Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice: The Empoli ESUS Atrial Fibrillation (E 2 AF) Study.

BACKGROUND: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS. METHODS: We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores. RESULTS: Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores. CONCLUSIONS: In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.

Predictive Factors for Hemorrhagic Transformation in Acute Ischemic Stroke in the REAL-World Clinical Practice.

BACKGROUND: Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to develop a score for predicting HT. METHODS: We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score. RESULTS: The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT. CONCLUSIONS: NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.

Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs.

Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air-Liquid Interface (ALI) models, yet the limited accessibility of the organoids' apical side has hindered their applications in studies focusing on host-pathogen interactions. Here, we describe a scalable, fast and efficient way to generate airway organoids with the apical side externally exposed. These apical-out airway organoids are generated in an Extracellular Matrix (ECM)-free environment from 2D-expanded bronchial epithelial cells and differentiated in suspension to develop uniformly-sized organoid cultures with robust ciliogenesis. Differentiated apical-out airway organoids are susceptible to infection with common respiratory viruses and show varying responses upon treatment with antivirals. In addition to the ease of apical accessibility, these apical-out airway organoids offer an alternative in vitro model to study host-pathogen interactions in higher throughput than the traditional air-liquid interface model.

Prognostic determinants in patients with non traumatic intracerebral hemorrhage: a real life report.

Background and aim: Nontraumatic intracerebral hemorrhage (ICH) remains a devastating disease for high in-hospital and long-term mortality and residual neurological disability. The aim of our study was to analyze the prognostic factors in patients managed for ICH in the real-life clinical practice.Materials and Methods: We retrospectively analyzed clinical and neuro-radiological data of consecutive patients admitted to our Hospital for ICH along 1 year. In-hospital mortality and 90-day modified Rankin scale (mRS) ≥4 were the study outcomes. Moreover, we compared patients admitted in Intensive Care Unit (ICU) with patients admitted in Stroke Unit (SU).Results: Ninety-eight patients with mean age ± SD 78 ± 12 years were enrolled. In-hospital and 90-day mortality were 36.7% and 41.8%, respectively. Patients who died had a significantly higher percentage of ICH volume >30 mL, irregular shape, lobar location, intraventricular hemorrhage (IVH), midline shift, hydrocephalus, hematoma enlargement, Glasgow Coma Scale (GCS) ≤9 at hospital admission, early neurological worsening (ENW), higher Hemphill ICH score, and underwent oro-tracheal intubation more frequently compared with patients who survived. Patients admitted to ICU were younger and significantly more critical compared with those who were admitted to SU. In-hospital mortality in patients admitted to ICU was 52.6% compared with 25% in patients admitted to SU (p < 0.01). Median mRS score at hospital discharge was 4 (IQR 3-5) and at 90 days was 4 (IQR 3-4). ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were found independent risk factors for in-hospital mortality, while age was found as independent risk factor for 90-day mRS ≥4).Conclusion: In real life, prognosis of ICH is associated with clinical and radiological determinants. In our study ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were associated with short-term mortality risk, while age with 90-day mRS ≥4.

Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice.

Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1 year (2017, November 1st-2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9 years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75 years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65 years, 24.2% (19.4% ESUS) of patients aged 65-74 years, 15.5% (9.2% ESUS) of patients ≥ 75 years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65 years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75 years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.

Direct Oral Anticoagulants in Patients Undergoing Urgent Reperfusion for Nonvalvular Atrial Fibrillation-Related Ischemic Stroke: A Brief Report on Literature Evidence.

INTRODUCTION: The optimal timing for starting anticoagulation in the early phase of nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains a challenge, especially in patients undergoing urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. The aim of our study was to review the literature evidence reporting on safety of direct oral anticoagulants (DOACs) starting in the early phase of NVAF-related AIS undergoing systemic thrombolysis and/or mechanical thrombectomy. MATERIALS AND METHODS: We reviewed the PubMed databases searching articles reporting on efficacy and safety of DOACs starting time within two weeks from AIS onset in patients undergoing systemic thrombolysis and/or mechanical thrombectomy. RESULTS: Three studies were selected, overall including one hundred and six patients (62 females, 58.4%). Median National Institute of Health Stroke Scale (NIHSS) score at hospital admission ranged from 9 to 13 points. Median DOACs starting time ranged from 2 to 6 days. Median CHA2DS2-VASC score ranged from 4 to 6 points. Follow-up was limited to 14 days in one study, 30 days in another, and 90 days in a third one. Overall, stroke recurrence and/or intracranial bleeding occurred in two patients (1.9%) and no patient died at follow-up. CONCLUSION: Small sample size real life studies seem to demonstrate that the introduction of DOACs in the early phase of NVAF-related AIS undergoing urgent reperfusion is efficacious and safe. Prospective RCTs are necessary to confirm these findings.

Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies.

Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. In the latest years a lot of real life studies on this topic have been published. The aim of our review was to focus on these. We reviewed the PubMed databases searching articles reporting on DOACs starting time within 2 weeks from AIS onset. We selected fifteen studies, eight with retrospective, six with prospective observational and one with a prospective, open-label, single arm design. Overall, 2920 patients (47.8% females) were included. In twelve studies median or mean age of patients was over 75 years. Mean or median NIHSS ad hospital admission was ≤ 12 in all studies. About one-third of patients (32.4%) received urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. About one-fifth of patients (22.8%) had large infarct size. Median starting time of DOACs was reported in thirteen studies and it ranged from 2 to 8 days. About one-half of patients (45.9%) received a low dose of DOACs. In studies reporting on median or mean CHA2DS2-VASC score, it was ≥ 3 in all. In studies reporting on median or mean HAS-BLED score, it was ≥ 2 in all. Ninety-day follow-up was available for nine studies, overall including about 2200 patients. Incidence of 90-day TIA/stroke recurrence, symptomatic haemorrhagic transformation or intracranial bleeding and all cause mortality was 2.25%, 0.90% and 1.5%, respectively. The real life evidence suggests that early starting of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality.