Assessing mortality and safety of IV thrombolysis in ischemic stroke patients on direct oral anticoagulants (DOACs): A systematic review and meta-analysis.

BACKGROUND: Intravenous thrombolysis (IVT) is considered a standard reperfusion therapy for acute ischemic stroke (AIS) patients presenting within 4.5 hours of the last known well (LKW). Current guidelines contraindicate the use of IVT in patients within the window who are on Direct Oral Anticoagulants (DOACs) and took their last dose within 48 hours of presentation, due to a risk of symptomatic intracranial hemorrhage (sICH). OBJECTIVE: To assess the safety of IVT as management of AIS in patients who take DOACs. METHODS: A thorough literature search of four databases (PubMed, Scopus, Medline, Google Scholar, Web of science and ScienceDirect) was done from inception until May 2023. Double-arm studies that reported outcomes of mortality, sICH, and mRS scores were selected. Results from these studies were presented as odds ratios (ORs) with 95 % confidence intervals (CIs) and were pooled using a random-effects model. RESULTS: Four eligible studies were included with a total of 238,425 stroke patients who underwent IVT (3330 in the DOAC arm and 235,217 in the placebo arm). The group with prior DOAC intake showed a significant decrease in sICH development and an increase in functional independence at 90 days compared to the control group. No significant association was seen between prior DOAC use and any serious alteplase-related complication within 36 hours, serious systemic or life-threatening hemorrhage within 36 hours, mortality within 3 months, or mRS score at 3 months. CONCLUSION: The pooled analysis suggests that IVT is a safe management option for acute ischemic stroke in patients with DOAC intake before symptom onset without an increased risk of serious adverse events.

Detection of multiple tick-borne pathogens in Ixodes scapularis from Hunterdon County, NJ, USA.

Several human pathogens vectored by the blacklegged tick (Ixodes scapularis Say; Acari: Ixodidae) are endemic in the state of New Jersey. Disease incidence data suggest that these conditions occur disproportionately in the northwestern portion of the state, including in the county of Hunterdon. We conducted active surveillance at three forested sites in Hunterdon County during 2020 and 2021, collecting 662 nymphal and adult I. scapularis. Ticks were tested for five pathogens by qPCR/qRT-PCR: Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan virus (POWV) lineage 2. Over 2 years, 25.4% of nymphs and 58.4% of adults were found infected with at least one pathogen, with 10.6% of all ticks infected with more than one pathogen. We report substantial spatial and temporal variability of A. phagocytophilum and B. burgdorferi, with high relative abundance of the human-infective A. phagocytophilum variant Ap-ha. Notably, POWV was detected for the first time in Hunterdon, a county where human cases have not been reported. Based on comparisons with active surveillance initiatives in nearby counties, further investigation of non-entomological factors potentially influencing rates of tick-borne illness in Hunterdon is recommended.

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD-ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective.

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2-RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.