Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR.

INTRODUCTION: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. METHODS: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. RESULTS: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. CONCLUSION: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Hydrothermally synthesized biofunctional ceria nanoparticles using orange peel extract: optimization, characterization, and antibacterial and antioxidant properties.

In this research, cerium oxide nanoparticles were synthesized using orange peel extract via a hydrothermal method. An equal ratio of orange peel extract to cerium nitrate salt led to the formation of cerium hydroxide carbonate, whereas a 1 : 10 ratio formed cerium oxide. The hydrothermal treatment was conducted for durations of 5 and 25 hours. Scanning electron microscopy (SEM) images revealed that the hydrothermal samples treated for 5 hours exhibited significant agglomeration in both extract to salt ratios after heat treatment. X-ray diffraction patterns confirmed that all samples were converted into cerium oxide after heating at 500 °C for 3 hours. Based on XRD and SEM results, three cerium oxide samples, including those synthesized through the 25 hours hydrothermal process with a 1 : 10 ratio and the 25 hours hydrothermal process with both ratios and subsequent heat treatment, were selected for further investigation. Fourier transform infrared (FT-IR) analysis revealed more adsorption of the functional groups of orange peel extract on the surface of the as-synthesized sample. Moreover, the heat-treated sample with a 1 : 10 ratio, initially cerium oxide, displayed a higher amount of surface functional groups than the one with a 1 : 1 ratio which was initially cerium hydroxide carbonate. The antibacterial activities of the samples were determined using the colony count method. Activities of all samples against Gram-negative bacteria are in the range of 91.5-93.2% with a negligible difference, whereas the as-synthesized sample exhibited a superior activity of 96.6 ± 1.8% against Gram-positive bacteria compared to the other two heat-treated samples. The 87.3% antioxidant activity of the as-synthesized sample significantly surpassed that of the other two samples, as evaluated by the DPPH radical scavenging method.

Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review.

INTRODUCTION: The common reported adverse effects of COVID-19 vaccination consist of the injection site's local reaction followed by several non-specific flu-like symptoms. However, rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) after viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. Herein we systemically reviewed the reported cases of CVST and VITT following the COVID-19 vaccination. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed until May 19, 2021, and the following Keywords were used: COVID Vaccine & Neurology, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, Janssen COVID vaccine, Johnson & Johnson COVID vaccine, Ad26.COV2 COVID vaccine. The authors evaluated the abstracts and titles of each article for screening and inclusion. English reports about post-vaccine CVST and VITT in humans were collected. RESULTS: Until May 19, we found 877 articles with the searched terms. We found 12 articles, which overall present clinical features of 36 patients with CVST and VITT after the ChAdOx1 nCoV-19 vaccine. Moreover, two articles were noted, which present 13 patients with CVST and VITT after Ad26.COV2 vaccine. The majority of the patients were females. Symptom onset occurred within one week after the first dose of vaccination (Range 4-19 days). Headache was the most common presenting symptom. Intracerebral hemorrhage (ICH) and/or Subarachnoid hemorrhage (SAH) were reported in 49% of the patients. The platelet count of the patients was between 5 and 127 cells×109/l, PF4 IgG Assay and d-Dimer were positive in the majority of the reported cases. Among 49 patients with CVST, at least 19 patients died (39%) due to complications of CVST and VITT. CONCLUSION: Health care providers should be familiar with the clinical presentations, pathophysiology, diagnostic criteria, and management consideration of this rare but severe and potentially fatal complication of the COVID-19 vaccination. Early diagnosis and quick initiation of the treatment may help to provide patients with a more favorable neurological outcome.

Hyperdense middle cerebral artery sign and response to combination of mechanical Thrombectomy plus intravenous thrombolysis in acute stroke patients.

BACKGROUND AND PURPOSE: Combining intra-arterial mechanical thrombectomy (IAMT) and intravenous thrombolysis (IVT) has shown to have an excellent recanalization rate and better clinical outcome in acute ischemic stroke (AIS) patients. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment non-contrast head CT scan of AIS patients is one of the early ischemic radiological findings in middle cerebral artery territory AIS. We aimed to evaluate whether the presence of HMCAS predicts the outcome of AIS patients receiving combination therapy with IAMT and IVT. METHODS: We retrospectively reviewed medical records and cerebrovascular images of the patients treated with IAMT and IVT for AIS in our center. Patients with occlusion in the terminal internal carotid artery or middle cerebral artery on pretreatment CT angiogram of the head were included. Clinical outcome was compared between subjects with HMCAS and those without. Modified Rankin Score (mRS) and symptomatic intracranial hemorrhage (sICH) were used as measures of efficacy and safety, respectively. RESULTS: Of 93 patients, 46 (49%) had HMCAS on their initial head CT scan. Both groups had comparable baseline characteristics and stroke severity. After adjusting for age, NIHSS score, time from symptom onset to starting IVT, and history of diabetes mellitus in multivariate logistic regression analysis, there was no difference in terms of a poor outcome (mRS >2) (OR = 0.5 [CI 0.2-1.4], p = 0.188) or rate of sICH (OR = 3.3 [CI 0.6-19.0], p = 0.190) between the two groups. CONCLUSIONS: HMCAS is not a predictor of poor outcome in AIS patients receiving combination therapy with IAMT and IVT and does not affect treatment safety.