Inpatient Outcomes of Cerebral Venous Thrombosis in Patients With Malignancy Throughout the United States.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT). METHODS: The 2016-2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality. RESULTS: Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes. CONCLUSION: Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Predictors of Outcomes and a Weighted Mortality Score for Moderate to Severe Subdural Hematoma.

As the incidence of subdural hematoma is increasing, it is important to understand symptomatology and clinical variables associated with treatment outcomes and mortality in this population; patients with subdural hematoma were selected from the National Inpatient Sample (NIS) Database between 2016 and 2020 using International Classification of Disease 10th Edition (ICD10) codes. Moderate-to-severe subdural hematoma patients were identified using the Glasgow Coma Scale (GCS). Multivariate regression was first used to identify predictors of in-hospital mortality and then beta coefficients were used to create a weighted mortality score. Of 29,915 patients admitted with moderate-to-severe subdural hematomas, 12,135 (40.6%) died within the same hospital admission. In a multivariate model of relevant demographic and clinical covariates, age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were independent predictors of mortality (p < 0.001 for all). Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were assigned a "1" in a weighted mortality score. The ROC curve for our model showed an area under the curve of 0.64. Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were predictive of mortality. We created the first clinically relevant weighted mortality score that can be used to stratify risk, guide prognosis, and inform family discussions.

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).

Acute Myocardial Injury in Spontaneous Intracerebral Hemorrhage: A Secondary Observational Analysis of the FAST Trial.

BACKGROUND: Acute myocardial injury is associated with poor outcomes in patients with acute ischemic stroke, but its prognostic significance in patients with spontaneous intracerebral hemorrhage remains unclear. We investigated whether acute myocardial injury and the direction of the cardiac troponin I (cTnI) change (rising versus falling) affect post-intracerebral hemorrhage outcomes. METHODS AND RESULTS: We re-analyzed the FAST (Factor-Seven-for-Acute-Hemorrhagic-Stroke) trial. Acute myocardial injury was defined as at least 1 cTnI value above the upper reference limit with a rise/fall of >20%. Logistic regression tested for associations (1) between acute myocardial injury (presence versus absence) and poor outcome (modified Rankin Scale 4-6) and mortality at 15 and 90 days; (2) among 3 groups (rising versus falling versus no acute myocardial injury) and outcomes. Among the 841 FAST participants, 785 patients were included. Acute myocardial injury was detected in 29% (n=227); 170 had rising cTnI. At 15 and 90 days, respectively, those with acute myocardial injury had higher odds of poor outcome (adjusted odds ratio) ([aOR] 2.3 [95% CI, 1.3-3.9]); and adjusted odds ratio 2.5 [95% CI, 1.6-3.9];, and higher odds of mortality (adjusted odds ratio 2.4 [95% CI, 1.4-4.3]; and adjusted odds ratio 2.2 [CI, 1.3-3.6]) than patients without. There was no interaction between FAST group assignment and myocardial injury, and associations between myocardial injury and outcomes were consistent across group assignments. Rising cTnI was associated with the highest risk of poor outcomes and mortality. CONCLUSIONS: In this secondary analysis of the FAST trial, acute myocardial injury was common and associated with poor outcomes. The direction of the cTnI change might provide additional risk stratification after intracerebral hemorrhage.

Code-ICH: A New Paradigm for Emergency Intervention.

PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) is the most devastating type of stroke, causing widespread disability and mortality. Unfortunately, the acute care of ICH has lagged behind that of ischemic stroke. There is an increasing body of evidence supporting the importance of early interventions including aggressive control of blood pressure and reversal of anticoagulation in the initial minutes to hours of presentation. This review highlights scientific evidence behind a new paradigm to care for these patients called Code-ICH. RECENT FINDINGS: While numerous trials aimed at decreasing hematoma expansion through single interventions had failed to show statistically significant effects on primary outcomes, time-sensitive, multifaceted, bundled care approaches have recently shown substantial promise in improving functional outcomes in patients with ICH. The concept of Code-ICH can serve as a structural platform for the practice of acute care neurology to continuously measure its performance, reflect on best practices, advance care, and address disparities.

Acute kidney injury in subarachnoid hemorrhage: Exploring its clinical significance and prognostic implications.

OBJECTIVES: Subarachnoid hemorrhage (SAH) from spontaneous aneurysm rupture is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in SAH patients. MATERIALS AND METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28. RESULTS: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89 %) had a comorbid diagnosis of AKI. SAH patients with AKI were older (p < 0.01) and more often obese (p < 0.01) compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p < 0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities. CONCLUSIONS: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to improve their chances of recovery.

Critical Care of Spinal Cord Injury.

PURPOSE OF REVIEW: Spinal cord injury (SCI) is a major cause of morbidity and mortality, posing a significant financial burden on patients and the healthcare system. While little can be done to reverse the primary mechanical insult, minimizing secondary injury due to ischemia and inflammation and avoiding complications that adversely affect neurologic outcome represent major goals of management. This article reviews important considerations in the acute critical care management of SCI to improve outcomes. RECENT FINDINGS: Neuroprotective agents, such as riluzole, may allow for improved neurologic recovery but require further investigation at this time. Various forms of neuromodulation, such as transcranial magnetic stimulation, are currently under investigation. Early decompression and stabilization of SCI is recommended within 24 h of injury when indicated. Spinal cord perfusion may be optimized with a mean arterial pressure goal from a lower limit of 75-80 to an upper limit of 90-95 mmHg for 3-7 days after injury. The use of corticosteroids remains controversial; however, initiation of a 24-h infusion of methylprednisolone 5.4 mg/kg/hour within 8 h of injury has been found to improve motor scores. Attentive pulmonary and urologic care along with early mobilization can reduce in-hospital complications.

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.

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.

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.

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.

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.