scholarly journals Role of Blood-Based Biomarkers in Ischemic Stroke Prognosis

Stroke ◽  
2021 ◽  
Vol 52 (2) ◽  
pp. 543-551 ◽  
Author(s):  
Felipe A. Montellano ◽  
Kathrin Ungethüm ◽  
Laura Ramiro ◽  
Aliona Nacu ◽  
Simon Hellwig ◽  
...  

Background and Purpose: Outcome prognostication in ischemic stroke patients remains challenging due to limited predictive properties of existing models. Blood-based biomarkers might provide additional information to established prognostic factors. We intended to identify the most promising prognostic biomarkers in ischemic stroke, their incremental prognostic value, and whether their predictive value differs among etiologies. Methods: We searched MEDLINE (Ovid) and Institute for Scientific Information Web of Knowledge for articles reporting the predictive performance of blood-based biomarkers measured up to 7 days after ischemic stroke and reporting functional outcome or death at least 7 days after stroke. This work updates a previous systematic review (up to January 2007), follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and was registered (International Prospective Register of Systematic Reviews PROSPERO 2018; https://www.crd.york.ac.uk/PROSPERO /; Unique identifier: CRD42018094671). Results: Two hundred ninety-one articles published between January 2007 and August 2018 comprising 257 different biomarkers met inclusion criteria. Median sample size was 232 (interquartile range, 110–455); 260 (89%) articles reported regression analyses with 78% adjusting for stroke severity, 82% for age, 67% for both, and 9% for none of them; 37% investigated discrimination, 5% calibration, and 11% reclassification. Including publications from a previous systematic review (1960–January 2007), natriuretic peptides, copeptin, procalcitonin, mannose-binding lectin, adipocyte fatty acid–binding protein, and cortisol were the biomarkers most consistently associated with poor outcome in higher-quality studies showing an incremental value over established prognostic factors. Other biomarkers were less consistently associated with poor outcome or were reported in lower quality studies. High heterogeneity among studies precluded the performance of a meta-analysis. Conclusions: The number of reports on prognostic blood-based biomarkers in ischemic stroke increased 3.5-fold in the period January 2007 to August 2018. Although sample size increased, methodological flaws are still common. Natriuretic peptides and markers of inflammation, atherogenesis, and stress response are the most promising prognostic biomarkers among identified studies.

BMJ ◽  
2019 ◽  
pp. l6373 ◽  
Author(s):  
Shannon M Fernando ◽  
Alexandre Tran ◽  
Wei Cheng ◽  
Bram Rochwerg ◽  
Monica Taljaard ◽  
...  

Abstract Objective To determine associations between important pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Design Systematic review and meta-analysis. Data sources Medline, PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 4 February 2019. Primary, unpublished data from the United Kingdom National Cardiac Arrest Audit database. Study selection criteria English language studies that investigated pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Data extraction PROGRESS (prognosis research strategy group) recommendations and the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist were followed. Risk of bias was assessed by using the QUIPS tool (quality in prognosis studies). The primary analysis pooled associations only if they were adjusted for relevant confounders. The GRADE approach (grading of recommendations assessment, development, and evaluation) was used to rate certainty in the evidence. Results The primary analysis included 23 cohort studies. Of the pre-arrest factors, male sex (odds ratio 0.84, 95% confidence interval 0.73 to 0.95, moderate certainty), age 60 or older (0.50, 0.40 to 0.62, low certainty), active malignancy (0.57, 0.45 to 0.71, high certainty), and history of chronic kidney disease (0.56, 0.40 to 0.78, high certainty) were associated with reduced odds of survival after in-hospital cardiac arrest. Of the intra-arrest factors, witnessed arrest (2.71, 2.17 to 3.38, high certainty), monitored arrest (2.23, 1.41 to 3.52, high certainty), arrest during daytime hours (1.41, 1.20 to 1.66, high certainty), and initial shockable rhythm (5.28, 3.78 to 7.39, high certainty) were associated with increased odds of survival. Intubation during arrest (0.54, 0.42 to 0.70, moderate certainty) and duration of resuscitation of at least 15 minutes (0.12, 0.07 to 0.19, high certainty) were associated with reduced odds of survival. Conclusion Moderate to high certainty evidence was found for associations of pre-arrest and intra-arrest prognostic factors with survival after in-hospital cardiac arrest. Systematic review registration PROSPERO CRD42018104795


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e039813
Author(s):  
Xinxing Lai ◽  
Jian Liu ◽  
Tianyi Zhang ◽  
Luda Feng ◽  
Ping Jiang ◽  
...  

IntroductionWith the threat of a worldwide pandemic of COVID-19, it is important to identify the prognostic factors for critical conditions among patients with non-critical COVID-19. Prognostic factors and models may assist front-line clinicians in rapid identification of high-risk patients, early management of modifiable factors, appropriate triaging and optimising the use of limited healthcare resources. We aim to systematically assess the clinical, laboratory and imaging predictors as well as prediction models for severe or critical illness and mortality in patients with COVID-19.Methods and analysisAll peer-reviewed and preprint primary articles with a longitudinal design that focused on prognostic factors or models for critical illness and mortality related to COVID-19 will be eligible for inclusion. A systematic search of 11 databases including PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang Data, SinoMed, bioRxiv, Arxiv and MedRxiv will be conducted. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction will be performed using the modified version of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and quality will be evaluated using the Newcastle-Ottawa Scale and the Quality In Prognosis Studies tool. The association between prognostic factors and outcomes of interest will be synthesised and a meta-analysis will be conducted with three or more studies reporting a particular factor in a consistent manner.Ethics and disseminationEthical approval was not required for this systematic review. We will disseminate our findings through publication in a peer-reviewed journal.PROSPERO registration numberCRD 42020178798.


2020 ◽  
Vol 9 (6) ◽  
pp. 1900 ◽  
Author(s):  
Eva Coll-de la Rubia ◽  
Elena Martinez-Garcia ◽  
Gunnar Dittmar ◽  
Antonio Gil-Moreno ◽  
Silvia Cabrera ◽  
...  

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these systems remain inaccurate. Therefore, identifying prognostic EC biomarkers is crucial for improving risk assessment pre- and postoperatively and to guide treatment decisions. This systematic review gathers all protein biomarkers associated with clinical prognostic factors of EC, recurrence and survival. Relevant studies were identified by searching the PubMed database from 1991 to February 2020. A total number of 398 studies matched our criteria, which compiled 255 proteins associated with the prognosis of EC. MUC16, ESR1, PGR, TP53, WFDC2, MKI67, ERBB2, L1CAM, CDH1, PTEN and MMR proteins are the most validated biomarkers. On the basis of our meta-analysis ESR1, TP53 and WFDC2 showed potential usefulness for predicting overall survival in EC. Limitations of the published studies in terms of appropriate study design, lack of high-throughput measurements, and statistical deficiencies are highlighted, and new approaches and perspectives for the identification and validation of clinically valuable EC prognostic biomarkers are discussed.


2020 ◽  
Vol 16 (5) ◽  
pp. 405-415 ◽  
Author(s):  
Lu Wang ◽  
Yuxiao Li ◽  
Changyi Wang ◽  
Wen Guo ◽  
Ming Liu

Background: A number of studies have explored the prognostic role of CRP in patients with acute ischemic stroke, however, the results have been inconclusive. The aim of our study was to investigate the impact of infection on the association between CRP and 3-month functional outcome by performing a registry study and systematic review. Methods: Patients admitted within 24 hours of acute ischemic stroke onset and had CRP measured within 24 hours after admission were included. Patients admitted between June 2016 and December 2018 in Chengdu Stoke Registry were enrolled. The PubMed database was searched up to July 2019 to identify eligible studies. Poor outcome was defined as modified Rankin Scale scores at 3-month more than 3. Results: Totally, 368 patients in the registry and 18 studies involving 15238 patients in the systematic review were included. A statistically significant association between CRP values on admission and 3-month poor outcome in patients without infection was found, both in our registry (CRP per 1-mg/L increment, OR 1.04, 95% CI 1.01 to 1.07, p=0.008) and meta-analysis (CRP per 1-mg/dL increment, OR 1.66 [95% CI 1.37 to 2.01, p<0.001]). In patients with infection, CRP was not associated with a 3-month poor outcome according to registry data (OR 1.00, 95% CI 0.99 to 1.01, p=0.663) and meta-analysis (OR 1.01, 95% CI 0.99 to 1.01, p=0.128). Conclusion: High CRP value was independently associated with a 3-month poor outcome after stroke in patients without infection. Further studies are required to examine the value of infection on CRP measures and long-term functional outcomes.


2012 ◽  
Vol 46 (1) ◽  
pp. 12-14
Author(s):  
Zahra Sohani

ABSTRACT The goal of a systematic review is to present a balanced summary of existing research. In order to accomplish this, systematic reviews include a thorough search of relevant articles, including published and unpublished, using explicitly defined and reproducible criteria. The main rationale for conducting a meta-analysis comes from the fact that combining individual studies provide an increased sample size, which consequently improves the statistical power to detect treatment effect. If all steps outlined are followed properly and authors remain transparent regarding the design and conduct of the meta-analysis, this technique provides an excellent and scientifically sound means of synthesizing evidence. How to cite this article Sohani Z. Meta-analysis: Statistical Trickery or Sound Science? J Postgrad Med Edu Res 2012; 46(1):12-14.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lane J. Liddle ◽  
Christine A. Dirks ◽  
Brittany A. Fedor ◽  
Mohammed Almekhlafi ◽  
Frederick Colbourne

Background: As not all ischemic stroke patients benefit from currently available treatments, there is considerable need for neuroprotective co-therapies. Therapeutic hypothermia is one such co-therapy, but numerous issues have hampered its clinical use (e.g., pneumonia risk with whole-body cooling). Some problems may be avoided with brain-specific methods, such as intra-arterial selective cooling infusion (IA-SCI) into the arteries supplying the ischemic tissue.Objective: Our research question was about the efficacy of IA-SCI in animal middle cerebral artery occlusion models. We hypothesized that IA-SCI would be beneficial, but translationally-relevant study elements may be missing (e.g., aged animals).Methods: We completed a systematic review of the PubMed database following the PRISMA guidelines on May 21, 2020 for animal studies that administered IA-SCI in the peri-reperfusion period and assessed infarct volume, behavior (primary meta-analytic endpoints), edema, or blood-brain barrier injury (secondary endpoints). Our search terms included: “focal ischemia” and related terms, “IA-SCI” and related terms, and “animal” and related terms. Nineteen studies met inclusion criteria. We adapted a methodological quality scale from 0 to 12 for experimental design assessment (e.g., use of blinding/randomization, a priori sample size calculations).Results: Studies were relatively homogenous (e.g., all studies used young, healthy animals). Some experimental design elements, such as blinding, were common whereas others, such as sample size calculations, were infrequent (median methodological quality score: 5; range: 2–7). Our analyses revealed that IA-SCI provides benefit on all endpoints (mean normalized infarct volume reduction = 23.67%; 95% CI: 19.21–28.12; mean normalized behavioral improvement = 35.56%; 95% CI: 25.91–45.20; mean standardized edema reduction = 0.95; 95% CI: 0.56–1.34). Unfortunately, blood-brain barrier assessments were uncommon and could not be analyzed. However, there was substantial statistical heterogeneity and relatively few studies. Therefore, exploration of heterogeneity via meta-regression using saline infusion parameters, study quality, and ischemic duration was inconclusive.Conclusion: Despite convincing evidence of benefit in ischemic stroke models, additional studies are required to determine the scope of benefit, especially when considering additional elements (e.g., dosing characteristics). As there is interest in using this treatment alongside current ischemic stroke therapies, more relevant animal studies will be critical to inform patient studies.


2019 ◽  
Vol 47 (5-6) ◽  
pp. 207-216 ◽  
Author(s):  
L. Servaas Dolmans ◽  
Frans H. Rutten ◽  
Niels C.T. Koenen ◽  
Marie-Louise E.L. Bartelink ◽  
Johannes B. Reitsma ◽  
...  

Background and Purpose: A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review current evidence for the diagnostic accuracy of blood biomarkers in the early diagnosis of TIA. Methods: This is a systematic review with quality appraisal of individual studies using the QUADAS-2 tool. MEDLINE and EMBASE databases were searched up to May 1, 2017, to select primary diagnostic accuracy studies evaluating potential biomarkers in blood for the diagnosis of TIA or ischemic stroke. Results: Of 4,215 studies retrieved, 78 met our eligibility criteria. Forty-five studies restricted their population to ischemic stroke patients, 32 included both TIA and ischemic stroke patients, and only one study was restricted to TIA patients. In total 62/78 (79.5%) studies had a case-control design comparing TIA or stroke patients with healthy subjects. Overall, 125 single biomarkers and 5 biomarker panels were studied, with a median number of participants per study of 92.0 (interquartile range 44.8–144.5), varying from 8 to 915. Sufficient information to extract 2 × 2 tables was available for 35 (44.9%) articles, and for 60 (48.0 %) biomarkers. Several markers, such as NR2A/B (antibodies), Parkinson 7, nucleoside diphosphate kinase A, ubiquitin fusion degradation protein-1, and heart-type fatty acid binding protein, have shown moderate to high diagnostic accuracy in multiple studies. Conclusions: Although the methodological quality of studies evaluating biomarkers of brain ischemia was poor, several biomarkers have shown the potential to detect transient brain ischemia in an early phase. Diagnostic accuracy studies in suspected cases of TIA are needed to determine their true clinical value.


2021 ◽  
pp. FSO713
Author(s):  
Ahmed Yassin ◽  
Ansam Ghzawi ◽  
Abdel-Hameed Al-Mistarehi ◽  
Khalid El-Salem ◽  
Amira Y Benmelouka ◽  
...  

Objective: To describe the mortality difference between acute ischemic stroke (AIS) and non-AIS groups within COVID-19 patients. Materials & methods: We included observational studies through September 2020 that categorized COVID-19 patients into two groups (with and without AIS). Results: Eight studies with a total sample size of 19,399 COVID-19 patients were included. The pooled risk difference showed that patients with COVID-19 who developed AIS had significantly higher mortality than those without AIS by a risk difference of 24% (95% CI: 0.10–0.39; p = 0.001). In two studies, the COVID-19+AIS group had significantly higher lymphocytes, procalcitonin and creatinine levels. Conclusion: Developing AIS significantly adds to the mortality of COVID-19. Timely interventions to manage those patients are strongly recommended.


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