagulation Management Strategies

Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14-33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5-1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy

Spontaneous regression of multiple flow-related aneurysms following treatment of an associated brain arteriovenous malformation: A case report

IntroductionThere is no consensus in the treatment strategy of intracranial aneurysms (IAs) associated with brain arteriovenous malformation (BAVM). In particular, it is unknown if a more aggressive approach should be considered in patients harboring a BAVM, in whom multiple aneurysms or a history of aneurysmal subarachnoid hemorrhage (aSAH) is present.Case presentationWe report on an elderly woman harboring multiple aneurysms with a history of SAH due to rupture of an unrelated IA. On evaluation, she was also found to harbor a contralateral, left parietal convexity BAVM. Following resection of the latter, spontaneous regression of two large flow-related aneurysms was encountered.DiscussionWe discuss the therapeutic decision-making, risk stratification, and functional outcome in this patient with regard to the pertinent literature on the risk of hemorrhage in IAs associated with BAVM

ERIS: revitalising an adaptive optics instrument for the VLT

ERIS is an instrument that will both extend and enhance the fundamental diffraction limited imaging and spectroscopy capability for the VLT. It will replace two instruments that are now being maintained beyond their operational lifetimes, combine their functionality on a single focus, provide a new wavefront sensing module that makes use of the facility Adaptive Optics System, and considerably improve their performance. The instrument will be competitive with respect to JWST in several regimes, and has outstanding potential for studies of the Galactic Center, exoplanets, and high redshift galaxies. ERIS had its final design review in 2017, and is expected to be on sky in 2020. This contribution describes the instrument concept, outlines its expected performance, and highlights where it will most excel.Comment: 12 pages, Proc SPIE 10702 "Ground-Based and Airborne Instrumentation for Astronomy VII

Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody

Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such as allergic airway inflammation. Herein, we have deciphered the molecular recognition features of the interaction of Siglec-8 with the mAb lirentelimab (2C4, under clinical development) and with a sialoside mimetic with the potential to suppress mast cell degranulation. The three-dimensional structure of Siglec-8 and the fragment antigen binding (Fab) portion of the anti-Siglec-8 mAb 2C4, solved by X-ray crystallography, reveal that 2C4 binds close to the carbohydrate recognition domain (V-type Ig domain) on Siglec-8. We have also deduced the binding mode of a high-affinity analogue of its sialic acid ligand (9-N-napthylsufonimide-Neu5Ac, NSANeuAc) using a combination of NMR spectroscopy and X-ray crystallography. Our results show that the sialoside ring of NSANeuAc binds to the canonical sialyl binding pocket of the Siglec receptor family and that the high affinity arises from the accommodation of the NSA aromatic group in a nearby hydrophobic patch formed by the N-terminal tail and the unique G–G′ loop. The results reveal the basis for the observed high affinity of this ligand and provide clues for the rational design of the next generation of Siglec-8 inhibitors. Additionally, the specific interactions between Siglec-8 and the N-linked glycans present on the high-affinity receptor FcεRIα have also been explored by NMR.This work was supported by operating grant PID2019-107770RA-I00 (J.E.-O.) from the Agencia Estatal Investigación of Spain and by the European Research Council (ERC-2017-AdG, 788143-RECGLYCANMR to J.J.-B.). We also thank the Marie-Skłodowska-Curie actions (ITN Glytunes grant agreement no. 956758 to J.E.-O and ITN BactiVax under grant agreement no. 860325 to U.A.). Additional funding was provided by CIBER, an initiative of Instituto de Salud Carlos III (ISCIII), Madrid, Spain. We also thank the Ikerbasque Basque Foundation of Science and the Spanish Ministry of Economy, Industry and Competitiveness (for the postdoctoral contract Juan de la Cierva Incorporación to J.E-O). X-ray diffraction experiments described in this paper were performed using the XALOC synchrotron beamline at ALBA (Spain) and PXIII in Swiss Light Source (Switzerland)

Patch test results with the European baseline series, 2019/20-Joint European results of the ESSCA and the EBS working groups of the ESCD, and the GEIDAC

BACKGROUND Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. OBJECTIVES To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. METHODS Anonymised or pseudonymised individual data, and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. RESULTS In 2019 and 2020, 22581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 (19.2-20.4)% positivity (95% confidence interval)). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43-7.19)% and 6.62 (6.25-7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 (2.16-2.85)% vs. 1.59 (1.33-1.88)); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 (3.16-3.82)%), followed by 2-hydroxyethyl methacrylate (2.32 (2.0-2.68)%). CONCLUSIONS Ongoing surveillance on the prevalence of contact sensitization contributes to an up-to-date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe. This article is protected by copyright. All rights reserved

TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8+ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients.These studies were supported by the Specific Targeted Research Project ALLFUN (FP7-HEALTH-2009 contract number 260338 to L.R.), by SYBARIS (FP7-HEALTH-2009 contract number 242220 to L.R.), and by the Italian Project AIDS 2010 by the Istituto Superiore di Sanita (contract number 40H40 to L.R.). A.C. and C.C. were supported by fellowships from Fundacao para a Ciencia e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009, respectively)