Outcomes of Nonagenarians with Acute Ischemic Stroke Treated with Intravenous Thrombolytics.

BACKGROUND: Nonagenarians are under-represented in thrombolytic trials for acute ischemic stroke (AIS). The effectiveness of intravenous thrombolytics in nonagenarians in terms of safety and outcome is not well established. MATERIALS AND METHODS: We used a multinational registry to identify patients aged 90 years or older with good baseline functional status who presented with AIS. Differences in outcomes-disability level at 90 days, frequency of symptomatic intracerebral hemorrhage (sICH), and mortality-between patients who did and did not receive thrombolytics were assessed using multivariable logistic regression, adjusted for prespecified prognostic factors. Coarsened exact matching (CEM) was utilized before evaluating outcome by balancing both groups in the sensitivity analysis. RESULTS: We identified 227 previously independent nonagenarians with AIS; 122 received intravenous thrombolytics and 105 did not. In the unmatched cohort, ordinal analysis showed a significant treatment effect (adjusted common odds ratio [OR]: .61, 95% confidence interval [CI]: .39-.96). There was an absolute difference of 8.1% in the rate of excellent outcome in favor of thrombolysis (17.4% versus 9.3%; adjusted ratio: .30, 95% CI: .12-.77). Rates of sICH and in-hospital mortality were not different. Similarly, in the matched cohort, CEM analysis showed a shift in the primary outcome distribution in favor of thrombolysis (adjusted common OR: .45, 95% CI: .26-.76). CONCLUSIONS: Nonagenarians treated with thrombolytics showed lower stroke-related disability at 90 days than those not treated, without significant difference in sICH and in-hospital mortality rates. These observations cannot exclude a residual confounding effect, but provide evidence that thrombolytics should not be withheld from nonagenarians because of age alone.

Investigation of the Association Between Carotid Artery Intima-Media Thickness (IMT) and Cardiac Risk Factors in Patients with Systemic Lupus Erythematosus.

BACKGROUND: The relationship between SLE and traditional risk factors for cardiovascular events was evaluated. METHODS: The data regarding sixty patients with SLE and 30 healthy controls (age and sex matched) were gathered using SLEDAI forms. Venous blood (10mL) from all the participants was examined for hs-CRP, homocysteine, VCAM1, CBC, anti-DNA antibody, C3, C4, low-density lipoprotein (LDL), cholesterol, FBS and triglyceride. The IMT of carotid arteries was determined bilaterally by ultrasound. Other measurements included insulin levels via Elisa (Linco/Millipore Corp) and the HOMA-IR index for insulin resistance. RESULTS: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively. The average IMT in the test group was directly related to serum levels of VCAM1 (p<0.001), homocysteine (p<0.001), cholesterol (p<0.009), LDL (p<0.001), TG (p<0.001), and FPG (p=0.004). The association between other risk factors, insulin resistance, carotid IMT and SLEDAI, was nonexistent. Mean insulin and insulin resistance levels in all the participants were 0.43±2.06 µU/mL and 0.09±0.44, respectively. There was no significant difference between the test and control groups regarding serum insulin and insulin resistance levels (p=0.42 and p=0.9, respectively). None of the risk factors, such as hsCRP, VCAM1, or homocysteine, were shown to be related to insulin resistance (p=0.6, p=0.6, p=0.09, respectively). CONCLUSION: Our findings did not show an increase in the prevalence of atherosclerosis in patients with SLE. There was no association between IMT and insulin resistance. However, the former was associated with FPG, total cholesterol, LDL, TG, homocystein and VCAM1.

Network meta-analysis of patent foramen ovale management strategies in cryptogenic stroke.

OBJECTIVE: To compare the outcomes of patent foramen ovale (PFO) closure vs antiplatelet agent (APA) vs oral anticoagulation therapy (OAT) for secondary prevention of stroke in patients with cryptogenic stroke, using direct and indirect evidence from existing randomized data. METHODS: Relevant randomized controlled trials were identified by a systematic review. The efficacy outcome was stroke recurrence, and safety outcomes were atrial fibrillation and bleeding complications at the end of follow-up. Bayesian network meta-analysis was performed to calculate risk estimates and the rank probabilities using APA therapy as the reference. RESULTS: In a network meta-analysis of 6 randomized controlled trials consisting of 3,497 patients (1,732 PFO closure, 1,252 APA, 513 OAT), PFO closure and OAT were associated with lower rates of recurrent stroke (odds ratio [OR] 0.30, 95% credibility interval [CrI] 0.17-0.49 and OR 0.42, 95% CrI 0.22-0.78, respectively) with equal efficacy of OR 0.70 (95% CrI 0.37-1.49). PFO closure had the highest top rank probability of atrial fibrillation and OAT had the highest risk of bleeding complications. CONCLUSIONS: These findings suggest that closure and OAT may be equally effective in recurrent stroke prevention in patients with PFO. There is an increased risk of atrial fibrillation and bleeding with closure and OAT therapy, respectively. A randomized trial is needed to identify patients who would benefit most from each strategy.

Hypoalbuminemia, systemic inflammatory response syndrome, and functional outcome in intracerebral hemorrhage.

PURPOSE: Hypoalbuminemia and systemic inflammatory response syndrome (SIRS) are reported in critically-ill patients, but their relationship is unclear. We sought to determine the association of admission serum albumin and SIRS with outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We used a multicenter, multinational registry of ICH patients to select patients in whom SIRS parameters and serum albumin levels had been determined on admission. Hypoalbuminemia was defined as the lowest standardized quartile of albumin; SIRS according to standard criteria. Primary outcomes were modified Rankin Scale (mRS) at discharge and in-hospital mortality. Regression models were used to assess for the association of hypoalbuminemia and SIRS with discharge mRS and in-hospital mortality. RESULTS: Of 761 ICH patients included in the registry 518 met inclusion criteria; 129 (25%) met SIRS criteria on admission. Hypoalbuminemia was more frequent in patients with SIRS (42% versus 19%; p<0.001). SIRS was associated with worse outcomes (OR: 4.68, 95%CI, 2.52-8.76) and in-hospital all-cause mortality (OR: 2.18, 95% CI, 1.60-2.97), while hypoalbuminemia was not associated with all-cause mortality. CONCLUSIONS: In patients with ICH, hypoalbuminemia is strongly associated with SIRS. SIRS, but not hypoalbuminemia, predicts poor outcome at discharge. Recognizing and managing SIRS early may prevent death or disability in ICH patients.

Role of emergent chest radiography in evaluation of hyperacute stroke.

OBJECTIVE: To use data from a large multicenter trial to assess the role and significance of chest radiograph (CXR) in the initial evaluation of acute stroke. METHODS: Predefined clinical characteristics of patients who had recorded data on CXR examination during the initial evaluation were collected. We compared features of patients who had a CXR done before IV thrombolytics with those who did not. Rates of adverse cardiopulmonary events, intubation, and in-hospital mortality were also compared. Logistic regression analysis was performed to evaluate for the association of CXR performance with door-to-needle time ≥60 minutes. RESULTS: In a cohort of 615 patients, 243 had CXR done before IV thrombolytics. Patients with CXR before treatment had significantly higher admission neurologic deficit, initial respiratory rates, and door-to-needle time than those with CXR after treatment. The rates of cardiopulmonary adverse events in the first 24 hours of admission, endotracheal intubation in the first 7 hours, and in-hospital mortality were not different between the 2 groups. Patients with CXR done before treatment had longer mean door-to-needle times than those without pretreatment radiography (75.8 vs 58.3 minutes, p = 0.0001). Performance of CXR was independently associated with door-to-needle time ≥60 minutes (odds ratio 2.78, 95% confidence interval 1.97-3.92; p = 0.00001). CONCLUSIONS: Performance of CXR prior to IV thrombolytics prolongs door-to-needle time in acute ischemic stroke patients. CXR before treatment should be reserved for situations wherein acute cardiopulmonary conditions would otherwise preclude the administration of IV thrombolytics or substantially influence management.

Altered mental status in the neurocritical care unit.

Altered mental status is a common pathological entity in critically ill patients and particularly in those with preexisting cerebral injury. In the neurological critical care unit, the prevalence of altered mental status is especially high because of the inherent nervous system disease of these patients. Altered mental status can be crudely divided into encephalopathy and delirium. Although often used interchangeably, the 2 pathological entities have subtle differences in etiology and presentation. This is a review of delirium and encephalopathy in the neurological critical care unit.

Simvastatin therapy reduces prooxidant-antioxidant balance: results of a placebo-controlled cross-over trial.

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.

Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial.

OBJECTIVE: This study aimed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins (HSPs) in dyslipidemic patients. DESIGN AND METHODS: Participants (n=102) were treated with simvastatin (40mg/day), or placebo in a randomized, double-blind, placebo-controlled, cross-over trial. Anti-HSP60, 65, 70, and hs-CRP levels were measured before and after each treatment period. Seventy-seven subjects completed the study. RESULTS: Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p<0.001). There have been previous reports of reductions in serum CRP with statin treatment, and although median CRP levels were 9% lower on simvastatin treatment, this did not achieve statistical significance. CONCLUSION: While it is unclear whether HSP antibodies are directly involved in atherogenesis, our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease.