Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis.

BACKGROUND: Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. METHODS: Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019. RESULTS: Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01). CONCLUSION: SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Ultra-Early Hemostatic Therapy for Acute Intracerebral Hemorrhage: An Updated Review.

Intracerebral hemorrhage (ICH) is the second most common type of stroke, accounting for approximately 10-20% of all strokes, and is linked to severe neurological disability and death. Since the most accurate predictor of outcome in patients with ICH is hematoma volume, there is a great need for pharmacologic therapy that can reduce hematoma expansion and resultant mass effect and edema. This is especially critical within the ultra-early window of 3-4 hours after the presentation. Hemostatic therapies are exceptionally important for those patients taking antiplatelet or anticoagulant medications to reverse the effects of these medications and therefore prevent hematoma expansion. Furthermore, the recent publication of the 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage by the American Heart Association/American Stroke Association, the first update to the guidelines since 2012, underscores the importance of optimizing anticoagulation reversal for this population. The purpose of this selective, nonsystematic review is to examine current literature regarding the use of hemostatic therapies in ICH, with particular attention paid to antiplatelet, anticoagulation, and antifibrinolytic therapies.

Research considerations for prospective studies of patients with coma and disorders of consciousness.

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

BACKGROUND: Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. METHODS: We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3 h of onset], at 24 h, and at 72 h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. RESULTS: A total of 781 patients with supratentorial ICH (mean age 65 years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6 mL, p = 0.053) and PHE volumes (11.1 vs. 10.5 mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24 h (19.0 vs. 14.0 mL, p < 0.001; 22.2 vs. 15.7 mL, p < 0.001) and 72 h (16.0 vs. 11.8 mL, p < 0.001; 28.7 vs. 19.9 mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6 mL at 24 h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5 mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. CONCLUSIONS: Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

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

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

Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Exploring Hematoma Expansion Shift With Recombinant Factor VIIa: A Pooled Analysis of 4 Randomized Controlled Trials.

BACKGROUND: Hematoma expansion shift (HES) analysis can be used to assess the biological effect of a hemostatic therapy for intracerebral hemorrhage. In this study, we applied HES analysis to individual patient data from 4 randomized controlled trials evaluating rFVIIa (recombinant factor VIIa) 80 µg/kg to placebo. METHODS: We generated polychotomous strata of HES using absolute growth thresholds (≤0/<6/≥6 mL) and quintiles of percent volume change. The relationship between treatment and HES was assessed using proportional odds models. Differences in subgroups based on baseline volume (≥ or <20 mL), and time from symptom onset to treatment (≤ or >2 hours) were explored with testing for interactions. RESULTS: The primary analysis included 721 patients. At 24 hours, 36% (134/369) of rFVIIa-treated patients exhibited no hematoma expansion as compared with 25% of placebo (88/352)-treated patients. Significant expansion (≥6 mL) was reduced by 10% in those treated with rFVIIa-(adjusted common odds ratio [acOR], 0.57 [95% CI, 0.43-0.75]). An examination of percent change similarly showed a shift across the spectrum of expansion (acOR, 0.61 [95% CI, 0.47-0.80]). In both groups, mild-to-moderate expansion was observed in 38% to 47% of patients, depending on the threshold used. Differences in absolute HES between the rFVIIa and placebo groups were more pronounced in patients with baseline hemorrhage volumes ≥20 mL (acOR, 0.48 [95% CI, 0.30-0.76] versus <20 mL: acOR, 0.67 [95% CI, 0.47-0.95]; Pinteraction=0.02). No treatment interaction in patients treated within 2 or after 2 hours from onset was observed (acOR, 0.42 [95% CI, 0.19-0.91 versus >2 hours: acOR, 0.59 [95% CI, 0.44-0.79]; Pinteraction=0.30). CONCLUSIONS: The association between rFVIIa and hematoma growth arrest is most pronounced in patients with larger baseline volumes but is evident across the full spectrum of treated patients.

Sex differences in perihematomal edema volume and outcome after intracerebral hemorrhage.

Objective: To determine whether in patients with intracerebral hemorrhage (ICH) perihematomal edema (PHE) volume trajectories differ by sex. Methods: We conducted a post-hoc analysis of the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial that randomized patients with ICH to receive recombinant activated Factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial CT scans (at baseline [within 3 hours of onset], at 24, and at 72 hours). Generalized estimating equations examined interactions between sex, CT-timepoints, and FAST treatment-arm on PHE and ICH volumes. Mixed and multivariate logistic models examined associations between sex, PHE, and outcomes. Results: 781 with supratentorial ICH (mean age 65 years) were included. Compared to women (n=296), men (n=485) had similar median ICH (14.9 versus 13.6 ml, p=0.053), and PHE volumes (11.1 versus 10.5 ml, p=0.56) at baseline but larger ICH and PHE at 24 hours (19.0 versus 14.0, p<0.001; 22.2 versus 15.7, p<0.001) and 72 hours (16.0 versus 11.8, p<0.001; 28.7 versus 19.9, p<0.001). Men had higher absolute PHE expansion (p<0.001), and more hematoma expansion (growth ≥33% or 6 mL at 24 hours, 33% versus 22%, p<0.001). An interaction between sex and CT-timepoints on PHE (p<0.001) but not on ICH volumes confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio, 1.19, 95%-confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Conclusions: PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation. What is already known on this topic: Prior research has reported sex differences in intracerebral hemorrhage (ICH) characteristics and some studies suggest worse outcome after ICH in women. However, we do not have a good understanding whether there are sex differences in perihematomal edema (PHE) volume trajectories, or whether sex, independent of confounders, is associated with poor after ICH. What this study adds: In this post-hoc analysis of 781 patients with supratentorial ICH from the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial in which patients underwent brain CT imaging time-locked to symptom onset (within 3 hours of symptom onset, at 24 hours, and at 72 hours), men compared to women had similar ICH and PHE volumes at baseline, but larger ICH expansion and PHE expansion on follow up imaging. The PHE but not the ICH volume trajectory across scans was significantly higher in men than in women. While PHE expansion was associated with poor outcome at 90 days, outcome between the sexes was similar at 90 days, and sex was not associated with outcome. How this study might affect research practice or policy: The finding of heightened early PHE and ICH expansion in men may inform study design, patient recruitment strategies, and pre-specification of subgroup analyses in future interventional trials. The findings of this study also suggest that focusing on sex-specific factors may allow novel mechanistic insight into PHE, a major cause of secondary injury and poor outcome after ICH.

Impact of pre-treatment cerebral microbleeds on the outcomes of endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVE/AIM: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. RESULTS: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. CONCLUSIONS: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

Significant increase in mortality and risk of acute ischemic stroke in infective endocarditis patients with subarachnoid hemorrhage secondary to mycotic aneurysms.

Infective Endocarditis (IE) patients are known to have a variety of complications with one of the rarest, but serious being cerebral mycotic aneurysm, which can result in subarachnoid hemorrhage (SAH). Using the National In-Patient Sample database, we sought to determine the rate of acute ischemic stroke (AIS) and outcomes in IE- patients with and without SAH. In total, we identified 82,844 IE-patients from 2010 to 2016, of which 641 had a concurrent diagnosis of SAH. IE patients with SAH had a more complicated course, higher mortality rate (OR 4.65 CI 95% 3.9-5.5, P < 0.001), and worse outcomes. This patient population also had a significantly higher rate of AIS (OR 6.3 CI 95% 5.4-7.4, P < 0.001). Overall, 41.5% of IE-patients with SAH had AIS during their hospitalization as compared to 10.1% of IE only patients. IE-patients with SAH were more likely to undergo endovascular treatment (3.6%) with 0.8% of the IE patients with AIS undergoing mechanical thrombectomy. While IE-patients are at risk for various complications, our study suggests a significant increase in the mortality and risk of AIS in those with SAH.

Aneurysmal Subarachnoid Hemorrhage and Cardiac Related Fatality: Who Dies and Why?

Medical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH. We found that the most common complications in aSAH patients (N = 170, 869) were hydrocephalus (29.3%) and hyponatremia (17.3%). Cardiac arrest was the most common cardiac complication (3.2%) and was associated with the highest case fatality rate overall (82%). Patients with cardiac arrest also had the highest odds of in-hospital mortality [odds ratio (OR), 22.92; 95% confidence interval (CI), 19.24-27.30; P < 0.0001], followed by patients with cardiogenic shock (OR, 2.96; 95% CI, 2.146-4.07; P < 0.0001). Advanced age and National Inpatient Sample-SAH Severity Score were found to be associated with an increased risk of in-hospital mortality (OR, 1.03; 95% CI, 1.03-1.03; P < 0.0001 and OR, 1.70; 95% CI, 1.65-1.75; P < 0.0001, respectively). Renal and cardiac complications are significant factors to consider in aSAH management, with cardiac arrest being the strongest indicator of case fatality and in-hospital mortality. Further research is needed to characterize factors that have contributed to the decreasing trend in case fatality rates identified for certain complications.

Tissue Clock Beyond Time Clock: Endovascular Thrombectomy for Patients With Large Vessel Occlusion Stroke Beyond 24 Hours.

BACKGROUND AND PURPOSE: Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). METHODS: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). RESULTS: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0-2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. CONCLUSION: In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients' age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Early tracheostomy in patients undergoing mechanical thrombectomy for acute ischemic stroke.

PURPOSE: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT. METHODS: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay. RESULTS: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002). CONCLUSION: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications.

Ruptured arteriovenous malformation mortality: Incidence, risk factors, and inpatient outcome score.

BACKGROUND: Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH. OBJECTIVE: We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score. METHODS: This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. RESULTS: We identified 6496 patients with ruptured AVMs comparing them to 627,185 admitted with ICH. Mortality was lower for ruptured AVMs (11%) compared to ICH (22%) [p < 0.01]. Mortality associated factors were liver disease (OR 2.64, CI 1.81-3.85, p < .001), diabetes mellitus (OR 2.42, CI 1.38-4.22, p = 0.002), alcohol abuse (OR 1.81, CI 1.31-2.49, p = 0.001), hydrocephalus (OR 3.35 CI 2.81-4.00, p < 0.001), cerebral edema (OR 1.5, 1.25-1.85, p < 0.001), cardiac arrest (OR 15, CI 7.9-30, p < 0.001), and pneumonia (OR 1.93, CI 1.51-2.47, p < 0.001). A 0-5 ruptured AVM mortality score was developed: Cardiac arrest (=3), age >60 (=1), Black race (=1), chronic liver failure (=1) diabetes mellitus (=1), pneumonia (=1), alcohol abuse (=1) and cerebral edema (=1). Mortality increased with score. No patient with 5 or more points survived. CONCLUSION: The Ruptured AVM Mortality Score allows for risk stratification on patients with ICH due to ruptured AVM. This scale could prove useful in prognostication and patient education.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Association Between Soluble Intercellular Adhesion Molecule-1 and Intracerebral Hemorrhage Outcomes in the FAST Trial.

BACKGROUND: Neutrophil-mediated inflammation in the acute phase of intracerebral hemorrhage (ICH) worsens outcome in preclinical studies. sICAM-1 (soluble intercellular adhesion molecule-1), an inducible ligand for integrins and cell-cell adhesion molecules, is critical for neutrophil extravasation. We aimed to determine whether serum levels of sICAM-1 are associated with worse outcomes after ICH. METHODS: We conducted a post hoc secondary analysis of an observational cohort using data from the FAST trial (Factor-VII for Acute Hemorrhagic Stroke Treatment). The study exposure was the admission serum level of sICAM-1. The coprimary outcomes were mortality and poor outcome (modified Rankin Scale score 4-6) at 90 days. Secondary radiological outcomes were hematoma expansion at 24 hours and perihematomal edema expansion at 72 hours. We used multiple linear and logistic regression analyses to test for associations between sICAM-1 and outcomes, after adjustment for demographics, ICH severity characteristics, change in the systolic blood pressure in the first 24 hours, treatment randomization arm, and the time from symptom onset to study drug administration. RESULTS: Of 841 patients, we included 507 (60%) with complete data. Hematoma expansion occurred in 169 (33%), while 242 (48%) had a poor outcome. In multivariable analyses, sICAM-1 was associated with mortality (odds ratio, 1.53 per SD increase [95% CI, 1.15-2.03]) and poor outcome (odds ratio, 1.34 per SD increase [CI, 1.06-1.69]). In multivariable analyses of secondary outcomes, sICAM-1 was associated with hematoma expansion (odds ratio, 1.35 per SD increase [CI, 1.11-1.66]), but was not associated with log-transformed perihematomal edema expansion at 72 hours. In additional analyses stratified by treatment assignment, similar results were noted in the recombinant activated factor-VII arm, but not in the placebo arm. CONCLUSIONS: Admission serum levels of sICAM-1 were associated with mortality, poor outcome, and hematoma expansion. Given the possibility of a biological interaction between recombinant activated factor-VII and sICAM-1, these findings highlight the need to further explore the role of sICAM-1 as a potential marker of poor ICH outcomes.