scholarly journals Monocytes carrying GFAP detect glioma, brain metastasis and ischemic stroke, and predict glioblastoma survival

Author(s):  
Wouter B L van den Bossche ◽  
Arnaud J P E Vincent ◽  
Cristina Teodosio ◽  
Jeroen Koets ◽  
Aladdin Taha ◽  
...  

Abstract Diagnosis and monitoring of primary brain tumours, brain metastasis and acute ischemic stroke all require invasive, burdensome and costly diagnostics, frequently lacking adequate sensitivity, particularly during disease monitoring. Monocytes are known to migrate to damaged tissues, where they act as tissue macrophages, continuously scavenging, phagocytizing, and digesting apoptotic cells and other tissue debris. We hypothesize that upon completion of their tissue-cleaning task, these tissue macrophages might migrate via the lymph system to the bloodstream, where they can be detected and evaluated for their phagolysosomal contents. We discovered a blood monocyte subpopulation carrying the brain-specific glial fibrillary acidic protein (GFAP) in glioma patients and in patients with brain metastasis and evaluated the diagnostic potential of this finding. Blood samples were collected in a cross-sectional study before or during surgery from adult patients with brain lesions suspected of glioma. Together with blood samples from healthy controls, these samples were flow cytometrically evaluated for intracellular GFAP in monocyte subsets. Acute ischemic stroke patients were tested at multiple time points after onset to evaluate the presence of GFAP-carrying monocytes in other forms of brain-tissue damage. Clinical data was collected retrospectively. High-grade gliomas (N = 145), brain metastasis (N = 21) and large stroke patients (>100cm3)(N = 3 vs. 6; multiple time points) had significantly increased frequencies of GFAP+CD16+ monocytes compared to healthy controls. Based on both a training and validation set, a cut-off value of 0.6% GFAP+CD16+ monocytes was established, with 81% sensitivity (95%CI 75%-87%) and 85% specificity (95%CI 80%-90%) for brain lesion detection. Acute ischemic strokes of > 100 cm3 reached >0.6% of GFAP+CD16+ monocytes within the first 2-8 hours after hospitalisation and subsided within 48 hours. Glioblastoma patients with >20% GFAP+CD16+ non-classical monocytes had a significantly shorter median overall survival (8.1 vs 12.1 months). Our results and the available literature, support the hypothesis of a tissue-origin of these GFAP-carrying monocytes. Blood monocytes carrying GFAP have a high sensitivity and specificity for detection of brain lesions and for glioblastoma patients with a decreased overall survival. Furthermore, their very rapid response to acute tissue damage identifies large areas of ischemic tissue damage within 8 hours after an ischemic event. These studies are the first to report the clinical applicability for brain tissue damage detection through a minimal invasive diagnostic method, based on blood monocytes and not serum markers, with direct consequences for disease monitoring in future (therapeutic) studies and clinical decision making in glioma and acute ischemic stroke patients.

2020 ◽  
Vol 49 (6) ◽  
pp. 639-646 ◽  
Author(s):  
Tomohisa Ishida ◽  
Takashi Inoue ◽  
Kuniyasu Niizuma ◽  
Natsumi Konno ◽  
Chitose Suzuki ◽  
...  

<b><i>Background and Purpose:</i></b> Transfer RNA (tRNA) is a noncoding RNA that delivers amino acids to ribosomes for protein synthesis. tRNA is also involved in cell stress response programs. Oxidative stress induces direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine (m1A), we can detect tRNA derivatives such as conformationally changed tRNA, tRNA-derived fragments, and mononucleotide-free m1A. Based on these findings, tRNA derivatives may have potential as an early tissue damage marker. The purpose of this study was to investigate the plasma tRNA derivatives in stroke patients to clarify whether tRNA derivatives in the acute phase can detect early brain damage and then predict the functional outcome. <b><i>Methods:</i></b> Patients (75 patients with ischemic and 66 with hemorrhagic stroke) and 22 healthy volunteers were prospectively enrolled for this study between November 2016 and February 2019. Plasma samples were collected within 24 h and at 1 day, 7 days, and 30 days from the onset. Plasma tRNA derivative concentrations were measured by ELISA kit using the anti-m1A antibody. <b><i>Results:</i></b> The plasma tRNA derivative level on admission was significantly increased in both ischemic (mean ± standard error, 232.2 ± 33.1 ng/mL) and hemorrhagic stroke patients (212 ± 23.4 ng/mL) compared to the healthy volunteers (86.0 ± 7.9 ng/mL) (<i>p</i> = 0.00042 and <i>p</i> = 0.00018, respectively). The infarction size (<i>r</i> = 0.445, <i>p</i> = 0.00018) and hematoma volumes (<i>r</i> = 0.33, <i>p</i> = 0.0072) were also significantly correlated with tRNA derivatives. The concentrations of tRNA derivatives were associated with poor functional outcome (Modified Rankin Scale score 3–6 at 30 days from the onset) in patients with ischemic stroke at 7 days after onset (<i>p</i> = 0.020). <b><i>Conclusions:</i></b> Stress-induced tRNA derivatives can detect brain tissue damage, predicting functional outcome in patients with ischemic stroke.


e-CliniC ◽  
2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Glen Y. C. R. Kabi ◽  
Rizal Tumewah ◽  
Mieke A. H. N. Kembuan

Abstract: Ischemic stroke is a clinical sign of dysfunction or brain tissue damage caused by lack of blood flow to the brain that disrupts the need for blood and oxygen to the brain. WHO defines stroke as a rapidly developing clinical signs of focal brain due to interference (or global) with symptoms - that last for 24 hours or more- and can cause death without any other obvious cause other than vascular. This study aimed to obtain an overview of risk factors in ischemic stroke patients in the Inpatient Neurology Department of Prof. Dr. R. D. Kandou Hospital Manado period July 2012 - June 2013. Data were taken by collecting data of ischemic stroke patients medical records. There were 60 patients during that period. Patients affected by stroke were aged between 51 - 65 years and had histories of hypertension.Keywords: risk factors, ischemic stroke.Abstrak: Stroke iskemik adalah tanda klinis disfungsi atau kerusakan jaringan otak yang disebabkan kurangnya aliran darah ke otak sehingga mengganggu kebutuhan darah dan oksigen di otak. WHO mendefiniskan stroke merupakan suatu tanda klinis yang berkembang cepat akibat gangguan otak fokal (atau global) dengan gejala - gejala yang berlangsung selama 24 jam atau lebih dan dapat menyebabkan kematian tanpa adanya penyebab lain yang jelas selain vaskuler. Penelitian ini bertujuan untuk mendapatkan gambaran tentang faktor resiko pada pasien stroke iskemik di rawat inap Neurologi RSUP Prof. Dr. R. D. Kandou Manado periode Juli 2012 - Juni 2013. Penelitian dilakukan dengan cara mengumpulkan data pasien yang terkena stroke iskemik di bagian rekam medik RSUP Prof. Dr. R. D. Kandou Manado. Didapatkan 60 pasiem selama periode Juli 2012 – Juni 2013. Berdasarkan hasil yang didapat maka disimpulkan bahwa pasien yang sering terkena stroke adalah pasien yang berumur antara 51-65 tahun, dan pasien yang memiliki riwayat hipertensi.Kata kunci: faktor risiko, stroke iskemik


2020 ◽  
Vol 15 (5) ◽  
pp. 540-554 ◽  
Author(s):  
Adnan I Qureshi ◽  
Foad Abd-Allah ◽  
Fahmi Al-Senani ◽  
Emrah Aytac ◽  
Afshin Borhani-Haghighi ◽  
...  

Background and purpose On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. Methods The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. Results This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. Conclusions These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.


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