Racial and Ethnic Differences in Mortality and Functional Outcomes Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Ischemic and hemorrhagic stroke incidence tends to be higher among minority racial and ethnic groups. The effect of race and ethnicity following an aneurysmal subarachnoid hemorrhage (aSAH) remains poorly understood. Thus, we aimed to explore the association between race and ethnicity and aSAH outcomes. METHODS: Single-center retrospective review of patients with aSAH from January 2009 to March 2023. Primary outcome was in-hospital mortality. Secondary outcomes included delayed cerebral ischemia, cerebral infarction, radiographic and symptomatic vasospasm, pulmonary complications, epileptic seizures, external ventricular drain placement, and modified Rankin Scale score at discharge and 3-month follow-up. Associations between race and ethnicity and outcomes were assessed using binary and ordinal regression models, with multivariable models adjusted for significant covariates. RESULTS: A total of 1325 patients with subarachnoid hemorrhage presented to our center. Among them, 443 cases were excluded, and data from 882 patients with radiographically confirmed aSAH were analyzed. Distribution by race and ethnicity was 40.8% (n=360) White, 31.4% (n=277) Hispanic, 22.1% (n=195) Black, and 5.7% (n=50) Asian. Based on Hunt-Hess and modified Fisher grade, aSAH severity was similar among groups (P=0.269 and P=0.469, respectively). In-hospital mortality rates were highest for Asian (14.0%) and Hispanic (11.2%) patients; however, after adjusting for patient sex, age, health insurance, smoking history, alcohol and substance abuse, and aneurysm treatment, the overall likelihood was comparable to White patients. Hispanic patients had higher risks of developing cerebral infarction (adjusted odds ratio, 2.17 [1.20-3.91]) and symptomatic vasospasm (adjusted odds ratio, 1.64 [1.05-2.56]) than White patients and significantly worse discharge modified Rankin Scale scores (adjusted odds ratio, 1.44 [1.05-1.99]). Non-White patients also demonstrated a lower likelihood of 0 to 2 discharge modified Rankin Scale scores (adjusted odds ratio, 0.71 [0.50-0.98]). No significant interactions between race and ethnicity and age or sex were found for in-hospital mortality and functional outcomes. CONCLUSIONS: Our study identified significant differences in cerebral infarction and symptomatic vasospasm risk between Hispanic and White patients following aSAH. A higher likelihood of worse functional outcomes at discharge was found among non-White patients. These findings emphasize the need to better understand predisposing risk factors that may influence aSAH outcomes. Efforts toward risk stratification and patient-centered management should be pursued.

Association Between Neutrophil-Lymphocyte Ratio and 30-Day Infection and Thrombotic Outcomes After Intraventricular Hemorrhage: A CLEAR III Analysis.

BACKGROUND: Serum neutrophil-lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH) and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. We hypothesized that NLR is associated with 30-day infection and thrombotic events after ICH. METHODS: We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial. The study exposure was the serum NLR obtained at baseline and on days 3 and 5. The coprimary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined through adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization. RESULTS: Among the 500 patients enrolled in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, we included 303 (60.6%) without missing data on differential white blood cell counts at baseline. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR ascertained at baseline (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.07, p = 0.03) and NLR ascertained at day 3 were associated with infection (OR 1.15; 95% CI 1.05-1.20, p = 0.001) but not with thrombotic events. Conversely, NLR at day 5 was associated with thrombotic events (OR 1.07, 95% CI 1.01-1.13, p = 0.03) but not with infection (OR 1.13; 95% CI 0.76-1.70, p = 0.56). NLR at baseline was not associated with either outcome. CONCLUSIONS: Serum NLR ascertained at baseline and on day 3 after randomization was associated with 30-day infection, whereas NLR obtained on day 5 was associated with thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.

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.

Timing of anticoagulation for venous thromboembolism after recent traumatic and vascular brain Injury.

Currently, there is no consensus guideline for initiating anticoagulation in patients with a traumatic or vascular brain injury. Initiating anticoagulation for management of venous thromboembolism (VTE) can vary significantly from 72 hours to 30 weeks due to the risk of hemorrhagic complications. The purpose of this study is to compare clinical outcomes using modified Rankin Score (mRS) in a patient population with early (≤ 3 days) versus late (> 3 days) initiation of therapeutic anticoagulation from the time VTE was diagnosed. This retrospective study included patients with a traumatic or vascular brain injury who developed either deep vein thrombosis (DVT) or pulmonary embolism (PE). Use of anticoagulation prior to admission, diagnosis with VTE on admission, or patients with a non-brain injury were exclusion criteria. Secondary outcomes measured were all-cause mortality, length of stay, and reasons for early interruption of anticoagulation. Therapeutic anticoagulation was started early in 76 (74%) patients compared to late initiation in 27 (26%) patients. Baseline characteristics were similar between the two groups. The mRS score 0-3 versus 4-6 was similar in patients who received early anticoagulation versus those who received it later. However, there was a trend favoring better outcomes in the early group [mRS 4-6; 78% vs. 93%; p = 0.085] and in subgroup analysis of patients with VTE diagnosed 4-7 days [mRS 4-6; 26% vs. 56%; p = 0.006] compared to the late group. In univariate and multivariable logistic regression, only age was associated with a significant worse outcome (median, IQR) 36 years (24-50) vs. 58 years (44-65) OR 1.07 (1.03-1.12); p < 0.001. In this study, early initiation of anticoagulation did not worsen clinical outcomes.

Characterization of Cerebral Hemodynamics with TCD in Patients Undergoing VA-ECMO and VV-ECMO: a Prospective Observational Study.

BACKGROUND: Extracorporeal membrane oxygenation has a high risk of acute brain injury and resultant mortality. Transcranial Doppler characterizes cerebral hemodynamics in real time, but limited data exist on its interpretation in ECMO. Here, we report TCD mean flow velocity and pulsatility index in a large ECMO population. METHODS: This was a prospective cohort study at a tertiary care center. The patients were adults on venoarterial ECMO or venovenous ECMO undergoing TCD studies. RESULTS: A total of 135 patients underwent a total of 237 TCD studies while on VA-ECMO (n = 95, 70.3%) or VV-ECMO (n = 40, 29.6%). MFVs were captured reliably (approximately 90%) and were similar to a published healthy cohort in all vessels except the internal carotid artery. Presence of a recordable PI was strongly associated with ECMO mode (57% in VA vs. 95% in VV, p < 0.001). Absence of TCD pulsatility was associated with intraparenchymal hemorrhage (14.7 vs. 1.6%, p = 0.03) in VA-ECMO patients. CONCLUSIONS: Transcranial Doppler analysis in a single-center cohort of VA-ECMO and VV-ECMO patients demonstrates similar MFVs and PIs. Absence of PIs was associated with a higher frequency of intraparenchymal hemorrhage and a composite bleeding event. However, cautious interpretation and external validation is necessary for these findings with a multicenter study with a larger sample size.

Systemic inflammatory markers of persistent cerebral edema after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH. METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early brain edema score' (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3-5 days [T3] and 6-8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2). RESULTS: Of the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002-1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE. CONCLUSIONS: We identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH.

Early Systemic Glycolytic Shift After Aneurysmal Subarachnoid Hemorrhage is Associated with Functional Outcomes.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) leads to a robust systemic inflammatory response. We hypothesized that an early systemic glycolytic shift occurs after aSAH, resulting in a unique metabolic signature and affecting systemic inflammation. METHODS: Control patients and patients with aSAH were analyzed. Samples from patients with aSAH were collected within 24 h of aneurysmal rupture. Mass spectrometry-based metabolomics was performed to assess relative abundance of 16 metabolites involved in the tricarboxylic acid cycle, glycolysis, and pentose phosphate pathway. Principal component analysis was used to segregate control patients from patients with aSAH. Dendrograms were developed to depict correlations between metabolites and cytokines. Analytic models predicting functional outcomes were developed, and receiver operating curves were compared. RESULTS: A total of 122 patients with aSAH and 38 control patients were included. Patients with aSAH had higher levels of glycolytic metabolites (3-phosphoglycerate/2-phosphoglycerate, lactate) but lower levels of oxidative metabolites (succinate, malate, fumarate, and oxalate). Patients with higher clinical severity (Hunt-Hess Scale score ≥ 4) had higher levels of glyceraldehyde 3-phosphate and citrate but lower levels of α-ketoglutarate and glutamine. Principal component analysis readily segregated control patients from patients with aSAH. Correlation analysis revealed distinct clusters in control patients that were not observed in patients with aSAH. Higher levels of fumarate were associated with good functional outcomes at discharge (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.15-2.82) in multivariable models, whereas higher levels of citrate were associated with poor functional outcomes at discharge (OR 0.36, 95% CI 0.16-0.73) and at 3 months (OR 0.35, 95% CI 0.14-0.81). No associations were found with delayed cerebral ischemia. Levels of α-ketoglutarate and glutamine correlated with lower levels of interleukin-8, whereas fumarate was associated with lower levels of tumor necrosis factor alpha. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage results in a unique pattern of plasma metabolites, indicating a shift toward glycolysis. Higher levels of fumarate and lower levels of citrate were associated with better functional outcomes. These metabolites may represent targets to improve metabolism after aSAH.

CSF and serum inflammatory response and association with outcomes in spontaneous intracerebral hemorrhage with intraventricular extension: an analysis of the CLEAR-III Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) results in a cascade of inflammatory cell activation with recruitment of peripheral leukocytes to the brain parenchyma and surrounding the hematoma. We hypothesized that in patients with ICH and intraventricular hemorrhage (IVH), a robust cerebrospinal fluid (CSF) inflammatory response occurs with leukocyte subtypes being affected by alteplase treatment and contributing to outcomes. METHODS: Serum and CSF cell counts from patients in the phase 3 Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) trial were analyzed. CSF leukocytes were corrected for the presence of red blood cells. Trends in cell counts were plotted chronologically. Associations were evaluated between serum and CSF leukocyte subtypes and adjudicated functional outcome (modified Rankin Scale; mRS) at 30 and 180 days and bacterial infection according to treatment with intraventricular alteplase versus saline. RESULTS: A total of 279 and 292 patients had ≥3 differential cell counts from serum and CSF, respectively. CSF leukocyte subtypes evolved during IVH resolution with a significantly augmented inflammatory response for all subtypes in alteplase- compared to saline-treated patients. CSF leukocyte subtypes were not associated with detrimental effect on functional outcomes in the full cohort, but all were associated with poor 30-day outcome in saline-treated patients with IVH volume ≥20 mL. Higher serum lymphocytes were associated with good functional outcomes (mRS 0-3) in the entire cohort and saline-treated but not alteplase-treated group. Conversely, increased serum neutrophil-to-lymphocyte ratio (NLR) in the entire cohort and saline group was associated with worse functional outcomes. Higher median serum lymphocytes were associated with the absence of infection at 7 days. CONCLUSIONS: Aseptic CSF inflammation after IVH involves all leukocyte subtypes. Serum lymphocytes may be associated with better outcomes by mitigating infection. Alteplase augments the inflammatory response without affecting outcomes.

Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19.

OBJECTIVE: Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes. METHODS: Plasma samples from 57 subjects at < 48 h of COVID-19 hospitalization, and 20 matched controls were interrogated for the levels of six BIMs-including GFAP, S100B, Syndecan-1, UCHLI, MAP2 and NSE, two EIMs-including sICAM1 and sVCAM1. Additionally, several cytokines/chemokines were analyzed by multiplex. Statistical and bioinformatics methods were used to measure differences in the marker profiles across (a) COVID-19 vs. controls and (b) men vs. women. RESULTS: Three BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (p < 0.05) elevated in the COVID-19 cohort compared to controls. Bioinformatics analysis reveal a stronger positive association between BIM/CC/EIMs in the COVID-19 cohort. Analysis across sex revealed that several BIMs and CCs including NSE, IL10, IL15 and IL8 were significantly (p < 0.05) higher in men compared to women. Men also expressed a more robust BIM/ EIM/CC association profile compared to women. CONCLUSION: The acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization are suggestive of brain and endothelial injury. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.

Antithrombotic Therapy for Stroke Patients with Cardiovascular Disease.

Prevention of ischemic stroke relies on the use of antithrombotic medications comprising antiplatelet agents and anticoagulation. Stroke risk is particularly high in patients with cardiovascular disease. This review will focus on the role of antithrombotic therapies in the context of different types of cardiovascular disease. We will discuss oral antiplatelet medications and both IV and parental anticoagulants. Different kinds of cardiovascular disease contribute to stroke via distinct pathophysiological mechanisms, and the optimal treatment for each varies accordingly. We will explore the mechanism of stroke and evidence for antithrombotic therapy in the following conditions: atrial fibrillation, prosthetic heart values (mechanical and bioprosthetic), aortic arch atherosclerosis, congestive heart failure (CHF), endocarditis (infective and nonbacterial thrombotic endocarditis), patent foramen ovale (PFO), left ventricular assist devices (LVAD), and extracorporeal membrane oxygenation (ECMO). While robust data exist for antithrombotic use in conditions such as atrial fibrillation, optimal treatment in many situations remains under active investigation.

Acute Brain Injury in Postcardiotomy Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: Acute brain injury (ABI) is common in venoarterial extracorporeal membrane oxygenation (VA-ECMO). One of the most common indications for use of VA-ECMO is postcardiotomy shock (PCS). The authors aimed to characterize the prevalence of ABI and its association with outcomes in this population. DESIGN: prospective observational. SETTING: Single-center tertiary care university hospital. PARTICIPANTS: Fifty-two consecutive patients treated for PCS with VA-ECMO from November 2017 to March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median age of patients was 64 (interquartile range 44-84), 62% were male. Of 52 PCS patients treated with extracorporeal membrane oxygenation, 38% (n = 20) experienced acute brain injury. Ischemic stroke was the most common (n = 13, 25%). Patients with central versus peripheral cannulation experienced more ischemic and hemorrhagic strokes (8% v 38%, p = 0.04). Patients with intracardiac thrombus experienced more brain injury (n = 4, 8% p = 0.02). The in-hospital mortality in patients with brain injury was 90% (n = 18/20) compared to 78% (n = 25/32) in patients without brain injury. CONCLUSIONS: ABI is common in postcardiotomy VA-ECMO and associated with worse outcome. Patients with central recanalization experienced the majority of acute strokes. Intracardiac thrombus was significantly associated with acute brain injury.

Perihematomal Edema After Intracerebral Hemorrhage in Patients With Active Malignancy.

Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (ß=1.29 [95% CI, 1.58-1.30] P=1.30×10-5) and platelet transfusion (ß=15.67 [95% CI, 3.61-27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] P=0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes.

AIMS: Osteocalcin contributes to the regulation of endocrine system. However, the association between osteocalcin and ketosis has not been evaluated. We thus aimed to explore the relationship between total osteocalcin and risk of ketosis in type 2 diabetes (T2DM). MATERIALS AND METHODS: We identified 6157 diabetes patients from Shanghai Tenth People's Hospital between 1 January 2011 and 1 March 2017. Six hundred eight subjects were enrolled in the retrospective cross-sectional study: 304 T2DM patients with ketosis whose age, gender, and body mass index were matched with 304 T2DM patients without ketosis. A further retrospective nested case-control study was conducted in 252 T2DM patients without ketosis for a mean duration of 21.58 ± 12.43 months to investigate the occurrence of ketosis. RESULTS: Osteocalcin levels were negatively correlated with blood ketones (adjusted r = -0.263) and urine ketones (adjusted r = -0.183). The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio [95% CI] = 2.56 [0.80-8.17], 3.71 [0.90-15.29], 10.77 [2.63-44.15], 23.81 [4.32-131.17] per osteocalcin quintile, respectively). Ketosis occurred in 17 of the 252 T2DM patients during follow-up. The Cox regression analysis indicated that osteocalcin was an independent protective factor against development of ketosis (adjusted hazard ratio [95% CI]: 0.668 [0.460-0.971]). CONCLUSIONS: Total osteocalcin can be used as a predictor of ketosis in T2DM.

Angiographic Blush after Mechanical Thrombectomy is Associated with Hemorrhagic Transformation of Ischemic Stroke.

BACKGROUND AND PURPOSE: Risk factors for hemorrhagic transformation of ischemic stroke after mechanical thrombectomy (MT) are not well established. We conducted a study to determine if prominent angiographic cerebral vascularity following recanalization with thrombectomy (angiographic blush) is associated with hemorrhagic transformation. METHODS: Using the Cornell AcutE Stroke Academic Registry, we identified stroke patients who had thrombectomy and achieved recanalization of anterior circulation large-vessel occlusion between 2012 and 2015. The exposure variable was presence of angiographic blush after recanalization, defined as capillary blush with or without early venous drainage. The primary outcome was volume of hemorrhagic transformation on brain imaging after thrombectomy, as determined by semiautomated volumetric analysis on computed tomography or magnetic resonance imaging among those adjudicated to have hemorrhagic conversion by neuroradiology investigators blinded to angiography results. Using a doubly robust estimator with propensity scores and outcome regression adjusting for demographics and known risk factors for hemorrhagic transformation, we evaluated whether angiographic blush after recanalization is associated with an increased volume of hemorrhagic transformation. RESULTS: Among 48 eligible patients, 31 (64.6%) had angiographic blush and 26 (54.2%) had radiographic hemorrhagic transformation (mean volume, 7.6 ml). Patients with angiographic blush averaged lower thrombolysis in cerebral infarction scores and more often received intravenous thrombolysis. In adjusted analysis, angiographic blush was associated with an increased volume of hemorrhagic transformation: mean volume, 10.3ml (95% CI, 3.7-16.9 ml) with blush versus 1.8ml (95% Confidence Interval (CII = Confidence Interval), 0.1-3.4 ml) without (P = .01). CONCLUSIONS: Presence of angiographic blush after MT was independently associated with the volume of hemorrhagic transformation.

Neutrophil-Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth. METHODS: We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil-lymphocyte ratio) and 24-hour PHE growth. RESULTS: A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (ß, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil-lymphocyte ratio was correlated with PHE growth (ß, 0.22; standard error, 0.08; P=0.005). CONCLUSIONS: Higher neutrophil-lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission.

Effects of melatonin on cardiovascular diseases: progress in the past year.

PURPOSE OF REVIEW: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland. Numerous studies have suggested that melatonin plays an important role in various cardiovascular diseases. In this article, recent progress regarding melatonin's effects on cardiovascular diseases is reviewed. RECENT FINDINGS: In the past year, studies have focused on the mechanism of protection of melatonin on cardiovascular diseases, including myocardial ischemia-reperfusion injury, myocardial hypoxia-reoxygenation injury, pulmonary hypertension, hypertension, atherosclerosis, valvular heart diseases, and other cardiovascular diseases. SUMMARY: Studies have demonstrated that melatonin has significant effects on ischemia-reperfusion injury, myocardial chronic intermittent hypoxia injury, pulmonary hypertension, hypertension, valvular heart diseases, vascular diseases, and lipid metabolism. As an inexpensive and well tolerated drug, melatonin may be a new therapeutic option for cardiovascular disease.

Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice.

BACKGROUND: Melatonin can regulate lipid metabolism, increase insulin sensitivity, regulate glucose metabolism and reduce body weight. This study is aimed to determine the effects and mechanism of action of melatonin on non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD) induced obese mice. METHODS: NAFLD was induced by HFD in C57BL/6 mice. A total of 24 mice were randomly assigned to 4 groups. Groups A and B were fed with HFD for 36 weeks while groups C and D were fed with a regular diet (RD). During the last 12 weeks, Groups A and C were treated with 10 mg/kg melatonin while Groups B and D were treated with water in the same volume by intragastric administration. Body and liver weight, blood glucose, serum transaminases and lipid levels, and markers of hepatic inflammation were measured. Histological analyses were also performed on liver tissue. RESULTS: After 12 weeks of treatment with melatonin, body weights (Group A: before 53.11 ± 0.72 vs after 12w treatment 39.48 ± 0.74) and liver weights (A 1.93 ± 0.09 g vs B 2.92 ± 0.19 g vs C 1.48 ± 0.09 g vs D 1.49 ± 0.10 g), fasting plasma glucose, alanine transaminase (A 24.33 ± 11.90 IU/L vs B 60.80 ± 10.18 IU/L vs C 13.01 ± 3.49 IU/L vs D 16.62 ± 2.00 IU/L), and low-density cholesterol (A 0.24 ± 0.06 mmol/L vs B 1.57 ± 0.10 mmol/L vs C 0.28 ± 0.06 mmol/L vs D 0.29 ± 0.03 mmol/L) were significantly decreased in HFD mice. HFD fed mice treated with melatonin showed significantly less liver steatosis. Treatment of HFD fed mice with melatonin led to a significant decrease in the expression of TNF-α, IL-1ß, and IL-6 measured using quantitative real-time polymerase chain reaction (qRT-PCR). HFD fed mice demonstrated increased phosphorylation of P38 and JNK1/2, which was reduced by melatonin treatment. CONCLUSIONS: The study concluded that melatonin could improve NAFLD by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the MAPK-JNK/P38 signaling pathway.

Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver.

BACKGROUND: Aberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice. RESULTS: We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria. CONCLUSIONS: We conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species.