Competitive leptomeningeal flow impact on thrombectomy reperfusion grade rating.

BACKGROUND: Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating. METHODS: Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification. RESULTS: A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5-75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12-22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8-10). Median last known well time to puncture was 7 hours (IQR 4-13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c-3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf's alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience. CONCLUSION: CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating.

New-onset as opposed to established atrial fibrillation as a risk factor for incident stroke.

BACKGROUND: Atrial fibrillation (AF) is an established risk factor for acute ischemic stroke (AIS). It remains unclear if new-onset AF confers a higher risk of AIS than longer-standing AF. METHODS: We retrospectively analyzed all stroke-free patients who underwent transthoracic echocardiography (TTE) in the Henry Ford Health System between March 6 and September 6, 2016. Incident AIS and new-onset AF were ascertained by the presence of new diagnostic codes in the electronic medical record over a follow-up period of up to 5 years. Cox proportional hazards regression was used to identify risk factors for new-onset AF or AIS. RESULTS: Of 7310 patients who underwent baseline TTE the mean age was 65 years, 54% were female, 51% were Caucasian, and 46% had left atrial enlargement (LAE). Of at-risk patients, 10.9% developed new-onset AF and 2.9% experienced incident AIS. The risk of new-onset AF among at-risk patients was 3.1 times higher among patients with any degree of LAE compared to those with normal LA size (95% CI 2.6-3.6, P < 0.0001). New-onset AF, more than established AF, in turn had a powerful association with incident AIS. The cumulative 5-year risk of AIS was 3.5% in those without AF, 5.9% in those with established AF prior to TTE, and 20.1% in those with new-onset AF (P < 0.0001). In multivariable analysis new-onset AF had the strongest association with incident AIS (P < 0.0001), followed by increasing age (P = 0.0025), black race (P = 0.0032), and smoking (P = 0.0063). CONCLUSIONS: New-onset AF has a strong relationship with incident AIS. LAE was present in nearly half of stroke-free patients undergoing TTE, and was associated with a significantly higher likelihood of new-onset AF during follow-up. Vigilant cardiac monitoring for AF in individuals with LAE, coupled with the timely initiation of anticoagulation, may be an important strategy for the primary prevention of AF-related stroke.

Spinal procedures, pneumocephalus, and cranial nerve palsies: A review of the literature.

Purpose: Minimally invasive and surgical spine procedures are commonplace with various risks and complications. Cranial nerve palsies, however, are infrequently encountered, particularly after procedures such as lumbar punctures, epidural anesthesia, or intrathecal injections, and are understandably worrisome for clinicians and patients as they may be interpreted as secondary to a sinister etiology. However, a less commonly considered source is a pneumocephalus which may, in rare cases, abut cranial nerves and cause a palsy as a benign and often self-resolving complication. Here, we present the case of a patient who underwent an intrathecal methotrexate infusion for newly diagnosed non-Hodgkin's T-cell lymphoma and subsequently developed an abducens nerve palsy due to pneumocephalus. We highlight the utility of various imaging modalities, treatment options, and review current literature on spinal procedures resulting in cranial nerve palsies attributable to pneumocephalus presenting as malignant etiologies.

In vitro and in silico analysis for elucidation of antioxidant potential of Djiboutian Avicennia Marina (Forsk.) Vierh. phytochemicals.

The present work aims to study the phytochemical composition, the antioxidant capacity of the crude extracts, and the fraction of extract giving the best antioxidant activity of Avicennia marina. The leaves contain high TFC compared to other parts of the plant, whereas fruits have the highest amount of TPC. Fat-soluble pigments are strongly present in the leaves of Avicennia marina i.e. ß-carotene, lycopene, chlorophyll a, and chlorophyll b. The crude methanolic flower extracts showed strong DPPH and ABTS radical scavenging activity with IC50 values of 0.30 and 0.33 mg/mL respectively compared to the leaf and stem methanolic extracts for the DPPH and ABTS models with a value IC50 greater than 1 mg/mL. The crude fruit extract shows good activity with the ABTS model, unlike the DPPH model whose IC50 values are 0.95 and 0.38 mg/mL, respectively. Fractionation improved the antioxidant effect of crude flower extract. The ethyl acetate fraction exhibits the best antioxidant activity for both DPPH and ABTS methods with IC50 values of 0.125 and 0.16 mg/mL. The HR-LCMS/MS led to the identification of 13 compounds: 6 flavonoids and 7 iridoid glycoside compounds in the different parts of the plant. A bioinformatics study was performed to evaluate the antioxidant activity of the three major Iridoid glycosides towards the target protein Catalase compound II through free binding energy. Out of these three iridoid glycosides, compound C10 does not represent any toxicity, unlike C8 and C9 which showed an irritancy effect. Furthermore, molecular dynamics shows good stability of the C10-2CAG complex. HighlightsExtraction and fractionation of different part (leaf, stem, flower and fruit) of Avicennia marina.Botanical description and phytochemical analysis of crude extract methanolic. Investigation by HR-LCMS characterization of polyphenols and iridoid glycosides.Evaluation the antioxidant activity of crudes extracts methanolics by two methods in vitro DPPH and ABTS.Antioxidant activity of the fraction of the crude flower extracts presenting the best biological response.Evaluate the contribution of three major compounds 2'-Cinnamoylmussaenosidic acid, 10-O-[E-Cinnamoyl]-geniposidic acid and 10-O-[(E)-p-Coumaroyl]-geniposidic acid in the ethyl acetate fraction on the antioxidant activity through docking and dynamic molecular.Communicated by Ramaswamy H. Sarma.

Rescue intracranial stenting for failed posterior circulation thrombectomy: analysis from the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study.

BACKGROUNDS: Recent trials have shown improved outcomes after mechanical thrombectomy (MT) for vertebrobasilar occlusion (VBO) stroke. However, there is a paucity of data regarding safety and outcomes of rescue intracranial stenting (RS) after failed MT (FRRS+) for posterior circulation stroke. We sought to compare RS to failed reperfusion without RS (FRRS-). METHODS: This is a retrospective analysis of the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study, a multicenter collaboration involving prospectively collected databases. Patients were included if they had posterior circulation stroke and failed MT. The cohort was divided into two groups: FRRS+ and FRRS- (defined as modified Thrombolysis In Cerebral Infarction (mTICI) score 0-2a). The primary outcome was a shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0-2 and mRS 0-3 at 90 days. Safety measures included rates of symptomatic intracranial hemorrhage (sICH), procedural complications, and 90-day mortality. Sensitivity and subgroup analyses were performed to identify outcomes in a matched cohort and in those with VBO, respectively. RESULTS: A total of 152 failed thrombectomies were included in the analysis. FRRS+ (n=84) was associated with increased likelihood of lower disability (acOR 2.24, 95% CI 1.04 to 4.95, P=0.04), higher rates of mRS 0-2 (26.8% vs 12.5%, aOR 4.43, 95% CI 1.22 to 16.05, P=0.02) and mRS 0-3 (35.4% vs 18.8%, aOR 3.13, 95% CI 1.08 to 9.10, P=0.036), and lower mortality (42.7% vs 59.4%, aOR 0.40, 95% CI 0.17 to 0.97, P=0.04) at 90 days compared with FRRS- (n=68). The rates of sICH and procedural complications were comparable between the groups. Sensitivity and subgroup analyses showed similar results. CONCLUSION: In patients with posterior circulation stroke who had failed MT, RS resulted in better functional outcomes with comparable safety profile to procedure termination.

Mechanical Thrombectomy for Acute Ischemic Stroke in Metastatic Cancer Patients: A Nationwide Cross-Sectional Analysis.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the standard treatment for large vessel occlusion (LVO) acute ischemic stroke. Patients with active malignancy have an increased risk of stroke but were excluded from MT trials. METHODS: We searched the National Readmission Database for LVO patients treated with MT between 2016-2018 and compared the characteristics and outcomes of cancer-free patients to those with metastatic cancer (MC). Primary outcomes were all-cause in-hospital mortality and favorable outcome, defined as a routine discharge to home (regardless of whether home services were provided or not). Multivariate regression was used to adjust for confounders. RESULTS: Of 40,537 LVO patients treated with MT, 933 (2.3%) had MC diagnosis. Compared to cancer-free patients, MC patients were similar in age and stroke severity but had greater overall disease severity. Hospital complications that occurred more frequently in MC included pneumonia, sepsis, acute coronary syndrome, deep vein thrombosis, and pulmonary embolism (P<0.001). Patients with MC had similar rates of intracerebral hemorrhage (20% vs. 21%) but were less likely to receive tissue plasminogen activator (13% vs. 23%, P<0.001). In unadjusted analysis, MC patients as compared to cancer-free patients had a higher in-hospital mortality rate and were less likely to be discharged to home (36% vs. 42%, P=0.014). On multivariate regression adjusting for confounders, mortality was the only outcome that was significantly higher in the MC group than in the cancerfree group (P<0.001). CONCLUSION: LVO patients with MC have higher mortality and more infectious and thrombotic complications than cancer-free patients. MT nonetheless can result in survival with good outcome in slightly over one-third of patients.

Reocclusion after successful endovascular treatment in acute ischemic stroke: systematic review and meta-analysis.

BACKGROUND: Endovascular treatment (EVT) is the standard of care for selected patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). OBJECTIVE: To systematically review the available data on: (1) incidence, predictors, and outcomes of patients with reocclusion after successful EVT for AIS and, (2) the characteristics, complications, and outcomes of patients with reocclusion treated with repeated EVT (rEVT) within 30 days of the first procedure. METHODS: PubMed was searched (between January 2012 and April 2021) to identify studies reporting reocclusion following successful EVT (Thrombolysis in Cerebral Infarction ≥2b) in patients with AIS due to LVO. Pooled incidence of reocclusion per 100 patients with successful recanalization following EVT was calculated using a random-effects model with Freeman-Tukey double arcsine transformation. Extracted incidences of reocclusion according to etiology and use of intravenous thrombolysis were pooled using random-effects meta-analytic models. RESULTS: A total of 840 studies was identified and seven studies qualified for the quantitative analysis, which described 91 same-vessel reocclusions occurring within the first 7 days after treatment among 2067 patients (4.9%; 95% CI 3% to 7%, I2=70.2%). Large vessel atherosclerosis was associated with an increased risk of reocclusion (OR=3.44, 95% CI 1.12 to 10.61, I2=50%). We identified 90 patients treated with rEVT for recurrent LVO, described in five studies. The rates of procedural complications, mortality, and unfavorable functional outcome at 3 months were 18.0%, 18.9%, and 60.3%, respectively. CONCLUSION: In cohorts of patients with AIS due to LVO, 5% of patients experienced reocclusion within 7 days after successful EVT. Repeated EVT can be a safe and effective treatment for selected patients with reocclusion.

A computer-aided drug design approach to explore novel type II inhibitors of c-Met receptor tyrosine kinase for cancer therapy: QSAR, molecular docking, ADMET and molecular dynamics simulations.

Small molecules such as 4-phenoxypyridine derivatives have remarkable inhibitory activity against c-Met enzymatic activity and proliferation of cancer cell lines. Since there is a relationship between structure and biological activity of these molecules, these little compounds may have great potential for clinical pharmaceutical use against various types of cancer caused by c-Met activity. The purpose of this study was to remodel the structures of 4-phenoxypyridine derivatives to achieve strong inhibitory activity against c-Met and provide favorable pharmacokinetic properties for drug design and discovery. Therefore, this paper describes the structure-activity relationship and the rationalization of appropriate pharmacophore sites to improve the biological activity of the investigated molecules, based on bioinformatics techniques represented by a computer-aided drug design approach. Accordingly, robust and reliable 3D-QSAR models were developed based on CoMFA and CoMSIA techniques. As a result, 46 lead molecules were designed and their biological and pharmacokinetic activities were predicted in silico. Screening filters by 3D-QSAR, Molecular Docking, drug-like and ADME-Tox identified the computer-designed compounds P54 and P55 as the best candidates to achieve high inhibition of c-Met enzymatic activity compared to the synthesized template compound T14. Finally, through molecular dynamics simulations, the structural properties and dynamics of c-Met free and complex (PDB code: 3LQ8) in the presence of 4-phenoxypyridine-derived compounds in an aqueous environment are discussed. Overall, the rectosynthesis of the designed drug inhibitors (P54 and P55) and their in vitro and in vivo bioactivity evaluation may be attractive for design and discovery of novel drug effective to inhibit c-Met enzymatic activity.Communicated by Ramaswamy H. Sarma.