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Background Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence.Objective This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU.Methods A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected.Results The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence.Conclusion The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary.

Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce.Patients and Methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0–2 at 3 months.Results: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10–2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93–0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59–3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25–0.72) and 0.55 (95% CI, 0.39–0.77), respectively.Conclusion: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Traumatic brain injury is often associated with a direct or secondary neurovascular pathology. In this review, we present recent advancements in endovascular neurosurgery that enable accurate and effective vessel reconstruction with emphasis on its role in early diagnosis, the expanding use of flow diversion in pseudoaneurysms, and traumatic arteriovenous fistulas. In addition, future directions in which catheter-based interventions could potentially affect traumatic brain injury are described: targeting blood brain barrier integrity using the advantages of intra-arterial drug delivery of blood brain barrier stabilizers to prevent secondary brain edema, exploring the impact of endovascular venous access as a means to modulate venous outflow in an attempt to reduce intracranial pressure and augment brain perfusion, applying selective intra-arterial hypothermia as a neuroprotection method mitigating some of the risks conferred by systemic cooling, trans-vessel wall delivery of regenerative therapy agents, and shifting attention using multimodal neuromonitoring to post-traumatic vasospasm to further characterize the role it plays in secondary brain injury. Thus, we believe that the potential of endovascular tools can be expanded because they enable access to the “highways” governing perfusion and flow and call for further research focused on exploring these routes because it may contribute to novel endovascular approaches currently used for treating injured vessels, harnessing them for treatment of the injured brain.

Ischemia and reperfusion damage to the liver is one of the major causes of hepatic dysfunction and liver failure after a liver transplant. The start of hepatic ischemia-reperfusion damage is linked to metabolic acidosis, Kupffer cells, neutrophils, excessive calcium, and changes in the permeability of the mitochondrial membrane. Hypoxia activates Kupffer cells, resulting in the production of reactive oxygen species (ROS). These ROS when accumulated, causes apoptosis and necrosis, as well as activate immune and inflammatory responses that involve many cells and signalling molecules. Numerous antioxidant compounds have been researched to lessen oxidative stress and thus serve as potential compounds to deal the ischemia-reperfusion damage. This article confers a deep understanding of the protective effects of some effective therapies, including hepatoprotective agents, attenuation of an increase in xanthine oxidase activity, and administration of antioxidants like N-acetylcysteine, superoxide dismutase (SOD), and ornithine.

BackgroundMoyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes.ObjectiveIn this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya.MethodsWe conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes.ResultsThe rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563).ConclusionSince both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient’s risk assessment.

Here, we describe a case of a woman suspected to have an anterior cerebral artery (ACA) aneurysm that was ultimately found to have an azygous ACA shield. This benign entity highlights the importance of thorough investigation with cerebral digital subtraction angiography (DSA). This 73-year-old female initially presented with dyspnea and dizziness. CT angiogram of the head suggested an incidental 5 mm ACA aneurysm. Subsequent DSA demonstrated a Type I azygos ACA supplied by the left A1 segment. Also noted was a focal dilatation of the azygos trunk as it gave rise to the bilateral pericallosal and callosomarginal arteries. Three-dimensional visualization demonstrated a benign dilatation secondary to the four vessels branching; no aneurysm was noted. Incidence of aneurysms at the distal dividing point of an azygos ACA ranges from 13% to 71%. However, careful anatomical examination is imperative as findings may be a benign dilatation for which case intervention is not indicated.

Genetic variants associated with complex traits are primarily noncoding, and their effects on gene-regulatory activity remain largely uncharacterized. To address this, we profile epigenomic variation of histone mark H3K27ac across 387 brain, heart, muscle and lung samples from Genotype-Tissue Expression (GTEx). We annotate 282 k active regulatory elements (AREs) with tissue-specific activity patterns. We identify 2,436 sex-biased AREs and 5,397 genetically influenced AREs associated with 130 k genetic variants (haQTLs) across tissues. We integrate genetic and epigenomic variation to provide mechanistic insights for disease-associated loci from 55 genome-wide association studies (GWAS), by revealing candidate tissues of action, driver SNPs and impacted AREs. Lastly, we build ARE–gene linking scores based on genetics (gLink scores) and demonstrate their unique ability to prioritize SNP–ARE–gene circuits. Overall, our epigenomic datasets, computational integration and mechanistic predictions provide valuable resources and important insights for understanding the molecular basis of human diseases/traits such as schizophrenia.

To determine whether a resident's medical school ranking predicts their scholarship during residency.

Background The utility of intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) in large vessel occlusion stroke (LVO) is controversial. Some data suggest IVT increases MT technical difficulty. Within our hub-and-spoke telestroke network, we examined how spoke-administered IVT affected hub MT procedure time and pass number.Methods Patients presenting to 25 spoke hospitals who were transferred to the hub and underwent MT from 2018 to 2020 were identified from a prospectively maintained database. MT procedure time, fluoroscopy time, and pass number were obtained from operative reports.Results Of 107 patients, 48 received IVT at spokes. Baseline characteristics and NIHSS were similar. The last known well (LKW)-to-puncture time was shorter among IVT patients (4.3 ± 1.9 h vs. 10.5 ± 6.5 h, p < 0.0001). In patients that received IVT, mean MT procedure time was decreased by 18.8 min (50.5 ± 29.4 vs. 69.3 ± 46.7 min, p = 0.02) and mean fluoroscopy time was decreased by 11.3 min (21.7 ± 15.8 vs. 33.0 ± 30.9 min, p = 0.03). Furthermore, IVT-treated patients required fewer MT passes (median 1 pass [IQR 1.0, 1.80] vs. 2 passes [1.0, 2.3], p = 0.0002) and were more likely to achieve reperfusion in ≤2 passes (81.3% vs. 59.3%, p = 0.01). An increased proportion of IVT-treated patients achieved TICI 2b-3 reperfusion after MT (93.9% vs. 83.8%, p = 0.045). There were no associations between MT procedural characteristics and LKW-to-puncture time.Conclusion Within our network, hub MT following spoke-administered IVT was faster, required fewer passes, and achieved improved reperfusion. This suggests spoke-administered IVT does not impair MT, but instead may enhance it.

Direct carotid cavernous fistulas (dCCF) are high-flow shunts between the internal carotid artery (ICA) and cavernous sinus and are commonly caused by traumatic injuries. Endovascular intervention using detachable coils, with or without stenting, is often the treatment of choice; however, migration or compaction of the coils can occur due to high-flow nature of dCCFs. Alternatively, deployment of a covered stent in ICA can be considered for treatment of dCCFs. We report a case of dCCF with tortuous intracranial ICA successfully treated by placement of a covered stent graft and we will illustrate the technical aspects of the procedure. In the presence of a tortuous ICA navigation and deployment of covered stents is technically complicated and requires modified maneuvers.

BackgroundThe Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status.MethodsOur data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up.ResultsThe study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation.ConclusionThere was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.

Despite advances in clinical diagnosis and increasing numbers of patients eligible for revascularisation, ischaemic stroke remains a significant public health concern accounting for 3.3 million deaths annually. In addition to recanalisation therapy, patient outcomes could be improved through cerebroprotection, but all translational attempts have remained unsuccessful. In this narrative review, we discuss potential reasons for those failures. We then outline the diverse, multicellular effects of ischaemic stroke and the complex temporal sequences of the pathophysiological cascade during and following ischaemia, reperfusion, and recovery. This evidence is linked with findings from prior cerebroprotective trials and interpreted for the modern endovascular era. Future cerebroprotective agents that are multimodal and multicellular, promoting cellular and metabolic health to different targets at time points that are most responsive to treatment, might prove more successful.

Triage describes the assignment of resources based on where they can be best used, are most needed, or are most likely to achieve success. Triage is of particular importance in time-critical conditions such as acute ischemic stroke. In this setting, one of the goals of triage is to minimize the delay to endovascular thrombectomy (EVT), without delaying intravenous thrombolysis or other time-critical treatments including patients who cannot benefit from EVT. EVT triage is highly context-specific, and depends on availability of financial resources, staff resources, local infrastructure, and geography. Furthermore, the EVT triage landscape is constantly changing, as EVT indications evolve and new neuroimaging methods, EVT technologies, and adjunctive medical treatments are developed and refined. This review provides an overview of recent developments in EVT triage at both the pre-hospital and in-hospital stages. We discuss pre-hospital large vessel occlusion detection tools, transport paradigms, in-hospital workflows, acute stroke neuroimaging protocols, and angiography suite workflows. The most important factor in EVT triage, however, is teamwork. Irrespective of any new technology, EVT triage will only reach optimal performance if all team members, including paramedics, nurses, technologists, emergency physicians, neurologists, radiologists, neurosurgeons, and anesthesiologists, are involved and engaged. Thus, building sustainable relationships through continuous efforts and hands-on training forms an integral part in ensuring rapid and efficient EVT triage.

BackgroundThe Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes.ObjectiveTo compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device.MethodsA retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications.ResultsA total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04).ConclusionTo our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations.

Spinal schwannomas are rare nerve root tumors that typically produce subtle symptoms from nerve root compression. These tumors are known to be heterogeneously hyperintense on T2-weighted MRI and avidly enhance with contrast. However, here we describe an L5 spinal schwannoma in a 66-year-old woman that was hypointense on T2-weighted imaging with other radiographic findings more closely aligning with a vascular lesion. The neuroradiologic characteristics on MRI, time resolved MR angiography, and catheter digital subtraction angiography are presented. The patient underwent a full workup for possible dural arteriovenous fistula and thrombosed venous varix before the nerve sheath tumor was discovered intraoperatively and confirmed as a schwannoma on histopathology.

No significant difference in the angiographic and clinical outcomes was observed for the treatment of sidewall versus bifurcation intracranial aneurysms with use of Woven EndoBridge.

Purpose Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion.Methods A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months’ clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment.Results We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter ≥10 mm (p= 0.012), pre-clinoid internal carotid artery location (p= 0.012), distal > proximal parent vessel diameter (p= 0.042), and later dual antiplatelet therapy (DAPT) discontinuation (p< 0.001) were predictive of retreatment. Multivariate analysis identified discontinuation of DAPT >12 months (p= 0.003) as a strong determinant of retreatment with dome diameter ≥10 mm trending toward statistical significance (p= 0.064). Large aneurysm neck diameter, presence of aneurysm branch vessels, patient age, smoking history, and hypertension were not determinant of retreatment on multivariate analysis.Conclusions Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

Objective To assess the clinical, racial, and social characteristics of victims of Gunshot wounds (GSWs) to the head and assess for associations between these factors and outcomes.Summary Background Data Previous literature has not focused on the association of race and socioeconomic factors with these specific injuries.Methods We identified patients with GSWs to the head who presented to 2 urban academic medical centers between 1998 and 2020, and extracted patient-level demographic data, information about the clinical and surgical course, and outcomes at discharge and follow-up.Results The cohort included 250 patients, 90% (n = 226) of whom were male, with a mean age of 28 years. Forty-five percent were white (n = 112), 19% Black (n = 48), 18% Latinx (n = 45), with 6% “other” (n = 16), and 12% “unknown” (n = 29). The majority of patients presented with assault-related trauma (n = 153, 61%) as compared to self-inflicted injuries (n = 97, 39%). Across the entire cohort, sex, age, race, and median income by ZIP code were not significant predictors of outcome. Victims of assault by GSW to the head were more likely to be age 18 or younger (OR 5.26, P = 0.01), between the ages of 19 and 33 years (OR 4.7, P = 0.001), Black (OR 6.66, P < .001), and Latinx (OR 2.65, P = 0.03). Most patients (n = 155, 63%) had a poor functional outcome (modified Rankin Score 3–6) at discharge.Conclusion Age, race, and income status were not independent predictors of mortality or functional outcome at discharge in our population. Assault-related GSWs to the head mostly involved young Black or Latinx men of lower socioeconomic status, while self-inflicted injuries were largely seen in older white men.

This international multicenter study found that adjunctive intravenous thrombolysis may not provide benefit to mechanical thrombectomy in patients with acute ischemic stroke caused by distal and medium vessel occlusion.

BackgroundRandomized trials have not demonstrated benefit from intravenous thrombolysis among patients undergoing endovascular thrombectomy (EVT). However, these trials included primarily patients presenting directly to an EVT capable hub center. We sought to study outcomes for EVT candidates who presented to spoke hospitals and were subsequently transferred for EVT consideration, comparing those administered alteplase at spokes (i.e., ‘drip-and-ship’ model) versus those not.MethodsConsecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pre-transfer CT angiography defined emergent large vessel occlusion and Alberta Stroke Program CT score ≥6 were identified from a prospectively maintained Telestroke database. Outcomes of interest included adequate reperfusion (Thrombolysis in Cerebral Infarction (TICI) 2b–3), intracerebral hemorrhage (ICH), discharge functional independence (modified Rankin Scale (mRS) ≤2), and 90 day functional independence.ResultsAmong 258 patients, median age was 70 years (IQR 60–81), median National Institutes of Health Stroke Scale (NIHSS) score was 13 (6-19), and 50% were women. Ninety-eight (38%) were treated with alteplase at spokes and 113 (44%) underwent EVT at the hub. Spoke alteplase use independently increased the odds of discharge mRS ≤2 (adjusted OR 2.43, 95% CI 1.08 to 5.46, p=0.03) and 90 day mRS ≤2 (adjusted OR 3.45, 95% CI 1.65 to 7.22, p=0.001), even when controlling for last known well, NIHSS, and EVT; it was not associated with an increased risk of ICH (OR 1.04, 95% CI 0.39 to 2.78, p=0.94), and there was a trend toward association with greater TICI 2b–3 (OR 3.59, 95% CI 0.94 to 13.70, p=0.06).ConclusionsIntravenous alteplase at spoke hospitals may improve discharge and 90 day mRS and should not be withheld from EVT eligible patients who first present at alteplase capable spoke hospitals that do not perform EVT. Additional studies are warranted to confirm and further explore these benefits.

BackgroundM2 segment occlusions represent approximately one-third of non-lacunar ischemic stroke and can lead to permanent neurological deficits. Various techniques are available for mechanical thrombectomy beyond the circle of Willis, but data evaluating their effectiveness and safety are lacking.MethodsA retrospective review of patients with ischemic stroke undergoing mechanical thrombectomy for M2 occlusions from 13 centers in North American and Europe was performed. Tandem or multiple-territory occlusions were excluded. The primary outcome was 90-day modified Rankin Scale and reperfusion rates across stent-retriever, direct aspiration and combined techniques.ResultsThere were 465 patients (mean age 71.48±14.03 years, 53.1% female) with M2 occlusions who underwent mechanical thrombectomy. Stent-retriever alone was used in 133 (28.6%), direct aspiration alone in 93 (20.0%) and the combined technique in 239 (51.4%) patients. Successful reperfusion was achieved with the combined technique in 198 (82.2%; OR 2.6 (1.1–6.9)), with stent-retriever alone in 112 (84.2%; OR 9.2 (1.9–44.6)) and with direct aspiration alone in 62 (66.7%; referencecategory). Intraprocedural subarachnoid hemorrhages (iSAH) were 36 (7.7%) and were more likely to occur in patients treated with the stent-retrievers (OR 5.0 (1.1–24.3)) and combined technique (OR 4.6 (1.1–20.9)). Good clinical outcome was achieved in 260 (61.8%) patients, while 59 (14.0%) patients died. Older age, higher baseline NIHSS (National Institutes of Health Stroke Scale), parenchymal hemorrhage and iSAH were associated with poor outcome while successful recanalization and higher baseline ASPECTS (Alberta Stroke Program Early CT Score) were associated with good outcome. No differences were found among the three techniques in terms of clinical outcome.ConclusionStent-retrievers and a combined approach for M2 occlusions seem more effective than direct aspiration, but with higher rates of iSAH. This leads to no detectable difference in clinical outcome at 3 months.

BackgroundTo analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome.MethodsMulticentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications.ResultsA total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome.ConclusionThere is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.

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A specific splicing isoform of RNASET2is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

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Background The Penumbra SMART coil is a novel device that becomes progressively softer from its distal to proximal end to maximize coil packing and prevent microcatheter prolapse or coil migration. Here, we report a large series of patients detailing the long-term experience of a single institution using the SMART coil among patients with intracranial aneurysms (IAs).Methods Prospective data of 105 consecutive patients with 106 IAs treated using SMART coils was collected between March 2015 and July 2018. Clinical and angiographic data were analyzed.Results Forty-nine patients (46.7%) presented with subarachnoid hemorrhage and 16 (14.2%) had recurrent aneurysms. Two patients had minor intraprocedural ruptures and remained neurologically stable. One patient had a thromboembolic complication with progressive neurologic decline. There was only one case microcatheter prolapse related to placement of a stent before coiling. An initial post-treatment modified Raymond-Roy Occlusion Classification (mRROC) I or II closure was achieved in 56 (52.8%) aneurysms. The average time to last follow-up was 8.4 months at which 70 (81.4%) aneurysms had mRROC I or II occlusion and a major recurrence was seen in 5 (5.8%) patients. Thirteen (12.3%) aneurysms required re-treatment of which one aneurysm was clipped.Conclusions The Penumbra SMART coil is safe and effective for the endovascular treatment of appropriately selected IAs. Additional studies at multiple centers comparing safety and efficacy profile over long-term periods to other mainstream coils are necessary.

The treatment of intracranial aneurysms (IA) began in the late 19th century. Some degree of controversy has always surrounded the best treatment modality for IA. Cushing and Dandy debated about cervical carotid ligation as the only surgical alternative before the introduction of microsurgical clipping. In the early 21st century, the debate has centered on surgical versus^ endovascular techniques. With the advent of newer endovascular techniques and devices, there has been a dramatic shift in treatment paradigms toward endovascular intervention that is preferred by both physicians and patients. However, there will always be a need for microsurgical cerebrovascular expertise since some aneurysms cannot or should not be embolized. This creates a difficult conundrum as only the most complex of aneurysms will require open surgery, but the lack of volume and training will be a challenge in teaching and maintaining the surgical expertise required to safely treat them. The purpose of this review is to discuss the history of IA treatment and critically evaluate the current state of the art of IA treatment, with a specific focus on the necessary role microsurgical clipping continues to play in the current treatment landscape.

BackgroundPersons with pre-existing disabilities represent over one-third of acute stroke presentations, but account for a far smaller proportion of those receiving endovascular thrombectomy (EVT) and thrombolysis. This is despite existing ethical, economic, legal, and social directives to maximize equity for this vulnerable population. We sought to determine associations between baseline modified Rankin Scale (mRS) and outcomes after EVT.MethodsIndividuals who underwent EVT were identified from a prospectively maintained database. Demographics, medical history, presentations, treatments, and outcomes were recorded. Baseline disability was defined as baseline mRS≥2. Accumulated disability was defined as the delta between baseline mRS and absolute 90-day mRS.ResultsOf 381 individuals, 49 had baseline disability (five with mRS=4, 23 mRS=3, 21 mRS=2). Those with baseline disability were older (81 vs 68 years, P<0.0001), more likely female (65% vs 49%, P=0.032), had more coronary disease (39% vs 20%, P=0.006), stroke/TIA history (35% vs 15%, P=0.002), and higher NIH Stroke Scale (19 vs 16, P=0.001). Baseline mRS was associated with absolute 90-day mRS ≤2 (OR=0.509, 95%CI=0.370–0.700). However, baseline mRS bore no association with accumulated disability by delta mRS ≤0 (ie, return to baseline, OR=1.247, 95%CI=0.943–1.648), delta mRS ≤1 (OR=1.149, 95%CI=0.906–1.458), delta mRS ≤2 (OR 1.097, 95% CI 0.869–1.386), TICI 2b–3 reperfusion (OR=0.914, 95%CI=0.712–1.173), final infarct size (P=0.853, β=−0.014), or intracerebral hemorrhage (OR=0.521, 95%CI=0.244–1.112).ConclusionsWhile baseline mRS was associated with absolute 90-day disability, there was no association with accumulated disability or other outcomes. Patients with baseline disability should not be routinely excluded from EVT based on baseline mRS alone.

BackgroundFlow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce.ObjectiveTo perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms.MethodsConsecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome.ResultsA total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04).ConclusionComparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

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Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Before approval of andexanet alfa, off‐label treatment with 4‐factor prothrombin complex concentrate (4F‐PCC) was often utilized for the management of life‐threatening hemorrhages associated with oral factor Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor‐associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F‐PCC.

Introduction We describe our initial experience with the React 68 catheter (Medtronic, Dublin, Ireland), an FDA-approved catheter designed for aspiration in cases of emergent large vessel occlusion, as compared with the ACE 68 catheter (Penumbra, Alameda, CA).Methods This observational study followed consecutive patients treated with the React catheter over a seven-month period at a comprehensive stroke center. Use of the device was per discretion of the operator. Patient demographics, thrombectomy technique, reperfusion scoring, and disposition were assessed. Performance was compared with patients treated with the ACE 68 catheter over a comparable period.Results We treated 47 patients using the React 68 catheter using either aspiration alone or a combination of aspiration and stent retriever technique. The catheter was used in a variety of circumstances including proximal and distal occlusions involving the anterior and posterior circulation. Modified TICI 2b-3 was achieved in 45 of the 47 patients. The React 68 was comparable to the ACE 68 by all performance measures.Conclusion The React 68 catheter is a large-bore reperfusion catheter with trackability suitable for use in direct aspiration for recanalization of emergent large vessel occlusion.

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Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo.Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications.Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30–1.00, p= 0.048), functional independence (OR = 2.52, 95% CI = 1.02–6.20, p= 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03–0.54, p= 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups.Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study’s observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population.

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT.Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12–36 h post-MT.Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes.Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Background Advancements in flow diversion technology have revolutionized the treatment of intracranial aneurysms. The pipeline embolization device (PED) and the flow redirection endoluminal device (FRED) have emerged as prominent tools in this field. This study aims to compare the safety and efficacy profiles of PED and FRED in the treatment of intracranial aneurysms.Methods Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, and Scopus databases. Studies comparing PED and FRED were included and data extraction focused on study characteristics, patient demographics, and clinical and radiological outcomes. Primary outcomes were favorable outcomes, described as modified Rankin scale (mRS) 0–2 score, and complete/near-complete occlusion, while secondary outcomes included retreatment rate and thromboembolic and hemorrhagic complications.Results Five studies, comprising 1238 patients, were included. No significant differences were found between PED and FRED in terms of complete occlusion at 6 months and 1 year, complete/near-complete occlusion at the last follow up, retreatment rates, and thromboembolic, in-stent thrombosis and hemorrhagic complications. However, FRED was significantly associated with higher favorable outcomes compared to PED (odds ratio: 0.37; confidence interval: 0.17 to 0.81; p = 0.01).Conclusion This study showed that both PED and FRED had comparable rates of complete occlusion, retreatment and complications, and FRED also demonstrated a higher likelihood of achieving favorable outcomes. The study underscores the need for further research with larger cohorts and longer follow up to consolidate these findings.