Clara Mandelli

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 ≧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.

Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori

Summary.  The prevalence of gastroduodenal lesions is higher in polycythaemia vera (PV) than in the general population. However, the role of Helicobacter pylori (H. pylori) in the pathogenesis of such lesions is unknown. The aim of our study was to evaluate the prevalence of gastroduodenal lesions in PV patients and dyspeptic controls, and to assess the role of PV and H. pylori infection in inducing them. Thirty‐five PV patients fulfilling selection criteria and 73 age‐ and sex‐matched controls underwent upper gastrointestinal endoscopy. Six gastric mucosal biopsies were taken in all patients and controls, and analysed for presence of H. pylori; serum anti‐CagA was assayed by Western blot. Data were analysed with descriptive statistics and multivariate regression analysis. Compared with controls, PV patients showed a significantly higher frequency of erosions (46% versus 12%), ulcers (29% versus 7%), H. pylori positivity (83% versus 57%), and anti‐CagA positivity (66% versus 37%). Fourteen out of 20 (70%) asymptomatic PV patients had gastroduodenal lesions. At multivariate analysis, H. pylori, presence of PV alone, and both PV and anti‐CagA were significantly and strongly associated with a higher frequency of gastroduodenal lesions (P < 0·05, P < 0·01 and P < 0·05 respectively). Both PV and H. pylori infection were independent risk factors for gastroduodenal lesions; the underlying pathogenetic mechanism responsible for gastroduodenal lesions in PV possibly involves blood mucosal flow and trophism. The higher susceptibility of H. pylori infection and the high frequency of asymptomatic gastroduodenal lesions in PV patients suggest a surveillance of these patients.

Comparable frequency of hepatocellular carcinoma in cirrhosis of different aetiology

Objective: To evaluate by multivariate analysis whether the risk of hepatocellular carcinoma (HCC) varies in cirrhosis of different aetiology. Design: Cohort study of patients monitored every 6 months by laboratory tests and ultrasonography. Setting: Three northern Italian hospitals. Patients: A total of 396 patients (285 men and 111 women; median age, 58 years) with cirrhosis (253 with Childs class A and 143 class B or C) attributable to alcohol abuse, chronic infection by hepatitis B or non-A non-B virus (hepatitis C virus in 79% of patients) and iron overload due to genetic haemochromatosis, were followed for 1–245 months (median, 50 months). Methods: Coxs regression model was used to evaluate sex, age, Childs class, and aetiology of cirrhosis as independent risk factors for HCC; interactions between aetiologic factors were also considered. Results: During follow-up, 143 patients died and 63 developed HCC. The cumulative probability of remaining free of HCC was 90, 80 and 68% at 2, 6 and 10 years. Age 58 years or more (hazard ratio, 4.26 versus age < 58 years; P< 0.001) and Childs class B or C (hazard ratio, 1.81 versus Childs class A; P<0.05) increased the risk of HCC. Conclusion: The aetiology of cirrhosis, when corrected for age, sex and the severity of cirrhosis, did not significantly affect the risk of HCC development.

A bioclinical pattern for the early diagnosis of cardioembolic stroke.

Background and Scope. Early etiologic diagnosis of ischemic stroke subtype guides acute management and treatment. We aim to evaluate if plasma biomarkers can predict stroke subtypes in the early phase from stroke onset. Methods. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP), D-dimer, C-reactive protein, serum albumin, and globulin levels have been investigated in 114 consecutive patients presenting at the emergency room within 6 hours of the ischemic stroke onset. Plasma levels of biomarkers have been correlated with stroke aetiology (based on TOAST criteria) by multivariable logistic regression analysis, adjusted for several covariates. Results. Of the 114 patients, 34 (30%) had cardioembolic stroke, 27 (23%) atherothrombotic stroke, 19 (17%) lacunar stroke, and 34 (30%) stroke of undetermined origin. Patients with cardioembolic stroke had significantly higher levels of NT-proBNP and lower globulin/albumin (G/A) ratio compared with the other subgroups. At multiple logistic regression NT-proBNP > 200 pg/mL, G/A ratio > 0.70, and NIHSS score were independent predictors of cardioembolic stroke with high accuracy of the model, either including (AUC, 0.91) or excluding (AUC, 0.84) atrial fibrillation. Conclusions. A prediction model that includes NT-proBNP, G/A ratio, and NIHSS score can be useful for the early etiologic diagnosis of ischemic stroke.

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 1st and 6th. 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 6th 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 6th day ABPM, both systolic BP and diastolic BP values were significantly reduced in clinically improved patients (Δ systolic BP 1st to 6th day = 9,9±13,3 in group C vs 0,5±17,6 in group D, p < 0,05; Δ diastolic BP 1st to 6th 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 Ascorbic Acid on Desferrioxamine-Induced Urinary Iron Excretion in Idiopathic Hemochromatosis

The effect on urinary iron excretion (UIE) of vitamin C administered orally 2 h after the start of an 8-hour desferrioxamine (DF) i.v. infusion was studied in 12 patients with untreated idiopathic hemochromatosis (IH). Mean +/- SEM basal UIE of 324.6 +/- 84.6 micrograms/24 h increased after a 1-gram i.v. DF infusion to 8,778.5 +/- 1,191.4 micrograms/24 h; when vitamin C 1 or 2 g were added to DF i.v. infusion, there were further increases to 11,241.5 +/- 1,486.1 (p less than 0.01) and 13,531.2 +/- 1,697.2 micrograms/24 h (p less than 0.05 versus the last value), respectively. Basal UIE did not significantly increase after oral vitamin C administration alone. No side effects were observed.