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We aimed to demonstrate the feasibility of 90-day cardiac monitoring with an external Holter device and to find a target population able to benefit from such a technique. Cryptogenic stroke patients were continuously monitored for 90 days with a textile wearable Holter (TWH). Compliance and quality of the monitoring were assessed by the number of hours of ECG stored per month. Mean predictors of pAF, including age, gender, stroke severity, and atrial size (LAVI), were evaluated. One-year follow-up assessed pAF detection outside per protocol monitoring. Out of 224 patients included in 5 stroke centers, 163 patients (72.76%) fulfilled the criteria for the protocol. Median monitoring time was similar among the three months. Per protocol pAF detection reached 35.37% at 90 days. The age (OR 1.095; 95% CI 1.03–1.14) and the LAVI (OR 1.055; 95% CI 1.01–1.09) independently predicted pAF. The cut-off point of 70 years (AUC 0.68) (95% CI 0.60–0.76) predicted pAF with a sensitivity of 75.8% and specificity of 50.5%. The LAVI cut-off point of 28.5 (AUC 0.67) (95% CI 0.56–0.77) had a sensitivity of 63.6% and a specificity of 61.8% to detect pAF. The combination of both markers enhanced the validity of pAF detection sensitivity to 89.6%, with a specificity of 27.59%. These patients had increased risk of pAF during the 90-day monitoring HR 3.23 ( χ 2 7.15) and beyond 90 days ( χ 2 5.37). Intensive 90-days TWH monitoring detected a high percentage of pAF. However, a significant number of patients did not complete the monitoring. Patients older than 70 years and with enlarged left atria benefitted more from the protocol.

Background and Purpose. BM-MNC transplantation improves recovery in experimental models of ischemic stroke. Clinical trials are ongoing to test efficacy in stroke patients. However, whether cell dose is related to outcomes is not known. Methods. We performed a pooling data analysis of two pilot clinical trials with autologous BM-MNCs transplantation in ischemic stroke patients. Cell dose and route were analyzed to evaluate their relation to good outcome (m-Rankin scale [mRS] score 0–2) at 6 months. Results. Twenty-two patients were included. A median of 153 × 106 (±121 × 106) BM-MNCs was injected. Intra-arterial route was used in 77.3% of cases. A higher number of cells injected were associated with better outcomes at 180 days (390 × 106 [320–422] BM-MNCs injected in those patients with mRS of 0–2 at 6 months versus 130 × 106 [89–210] in those patients with mRS 3–6, p = 0.015 ). In the intra-arterially treated patients, a strong correlation between dose of cells and disability was found ( r = - 0.63 , p = 0.006 ). A cut point of 310 × 106 injected cells predicted good outcome with 80% sensitivity and 88.2% specificity. Conclusions. Similar to preclinical studies, a higher dose of autologous BM-MNC was related to better outcome in stroke patients, especially when more than 310 × 106 cells are injected. Further interventional studies are warranted to confirm these data.

Background and objectiveTK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d.MethodsWe studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics.ResultsWe found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features.ConclusionsBy analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.

BackgroundSeveral antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk–benefit is not well known.ObjectiveTo investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS.MethodsWe conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250–500 mg single-dose) versus tirofiban (500 μg bolus+200 μg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours.ResultsDuring the period 2019–2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c–3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months.ConclusionsPeriprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

Background and Aims: The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients. Methods and Results: Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF Conclusion: Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF.

In the article titled “Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials” [1], the name of the thirteenth author was given incorrectly as Grabriel R. de Freitas. The author’s name should have been written as Gabriel R. de Freitas. The revised authors’ list is shown above.

Glial fibrillar acidic protein (GFAP) in serum has been evaluated as a promising biomarker to differentiate between intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS). We assessed its value as diagnostic and prognostic tool for ICH through a literature systematic review and individual patient data (IPD) meta-analysis.We performed a systematic search in PubMed database until November 2018 for publications that evaluated GFAP to differentiate AIS and ICH within 4.5 hours after symptoms onset. Thereafter, we invited authors of selected studies to participate in this work by providing IPD from their cohorts. We used standardized individual subject’s data to evaluate the association of GFAP concentrations with stroke subtype, demographics, stroke characteristics and factors related with GFAP measurement.From 4 selected studies, we collected data of 340 patients (236 AIS and 104 ICH). Standardized GFAP blood levels were significantly elevated in ICH compared with those with AIS (median and IQR: 0.84 (0.781–1.24), 0.79 (0.74–0.81); p<0.0001). In both stroke types, GFAP concentrations correlated with baseline stroke severity (r=0.27, p<0.0001; r=0.36, p<0.001; for AIS and ICH, respectively) but no correlation was found regarding time to sampling. Limited data precluded the evaluation of GFAP levels and functional outcome.These findings demonstrate substantially different levels of GFAP in the blood of patients with ICH compared with patients with AIS soon after the event, while no association was found with outcome. In summary, GFAP could be a valuable diagnostic tool to assist in medical decision-making and to optimize management of stroke in the acute setting.

The aim of the study was to determine markers of atrial dysfunction in patients with cryptogenic stroke to predict episodes of paroxysmal atrial fibrillation with high risk of embolization (HpAF). We classified patients included in the Crypto-AF study, Cryptogenic Stroke registry, to detect paroxysmal atrial fibrillation (pAF) with wearable Holter, according to the longest episode of pAF in three groups: without pAF detection, episodes of pAF shorter than 5 h, and episodes of pAF longer than 5 h (HpAF). Atrial dysfunction surrogates were evaluated: EKG pattern, Holter record and echocardiography parameters (left atria volume (LAVI), and peak atrial longitudinal and contraction strain (PALS and PACS). The level of N-terminal pro b-type natriuretic peptide (NT-proBNP) was determined. All patients were followed for 2 years to detect pAF and stroke recurrence. From 308 patients, 253 patients with high quality Holter analysis were selected. The distribution was No pAF 78.6% ( n  = 199), pAF < 5 h 7.9% ( n  = 20), and HpAF > 5 h 13.4% ( n  = 34). Age of the patients and combination of PALS and NT-proBNP independently predicted HpAF OR 1.07 (1.00; 1.15) and OR 3.05 (1.08; 8.60) respectively. The validity of PALS and NT-proBNP to detect patients at risk of HpAF was higher than the validity of age (AUC 0.82, sensitivity 78.95%, specificity 63%). Patients with PALS < 25% and NT-proBNP > 283 pg/ml had more detection of pAF during follow-up 35% vs. 5.1% OR 2.33 (1.05–5.13) ( p  < 0.001). Multimodal assessment of atrial dysfunction with PALS and NT-proBNP improved the prediction of pAF episodes with high embolic risk in patients with cryptogenic stroke.

Background Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI. Objectives The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS 2 and CHA 2 DS 2 VASc score. Methods Patients with a history of AF based on medical records who scored 0–1 in the CHADS 2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50 years and with absence of neurological symptoms. Results 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA 2 DS 2 VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07–13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15–8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33–7.63). Conclusions LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS 2 and in the low-risk population according to CHA 2 DS 2 VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.

Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (http://www.clinicaltrials.gov; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p<0.001), whereas miRNA-133b showed a significant increase in the low-dose BM-MNC group at 90 days. Intra-arterial BM-MNC transplantation in patients with ischemic stroke seems to modulate early circulating miRNA-34a levels, which have been related to precursor cell migration in stroke and smaller infarct volumes.