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The purpose of this study is to retrospectively evaluate the clinical and surgical outcomes of a large surgical series of vestibular schwannoma from North America over 20 years.After institutional review board approval a retrospective review of the senior author's personal case logs to identify patients who had operations for vestibular schwannoma was performed. The clinical notes, operative record, preoperative and postoperative imagings, and long-term clinical follow-up notes were evaluated.A total of 415 patients who underwent 420 surgeries were identified from the years 1998-2021. The average length of follow-up was 3 years and 9 months. Overall, at last follow-up the rate of "good" facial nerve outcomes (House-Brackmann [HB] score I and II) was 86% and "poor" facial nerve outcomes (HB III-VI) was 14%. The amount of cerebellopontine angle extension (P = 0.023), tumor volume (P = 0.015), facial nerve consistency (P0.001), preoperative HB score (P0.001), and FN stimulation threshold at the end of the procedure (P0.001) were correlated to facial nerve function at the last follow-up.This study represents one of the largest recently reported surgical series of vestibular schwannoma in North American literature with available long term follow-up. Facial nerve outcomes correlated with cerebellopontine angle extension, tumor volume, facial nerve stimulation threshold, facial nerve consistency, preoperative facial nerve function, and history of a prior resection. Tumor recurrence remains significantly higher after subtotal resection. We believe the data supports a continuation of a strategy of general intent of gross total resection, greatly modifiable by intraoperative findings and judgment.

Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports.To report a multicenter experience assessing microsurgery safety/efficacy.Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021).Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%. Favorable last follow-up modified Rankin Scale of 0 to 2 was recorded in 81.6% of the patients with procedural complications of 2.6%.Craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point. This approach was associated with a high rate of angiographic cure and favorable clinical outcomes.

Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1β, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-β, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.

BackgroundThe coastal wetland tree speciesMelaleuca quinquenervia(Cav.) S.T.Blake (Myrtaceae), commonly named the broad-leaved paperbark, is a foundation species in eastern Australia, Indonesia, Papua New Guinea, and New Caledonia. The species has been widely grown as an ornamental, becoming invasive in areas such as Florida in the United States. Long-lived trees must respond to a wide range pests and pathogens throughout their lifespan, and immune receptors encoded by the nucleotide- binding domain and leucine-rich repeat containing (NLR) gene family play a key role in plant stress responses. Expansion of this gene family is driven largely by tandem duplication, resulting in a clustering arrangement on chromosomes. Due to this clustering and their highly repetitive domain structure, comprehensive annotation of NLR encoding genes within genomes has been difficult. Additionally, as many genomes are still presented in their haploid, collapsed state, the full allelic diversity of the NLR gene family has not been widely published for outcrossing tree species.ResultsWe assembled a chromosome-level pseudo-phased genome forM.quinquenerviaand describe the full allelic diversity of plant NLRs using the novel FindPlantNLRs pipeline. Analysis reveals variation in the number of NLR genes on each haplotype, differences in clusters and in the types and numbers of novel integrated domains.ConclusionsWe anticipate that the high quality of the genome forM. quinquenerviawill provide a new framework for functional and evolutionary studies into this important tree species. Our results indicate a likely role for maintenance of NLR allelic diversity to enable response to environmental stress, and we suggest that this allelic diversity may be even more important for long-lived plants.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

A molecular phylogeny of Chloantheae (Lamiaceae) based on a three-marker chloroplast and nuclear DNA dataset was used to test the monophyly of Lachnostachys Hook., Newcastelia F.Muell. and Physopsis Turcz. A clade consisting of at least one species from each of these genera was recovered separately from the ‘core’ Lachnostachys, Newcastelia and Physopsis clades. The members of this composite clade are here transferred to the new genus, Apatelantha T.C.Wilson & M.J.Henwood, which can be recognised by a combination of the base of the style being glabrous or with only non-glandular trichomes (glandular trichomes lacking), apex of corolla lobes (when present) acute to obtuse (not extending into an apical protrusion) and thin-textured (not distinctively thickened), pherophylls subtending three flowers, and anther connectives glabrous (sessile glands absent). A description of the new genus, together with new combinations for five species of Apatelantha, and amended descriptions of Lachnostachys, Newcastelia and Physopsis, are provided. A new species, Newcastelia clavipetala T.C.Wilson & Radunz, is described and illustrated. A taxonomic key to genera of Chloantheae, and keys to species of Lachnostachys, Newcastelia, Physopsis and Apatelantha are provided.

BackgroundRadial artery access for transarterial procedures has gained recent traction in neurointerventional due to decreased patient morbidity, technical feasibility, and improved patient satisfaction. Upper extremity transvenous access (UETV) has recently emerged as an alternative strategy for the neurointerventionalist, but data are limited. Our objective was to quantify the use of UETV access in neurointerventions and to measure failure and complication rates.MethodsAn international multicenter retrospective review of medical records for patients undergoing UETV neurointerventions or diagnostic procedures was performed. We also present our institutional protocol for obtaining UETV and review the existing literature.ResultsOne hundred and thirteen patients underwent a total of 147 attempted UETV procedures at 13 centers. The most common site of entry was the right basilic vein. There were 21 repeat puncture events into the same vein following the primary diagnostic procedure for secondary interventional procedures without difficulty. There were two minor complications (1.4%) and five failures (ie, conversion to femoral vein access) (3.4%).ConclusionsUETV is safe and technically feasible for diagnostic and neurointerventional procedures. Further studies are needed to determine the benefit over alternative venous access sites and the effect on patient satisfaction.

Background Lung carcinoma metastasizing to a skull base meningioma remains an extremely rare phenomenon, with only 3 studies reported. Furthermore, no documented cases have been reported in the petroclival region. Thus, we have presented the first 2 cases of tumor-to-tumor metastasis (TTM) in which a petroclival lesion, initially thought to be purely meningioma, was also found to contain metastatic lung adenocarcinoma. Case Description We present the cases of 2 patients with a known history of lung adenocarcinoma and stable petroclival meningioma who had presented with new-onset neurologic deficits. Repeat imaging studies for both patients found an increased lesion size and peritumoral enhancement; thus, both patients underwent emergent craniotomy for complete lesion resection. Intraoperatively, both lesions had zones of markedly different tumoral texture. On histologic analysis, both lesions showed metastatic lung adenocarcinoma contained within the primary petroclival meningioma. Conclusion Skull base TTM is a rare entity for which no specific management guidelines have been created. Therefore, even if the imaging characteristics suggest a more benign process, skull base TTM should remain high on the differential diagnosis for patients with a known primary cancer and new-onset, rapidly progressive, neurologic deficits. Close clinical follow-up with short-interval repeat imaging in this subset of patients might prevent misdiagnosis and facilitate prompt treatment.

OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. The objective of this study was to identify risk factors associated with recurrence of dAVF after putative cure. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) data were retrospectively reviewed. All patients with angiographic cure after treatment and subsequent angiographic follow-up were included. The primary outcome was recurrence, with risk factor analysis. Secondary outcomes included clinical outcomes, morbidity, and mortality associated with recurrence. Risk factor analysis was performed comparing the group of patients who experienced recurrence with those with durable cure (regardless of multiple recurrences). Time-to-event analysis was performed using all collective recurrence events (multiple per patients in some cases). RESULTS Of the 1077 patients included in the primary CONDOR data set, 457 met inclusion criteria. A total of 32 patients (7%) experienced 34 events of recurrence at a mean of 368.7 days (median 192 days). The recurrence rate was 4.5% overall. Kaplan-Meier analysis predicted long-term recurrence rates approaching 11% at 3 years. Grade III dAVFs treated with endovascular therapy were statistically significantly more likely to experience recurrence than those treated surgically (13.3% vs 0%, p = 0.0001). Tentorial location, cortical venous drainage, and deep cerebral venous drainage were all risk factors for recurrence. Endovascular intervention and radiosurgery were associated with recurrence. Six recurrences were symptomatic, including 2 with hemorrhage, 3 with nonhemorrhagic neurological deficit, and 1 with progressive flow-related symptoms (decreased vision). CONCLUSIONS Recurrence of dAVFs after putative cure can occur after endovascular treatment. Risk factors include tentorial location, cortical venous drainage, and deep cerebral drainage. Multimodality therapy can be used to achieve cure after recurrence. A delayed long-term angiographic evaluation (at least 1 year from cure) may be warranted, especially in cases with risk factors for recurrence.

OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120–1038.5 days). CONCLUSIONS With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.

OBJECTIVE Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time. RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001). CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

Background Pituitary apoplexy is defined as a sudden neurologic deficit owing to infarction or hemorrhage within the pituitary gland. We report a rare case of apoplexy manifesting with cerebral infarction due to direct compression of the internal carotid artery (ICA) and review the literature. Case Description A 31-year-old man presented with sudden-onset headache, right hemiparesis, decreased left monocular visual acuity, and a nasal visual field deficit of the left eye. Computed tomography angiography revealed evidence of a hyperdense sellar/suprasellar mass with stenosis of the cavernous and supraclinoid segments of the ICAs bilaterally. Magnetic resonance angiography performed the following day showed complete occlusion of the left cervical ICA and cystic changes of the sellar and suprasellar mass suggestive of pituitary hemorrhage. The patient underwent urgent endoscopic endonasal decompression of the mass, and postoperative digital subtraction angiography demonstrated restored flow within the left cervical ICA. Conclusions Of 29 previously published cases of cerebral infarction due to pituitary apoplexy, the majority of cases were related to direct ICA compression. Vascular compression is associated with a high rate of mortality (24%) and should be treated urgently by surgical decompression in cases of severe or progressive neurologic symptoms.

BackgroundMany neurointerventionalists have transitioned to transradial access (TRA) as the preferred approach for neurointerventions as studies continue to demonstrate fewer access site complications than transfemoral access. However, radial artery spasm (RAS) remains one of the most commonly cited reasons for access site conversions. We discuss the benefits, techniques, and indications for using the long radial sheath in RAS and present our experience after implementing a protocol for routine use.MethodsA retrospective review of all patients undergoing neurointerventions via TRA at our institution from July 2018 to April 2020 was performed. In November 2019, we implemented a long radial sheath protocol to address RAS. Patient demographics, RAS rates, radial artery diameter, and access site conversions were compared before and after the introduction of the protocol.Results747 diagnostic cerebral angiograms and neurointerventional procedures in which TRA was attempted as the primary access site were identified; 247 were performed after the introduction of the long radial sheath protocol. No significant differences in age, gender, procedure type, sheath sizes, and radial artery diameter were seen between the two cohorts. Radial anomalies and small radial diameters were more frequently seen in patients with RAS. Patients with clinically significant RAS more often required access site conversion (pConclusionIn our experience, we have found that the use of long radial sheaths significantly reduces the need for access site conversions in patients with RAS during cerebral angiography and neurointerventions.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare benign lesions that can arise anywhere within the central nervous system. The etiology of these lesions remains unknown and diagnosis is made on pathohistological analysis. We present the case of a 35-year-old male patient with a history of epilepsy since childhood who was evaluated for refractory seizures. MRI revealed a small lesion in the left-posterior temporal lobe suspected to be a cavernoma. A gross total resection of the lesion was achieved via a left temporal craniotomy and pathological analysis revealed CAPNON. At 6 months follow-up, the patient remained neurologically intact and his seizures had ceased.

Background Transradial access (TRA) has recently gained traction as the preferred approach in a variety of neurointerventions after studies have demonstrated equivalent outcomes with fewer complications than transfemoral access (TFA). However, multiple access sites are occasionally necessary when simultaneous selective catheterization of 2 vessels is required. We present the first cases detailing bilateral TRA for complex posterior circulation interventions. Case Descriptions All neuroendovascular cases in which bilateral TRA was obtained at the University of Miami/Jackson Health System were reviewed. Two patients, each with complex left vertebral artery aneurysms, were identified. In each case, bilateral TRA was chosen because 1) left vertebral artery catheterization via right TRA can be technically challenging; 2) simultaneous catheterization of both vertebral arteries was felt to be necessary; 3) prior angiograms had demonstrated that the subclavian arteries would provide the most direct, anatomically feasible access route; and 4) the primary surgeon preferred to avoid TFA. Right TRA and left distal transradial access via the anatomic snuffbox were obtained in both cases to allow both arms to sit on the operator side of the table. Neither patient experienced any perioperative complications. Conclusions Bilateral TRA can be an effective method for catheterizing both vertebral arteries during complex posterior circulation interventions and obviates the need for TFA when multiple arterial access sites are required. Furthermore, distal transradial access allows the left hand to remain more anatomically neutral while being positioned on the right side of the table so that both access sites remain ergonomically favorable for the interventionalist.

OBJECTIVEUntreated hydrocephalus poses a significant health risk to children in the developing world. In response to this risk, global neurosurgical efforts have increasingly focused on endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) in the management of infantile hydrocephalus in low- and middle-income countries (LMICs). Here, the authors report their experience with ETV/CPC at the Hospital Bernard-Mevs/Project Medishare (HBMPM) in Port-au-Prince, Haiti.METHODSThe authors conducted a retrospective review of a series of consecutive children who had undergone ETV/CPC for hydrocephalus over a 1-year period at HBMPM. The primary outcome of interest was time to ETV/CPC failure. Univariate and multivariate analyses using a Cox proportional hazards regression were performed to identify preoperative factors that were associated with outcomes.RESULTSOf the 82 children who underwent ETV/CPC, 52.2% remained shunt free at the last follow-up (mean 6.4 months). On univariate analysis, the ETV success score (ETVSS; p = 0.002), success of the attempted ETV (p = 0.018), and bilateral CPC (p = 0.045) were associated with shunt freedom. In the multivariate models, a lower ETVSS was independently associated with a poor outcome (HR 0.072, 95% CI 0.016–0.32, p < 0.001). Two children (2.4%) died of postoperative seizures.CONCLUSIONSAs in other LMICs, ETV/CPC is an effective treatment for hydrocephalus in children in Haiti, with a low but significant risk profile. Larger multinational prospective databases may further elucidate the ideal candidate for ETV/CPC in resource-poor settings.

BackgroundThe transradial approach (TRA) has gained increasing popularity for neuroendovascular procedures. However, the experience with TRA in neuroangiography is still in early stages in most centers, and the safety and feasibility of this approach have not been well established. The purpose of this study is to report the safety and feasibility of TRA for neuroendovascular procedures.MethodsWe reviewed charts from six institutions in the USA to include consecutive patients who underwent diagnostic or interventional neuroendovascular procedures through TRA from July 2018 to July 2019. Collected data included baseline characteristics, procedural variables, complications, and whether there was a crossover to transfemoral access.ResultsA total of 2203 patients were included in the study (age 56.1±15.2, 60.8% women). Of these, 1697 (77%) patients underwent diagnostic procedures and 506 (23%) underwent interventional procedures. Successfully completed procedures included aneurysm coiling (n=97), flow diversion (n=89), stent-assisted coiling (n=57), balloon-assisted coiling (n=19), and stroke thrombectomy (n=76). Crossover to femoral access was required in 114 (5.2%). There were no major complications related to the radial access site. Minor complications related to access site were seen in 14 (0.6%) patients.ConclusionIn this early stage of transforming to the ‘radial-first’ approach for neuroendovascular procedures, TRA was safe with low complication rates for both diagnostic and interventional procedures. A wide range of procedures were completed successfully using TRA.

Telopea speciosissima, the New South Wales waratah, is an Australian endemic woody shrub in the family Proteaceae. Waratahs have great potential as a model clade to better understand processes of speciation, introgression and adaptation, and are significant from a horticultural perspective. Here, we report the first chromosome-level genome for T. speciosissima. Combining Oxford Nanopore long-reads, 10x Genomics Chromium linked-reads and Hi-C data, the assembly spans 823 Mb (scaffold N50 of 69.0 Mb) with 97.8% of Embryophyta BUSCOs "Complete". We present a new method in Diploidocus (https://github.com/slimsuite/diploidocus) for classifying, curating and QC-filtering scaffolds, which combines read depths, k-mer frequencies and BUSCO predictions. We also present a new tool, DepthSizer (https://github.com/slimsuite/depthsizer), for genome size estimation from the read depth of single-copy orthologues and estimate the genome size to be approximately 900 Mb. The largest 11 scaffolds contained 94.1% of the assembly, conforming to the expected number of chromosomes (2n = 22). Genome annotation predicted 40,158 protein-coding genes, 351 rRNAs and 728 tRNAs. We investigated CYCLOIDEA (CYC) genes, which have a role in determination of floral symmetry, and confirm the presence of two copies in the genome. Read depth analysis of 180 "Duplicated" BUSCO genes using a new tool, DepthKopy (https://github.com/slimsuite/depthkopy), suggests almost all are real duplications, increasing confidence in the annotation and highlighting a possible need to revise the BUSCO set for this lineage. The chromosome-level T. speciosissima reference genome (Tspe_v1) provides an important new genomic resource of Proteaceae to support the conservation of flora in Australia and further afield.

Background and Purpose: Since the publication of ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), outcomes in treated and untreated patients with unruptured arteriovenous malformation have been thoroughly compared. However, no prior analysis of ARUBA patients has sought to identify risk factors for perioperative stroke. Improved understanding of risks within the ARUBA cohort will help clinicians apply the study’s findings in a broader context. Methods: The National Institute of Neurological Disorders and Stroke database was queried for all data relating to ARUBA patients, including demographics, interventions undertaken, and timing of stroke. Retrospective cohort analysis was performed with the primary outcome of perioperative stroke in patients who underwent endovascular intervention, and stroke risk was modeled with multivariate analysis. Results: A total of 64 ARUBA patients were included in the analysis. One hundred and fifty-ninth interventions were performed, and 26 (16%) procedures resulted in stroke within 48 hours of treatment. Posterior cerebral artery supply (adjusted odds ratio, 4.42 [95% CI, 1.23–15.9], P =0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20–50.3], P =0.03; 9.64 [95% CI, 1.36–68.4], P =0.04, respectively) were associated with increased perioperative stroke risk in patients who underwent endovascular intervention. Patients treated in the United States or Germany had a significantly lower stroke risk than patients treated in other countries (adjusted odds ratio, 0.18 [95% CI, 0.04–0.82], P =0.02). Conclusions: Knowing patient and lesion characteristics that increase risk during endovascular treatment can better guide clinicians managing unruptured brain arteriovenous malformation. Our analysis suggests risk of perioperative stroke is dependent on Spetzler-Martin grade and posterior-circulation arterial supply. Differences in regional treatment paradigms may also affect stroke risk.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72–84), compared with 63 years (54–74) for NHB, and 71 years (60–80) for NHW patients ( P P P P Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Fusiform middle cerebral artery (MCA) aneurysms that require treatment can often necessitate complex endovascular or microsurgical treatment. We present a case of a 25-yr-old female with an incidentally discovered left 14-mm fusiform MCA aneurysm incorporating the frontal MCA trunk origin in its dome. The location and anatomy were not favorable for endovascular treatment with flow diversion. The patient was offered continued observation or microsurgical treatment. Direct clipping of this aneurysm was not possible. After a thorough discussion of the risks, benefits, indications, and natural history of the lesion, the patient desired to have the aneurysm treated given her young age, location, size of the aneurysm, and the significant clinical experience of the treating team in bypass surgery. The patient underwent superficial temporal artery to frontal M2 (STA-FM2) direct bypass for flow replacement followed by microsurgical trapping and clip ligation. The patient was maintained on antiplatelet therapy preoperatively and postoperatively. The patient had a transient aphasia and mild right upper extremity weakness (4/5) in the immediate postoperative period, which fully recovered by the time of patient discharge. The case presentation, surgical anatomy, technique, and postoperative course and outcome are reviewed. The different strategies for bypass and clip ligation are reviewed with particular focus on the anatomic constraints for each bypass configuration. The outcomes of bypass surgery for MCA aneurysms are reviewed.1-7 The patient gave verbal consent for participating in the procedure, surgical video, and publication of their image.

The radial access route has significantly lower complications compared to the femoral access route. Often users have become used to the femoral approach and its attendant complications but it is worth reviewing that despite its minimally invasive nature as opposed to open craniotomy, endovascular transfemoral access is certainly not without risk. These risks include life threatening retroperiotenal hematoma formation and local hematoma formation as well as limb threatening occlusion of the femoral artery, which is an end artery thus must be urgently revascularlized in the event of compromise. The complications of femoral access are reviewed as well as strategies for management.

The majority of neurointerventions can be performed via the radial approach, even with the femoral catheters. The specific case set-up depends on the goals of the intervention. If using the femoral catheters, one is limited to the 6F and 8F systems. The former offers the protection of a radial sheath, the latter must be performed sheathlessly. The size of the radial artery and difficulty and support demands of the case dictate the preferred setup. With minimal experience, once diagnostic angiography is mastered, interventions can easily be learned. The technical pearls and nuances of performing complex neurointervention via the radial approach are reviewed.

Performing a mechanical thrombectomy via the radial approach is a critical skill to be learned in the armamentarium of the neurointerventionalist. In addition to potential safety advantages, patient anatomy often renders femoral access to the internal carotid artery impossible. Morbid obesity, severe aortic arch tortuosity, or aortofemoral occlusive disease can cause significant delays in accessing the target vessel or even complete failure. There are unique challenges to performing mechanical thrombectomy via the radial approach, given the need for speed and qualified metrics of technical success. The technical nuances and pearls of performing a mechanical thrombectomy via the radial approach are reviewed.

Over 20 years of investigation and experience have gone into pioneering the radial approach for cardiac interventions. This has shown the technique to be superior to the traditional transfemoral technique for a variety of reasons. Neurointerventionalists have until recently been unaware of this innovation and are only starting to use it in their practice. Most of the data from the interventional cardiology journey into radial access is unknown to the neurointerventionalist audience, and concepts that underpin radial access are unfamailiar. Even basic concepts such as radial arterial anatomy, collateral circulation of the hand, and low rates of ischemic complications have been siloed in the cardiology literature. The core rationale for the transradial approach is reviewed.

The room set-up and patient positioning of the transradial approach (TRA) are different from that of the transfemoral approach (TFA). This is critical to the success of transitioning a medical practice. The most important areas are keeping the hand tight on the patient’s hip, minimal hand supination, and building up the space next to the knee to provide a platform for the catheters to lie during a transradial procedure. The initial patient positioning, room set-up, access techniques, and medications are reviewed, including cocktail, puncture techniques and sheath placement, as well as setup and hand positioning for left radial access procedures.

The distal radial or “snuffbox” approach is a modification of the traditional radial approach that uses a more distal location of the radial artery for puncture. The radial artery at this location is beyond the palmer arch thus puncturing has a theoretically lower risk of hand or thumb ischemia. In addition, the hand is positioned in the neutral position so it is more comfortable for the patient. Finally, the compression times are shorter so the patient can be discharged earlier after diagnostic procedures. This was originally an interventional cardiology innovation because of the frequent use of left radial access in interventional cardiology, but the approach has benefits for right radial access in neurointervention as well. The patient positioning and technical nuances of the snuffbox approach are reviewed.

IntroductionTransradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions.MethodsA retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time.ResultsNineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications.ConclusionsLeft transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access.

BackgroundNumerous large randomized trials have shown a significant morbidity and mortality benefit with the transradial approach (TRA) over the transfemoral approach (TFA) for endovascular procedures. However, this technique is routinely avoided or aborted due to unfamiliarity with the technique and the associated anatomical difficulties that may be faced in this approach. The objective of this review is to identify both the common and uncommon challenges that may be encountered during a transradial approach for cerebrovascular catheterization and to provide tips and tricks to overcome the transradial learning curve.MethodA careful review of the literature and of all our transradial cases was carried out to identify the common challenges and complications that are encountered when using TRA for diagnostic cerebral angiography and neurointerventions.ResultsA stepwise approach is provided to prevent and manage common challenges including radial artery access failure, radial artery spasm, radial artery anomalies and tortuosity, radial artery occlusion, radial artery perforation and hematoma, subclavian tortuosity and anomalies, and catheter knots and kinks.ConclusionThe ability to recognize and navigate anatomical variations and complications unique to TRA will accelerate learning, decrease unnecessary morbidity and mortality, and further advance the neurovascular field.

Background Intracranial pseudoaneurysms (PSAs) are associated with high rupture and mortality rates and have traditionally been treated by parent vessel sacrifice. There has been recent interest in using flow-diverting devices for treatment of these complex lesions while preserving flow through the parent artery. The objective of this study is to examine the safety and efficacy of these devices in the treatment of intracranial PSA. Methods We performed a multi-institutional retrospective study of intracranial PSAs treated with the Pipeline Embolization Device (PED) between 2014 and 2017 at 7 institutions. Complications and clinical and radiographic outcomes were reviewed. Results A total of 19 patients underwent PED placement for intracranial PSA. Iatrogenic injury and trauma comprised most etiologies in our series. The mean pseudoaneurysm diameter was 8.8 mm, and 18 of 19 PSAs (95%) involved the internal carotid artery (ICA). Multiple PEDs were deployed in a telescoping fashion in 7 patients (37%). Of the 18 patients with follow up imaging, 14 (78%) achieved complete pseudoaneurysm obliteration and 2 achieved near-complete obliteration (11%). Two patients (11%) were found to have significant pseudoaneurysm progression on short-term follow-up and required ICA sacrifice. No patients experienced new neurologic deficits or deterioration secondary to PED placement. No patients experienced bleeding or rebleeding from PSA. Conclusions In well-selected patients, the use of flow-diverting stents may be a feasible alternative to parent vessel sacrifice. Given the high morbidity and mortality associated with PSA, we recommend short- and long-term radiographic follow-up for patients treated with flow-diverting stents.

Polyploidy resulting from whole genome duplication is common in plants and is increasingly being recognised as a critical factor in conservation actions, particularly when within-species variation in ploidy exists. Pomaderris (Rhamnaceae), a genus of 70 species endemic to Australia and New Zealand, has many species listed as threatened and that are subject to conservation management but of unknown ploidy. To provide a better understanding of polyploidy in the genus we sampled 36 of 70 species of Pomaderris and used flow cytometry to establish genome sizes and infer ploidy. Additionally, to examine within-species variation, we screened 104 individuals of eight rare species subject to conservation management. We did not find evidence for infraspecific variation in ploidy, suggesting that from a cytological perspective, conspecific individuals from the screened populations do not need to be kept geographically separated in conservation management. There is, however, considerable variation among species, with genome sizes suggesting the occurrence of diploidy, triploidy, tetraploidy and hexaploidy. Finding several species to be triploid but capable of seed production, we then explored reproductive biology using the flow cytometric seed screen. Results suggested that triploid species produce seeds asexually, as previously reported for two New Zealand congeners. While asexual reproduction through apomixis is generally a means of odd-ploid taxa overcoming sterility, we found that more than half of examined diploids and tetraploids also produced seeds asexually. Asexual reproduction means genetic diversity is potentially low, and these results should therefore be considered in future conservation actions and seed sampling designs.

Objective: Mechanical thrombectomy is the standard treatment for large vessel occlusion (LVO) in acute ischemic stroke (AIS) up to 6 h after onset. Recent trials have demonstrated a benefit for wake-up strokes and patients beyond 6 h. Methods: A systematic literature review was conducted for multicenter randomized clinical trials (RCTs) investigating endovascular stroke treatment using perfusion imaging to identify patients that may benefit from mechanical thrombectomy for AIS beyond 6 h of onset. Random effects meta-analysis was used to analyze the following outcomes: 90-day functional independence rates with modified Rankin Scale (mRS ≤2), 90-day mortality, and symptomatic intracranial hemorrhage (sICH) rates. Further stratification was carried out by age and presentation. Results: Two multicenter RCT’s were included as follows: DAWN and DEFUSE-3. Pooled 90-day functional independence rates favored endovascular management (odds ratio [OR] 5.01; P < 0.00001). Subgroup analysis demonstrated continued 90-day functional independence benefit for endovascular management regardless of age (≥80 years, OR 5.65, P = 0.01; ≤80 years, OR 4.92, P < 0.00001). When stratified for the manner of stroke discovery, 90-day functional independence rates favored endovascular management for wake-up strokes (OR 8.74, P < 0.00001) and known-time onset strokes (OR 5.08, 95% confidence interval [CI] 2.04–12.65, P = 0.0005), although no benefit was observed for unwitnessed strokes (OR 1.64, 95% CI 0.17–16.04, P = 0.67). No difference observed in 90-day mortality rates (OR 0.71; P = 0.14) or in SICH rates (OR 1.67; P = 0.29). Conclusions: This meta-analysis reinforces that endovascular management is superior to standard medical management alone for the treatment of AIS due to LVO beyond 6 h of onset in patients with perfusion-imaging selection.

Background The distal transradial approach (dTRA) is being widely adopted by interventional cardiologists, primarily owing to reduced morbidity and mortality from access site complications. The distal radial artery has advantages over standard radial access in relation to procedural positioning and radial artery preservation, particularly in patients who may require multiple angiograms. One disadvantage is the smaller diameter of the artery with more challenging puncture of a smaller, weaker artery. We demonstrate the feasibility of dTRA in 2 patients who underwent successful diagnostic angiography and mechanical thrombectomy. Case Description Two patients underwent dTRA for neurointerventions. In patient 1, a 5-F Glidesheath Slender and a Sim2 catheter were used for a 6-vessel cerebral angiogram. In patient 2, an 0.88-inch sheathless guide catheter was used to perform a mechanical thrombectomy. Successful hemostasis in both cases was achieved with a Safeguard Radial Compression Device; no complications were observed. Conclusions Neurovascular access via dTRA is feasible, and further exploration is warranted.

BackgroundThe transradial approach (TRA) to endovascular procedures decreases access site morbidity and mortality in comparison with the traditional transfemoral technique (TFA). Despite its improved safety profile, there is a concern that TRA is less favorable for neurointerventional procedures that require large coaxial systems to manage the small tortuous cerebral vessels.ObjectiveTo report our experience with TRA for flow diverter placement for treatment of unruptured cerebral aneurysms.MethodsWe performed a retrospective review of prospective institutional databases at two high-volume centers to identify 49 patients who underwent flow diversion for aneurysm treatment via primary TRA between November 2016 and November 2018. Patient demographics, procedural techniques, and clinical data were recorded.ResultsOf the 49 patients, 39 underwent successful flow diversion placement by TRA. Ten patients were converted to TFA after attempted TRA. There were no procedural complications. Reasons for failure included tortuosity in eight patients and severe radial artery spasm in two.ConclusionsIn the largest reported series to date of flow diverter deployment via TRA for aneurysm treatment, we demonstrate the technical feasibility and safety of the method. The most common reason for failure of TRA was an acute angle of left common carotid artery origin or left internal carotid artery tortuosity. Overall, our data suggest that increasing adoption of TRA is merited given its apparent equivalence to the current TFA technique and its documented reduction in access site complications.

BackgroundAnterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs.MethodsThe CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990–2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed.Results60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs.ConclusionMost ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

Background Reperfusion time influences patient outcome in mechanical thrombectomy for large vessel occlusion. We analyzed anatomic features that could be used to make preoperative and intraoperative decisions to minimize revascularization time. Methods We reviewed a prospectively maintained database for patients with stroke evaluated from February 2015 to July 2016. Patients received a score based on bovine arch, aortic arch, and internal carotid artery dolichoarteriopathy (B.A.D. score), which we correlated with procedural times and outcomes. Univariate analysis was performed to identify predictors of procedural times, revascularization, complications, and outcome. Relevant variables were assessed via multivariate regression. Results We identified 61 patients (31 men) who underwent transfemoral thrombectomy. Mean puncture to reperfusion time was 46 minutes. Age >75 years (odds ratio [OR] = 3.98; 95% confidence interval [CI], 1.17–13.54; P = 0.027) and high B.A.D. score (OR = 2.55; 95% CI, 1.17–5.57; P = 0.019) were significant predictors of puncture to reperfusion time >40 minutes. Mean puncture to first-pass time was 24 ± 14.2 minutes. Age >65 years (OR = 4.68; 95% CI, 1.07–20.55; P = 0.041) and high B.A.D. score (OR = 2.84; 95% CI, 1.18–6.85; P = 0.020) were independently predictive of time to first pass >20 minutes. Lower scores predicted higher Thrombolysis In Cerebral Infarction score (OR = 0.07; 95% CI, 0.01–0.81; P = 0.033). Higher scores predicted hemorrhagic transformation (OR = 4.8; 95% CI, 1.19–12.29; P = 0.024) and modified Rankin Scale score >4 (OR = 3.0; 95% CI, 1.15–7.92; P = 0.025) after thrombectomy. Conclusions Bovine variation, aortic arch type, and internal carotid artery dolichoarteriopathy are associated with increased revascularization time and poor outcomes in thrombectomy. We developed the B.A.D. score to predict reperfusion time and outcomes, demonstrating need for preoperative anatomic evaluation to guide treatment.

Background Dural arteriovenous fistulas (DAVFs) are pathologic vascular connections that shunt dural arterial flow directly to dural venous drainage. Only a few isolated case reports describe syncope on presentation. We report the first case of DAVF causing recurrent, progressive syncope in an otherwise asymptomatic patient. Case report A female in her late 20s presented with a 9-year history of syncopal episodes and was found to have a DAVF. Syncopal episodes were exacerbated by positional changes, strenuous activity and emotional stressors. Symptoms occurred upon wakening and lasted for 2 to 3 hours before she was able to regain functionality. Physical examination revealed no abnormalities. Magnetic resonance imaging of the brain showed no irregularities. Magnetic resonance angiography revealed abnormal serpiginous structures in the left jugular foramen which communicated with the ascending pharyngeal branch of the left external carotid artery. Cerebral angiogram disclosed a left jugular bulb DAVF supplied by the left ascending pharyngeal and left occipital arteries. The DAVF was successfully managed by progressive endovascular embolization with coils and Onyx 34. On clinical follow-up evaluation, the patient had no further episodes of dizziness or syncope. Conclusion We present an atypical case of DAVF in a patient presenting with recurrent syncope. Only 4 cases of DAVF causing syncope have been reported, all in combination with other neurological symptoms. In comparison, we report a unique case of DAVF presenting solely with recurrent syncope, a previously undocumented finding in the literature. Our case adds to other reports of nonspecific DAVF presentations and highlights the importance of considering this etiology.

Introduction: Previous studies have reported that Hispanic stroke patients have limited access to mechanical thrombectomy (MT) compared to other ethnic groups. This has resulted in worse stroke outcomes in this group. However, limited data is available about the outcomes of MT in Hispanic patients. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR) that combined the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. Consecutive patients who underwent MT were included in these analyses and patients were divided into 2 groups (Hispanics vs. non-Hispanics). Baseline features, time from symptom onset, thrombolysis receipt, final thrombolysis in cerebral infarction (TICI) score, symptomatic hemorrhage, and 90-day functional outcomes (measured by modified Rankin scale-mRS) were compared between Hispanic and non-Hispanics patients. A generalized linear model with logit link was used to assess the relationship between ethnicity and favorable outcomes at 90-day (mRS 0-2) controlling for confounders. Results: We included 2015 patients in these analyses. Of those, 285 (14.1%) were Hispanic. As shown in table 1, Hispanic patients were older (72 vs. 70, p=0.007), more likely to have diabetes (41.1% vs. 26.5%, p Conclusion: Hispanic patients receiving MT have higher rate of stroke risk factors including diabetes and hypertension. Moreover, Hispanic ethnicity was independently associated with lower probability of favorable 90-day outcome.