OBJECTIVE: To investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebilizumab on these biomarkers in N-MOmentum. METHODS: N-MOmentum randomised participants to receive inebilizumab or placebo with a randomised controlled period (RCP) of 28 weeks and an open-label follow-up period of ≥2 years. The sNfL, sUCHL1, sTau and sGFAP were measured using single-molecule arrays in 1260 scheduled and attack-related samples from N-MOmentum participants (immunoglobulin G (IgG) autoantibodies to aquaporin-4-positive, myelin oligodendrocyte glycoprotein-IgG-positive or double autoantibody-negative) and two control groups (healthy donors and patients with relapsing-remitting multiple sclerosis). RESULTS: The concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R2=0.40; p=0.01) and prediction of disability worsening after attacks (sNfL cut-off 32 pg/mL; area under the curve 0.71 (95% CI 0.51 to 0.89); p=0.02), but only sGFAP predicted upcoming attacks. At RCP end, fewer inebilizumab-treated than placebo-treated participants had sNfL>16 pg/mL (22% vs 45%; OR 0.36 (95% CI 0.17 to 0.76); p=0.004). CONCLUSIONS: Compared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo. TRIAL REGISTRATION NUMBER: NCT02200770.
- Keywords
- CLINICAL NEUROLOGY, RANDOMISED TRIALS,
- MeSH
- Biomarkers MeSH
- Double-Blind Method MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Humans MeSH
- Neuromyelitis Optica * blood drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Biomarkers MeSH
- Antibodies, Monoclonal, Humanized MeSH
- inebilizumab MeSH Browser
Stroke is one of the most devastating pathologies of the early twenty-first century demonstrating 1-month case-fatality rates ranging from 13 to 35% worldwide. Though the majority of cases do occur in individuals at an advanced age, a persistently increasing portion of the patient cohorts is affected early in life. Current studies provide alarming statistics for the incidence of "young" strokes including adolescents. Young stroke is a multifactorial disease involving genetic predisposition but also a number of modifiable factors, the synergic combination of which potentiates the risks. The article analyzes the prevalence and impacts of "traditional" risk factors such as sedentary lifestyle, smoking, abnormal alcohol consumption, drug abuse, overweight, hypertension, abnormal sleep patterns, and usage of hormonal contraceptives, among others. Further, less explored risks such as primary vascular dysregulation and associated symptoms characteristic for Flammer syndrome (FS) are considered, and the relevance of the FS phenotype for the stroke predisposition at young age is hypothesized. Considering the high prevalence of known genetic and modifiable risk factors in the overall predisposition to the young stroke, the risk mitigating measures are recommended including innovative screening programs by application of specialized questionnaires and biomarker panels as well as educational programs adapted to the target audiences such as children, adolescents, and young adults.
- Keywords
- Abnormal BMI, Altered sensation, Baroreceptor sensitivity, Blood flow, Body dehydration, Cardiac, Circadian rhythm, Etiology, Flammer syndrome, Hormonal regulation, Individualized patient profile, Life style, Microcirculation, Migraine, Phenotype, Predictive preventive personalized medicine, Psychology, Questionnaire, Risk assessment, Risk factors, Screening program, Sleep patterns, Stress, Stroke, Thermoregulation, Tinnitus, Vascular, Young adults,
- Publication type
- Journal Article MeSH
- Review MeSH
The model of centralized stroke care in the Czech Republic was created in 2010-2012 by Ministry of Health (MH) in cooperation with professional organization-Cerebrovascular Section of the Czech Neurological Society (CSCNS). It defines priorities of stroke care, stroke centers, triage of suspected stroke patients, stroke care quality indicators, their monitoring, and reporting. Thirteen complex cerebrovascular centers (CCC) provide sophisticated stroke care, including intravenous thrombolysis (IVT), mechanical thrombectomy (MTE), as well as other endovascular (stenting, coiling) and neurosurgical procedures. Thirty-two stroke centers (SC) provide stroke care except endovascular procedures and neurosurgery. The triage is managed by emergency medical service (EMS). The most important quality indicators of stroke care are number of hospitalized stroke patients, number of IVT, number of MTE, stenting and coiling, number of neurosurgical procedures, and percentage of deaths within 30 days. Indicators provided into the register of stroke care quality (RES-Q) managed by CSCNS are time from stroke onset to hospital admission, door-to-needle time, door-to-groin time, type of ischemic stroke, and others. Data from RES-Q are shared to all centers. Within the last 5 years, the Czech Republic becomes one of the leading countries in acute stroke care. The model of centralized stroke care is highly beneficial and effective. The quality indicators serve as tool of control of stroke centers activities. The sharing of quality indicators is useful tool for mutual competition and feedback control in each center. This comprehensive system ensures high standard of stroke care. This system respects the substantial principles of personalized medicine-individualized treatment of acute stroke and other comorbidities at the acute disease stage; optimal prevention, diagnosis and treatment of possible complications; prediction of further treatment and outcome; individualized secondary prevention, exactly according to the stroke etiology. The described model of stroke care optimally meets criteria of predictive, preventive, and personalized medicine (PPPM), and could be used in other countries as well with the aim of improving stroke care quality in general.
INTRODUCTION: Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor characterized by pathological vascularization. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) were observed in GBM. We aimed to assess the intra-tumor hypoxia, angiogenesis and microvessel formation in GBM and to find their associations with IDH1 mutation status and patients prognosis. METHODS: 52 patients with a diagnosis of GBM were included into the study. IDH1 R132H mutation was assessed by RT-PCR from FFPE tumor samples obtained during surgery. The expression of markers of hypoxia (HIF2α), angiogenesis (VEGF), tumor microvascularity (CD31, CD34, vWF, CD105), and proliferation (Ki-67) were assessed immunohistochemically (IHC). IDH1 mutation and IHC markers were correlated with the patient survival. RESULTS: 20 from 52 GBM tumor samples comprised IDH1 R132H mutation (38.5%). The majority of mutated tumors were classified as secondary glioblastomas (89.9%). Patients with IDH1 mutated tumors experienced better progression-free survival (P = 0.037) as well as overall survival (P = 0.035) compared with wild type tumors. The significantly lower expression of VEGF was observed in GBM with IDH1 mutation than in wild type tumors (P = 0.01). No such association was found for microvascular markers. The increased expression of newly-formed microvessels (ratio CD105/CD31) in tumor samples was associated with worse patient's progression-free survival (P = 0.026). SUMMARY: No increase in HIF/VEGF-mediated angiogenesis was observed in IDH1-mutated GBM compared with IDH1 wild type tumors. The histological assessment of the portion of newly-formed microvessels in tumor tissue can be used for the prediction of GBM patient's prognosis.
- Keywords
- biomarkers, glioblastoma multiforme, isocitrate dehydrogenase, microvascularity, microvessel,
- Publication type
- Journal Article MeSH
