Refinement of the taxonomic structure of 16SrXI and 16SrXIV phytoplasmas of gramineous plants using multilocus sequence typing

Phytoplasmas that infect gramineous plants, including Napier grass stunt, sugarcane whiteleaf, sugarcane grassy shoot, and Bermuda grass whiteleaf, have been classified into two closely related groups, 16SrXI and 16SrXIV, based on the 16S ribosomal RNA (rRNA) gene. Subsequently, phytoplasmas associated with coconut and Areca palm in southern India and Sri Lanka have been added into the 16SrXI group. However, the 16S rRNA gene gives relatively poor resolution between these phytoplasmas. In this study, a new set of universal phytoplasma primers that amplify approximately 1 kb of the leucyl transfer RNA synthetase (leuS) gene have been validated on a broad range of phytoplasma taxonomic groups. These have been used along with partial sequences of the secA gene to clarify the taxonomic classification of 16SrXI and 16SrXIV phytoplasmas. Based on this data, the sugarcane whiteleaf and grassy shoot phytoplasmas appear to be the same phytoplasma. The Napier grass stunt phytoplasma forms a distinct group from the Bermuda grass whiteleaf and sugarcane phytoplasmas, suggesting that Napier grass stunt should be in its own ‘Candidatus Phytoplasma sp.’. The phytoplasmas associated with coconut and arecanut in southern India and Sri Lanka, which are in the same 16SrXI group, appear in different groups based on secA analysis

Embolic strokes of undetermined source: prevalence and patient features in the ESUS Global Registry

Background: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims: We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods: Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results: Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation (n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years (p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions: This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions

Global survey of the frequency of atrial fibrillation-associated stroke: embolic stroke of undetermined source global registry

Background and Purpose—Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods—Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results—Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). Conclusions—This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov. Unique identifier: NCT 02313909

Chronic ischemic lesions and presence of patent foramen ovale in young adults with embolic stroke of undetermined source - Results of the Young ESUS Patient Registry.

BACKGROUND Chronic ischemic lesions (CIL) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from 10/2017 to 10/2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either MRI or CT). RESULTS Overall, 535 patients were enrolled (mean age 40.4 (SD 7.3) years, 238 (44%) female). CIL were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (IQR: 1 to 2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (RR 0.17 (0.05-0.61). In Y-ESUS with PFO, CIL were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% P<0.001). CONCLUSIONS One in seven Y-ESUS patients has additional CIL. CIL were associated with several vascular risk factors, lower probability of a pathogenic PFO and lower stroke recurrence

Stroke type and severity in patients with subclinical atrial fibrillation:An analysis from the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT)

Background: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) demonstrated that subclinical atrial fibrillation (SCAF) was associated with a 2.5-fold increased risk of stroke. However, the absolute stroke rate was only 1.7% per year and fewer than 20% patients with stroke had SCAF in the preceding 30 days. This raises the possibility that SCAF is merely a risk marker for stroke rather than the cause. Systematic characterization of stroke subtypes among patients with SCAF would help clarify this issue. Methods: All ischemic strokes that occurred in the ASSERT trial were blindly adjudicated by stroke neurologists, classified as cortical versus subcortical, and subtyped using modified TOAST criteria. Stroke severity was measured using the modified Rankin Score. Results: Of the 44 participants who had an ischemic stroke, 14 had SCAF before stroke. Among patients with SCAF who had stroke, 57% of strokes (n=8) were judged to be cardioembolic, 36% to be lacunar (n=5), and 7% (n= 1) to be large artery disease. However, of 5 patients who had SCAF detected within 30 days before their index stroke, 4 patients had a cardioembolic stroke. The average duration of SCAF in these 4 patients was 6.0 +/- 6.1 h/d. The modified Rankin score at 30 days was similar between patients with (2.7 +/- 2.3) and without SCAF (2.3 +/- 2.0; P =.68). Conclusions: In patientswith SCAF and stroke, SCAF seems probably causal inmany cases; however, in more than 40%, it seems to be acting only as a risk marker. (C) 2018 Elsevier Inc. All rights reserved

Global survey of the frequency of atrial fibrillation–associated stroke

Background and Purpose-Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods-Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results-Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3-5.4; P&amp;lt;0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). Conclusions-This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (&amp;gt;75 years old) and more often women