Dataset Information

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi.

ABSTRACT: The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1? through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinical and procedural outcomes of mechanical thrombectomy for AIS. Electron microscopy and immunofluorescence indicate the presence of NETs in thrombi of patients with AIS. Moreover, the inflammasome signaling proteins caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) were also present in clots associated with the marker of NETosis citrullinated histone ³H (CitH3). Analysis of protein levels by a simple plex assay show that caspase-1, ASC and interleukin (IL)-1? were significantly elevated in clots when compared to plasma of AIS patients and healthy controls, while IL-18 levels were lower. Moreover, multivariate analyses show that IL-1? levels in clots contribute to the number of passes to achieve complete recanalization, and that ASC, caspase-1 and IL-18 are significant contributors to time to recanalization. Thus, inflammasome proteins are elevated in NETs present in thrombi of patients with AIS that contribute to poor outcomes following stroke.

SUBMITTER: Chen SH

PROVIDER: S-EPMC7868597 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Netosis and Inflammasomes in Large Vessel Occlusion Thrombi.

Chen Stephanie H SH Scott Xavier O XO Ferrer Marcelo Yoandy Y Almeida Vania W VW Blackwelder Patricia L PL Yavagal Dileep R DR Peterson Eric C EC Starke Robert M RM Dietrich W Dalton WD Keane Robert W RW de Rivero Vaccari Juan Pablo JP

Frontiers in pharmacology 20210122

The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1β through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinic ...[more]

PMID: 33569001

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Project description:It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent in situ hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of Proteobacteria, mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and Enterobacteriaceae were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. IMPORTANCE In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of Proteobacteria in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and Enterobacteriaceae in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.

Project description:BACKGROUND AND PURPOSE:Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales. MATERIALS AND METHODS:We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and ?. Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders. RESULTS:In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large-vessel occlusion. CONCLUSIONS:The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.

Project description:Background and objectivesEndovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time to EVT by allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic accuracy of dry electrode EEG for the detection of LVO-a stroke in the prehospital setting.MethodsELECTRA-STROKE was an investigator-initiated, prospective, multicenter, diagnostic study, performed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed by the attending ambulance nurse) and symptom onset <24 hours. A single dry electrode EEG recording (8 electrodes) was performed by ambulance personnel. Primary endpoint was the diagnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1, or proximal M2 occlusion) detection among patients with EEG data of sufficient quality, expressed as the area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results.ResultsBetween August 2020 and September 2022, 311 patients were included. The median EEG duration time was 151 (interquartile range [IQR] 151-152) seconds. For 212/311 (68%) patients, EEG data were of sufficient quality for analysis. The median age was 74 (IQR 66-81) years, 90/212 (42%) were women, and the median baseline NIH Stroke Scale was 1 (IQR 0-4). Six (3%) patients had an LVO-a stroke, 109/212 (51%) had a non-LVO-a ischemic stroke, 32/212 (15%) had a transient ischemic attack, 8/212 (4%) had a hemorrhagic stroke, and 57/212 (27%) had a stroke mimic. AUC of the theta/alpha ratio was 0.80 (95% CI 0.58-1.00). Of the secondary endpoints, the pairwise derived Brain Symmetry Index in the delta frequency band had the highest diagnostic accuracy (AUC 0.91 [95% CI 0.73-1.00], sensitivity 80% [95% CI 38%-96%], specificity 93% [95% CI 88%-96%], positive likelihood ratio 11.0 [95% CI 5.5-21.7]).DiscussionThe data from this study suggest that dry electrode EEG has the potential to detect LVO-a stroke among patients with suspected stroke in the prehospital setting. Toward future implementation of EEG in prehospital stroke care, EEG data quality needs to be improved.Trial registration informationClinicalTrials.gov identifier: NCT03699397.Classification of evidenceThis study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients with suspected acute stroke.

Project description:Introduction: A significant proportion of acute ischemic stroke (AIS) patients who are evaluated through telestroke consultation are transferred to thrombectomy-capable stroke centers (TSCs) for concern of large vessel occlusion (LVO). Patient triage selection is commonly based on the clinical suspicion of LVO, which lacks specificity and could result in unnecessary transfers. In this study, we aimed to assess the accuracy of the most commonly used LVO recognition scales in telestroke setting. Methods: AIS patients transferred to TSCs for suspicion of an LVO were included in this retrospective study. Patients were evaluated by a stroke neurologist through a telestroke consult before transfer. The National Institute of Health Stroke Scale (NIHSS) score documented by the stroke neurologist was retrieved from medical records and used to calculate five other LVO recognition scales (Rapid Arterial Occlusion Evaluation Scale [RACE], Field Assessment Stroke Triage for Emergency Destination [FAST-ED], Cincinnati Prehospital Stroke Severity Scale [CPSSS], 3-item stroke scale [3I-SS], and Prehospital Acute Stroke Severity Scale [PASS]). We calculated the sensitivity, specificity, accuracy, positive and negative predictive values, false positive rate (FPR), and false negative rate (FNR) of each score using published cutoffs and then examined all possible cutoff values for each of these scales in addition to the NIHSS. Results: A total of 439 patients were included in the final analysis. A total of 48.5% of patients had an LVO confirmed on computed tomography angiogram. RACE score had the highest accuracy (78%). Overall, the five derived LVO recognition scores have at least 10% FNR. When examining all possible cutoff values, the NIHSS (cutoff of 6) had a 3% FNR but 73% FPR (false transfer). Conclusion: The use of the NIHSS and other LVO recognition scores over telestroke may result in unnecessary transfers. Better diagnostic tools that could maximize sensitivity with acceptable specificity are urgently needed.

Dataset Information

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi.

Publications

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi.

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