Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke.

BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). RESULTS: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 µg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 µg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 µg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 µg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001). CONCLUSIONS: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.

A spontaneous decrease of blood pressure occurs in acute ischemic stroke with favourable neurological course.

BACKGROUND: In the acute phase of ischemic stroke the relationship between blood pressure (BP) and clinical outcome remains not clear. The aim of our study was to evaluate the association of stroke severity and BP measurements in the acute phase of stroke, and whether early variation of neurological status affects BP profiles. METHODS: BP on admission was obtained with mercurial sphygmomanometer and 24h-ambulatory BP monitoring (ABPM) was performed on days 1(st) and 6(th). Enrolled patient were grouped according to the neurological deficit at onset (graded by the NIHSS) in group A, (NIHSS score ≤ 10, mild/moderate) and group B (NIHSS score > 10, moderate/severe) and according to the occurrence of early neurological improvement, defined as a NIHSS score reduction of at least 4 points at the 6(th) day in group C (improved) and in group D (not improved). RESULTS: A total of 57 patients were enrolled. On admission sphygmomanometric systolic BP values were higher in group A with respect to group B (158,5 mmHg ± 26,9 vs 147,7 mmHg ± 15,5 respectively; p = 0.6) whereas no difference was found in ABPM. On admission sphygmomanometric BP and ABPM were similar in group C and group D. At the 6(th) day ABPM, both systolic BP and diastolic BP values were significantly reduced in clinically improved patients (Δ systolic BP 1(st) to 6(th) day = 9,9±13,3 in group C vs 0,5±17,6 in group D, p < 0,05; Δ diastolic BP 1(st) to 6(th) day = 5,1± 8,4 mmHg in group C vs 1,3 ± 9,7 mmHg in group D, p = ns) whereas no change in the 24-h BP profile was observed in patients without early improvement. CONCLUSION: BP on admission in not related to the stroke severity and does not predict early neurological outcome and patients that show an early neurological improvement show also a reduction of the BP profile.

Effect of intravenous tirofiban and aspirin in reducing short-term and long-term neurologic deficit in patients with ischemic stroke: a double-blind randomized trial.

BACKGROUND: Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h. METHODS: 150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5-25. Outcome variables were the proportion of patients with a NIHSS score reduction of > or =4 points after 72 h, and the proportion of patients with an mRS score of 0-1 at 3 months. RESULTS: The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA). CONCLUSION: In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.

Factors influencing delay in presentation for acute stroke in an emergency department in Milan, Italy.

BACKGROUND AND AIMS: Early treatment is critical for successful intervention in acute stroke. The aim of this study was to describe delays in presentation to hospital and in the emergency department (ED) management of patients with acute stroke and to identify factors influencing these delays in an Italian urban hospital. METHODS: The present series includes all patients presenting with acute stroke, in whom arrival delay was ascertainable. To describe delays into the ED, the triage-visit delay, visit-computed tomography (CT) delay and visit-CT report delay were registered. Type of stroke, severity of stroke assessed using the modified National Institute of Health Stroke Scale (mNIHSS) scale, level of consciousness, history of previous stroke or previous hospital admission, use of the emergency medical service (EMS), onset of stroke during day or night and admission during working or non-working day were registered for every patient. Univariate and multivariate analysis were performed to evaluate factors influencing early arrival. RESULTS: Over a one-year period 537 patients with acute stroke were evaluated; 375 patients in whom arrival delay was ascertainable were included in the study. Median arrival delay was 5.4 h (interquartile range (IQR) 2.7-11.6); 104 patients (28%) arrived within 3 h and 198 (53%) within 6 h. Triage-visit delay was 0.3 h (IQR 0.2-0.7), visit-CT scan delay was 1.2 h (IQR 0.8-1.9), visit-CT report delay was 2.7 h (IQR 1.7-4.5). Triage-visit delay and visit-CT delay were shorter for patients presenting within 3 h. The type of stroke was ischaemic in 240 (64%), haemorrhagic in 61 (16%) and transient ischaemic attack in 74 (20%). The median basal mNIHSS score was 5 (IQR 3-10); 64 patients (17%) had an altered level of consciousness, 103 (27%) had had a previous stroke, 223 (59%) had had a previous hospital admittance. In this series 214 patients (57%) arrived with the EMS, 323 (86%) presented with symptoms during the day, 261 (70%) were admitted during working days. Univariate analysis showed a significantly shorter arrival delay in patients calling the EMS (median 4.2 vs 7.2 h; p<0.001) and in patients with a higher basal mNIHSS score (Spearman rho = -0.204; p<0.001) or altered level of consciousness (normal 5.8 h, not alert but arousable 3.8, not alert but arousable with strong stimulation 2.5, totally unresponsive 6.0; p = 0.005). Multivariate analysis showed that use of the EMS and higher basal mNIHSS score were independent variables associated with a shorter arrival delay. CONCLUSION: A substantial proportion of patients does not arrive at the ED in a suitable time for reperfusion therapy. Patients using the EMS have a shorter arrival delay. Approximately half of the patients with stroke are sufficiently aware of the urgency of this clinical condition to activate the emergency telephone system.

Minor stroke and major vascular occlusion. A case report.

Occlusion of middle cerebral artery (MCA) is generally associated to severe stroke and poor prognosis; however a few patients with mild to moderate presentation and long-term reversibility of neurological deficits have been reported. A 66-year-old male presented with left-side weakness and dysarthria (NIHSS score 7), which progressively resolved within a few days; ischaemic lesion of the anterior arm of the right internal capsule was found at brain CT obtained 72 h after presentation. Transcranial Colour Doppler showed absence of flow of the right MCA. Cerebral angiography showed occlusion of the right MCA that was retrogradely revascularised by leptomeningeal collaterals. Non-invasive intracranial vascular examinations could identify major intracranial artery lesions in patients who present with mild to moderate stroke symptoms. These patients could be identified and followed to clarify their best treatment and prognosis.

The pharmacokinetics of liposomal encapsulated daunorubicin are not modified by HAART in patients with HIV-associated Kaposi's sarcoma.

PURPOSE: To investigate the pharmacokinetics of liposomal daunorubicin (DaunoXome) administered alone or in combination with antiviral therapy including protease inhibitors (PI) to HIV-positive patients affected by Kaposi's sarcoma (KS). PATIENTS AND METHODS: A group of 18 patients with extensive or rapidly progressing AIDS-related KS received DaunoXome at a dose of 40 mg/m2 alone or in association with a triple combination therapy consisting of one PI plus two nucleoside reverse transcriptase inhibitors (NRTI). Daunorubicin pharmacokinetics were determined in a total of 23 cycles, 6 with DaunoXome alone, 9 in combination with indinavir, 6 with ritonavir and 2 with saquinavir. Plasma samples were obtained at different times during the 72 h after DaunoXome administration. Daunorubicin and daunorubicinol plasma levels were determined by high-performance liquid chromatography. RESULTS: After the DaunoXome infusion, daunorubicin was rapidly cleared from the body following, in most cases, a one-compartment open kinetic model. The daunorubicin peak concentrations, clearances and elimination half-lives were (means +/- SD): 16.3 +/- 2.8 microg/ml, 0.3 +/- 0.1 l/h per m2 and 5.6 +/- 2.6 h after DaunoXome alone; 15.1 +/- 4.9 microg/ml, 0.5 +/- 0.3 l/ h per m2 and 5.8 +/- 2.1 h after the combination with indinavir; and 14.5 +/- 2.8 microg/ml, 0.4 +/- 0.2 l/h per m2 and 6.5 +/- 3.9 h after the combination with ritonavir. In all groups, daunorubicinol plasma levels were approximately 25-30 times lower than those of the parent drug. CONCLUSION: Our data show that there are no significant differences in the pharmacokinetic parameters of daunorubicin in patients receiving DaunoXome in combination with indinavir and ritonavir compared with those in patients not receiving PIs. Therefore in patients affected by AIDS-related KS treated with Highly Active AntiRetroviral Therapy (HAART) there is no pharmacokinetic justification for reducing the doses of DaunoXome.