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Background Cancer in stroke patients is associated with higher levels of inflammatory biomarkers and unfavorable poststroke outcomes. We thus explored whether there is a link between cancer and stroke-associated infections. Methods Medical records of patients with ischemic stroke in 2014–2016 registered in the Swiss Stroke Registry of Zurich were retrospectively analyzed. Incidence, characteristics, treatment, and outcome of stroke-associated infections diagnosed within 7 days after stroke onset were tested for an association with cancer. Results Among 1181 patients with ischemic stroke, 102 patients with cancer were identified. Stroke-associated infections occurred in 179 and 19 patients (17% and 19%) without and with cancer (P = .60), respectively, among them pneumonia in 95 and 10 patients (9% and 10%) and urinary tract infections in 68 and 9 patients (6% and 9%) (P = .74 and P = .32). Use of antibiotics was similar between groups. Levels of C-reactive protein (CRP) (P < .001), erythrocyte sedimentation rate (ESR) (P = .014) and procalcitonin (P = .015) were higher and levels of albumin (P = .042) and protein (P = .031) were lower in patients with cancer than without cancer. Among patients without cancer, higher CRP (P < .001), ESR (P < .001) and procalcitonin (P = .04) and lower albumin (P < .001) were associated with stroke-associated infections. Among cancer patients with or without infections, no significant differences in these parameters were observed. In-hospital mortality was associated with cancer (P < .001) and with stroke-associated infections (P < .001). However, among patients with stroke-associated infections, cancer was not associated with in-hospital mortality (P = .24) or 30-day mortality (P = .66). Conclusions Cancer does not represent a risk factor for stroke-associated infections in this patient cohort.

Background: We investigated 92 blood biomarkers implicated in the pathophysiological pathways of ischemic injury, inflammation, hemostasis, and regulation of vascular resistance to predict post-stroke mortality. Aim: Based on the most promising markers, we aimed to create a novel Biomarker Panel Index (BPI) for risk stratification. Methods: In this prospective study, we measured 92 biomarkers in 320 stroke patients. The primary outcome measure was mortality within 90 days. We estimated the association of each biomarker using logistic regression adjusting for multiple testing. The most significant 16 biomarkers were used to create the BPI. We fitted regression models to estimate the association and the discriminatory accuracy of the BPI with mortality and stroke etiology. Results: Adjusted for demographic and vascular covariates, the BPI remained independently associated with mortality (odds ratio (OR) 1.68, 95% confidence interval (CI): 1.29–2.18) and cardioembolic stroke etiology (OR 1.38, 95% CI: 1.10–1.74), and improved the discriminatory accuracy to predict mortality (area under the receiver operating characteristic curve (AUC) 0.93, 95% CI: 0.89–0.96) and cardioembolic stroke etiology (AUC 0.70, 95% CI: 0.64–0.77) as compared to the best clinical prediction models alone (AUC 0.89, 95% CI: 0.84–0.94 and AUC 0.66, 95% CI: 0.60-0.73, respectively). Conclusions: We identified a novel BPI improving risk stratification for mortality after ischemic stroke beyond established demographic and vascular risk factors. Furthermore, the BPI is associated with underlying cardioembolic stroke etiology. These results need external validation.

Background Blood pressure variability (BPV) is associated with outcome after endovascular thrombectomy in acute large vessel occlusion stroke. We aimed to provide the optimal sampling frequency and BPV index for outcome prediction by using high-resolution blood pressure (BP) data. Methods Patient characteristics, 3-month outcome, and BP values measured intraarterially at 1 Hz for up to 24 h were extracted from 34 patients treated at a tertiary care center neurocritical care unit. Outcome was dichotomized (modified Rankin Scale 0–2, favorable, and 3–6, unfavorable) and associated with systolic BPV (as calculated by using standard deviation, coefficient of variation, averaged real variability, successive variation, number of trend changes, and a spectral approach using the power of specific BP frequencies). BP values were downsampled by either averaging or omitting all BP values within each prespecified time bin to compare the different sampling rates. Results Out of 34 patients (age 72 ± 12.7 years, 67.6% men), 10 (29.4%) achieved a favorable functional outcome and 24 (70.6%) had an unfavorable functional outcome at 3 months. No group differences were found in mean absolute systolic BP (SBP) (130 ± 18 mm Hg, p = 0.82) and diastolic BP (DBP) (59 ± 10 mm Hg, p = 1.00) during the monitoring time. BPV only reached predictive significance when using successive variation extracted from downsampled (averaged over 5 min) SBP data (median 4.8 mm Hg [range 3.8–7.1]) in patients with favorable versus 7.1 mmHg [range 5.5–9.7] in those with unfavorable outcome, area under the curve = 0.74 [confidence interval (CI) 0.57–0.85; p = 0.031], or the power of midrange frequencies between 1/20 and 1/5 min [area under the curve = 0.75 (CI 0.59–0.86), p = 0.020]. Conclusions Using high-resolution BP data of 1 Hz, downsampling by averaging all BP values within 5-min intervals is essential to find relevant differences in systolic BPV, as noise can be avoided (confirmed by the significance of the power of midrange frequencies). These results demonstrate how high-resolution BP data can be processed for effective outcome prediction.

[Background] Midregional pro-atrial natriuretic peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS)., [Objectives] This study aimed to determine the role of MR-proANP for classification as cardioembolic (CE) stroke, identification of newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE)., [Methods] This study measured MR-proANP prospectively collected within 24 hours after symptom-onset in patients with AIS from the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study. Primary outcomes were CE stroke etiology and NDAF after prolonged cardiac monitoring, as well as a composite outcome of MACE (recurrent cerebrovascular events, myocardial infarction, or cardiovascular death) within 1 year. Logistic/Poisson and subproportional hazard regression were applied to evaluate the association between MR-proANP levels and outcomes. Additionally, a model for prediction of NDAF was derived and validated as a decision tool for immediate clinical application., [Results] Between October 1, 2014, and October 31, 2017, this study recruited 1,759 patients. Log10MR-proANP levels were associated with CE stroke (OR: 7.96; 95% CI: 4.82-13.14; risk ratio: 3.12; 95% CI: 2.23-4.37), as well as NDAF (OR: 35.3; 95% CI: 17.58-71.03; risk ratio: 11.47; 95% CI: 6.74-19.53), and MACE (subdistributional HR: 2.02; 95% CI: 1.32-3.08) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81 (95% CI: 0.76-0.86), was well calibrated (calibration in the large: −0.086; calibration slope 1.053), and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA2DS2-VASc [Congestive Heart Failure, Hypertension, Age ≥65 or ≥75, Diabetes, Prior Cardioembolic Event, (female) Sex, or Vascular Disease] score)., [Conclusions] MR-proANP is a valid biomarker to determine risk of NDAF and MACE in patients with AIS and can be used as a decision tool to identify patients for prolonged cardiac monitoring. (Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL study [BIOSIGNAL]; NCT02274727), This study was supported by the Swiss National Science Foundation (grant 142422), the Swiss Heart Foundation, and the Baasch Medicus Foundation.

© 2020 American Heart Association, Inc., Data generation, collection, storage, and accessibility are growing exponentially, and most fields of science are already undergoing a big data revolution. Vast pools of electronic data are collected in billions of devices and medical records systems embedded in health organizations all over the world. However, although it is clear that this explosion of digital information could lead to major breakthroughs, such large datasets are still challenging to work with, and there are several obstacles in translating this real-world data into real-world evidence, with tangible benefits for research and, ultimately, clinical practice.

Background and Purpose- MRproANP (midregional proatrial natriuretic peptide) is known to be independently associated with cardioembolic stroke cause and to improve risk stratification for 90-day mortality when measured within 24 to 72 hours after symptom onset in patients with acute ischemic stroke. However, the optimal time point for assessment remains unclear. This study aimed to evaluate prognostic utility of MRproANP at different time points during the first 5 days of hospitalization in patients with acute ischemic stroke. Methods- Samples of MRproANP were collected on admission (

Blood biomarkers are increasingly beginning to play a role in the diagnosis, management, and prognostication of patients with acute ischemic stroke. While imaging biomarkers have played the largest role in determining acute therapies, blood-based biomarkers may have important contributions to make in settings where imaging is not readily available, or when making predictions about future complications and recurrent stroke. Though more research in large, diverse patient populations are needed before blood-based biomarkers become widely accepted for stroke management, preliminary reports suggest their value in several settings and the use of biomarkers is gaining traction. This article discusses the role of several selected readily available protein biomarkers in stroke diagnosis, acute management decisions, and prognosis. Protein biomarkers were primarily selected based on the fact that they have been evaluated in cohort studies and ideally that they have been validated by independent groups.

Background and Purpose Micro ribonucleic acid-150-5p (miR-150-5p) regulates proinflammatory cytokines as well as vessel integrity. We evaluated the incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after ischemic stroke. Methods In a prospective cohort study, levels of miR-150-5p were measured within 72 hours of symptom onset in 329 ischemic stroke patients. The outcome measures were unfavorable functional outcome (assessed by the modified Rankin Scale score >2) and mortality within 90 days. Logistic regression and Cox proportional hazards models were fitted to estimate odds ratio (OR), respectively hazard ratio (HR) and 95% confidence interval (CI) for the association between log-miR-150-5p and the outcome measures. The discriminatory accuracy was assessed with the area under the receiver-operating-characteristic curve (AUC) and the incremental prognostic value was estimated with the net reclassification index. Results After adjusting for demographic and vascular risk factors, lower log-miR-150-5p levels were independently associated with mortality (HR 0.21 [95% CI, 0.08–0.51], P=0.001) but not functional outcome (OR 1.10 [95% CI, 0.54–2.25], P=0.79). Adding log-miR-150-5p improved the discriminatory accuracy of the best multivariate model to predict mortality from an AUC of 0.91 (95% CI, 0.88–0.95) to 0.92 (95% CI, 0.88–0.96 Likelihood-ratio test-P

To prevent stroke recurrence, we treat patients based on the presumed underlying etiology; however, in clinical practice, the underlying mechanism remains undetermined in up to 30% of patients.1 Atrial fibrillation (AF), a known and frequent culprit for cardioembolic stroke, can be transient and not present at the time of evaluation following a stroke. Treatment differs for patients who have strokes caused by AF because of the high risk of recurrent stroke with AF and the high degree of effectiveness of oral anticoagulants to reduce cardioembolic stroke risk. Several guidelines recommend a minimum of 24 to 48 hours of Holter monitoring in all patients with stroke to identify AF as the underlying source of stroke.2 Previous studies found that Holter ECG monitoring (24–72 hours) detects paroxysmal AF in approximately 5% of patients with stroke, and longer duration ECG monitoring detects AF in an additional 5% to 30% of patients depending on the type and duration of monitoring.2–4

ObjectiveTo validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables.MethodsIn this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization.ResultsOf 788 included patients, 783 completed their 90-day follow-up, and 118 patients (15%) died. After full adjustment, MR-proANP levels were associated with 90-day mortality (adjusted hazard ratio 6.12, 95% confidence interval [CI] 2.36–15.84, p = 0.01) and functional outcome (adjusted odds ratio [aOR] 2.46, 95% CI 1.05–5.74, p = 0.038). For mortality prediction, adding MR-proANP to the regression model increased its discriminatory accuracy, and the continuous net reclassification index (cNRI) was 49% (95% CI 26%–78%, p < 0.001). For functional outcome, there was no significant improvement in discrimination or reclassification. Cardioembolic stroke etiology and the diagnosis of atrial fibrillation at hospital discharge were associated with MR-proANP with an aOR of 2.10 (95% CI 1.11–3.97, p = 0.02) and 18.35 (95% CI 7.94–42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95% CI 60%–89%, p < 0.001). MR-proANP levels ≥289 pmol/L had a specificity of 86% and sensitivity of 48% for the diagnosis of atrial fibrillation.ConclusionMR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.

Stroke research fellowships are post-graduate training opportunities for vascular neurologists or other candidates (MD or PhD) desiring advanced training in the research field of cerebrovascular disease. There are several universities in the United States that are among the highest-ranked research institutions in the world in terms of scientific and medical research activity. These institutions, many with specialized, renowned stroke centers, offer research fellowships in which the stroke fellow, under the guidance of experienced mentors, can dedicate himself or herself to stroke research on a full-time basis. To gain the most from a stroke research fellowship, it is advisable to prepare oneself well in advance of applying. Previous research activity, including publications in peer-reviewed research journals, increases the probability of obtaining funding for and acceptance to a stroke research fellowship. It is important that one choose a mentor and institution wisely—not just from a career point of view—but also to suit personal needs. Consider a lesser known institution if a mentor is particularly supportive and inspiring. Going abroad and adapting to different environments or cultures opens the mind and helps the fellow to conduct creative and innovative research. Ideally, such a transatlantic experience will afford the fellow valuable personal experience, provide him or her with a solid research framework, and build a network for future collaborative efforts, acting as a catalyst for a successful independent career. There is a long tradition of US excellence in clinical and epidemiological stroke research.1 When evaluating educational systems, several US universities have been found to excel in training for biomedical and health sciences (eg, according to the Centre for Science and Technology Studies Leiden Ranking and the Shanghai Ranking systems). Teaching and mentoring both play an important role in such training and are critical to its continued success. Several US universities provide excellent programs …

We hypothesized that infectious burden (IB), a composite serologic measure of exposure to common pathogens (i.e., Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) associated with vascular risk in the prospective Northern Manhattan Study (NOMAS), would also be associated with cognition.Cognition was assessed using the Mini-Mental State Examination (MMSE) at enrollment and the modified Telephone Interview for Cognitive Status (TICS-m) at annual follow-up visits. Adjusted linear and logistic regressions were used to measure the association between IB index and MMSE. Generalized estimating equation models were used to evaluate associations with TICS-m and its change over time.Serologies and cognitive assessments were available in 1,625 participants of the NOMAS cohort. In unadjusted analyses, higher IB index was associated with worse cognition (change per standard deviation [SD] of IB for MMSE was -0.77, p0.0001, and for first measurements of TICS-m was -1.89, p0.0001). These effects were attenuated after adjusting for risk factors (for MMSE adjusted change per SD of IB = -0.17, p = 0.06, for TICS-m adjusted change per SD IB = -0.68, p0.0001). IB was associated with MMSE ≤24 (compared to MMSE24, adjusted odds ratio 1.26 per SD of IB, 95% confidence interval 1.06-1.51). IB was not associated with cognitive decline over time. The results were similar when IB was limited to viral serologies only.A measure of IB associated with stroke risk and atherosclerosis was independently associated with cognitive performance in this multiethnic cohort. Past infections may contribute to cognitive impairment.