The role of hyperglycemia in the outcome of intracerebral hemorrhage: A causative analysis.

BACKGROUND: Hyperglycemia in the acute phase of intracerebral hemorrhage (ICH) has been associated with poor functional outcomes, however all interventions to lower glucose have yielded neutral or negative results. We attempt an explanation of the causal role of hyperglycemia in ΙCH outcome using generalized structural equation modeling. MATERIALS AND METHODS: Consecutive primary ICH patients admitted to an academic hospital between 2007 and 2018 were identified. Patients with missing baseline or follow up CT scans and without 90 day follow up status were excluded. We constructed a causal model accounting for pre-defined markers of ICH severity to evaluate the association between mean 72 h glucose and 90 day functional outcome measured by modified Rankin Scale, dichotomized as favorable ≤2 or unfavorable >2. RESULTS: Primary analyses included 410 patients (70.4 ± 13.8years, 43 % female). Mean 72 h glucose was 137.5 ± 33.4mg/dl and 102 (25 %) patients were diabetic. On univariable analysis, higher glucose levels were negatively correlated with favorable outcome (p < 0.0001). However in the structural equation model, this relationship was significantly attenuated (p = 0.06) after accounting for the causal effect of diabetes (p < 0.0001), hematoma volume (p < 0.0001), intraventricular extension (p = 0.01) and Glasgow coma scale (p = 0.001) on glucose levels. On secondary analyses stratifying by diagnosis of diabetes, higher glucose levels were negatively correlated with favorable outcome in patients without diabetes (p = 0.04), but not in patients with diabetes (p = 0.35). CONCLUSIONS: Hyperglycemia may be a downstream effect of other markers of ICH severity, particularly among patients without diabetes, suggesting a possible explanation for the limited evidence of glucose lowering interventions in outcome.

Survey of Current Management Practices for Carotid Webs.

Background: Carotid webs are thick, fibrous intimal bands that appear as intraluminal shelf-like defects at the carotid bifurcation on vascular imaging. These lesions are a potential underrecognized cause of cryptogenic ischemic stroke. Although the recognition of carotid webs has increased, no evidence-based treatment guidelines are available. We surveyed subspecialists across multiple neurologic disciplines to assess the state of current clinical practice. Methods: An 8-question multiple-choice style survey of neurologists and radiologists assessed familiarity with this disease entity, preferred imaging modalities, and management strategies for asymptomatic and symptomatic (producing stroke) carotid webs. Responses were collected through SurveyMonkey software via anonymous responses to a posted survey link on the Society of Neurointerventional Surgery website in addition to invitation emails sent to colleagues in corresponding fields. Results: Of the 74 total respondents, 64% identified as neurointerventionalists. Respondents identified computed tomography angiography as the most commonly used imaging modality to place carotid webs in the differential diagnosis (57% of respondents' preference), while conventional digital subtraction angiogram was the preferred modality to confirm a web (54% of respondents' preference). Respondents preferred single and dual antiplatelet therapy to manage asymptomatic and acute stroke-producing carotid webs, while invasive treatment was most commonly sought for webs producing recurrent strokes. Conclusion: Familiarity with carotid webs varied across subspecialties. We found some consensus among respondents on the imaging modality preferred to identify webs, on asymptomatic carotid web management, and on recurrently symptomatic (multiple strokes) carotid web management. Less consistency was seen regarding preferences for confirmatory imaging and management of acutely symptomatic (initial stroke) carotid webs.

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage.

BACKGROUND: Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for "airway protection" with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. METHODS: We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. RESULTS: Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48-7.22; p < 0.0001) and 4.32 (95% CI 2.5-7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. CONCLUSION: In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.

Acute Ischemic Stroke Therapy Overview.

The treatment of acute ischemic stroke has undergone dramatic changes recently subsequent to the demonstrated efficacy of intra-arterial (IA) device-based therapy in multiple trials. The selection of patients for both intravenous and IA therapy is based on timely imaging with either computed tomography or magnetic resonance imaging, and if IA therapy is considered noninvasive, angiography with one of these modalities is necessary to document a large-vessel occlusion amenable for intervention. More advanced computed tomography and magnetic resonance imaging studies are available that can be used to identify a small ischemic core and ischemic penumbra, and this information will contribute increasingly in treatment decisions as the therapeutic time window is lengthened. Intravenous thrombolysis with tissue-type plasminogen activator remains the mainstay of acute stroke therapy within the initial 4.5 hours after stroke onset, despite the lack of Food and Drug Administration approval in the 3- to 4.5-hour time window. In patients with proximal, large-vessel occlusions, IA device-based treatment should be initiated in patients with small/moderate-sized ischemic cores who can be treated within 6 hours of stroke onset. The organization and implementation of regional stroke care systems will be needed to treat as many eligible patients as expeditiously as possible. Novel treatment paradigms can be envisioned combining neuroprotection with IA device treatment to potentially increase the number of patients who can be treated despite long transport times and to ameliorate the consequences of reperfusion injury. Acute stroke treatment has entered a golden age, and many additional advances can be anticipated.

Circulating adipocytokines and chronic kidney disease.

BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

Hepatitis C and recurrent treatment-resistant acute ischemic stroke.

Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C-associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention.

Short-term bleeding events observed with clopidogrel loading in acute ischemic stroke patients.

INTRODUCTION: The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity. METHODS: Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding). RESULTS: AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04). DISCUSSION: Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.

Elevated Plasma Factor VIII in Patients with Ischemic Stroke: Does it have any Association with Hypertensive Heart Disease?

BACKGROUND: Elevated factor VIII (FVIII) has been linked with higher risk of vascular events. We aimed to determine the relationship between FVIII and hypertension in patients with acute ischemic stroke. METHODS: FVIII levels and transthoracic echocardiogram reports were reviewed in patients with acute ischemic stroke who presented to our stroke center between July 2008 and September 2011. Presenting systolic and diastolic blood pressure, history of hypertention, left ventricular hypertrophy, diastolic dysfunction, and depressed left ventricular function (ejection fraction <50%) were compared in patients with normal and elevated FVIII levels. RESULTS: No differences in presenting blood pressure or frequency of hypertension history were found based on FVIII level. Patients with elevated FVIII had demonstrated a statistically significant higher frequency of diastolic dysfunction (64.8 vs. 43.6%, p=0.042) and a trend towards higher frequency of left ventricular hypertrophy (18.5 vs 5.1%, p=0.073). Median FVIII was significantly higher in patients with left ventricular hypertrophy (194.4 vs 152.9%, p=0.042) and diastolic dysfunction (180.5 vs 149.3%, p=0.031) than patients without these findings. CONCLUSIONS: Among patients with acute ischemic stroke, FVIII levels were higher when there was evidence of hypertensive heart disease. Synthesis of FVIII may be augmented by the ongoing presence of shear stress and could contribute to the higher risk of vaso-occlusive events in patients with elevated FVIII.