Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT

Hemorrhagic transformation in acute ischemic stroke patients and atrial fibrillation: time to initiation of anticoagulants and outcome

Background: In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results: HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions: In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

Anticoagulation After Stroke in Patients With Atrial Fibrillation : To Bridge or Not With Low-Molecular-Weight Heparin?

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.Peer reviewe

Healing properties of papain-based gel on oral ulcers

The oral mucous membrane is prone to developing ulcers originating from traumatic or immunological processes. Aim: The aim of the present study was to perform a histological evaluation of the antiinflammatory and healing properties of PapacarieTM applied to oral ulcers. Methods: Fifty adult female albino Wistar rats were randomly separated into two groups: control and PapacarieTM. The animals were anesthetized, placed in prone position and ulcers were induced in the middle dorsum of the tongue through a 3-mm-diameter punch. The control group received no treatment thereafter, while those in the PapacarieTM group received an application of the gel twice a day for 14 days. Five animals from each group were euthanized on days 1, 3, 5, 7 and 14. The tongues were removed, fixed, routinely processed for hematoxylin-eosin staining and analyzed by two blind, calibrated pathologists for the presence or absence of ulcer, inflammatory infiltrate and neutrophils. Data were submitted to statistical analysis by the Fisher’s exact test. Results: On day 1, both groups exhibited ulceration and dense acute inflammatory infiltrate. On day 5, reepithelization and scanty chronic inflammatory infiltrate were observed. On day 14, all animals were healed. There were no statistically significant differences between groups with regard to ulceration (p=0.81), inflammation (p=0.55) or neutrophils (p=0.53). Conclusions: Oral ulcers treated with a papainbased gel exhibited the same inflammatory reaction and healing aspects as those of the nontreated control group

Healing properties of papain-based gel on oral ulcers

The oral mucous membrane is prone to developing ulcers originating from traumatic or immunological processes. Aim: The aim of the present study was to perform a histological evaluation of the antiinflammatory and healing properties of PapacarieTM applied to oral ulcers. Methods: Fifty adult female albino Wistar rats were randomly separated into two groups: control and PapacarieTM. The animals were anesthetized, placed in prone position and ulcers were induced in the middle dorsum of the tongue through a 3-mm-diameter punch. The control group received no treatment thereafter, while those in the PapacarieTM group received an application of the gel twice a day for 14 days. Five animals from each group were euthanized on days 1, 3, 5, 7 and 14. The tongues were removed, fixed, routinely processed for hematoxylin-eosin staining and analyzed by two blind, calibrated pathologists for the presence or absence of ulcer, inflammatory infiltrate and neutrophils. Data were submitted to statistical analysis by the Fisher’s exact test. Results: On day 1, both groups exhibited ulceration and dense acute inflammatory infiltrate. On day 5, reepithelization and scanty chronic inflammatory infiltrate were observed. On day 14, all animals were healed. There were no statistically significant differences between groups with regard to ulceration (p=0.81), inflammation (p=0.55) or neutrophils (p=0.53). Conclusions: Oral ulcers treated with a papainbased gel exhibited the same inflammatory reaction and healing aspects as those of the nontreated control group

Healing properties of papain-based gel on oral ulcers

The oral mucous membrane is prone to developing ulcers originating from traumatic or immunological processes. Aim: The aim of the present study was to perform a histological evaluation of the antiinflammatory and healing properties of PapacarieTM applied to oral ulcers. Methods: Fifty adult female albino Wistar rats were randomly separated into two groups: control and PapacarieTM. The animals were anesthetized, placed in prone position and ulcers were induced in the middle dorsum of the tongue through a 3-mm-diameter punch. The control group received no treatment thereafter, while those in the PapacarieTM group received an application of the gel twice a day for 14 days. Five animals from each group were euthanized on days 1, 3, 5, 7 and 14. The tongues were removed, fixed, routinely processed for hematoxylin-eosin staining and analyzed by two blind, calibrated pathologists for the presence or absence of ulcer, inflammatory infiltrate and neutrophils. Data were submitted to statistical analysis by the Fisher’s exact test. Results: On day 1, both groups exhibited ulceration and dense acute inflammatory infiltrate. On day 5, reepithelization and scanty chronic inflammatory infiltrate were observed. On day 14, all animals were healed. There were no statistically significant differences between groups with regard to ulceration (p=0.81), inflammation (p=0.55) or neutrophils (p=0.53). Conclusions: Oral ulcers treated with a papainbased gel exhibited the same inflammatory reaction and healing aspects as those of the nontreated control group

Healing properties of papain-based gel on oral ulcers

l mucous membrane is prone to developing ulcers originating from traumatic or immunological processes. Aim: The aim of the present study was to perform a histological evaluation of the antiinflammatory and healing properties of PapacarieTM applied to oral ulcers. Methods: Fifty adult female albino Wistar rats were randomly separated into two groups: control and PapacarieTM. The animals were anesthetized, placed in prone position and ulcers were induced in the middle dorsum of the tongue through a 3-mm-diameter punch. The control group received no treatment thereafter, while those in the PapacarieTM group received an application of the gel twice a day for 14 days. Five animals from each group were euthanized on days 1, 3, 5, 7 and 14. The tongues were removed, fixed, routinely processed for hematoxylin-eosin staining and analyzed by two blind, calibrated pathologists for the presence or absence of ulcer, inflammatory infiltrate and neutrophils. Data were submitted to statistical analysis by the Fishers exact test. Results: On day 1, both groups exhibited ulceration and dense acute inflammatory infiltrate. On day 5, reepithelization and scanty chronic inflammatory infiltrate were observed. On day 14, all animals were healed. There were no statistically significant differences between groups with regard to ulceration (p=0.81), inflammation (p=0.55) or neutrophils (p=0.53). Conclusions: Oral ulcers treated with a papainbased gel exhibited the same inflammatory reaction and healing aspects as those of the nontreated control group