Intraplaque hemorrhage, a potential consequence of periodontal bacteria gathering in human carotid atherothrombosis

Periodontal diseases are multifactorial inflammatory diseases, caused by a bacterial biofilm involving both innate and adaptative immunity, characterized by the destruction of tooth-supporting tissues. In the context of periodontitis, the spread of weak pathogenic bacteria into the bloodstream has been described. These bacteria will preferentially localize to existing clot within the circulation. Atherothrombosis of the carotid arteries is a local pathology and a common cause of cerebral infarction. Intraplaque hemorrhages render the lesion more prone to clinical complications such as stroke. The main objective of this study is to explore the biological relationship between carotid intraplaque hemorrhage and periodontal diseases. This study included consecutive patients with symptomatic or asymptomatic carotid stenosis, admitted for endarterectomy surgical procedure (n=41). In conditioned media of the carotid samples collected, markers of neutrophil activation (myeloperoxidase or MPO, DNA-MPO complexes) and hemoglobin were quantified. To investigate the presence of DNA from periodontal bacteria in atherosclerotic plaque, PCR analysis using specific primers was performed. Our preliminary results indicate an association between neutrophil activation and intraplaque hemorrhages, reflected by the release of MPO (p<0,01) and MPO-DNA complexes (p<0,05). Presence of DNA from periodontitis-associated bacteria was found in 32/41 (78%) atheromatous plaque samples. More specifically, DNA from Pg, Tf, Pi, Aa was found in 46%, 24%, 34% and 68% of the samples, respectively. Hemoglobin levels were higher in conditioned media in carotid samples where the bacteria were found, but this was not statistically significant. Our data confirm the relationship between intraplaque hemorrhage and neutrophil activation. In addition, the presence of periodontal bacteria DNA in carotid atheromatous plaque, may contribute to this activation. Further analysis is needed to fully explore the raw data and specimens

0171: Identification of complicated carotid plaques by adding functional fluorodeoxyglucose-positron emission tomographic imaging to morphological characteristics on computed tomographic angiography

AimWe developed a simple semi-quantitative score for the analysis of carotid plaques with FDG-PET-CTA imaging and tested whether adding functional imaging criteria extracted from FDG-PET imaging to morphological plaque characteristics identified with CTA might improve the detection of complicated plaques.Material and MethodsTwenty-eight patients scheduled for carotid endarterectomy were imaged with PET after injection of FDG followed by CTA of the supra-aortic trunks. Morphological aspects of plaques identified with CTA and metabolic activity quantified with FDG-PET (Tissue to Background ratio, TBR) were measured in the carotid segment with the highest degree of luminal stenosis and graded using semi-quantitative CT and PET scores. Combined score was calculated for each carotid artery by summing CT and PET scores. After carotid endarterectomy, vascular surgeons classified carotid plaques macroscopically as complicated or non-complicated.ResultsTwenty-eight carotid arteries were operated in 26 patients (24 symptomatic patients). Sixteen plaques were classified macroscopically as complicated. CTA detected hypodense regions and ulcerations in 81% and 25%, of complicated plaques, and in 33% and 0% of non-complicated plaques, respectively. Hypodense areas on CTA identified complicated plaques with a sensitivity of 87% and a specificity of 67%. Mean TBR with FDG-PET was measured at 2.2±0.4 in complicated plaques and 1.9±0.3 in non-complicated plaques (p<0.05). Values for the semi-quantitative score based on plaques characteristics with CTA and FDG-PET were 5.4±1.7 in complicated plaques and 2.5±2.4 in non-complicated plaques (p<0.05). A combined PET-CT score≥3 identified complicated plaques with a sensitivity of 100% and a specificity of 67%.ConclusionsAdding FDG-PET imaging criteria to morphological characteristics of plaques on CTA improved the sensitivity of the detection of complicated carotid plaques

Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies.

peer reviewedDuring the last decade, significant progress has been made in understanding thrombus composition and organization in the setting of acute ischemic stroke (AIS). In particular, thrombus organization is now described as highly heterogeneous but with 2 preserved characteristics: the presence of (1) two distinct main types of areas in the core-red blood cell (RBC)-rich and platelet-rich areas in variable proportions in each thrombus-and (2) an external shell surrounding the core composed exclusively of platelet-rich areas. In contrast to RBC-rich areas, platelet-rich areas are highly complex and are mainly responsible for the thrombolysis resistance of these thrombi for the following reasons: the presence of platelet-derived fibrinolysis inhibitors in large amounts, modifications of the fibrin network structure resistant to the tissue plasminogen activator (tPA)-induced fibrinolysis, and the presence of non-fibrin extracellular components, such as von Willebrand factor (vWF) multimers and neutrophil extracellular traps. From these studies, new therapeutic avenues are in development to increase the fibrinolytic efficacy of intravenous (IV) tPA-based therapy or to target non-fibrin thrombus components, such as platelet aggregates, vWF multimers, or the extracellular DNA network

Early Intubation in Endovascular Therapy for Basilar Artery Occlusion:A Post Hoc Analysis of the BASICS Trial

BACKGROUND: The optimal anesthetic management for endovascular therapy (EVT) in patients with posterior circulation stroke remains unclear. Our objective was to investigate the impact of early intubation in patients enrolled in the BASICS trial (Basilar Artery International Cooperation Study). METHODS: BASICS was a multicenter, randomized, controlled trial that compared the efficacy of EVT compared with the best medical care alone in patients with basilar artery occlusion. In this post hoc analysis, early intubation within the first 24 hours of the estimated time of basilar artery occlusion was examined as an additional covariate using regression modeling. We estimated the adjusted relative risks (RRs) for favorable outcomes, defined as modified Rankin Scale scores of 0 to 3 at 90 days. An adjusted common odds ratio was estimated for a shift in the distribution of modified Rankin Scale scores at 90 days. RESULTS: Of 300 patients in BASICS, 289 patients were eligible for analysis (151 in the EVT group and 138 in the best medical care group). compared with medical care alone, EVT was related to a higher risk of early intubation (RR, 1.29 [95% CI, 1.09–1.53]; P&lt;0.01), and early intubation was negatively associated with favorable outcome (RR, 0.61 [95% CI, 0.45–0.84]; P=0.002). Whereas there was no overall treatment effect of EVT on favorable outcome (RR, 1.22 [95% CI, 0.95–1.55]; P=0.121), EVT was associated with favorable outcome (RR, 1.34 [95% CI, 1.05–1.71]; P=0.018) and a shift toward lower modified Rankin Scale scores (adjusted common odds ratio, 1.63 [95% CI, 1.04–2.57]; P=0.033) if adjusted for early intubation. CONCLUSIONS: In this post hoc analysis of the neutral BASICS trial, early intubation was linked to unfavorable outcomes, which might mitigate a potential benefit from EVT by indirect effects due to an increased risk of early intubation. This relationship may be considered when assessing the efficacy of EVT in patients with basilar artery occlusion in future trials.</p

Mechanical thrombectomy in acute ischemic stroke : Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).Peer reviewe

Gadolinium-Enhanced Extracranial MRA Prior to Mechanical Thrombectomy Is Not Associated With an Improved Procedure Speed

Objectives: To assess whether performing a pre-intervention gadolinium-enhanced extracranial magnetic resonance angiogram (MRA) in addition to intracranial vascular imaging is associated with improved thrombectomy time metrics.Methods: Consecutive patients treated by MT at a large comprehensive stroke center between January 2012 and December 2017 who were screened using pre-intervention MRI were included. Patients characteristics and procedural data were collected. Univariate and multivariate analysis were performed to compare MT speed, efficacy, complications, and clinical outcomes between patients with and without pre-intervention gadolinium-enhanced extracranial MRA.Results: A total of 912 patients were treated within the study period, including 288 (31.6%) patients with and 624 (68.4%) patients without extracranial MRA. Multivariate analysis showed no significant difference between groups in groin puncture to clot contact time (RR = 0.93 [0.85–1.02], p = 0.14) or to recanalization time (RR = 0.92 [0.83–1.03], p = 0.15), rates of successful recanalization (defined as a mTICI 2b or 3, RR = 0.93 [0.62–1.42], p = 0.74), procedural complications (RR = 0.81 [0.51–1.27], p = 0.36), and good clinical outcome (defined by a mRS ≤ 2 at 3 months follow-up, RR = 1.05 [0.73–1.52], p = 0.79).Conclusion: Performing a pre-intervention gadolinium-enhanced extracranial MRA in addition to non-contrast intracranial MRA at stroke onset does not seem to be associated with a delay or shortening of procedure times

Anaesth Crit Care Pain Med

PURPOSE: To provide recommendations for the anaesthetic and peri-operative management for thrombectomy procedure in stroke patients DESIGN: A consensus committee of 15 experts issued from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation, SFAR), the Association of French-language Neuro-Anaesthetists (Association des Neuro-Anesthésistes Réanimateurs de Langue Francaise, ANARLF), the French Neuro-Vascular Society (Société Francaise de Neuro-Vasculaire, SFNV), the French Neuro-Radiology Society (Société Francaise de Neuro-Radiologie, SFNR) and the French Study Group on Haemostasis and Thrombosis (Groupe Français d'Études sur l'Hémostase et la Thrombose, GFHT) was convened, under the supervision of two expert coordinators from the SFAR and the ANARLF. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were required to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. METHODS: Four fields were defined prior to the literature search: (1) Peri-procedural management, (2) Prevention and management of secondary brain injuries, (3) Management of antiplatelet and anticoagulant treatments, (4) Post-procedural management and orientation of the patient. Questions were formulated using the PICO format (Population, Intervention, Comparison, and Outcomes) and updated as needed. Analysis of the literature was then conducted and the recommendations were formulated according to the GRADE methodology. RESULTS: The SFAR/ANARLF/SFNV/SFNR/GFHT guideline panel drew up 18 recommendations regarding anaesthetic management of mechanical thrombectomy procedures. Due to a lack of data in the literature allowing to conclude with high certainty on relevant clinical outcomes, the experts decided to formulate these guidelines as "Professional Practice Recommendations" (PPR) rather than "Formalized Expert Recommendations". After two rounds of rating and several amendments, a strong agreement was reached on 100% of the recommendations. No recommendation could be formulated for two questions. CONCLUSIONS: Strong agreement among experts was reached to provide a sizable number of recommendations aimed at optimising anaesthetic management for thrombectomy in patients suffering from stroke

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage:a randomised controlled clinical trial

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone.METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed.FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment.INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups.FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.</p

Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator