A systematic review of the effects of temperature and precipitation on pollen concentrations and season timing, and implications for human health.

Climate and weather directly impact plant phenology, affecting airborne pollen. The objective of this systematic review is to examine the impacts of meteorological variables on airborne pollen concentrations and pollen season timing. Using PRISMA methodology, we reviewed literature that assessed whether there was a relationship between local temperature and precipitation and measured airborne pollen. The search strategy included terms related to pollen, trends or measurements, and season timing. For inclusion, studies must have conducted a correlation analysis of at least 5 years of airborne pollen data to local meteorological data and report quantitative results. Data from peer-reviewed articles were extracted on the correlations between seven pollen indicators (main pollen season start date, end date, peak date, and length, annual pollen integral, average daily pollen concentration, and peak pollen concentration), and two meteorological variables (temperature and precipitation). Ninety-three articles were included in the analysis out of 9,679 articles screened. Overall, warmer temperatures correlated with earlier and longer pollen seasons and higher pollen concentrations. Precipitation had varying effects on pollen concentration and pollen season timing indicators. Increased precipitation may have a short-term effect causing low pollen concentrations potentially due to "wash out" effect. Long-term effects of precipitation varied for trees and weeds and had a positive correlation with grass pollen levels. With increases in temperature due to climate change, pollen seasons for some taxa in some regions may start earlier, last longer, and be more intense, which may be associated with adverse health impacts, as pollen exposure has well-known health effects in sensitized individuals.

Impact of prescription drugs on second fragility fractures among US Medicare patients.

Drugs that increase the risk of fracture are commonly prescribed to survivors of a fragility fracture. This study shows that starting new high-risk medications after fracture increases the risk of a second, potentially preventable fracture. For most drug classes, however, it is safe to continue medications taken before the fracture. INTRODUCTION: Most patients who survive a fragility fracture are subsequently exposed to prescription drugs that have been linked to increased fracture risk. This study was designed to quantify the extent to which current prescribing practices result in potentially preventable second fractures. METHODS: We analyzed a cohort of 138,526 Medicare beneficiaries who returned to the community after a fragility fracture. Post-fracture drug use was defined using retail pharmacy fills. The risk of second fracture associated with individual drug classes was analyzed using Cox proportional hazard models. Data were further analyzed to determine whether there is a difference in risk between continuing previous therapy and initiating new therapy after fracture. RESULTS: Many drug classes previously identified as increasing fracture risk were not associated with increased fracture risk in this cohort. Discontinuing therapy at the time of fracture was only beneficial for patients taking selective serotonin reuptake inhibitors; however, initiating therapy in previous non-users increased second fracture risk for five classes of drugs (selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, proton pump inhibitors, and non-benzodiazepine hypnotics). CONCLUSION: Discontinuing high-risk drugs after fracture was not generally protective against subsequent fractures. Preventing the addition of new medications may result in greater improvements in post-fracture care.

Regional anesthesia decreases complications and resource utilization in shoulder arthroplasty patients.

BACKGROUND: Regional anesthesia can be used as part of the anesthetic to optimize anesthesia and analgesia during shoulder arthroplasty, but little is known about the overall effect that regional anesthesia has on perioperative outcomes and resource utilization. We hypothesized that regional anesthesia may decrease complication rates and resource utilization in shoulder arthroplasty patients. METHODS: We examined administrative data from 588 US hospitals from 2010 to 2015. Logistic regression was used to examine the relationship between type of anesthesia and perioperative complications. RESULTS: Among patients who underwent shoulder arthroplasty, 79.1% (53,243) had general anesthesia alone, 17.8% (12,011) had general anesthesia and a nerve block, and 3.1% (2062) had a nerve block alone. Overall, the complication rate was 13.3% and 30-day mortality was 1.2 per 1000 (95% CI 0.9, 1.4). In adjusted analyses, patients who had general anesthesia alone (compared to general anesthesia and nerve block) had a 16% increase in all cause infectious complications (OR 1.16, 95% CI: 1.03, 1.31) and were 2.6 times more likely to develop pulmonary complications (OR 2.6, 95% CI: 1.14, 5.78). General anesthesia alone (relative to either block only or general anesthesia and block) was associated with substantial increases in the likelihood of blood transfusions, intensive care unit transfers, and prolonged length of stay. CONCLUSION: Patients receiving regional anesthesia for shoulder arthroplasty may have a reduction in perioperative complications, the need for intensive care unit transfers, blood transfusions, and prolonged hospital stays.

Second fractures among older adults in the year following hip, shoulder, or wrist fracture.

UNLABELLED: We report on second fracture occurrence in the year following a hip, shoulder or wrist fracture using insurance claims. Among 273,330 people, 4.3 % had a second fracture; risk did not differ by first fracture type. Estimated adjusted second fracture probabilities may facilitate population-based evaluation of secondary fracture prevention strategies. INTRODUCTION: The purpose of this study was estimate second fracture risk for the older US population in the year following a hip, shoulder, or wrist fracture. METHODS: Observational cohort study of Medicare fee-for-service beneficiaries with an index hip, shoulder, or wrist fragility fracture in 2009. Time-to-event analyses using Cox proportional hazards models to characterize the relationship between index fracture type (hip, shoulder, wrist) and patient factors (age, gender, and comorbidity) on second fracture risk in the year following the index fracture. RESULTS: Among 273,330 individuals with fracture, 11,885 (4.3 %) sustained a second hip, shoulder or wrist fracture within one year. Hip fracture was most common, regardless of the index fracture type. Comparing adjusted second fracture risks across index fracture types reveals that the magnitude of second fracture risk within each age-comorbidity group is similar regardless of the index fracture. Men and women face similar risks with frequently overlapping confidence intervals, except among women aged 85 years or older who are at greater risk. CONCLUSIONS: Regardless of index fracture type, second fractures are common in the year following hip, shoulder or wrist fracture. Secondary fracture prevention strategies that take a population perspective should be informed by these estimates which take competing mortality risks into account.

N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 µL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning.

Mineralocorticoid receptor mRNA expression is increased in human hippocampus following brief cerebral ischaemia.

BACKGROUND: We have previously reported that neuronal endangerment in vitro and hypothermic transient global ischaemia in vivo each result in increased mineralocorticoid receptor (MR) expression. In both models MR induction is associated with increased neuronal survival, and blocking MR signalling reduces neuronal survival. Furthermore, transgenic overexpression of human MR promotes neuronal survival both in vitro and in vivo. AIMS: Here we have assessed whether brief periods of cerebral ischaemia in human subjects, such as occurs in cardiac arrest from which successful resuscitation is achieved, are associated with a sustained increase in hippocampal MR mRNA expression. METHODS: Human post-mortem brain sections from patients who had died in the weeks following cardiac arrest were analysed for MR mRNA expression by in situ hybridization. RESULTS: Sustained upregulation of MR mRNA expression was observed in the dentate gyrus region of human hippocampus following a brief episode of cerebral ischaemia. CONCLUSIONS: This confirms that MR mRNA expression is regulated following neuronal injury in human brain, and suggests that the benefits of increased MR expression seen in animal models of ischaemia may also be observed in humans.

The Neuropathology of HIV/AIDS.

The introduction of Highly Active Anti-retroviral Therapy (HAART) has resulted in significant decreases in morbidity and mortality for subjects infected with HIV. The brain is a major target organ for HIV resulting in significant neuropathological changes in most HIV infected subjects and a wide range of clinical neurological symptoms including HIV associated dementia. In the pre-HAART era HIV associated dementia was a common complication of AIDS. However, since the introduction of HAART the incidence of HIV associated dementia has fallen, but the prevelance has actually risen due to the increasing number of infected subjects and increased life expectancy. HIV associated dementia correlates most closely with neuroinflammation rather than directly with viral load or HIV encephalitis. HIV related clinical and neuropathological disorders are more prevalent in drug abusers than in other risk groups. This review focuses on the shifting pathology observed in HIV infected subjects since the introduction of HAART, discussing the clinical manifestations of these and the influence of confounding factors such as drug abuse and Hepatitis C co-infection.

An immune control model for viral replication in the CNS during presymptomatic HIV infection.

The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P < 0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P < 0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.

Infective dementias.

A wide range of infectious diseases can result in dementia, although the identity and nature of these diseases has changed over time. Two of the most significant current groups in terms of scientific complexity are HIV/AIDS and prion diseases. In these disorders, dementia occurs either as a consequence of targeting the brain and selectively damaging neurones, or by an indirect effect of neuroinflammation. In prion diseases, both direct neurotoxicity and neuroinflammation may act to result in neuronal damage. In HIV encephalitis, the progression of the dementia is slower, perhaps reflecting indirect damage that appears to result from neuroinflammation as a main cause of neuronal death. An ever-increasing range of model systems is now available to study the neuronal damage in infectious dementias, ranging from cell culture systems to animal models, some of which, particularly in the case of prion diseases, are very well characterised and amenable to controlled manipulation in terms of both host and agent parameters. As valuable as these experimental models are, they do not allow a direct approach to an understanding of dementia, the complexities of which cannot readily be studied in vitro or in animal models, but they do allow studies of interventions and therapeutic strategies. This review summarises the current state of knowledge regarding the major infective dementias.

Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions.

Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

Brain damage and axonal injury in a Scottish cohort of neonatal deaths.

Despite the clinical and medicolegal significance attached to perinatal asphyxia, the neuropathological basis of this condition remains obscure. There are very few studies in the literature which correlate the pathological findings in neonatal brains with detailed epidemiological data, and none which are population based. In a Scotland-wide study of neonatal deaths, 70 brains have been examined. On the basis of glial and macrophage reactions, we previously identified infants with putative antepartum brain damage in this cohort and have related these reactions to signs of birth asphyxia. The present study explores the extent of neuronal/axonal injury in these infants since this is likely to be the basis for neurological deficits in surviving infants. We have also investigated these brains for beta-amyloid precursor protein (betaAPP) positivity to determine whether this is a useful marker of neuronal injury in neonates. Neuronal eosinophilia and karyorrhexes were detected in 43% and 27% of the cohort, respectively; maximally in the subiculum and ventral pons, but often present elsewhere. White matter damage was detected in 24% of cases but without classic cystic lesions of periventricular leucomalacia. betaAPP positivity was present in neuronal soma in 52% of cases and, in axons, in 27% of cases, and was seen from as early as 25-weeks gestation. Axonal bulbs were clearly delineated by betaAPP positivity and were usually located in the cerebral white matter and internal capsule, and infrequently in the brain stem. Although white matter damage and betaAPP axonal positivity were often detected in the same cases (P = 0.034), these features also occurred independently of each other. Both neuronal karyorrhexes and white matter betaAPP positivity were significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both betaAPP and glial fibrillary acidic protein proved useful in detecting neuropathological features which escaped detection on routine examination, particularly in preterm infants. The presence together of recent and older damage in individual brains suggests that there is an ongoing neuronal response to cerebral insults. We find that betaAPP is a useful marker of white matter damage in the neonatal brain. Immunopositivity for betaAPP in these circumstances is not attributable to inflicted or accidental trauma. While birth-related trauma cannot be ruled out, hypoxia/ischaemia is a likely cause in these infants. However, the exact pathogenesis of neuronal/axonal injury in the neonatal brain remains unclear.

Demonstration of the existence, and partial characterization, of a cell-surface beta-hexosaminidase from rat splenocytes.

Rat splenocytes are shown to exhibit cell-surface located beta-N-acetylglucosaminidase and beta-galactosidase activities. Preincubation experiments, solubilization experiments and chemical cross-linking experiments show that these enzymatic activities are indeed cell-surface localized. The solubilization and partial purification of the beta-N-acetylglucosaminidase activity is reported. Kinetic studies of the partially purified material with a variety of competitive inhibitors at several pH values suggest that at physiological pH the cell surface beta-N-acetylglucosaminidase may function as a carbohydrate binding protein rather than as a glycosidase.

Conformational changes of glyceraldehyde-3-phosphate dehydrogenase induced by the binding of NAD. A unified model for positive and negative cooperativity.

The fluorescence of the natural coenzyme, NADH, is used to monitor the environment of the nicotinamide moiety at the active centre of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Changes of the fluorescence quantum yield and polarization of a small amount of NADH, totally bound by an excess of enzyme, show that at half-saturation of the oligomer with NAD a conformational change is induced which affects the active centre regions of the remaining subunits. This conformational transition is not effected by adenosine diphosphoribose, suggesting that the binding of the nicotinamide moiety of NAD to two subunits is essential for the change of tertiary structure of the remaining subunits that causes the observed changes of the fluorescence properties of the ADH "tracer probe". It is suggested that this conformational transition of the oligomer is responsible for the major decrease of affinity for NAD which occurs at half-saturation, and possibly for the activation by NAD+ of the reductive dephosphorylation reaction catalysed by the enzyme. It is also suggested, by analogy with haemoglobin, that the molecular basis of the negative cooperativity may be the creation of additional intersubunit bonds during the binding of the first two NAD molecules to the tetramer, and a change from a "relaxed" quaternary structure to a "tense" structure at half-saturation.

Studies of coenzyme binding to rabbit muscle glyceraldehyde-3-phoshate dehydrogenase.

The binding of NAD+, NADH and adenosine diphosphoribose (Ado-PP-Rib) to a stable, highly active and nucleotide-free preparation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) has been studied. All three nucleotides quench the protein fluorescence to the same extent when they bind to the enzyme, and this property has been used to measure the dissociation constants for the two high-affinity binding sites for the nucleotides. The results indicate negative interactions between, or non-identify of, these two binding sites, to which NAD+ and NADH bind with similar affinity. The binding of NAD+ to the enzyme has been studied by spectrophotometric titrations at 360 nm. It appears that the binding of NAD+ to each of the four subunits of the enzyme contributes equally to the intensity of this 'Racker' band. The dissociation constants associated with the binding of the third and fourth molecules of NAD+ estimated from such titrations confirm some previous estimates. The binding of NADH to the enzyme causes a decrease of intensity of the absorbance of the coenzyme at 340 nm, and the dissociation constants for binding of the third and fourth molecules of NADH have been estimated from spectrophotometric titrations. They are the same as those for NAD+. Judging by the apparent dissociation constants, negative interactions on binding the third molecule of NAD+ or NADH are more marked than those associated with the binding of the second and fourth molecules, suggesting that a major conformational change occurs at half-saturation of the tetramer with coenzyme.

Glutamate dehydrogenase in Reye's syndrome. Evidence for the presence of an altered enzyme in serum with increased susceptibility to inhibition by GTP.

The glutamate dehydrogenase activity found in the serum of patients with Reye's syndrome is shown to be inhibited about 1000-fold more potently by GTP than is the normal human enzyme. 1 mM ADP, which with the normal enzyme effectively reverses GTP inhibition, has no effect in the GTP inhibition of the Reye's syndrome serum activity.

The partial amino acid sequence of the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum: implications for the evolution and structural basis of coenzyme specificity.

The amino acid sequence is reported for CNBr and tryptic peptide fragments of the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum. Together with the N-terminal sequence, these make up about 75% of the total sequence. The sequence shows extensive similarity with that of the NADP(+)-dependent glutamate dehydrogenase of Escherichia coli (52% identical residues out of the 332 compared) allowing confident placing of the peptide fragments within the overall sequence. This demonstrated sequence similarity with the E. coli enzyme, despite different coenzyme specificity, is much greater than the similarity (31% identities) between the GDH's of C. symbiosum and Peptostreptococcus asaccharolyticus, both NAD(+)-linked. The evolutionary implications are discussed. In the 'fingerprint' region of the nucleotide binding fold the sequence Gly X Gly X X Ala is found, rather than Gly X Gly X X Gly. The sequence found here has previously been associated with NADP+ specificity and its finding in a strictly NAD(+)-dependent enzyme requires closer examination of the function of this structural motif.

Influence of HAART on HIV-related CNS disease and neuroinflammation.

Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era. In this autopsy study we examined post-HAART cases in Edinburgh for the presence of HIV-related pathology and in well-treated cases for evidence of neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas of the brain for cognitive functioning and compared pre- and post-HAART cases for neuroinflammatory status. We find evidence, post-HAART, that there is a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated cases showed significantly higher levels of CD68-positive microglia/macrophages than in control brains (p = 0.004), and in the hippocampus levels were significantly higher than those seen in control cases, pre-HAART AIDS, and presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas examined were low in HAART-treated cases. We conclude that there is a surprising degree of ongoing neuroinflammation in HAART-treated patients, particularly in the hippocampus. This may pose a threat for the future health of individuals maintained long-term on HAART therapy.

Evidence of a breakdown of corticostriatal connections in Parkinson's disease.

Dendritic spines are important structures which receive synaptic inputs in many regions of the CNS. The goal of this study was to test the hypothesis that numbers of dendritic spines are significantly reduced on spiny neurones in basal ganglia regions in Parkinson's disease as we had shown them to be in a rat model of the disease [Exp Brain Res 93 (1993) 17]. Postmortem tissue from the caudate and putamen of patients suffering from Parkinson's disease was compared with that from people of a similar age who had no neurological damage. The morphology of Golgi-impregnated projection neurones (medium-sized spiny neurones) was examined quantitatively. The numerical density of dendritic spines on dendrites was reduced by about 27% in both nuclei. The size of the dendritic trees of these neurones was also significantly reduced in the caudate nucleus from the brains of PD cases and their complexity was changed in both the caudate nucleus and the putamen. Dendritic spines receive crucial excitatory input from the cerebral cortex. Reduction in both the density of spines and the total length of the remaining dendrites is likely to have a grave impact on the ability of these neurones to function normally and may partly explain the symptoms of the disorder.

Application of a Novel Brain Arteriovenous Malformation Endovascular Grading Scale for Transarterial Embolization.

BACKGROUND AND PURPOSE: The advent of modern neuroendovascular techniques has highlighted the need for a simple, effective, and reliable brain arteriovenous malformation endovascular grading scale. A novel scale of this type has recently been described. It incorporates the number of feeding arteries, eloquence, and the presence of an arteriovenous fistula component. Our aim is to assess the validity of this grading scale. MATERIALS AND METHODS: We retrospectively reviewed all suspected brain arteriovenous malformations at Massachusetts General Hospital from 2005 to 2013, identifying 126 patients who met the inclusion criteria. Spearman correlations between endovascular and Spetzler-Martin grading scales and long-term outcomes were performed. Median endovascular grades were compared between treatment modalities and endovascular outcomes. Binary regression analysis was performed with major endovascular complications as a dichotomized dependent variable. Intraclass correlation coefficients were calculated for interobserver reliability of the endovascular grading scale. RESULTS: A significant Spearman correlation between the endovascular grade and the Spetzler-Martin grade was demonstrated (ρ = 0.5, P < .01). Differences in the median endovascular grades between the endovascular cure (median = 2) and endovascular complication groups (median = 4) (P < .05) and between the endovascular cure and successful multimodal treatment groups (median = 3) (P < .05) were demonstrated. The endovascular grade was the only independent predictor of complications (OR = 0.5, P < .01). The intraclass correlation coefficient of the endovascular grade was 0.71 (P < .01). CONCLUSIONS: Validation of a brain arteriovenous malformation endovascular grading scale demonstrated that endovascular grades of ≤II were associated with endovascular cure, while endovascular grades of ≤III were associated with multimodal cure or significant lesion reduction and favorable outcome. The endovascular grade provides useful information to refine risk stratification for endovascular and multimodal treatment.