Luca Masotti

Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members

Background and Purpose— Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. Summary of Review— CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. Conclusion— At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Multidetector CT scan for acute pulmonary embolism: Embolic burden and clinical outcome

BACKGROUND In patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan. METHODS Embolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics. RESULTS Overall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. CONCLUSIONS In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies.

C-Reactive Protein Level Measurement Improves Mortality Prediction When Added to the Spontaneous Intracerebral Hemorrhage Score

Background and Purpose— Hyperglycemia and inflammation are involved in the progression of spontaneous intracerebral hemorrhage (sICH)-induced brain injury, but their role in predicting clinical outcome is not clear. We sought to determine whether elevation of white blood cell count (WBC), C-reactive protein (CRP), and blood glucose (BG) concentration at presentation prognosticate poor outcome in sICH patients. Methods— Between November 1, 2005 and October 31, 2009, 210 patients admitted to 2 intensive care units were prospectively consecutively evaluated after exclusion of patients with underlying inflammatory conditions. WBC, CRP, and BG were measured and ICH scores were calculated on first evaluation. Primary outcome was 30-day mortality. Secondary outcome was 30-day functional outcome using the Glasgow Outcome scale. Results— The median CRP concentration was 7.85 mg/L (interquartile range, 4.0–12.0 mg/L), median WBC count was 8.05×109/L (interquartile range, 6.45–9.9×109/L) and median glucose concentration was 7.66 mmol/L (interquartile range, 6.11–10.83 mmol/L). At 30 days, 63 patients (30%) were dead and 101 (48.1%) had poor outcome (Glasgow Outcome scale score, 1–3). Higher WBC (P<0.001), CRP (P<0.05), and BG (P<0.001) were associated with mortality on univariate analyses, but only CRP remained associated with mortality (P<0.005) after adjustment for multiple confounders. CRP improved mortality prediction when added to the ICH score. None of the markers tested had significant associations with functional outcome. Conclusions— Higher WBC, CRP, and BG are associated with increased mortality in sICH patients. Only CRP elevation portends higher risk of death independently of other indicators of sICH severity.

Prognostic stratification of acute pulmonary embolism: Focus on clinical aspects, imaging, and biomarkers

Pulmonary embolism (PE) represents a common disease in emergency medicine and guidelines for diagnosis and treatment have had wide diffusion. However, PE morbidity and mortality remain high, especially when associated to hemodynamic instability or right ventricular dysfunction. Prognostic stratification to identify high risk patients needing to receive more aggressive pharmacological and closer monitoring is of utmost importance. Modern guidelines for management of acute PE are based on risk stratification using either clinical, radiological, or laboratory findings. This article reviews the modern treatment of acute PE, which is customized upon patient prognosis. Accordingly the current risk stratification tools described in the literature such as clinical scores, echocardiography, helical computer tomography, and biomarkers will be reviewed.

The practical management of intracerebral hemorrhage associated with oral anticoagulant therapy.

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10–20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15–30 ml/kg) or recombinant activated factor VII (15–120 μg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications.

C-reactive protein in intracerebral hemorrhage Time course, tissue localization, and prognosis

Objectives: We examined the C-reactive protein (CRP) response after spontaneous intracerebral hemorrhage (sICH) and its relationship to outcome. We additionally characterized early brain localization of CRP. Methods: In this prospective, multicenter, international, collaborative, longitudinal study with cross-sectional immunohistochemical analysis of brain tissue, 223 patients (M/F: 132/91) were recruited during the 2010 calendar year. CRP was evaluated at admission (median 93 minutes from symptom onset), 24 hours, 48 hours, and 72 hours after sICH. Brains of 5 subjects with sICH were compared to brains of 2 aged controls without evidence of brain pathology and 7 patients with ischemic stroke. Plasma CRP was measured over 72 hours following sICH and its relationship to 30-day mortality and functional outcome at 30 days (Glasgow Outcome Scale) was determined. CRP immunostaining patterns were analyzed in samples of sICH autopsy brains. Results: Plasma CRP increased over the 48 hours from admission and was significantly (p < 0.001) related to hematoma volume at later time points. The predictive utility of CRP for morbidity and mortality were maintained when adjusted for other risk factors and improved at 48 hours and 72 hours when compared with admission values. Although an early CRP localization was present in both ischemic and hemorrhagic lesions, an intense and diffuse neuropil staining was only present in sICH patients and particularly evident proximal to the hemorrhagic areas. Conclusions: Plasma CRP production increases markedly over the 48 hours to 72 hours period following sICH and is related to outcome. CRP is also present in large amounts around the hemorrhagic lesion and within neurons and glia of patients who died within 12 hours of sICH. Neurology® 2012;79:690–699

The Risk-based Treatment of Acute Pulmonary Embolism

Risk evaluation and prognostic stratification based upon clinical and radiological findings and new cardiac biomarkers, such as natriuretic peptides (NP) and troponins, represent key points in modern management of acute pulmonary embolism (PE). Literature evidence shows that normotensive PE with right heart dysfunction (RHD), defined as submassive PE, has poorer prognosis when compared to normotensive PE without RHD, defined as non-massive PE; thus whether submassive PE should be managed more aggressively and with closer monitoring represents the crucial question about acute PE treatment. Although the answer is yet unclear, the most recent guidelines address to thrombolysis as treatment choice in selected high risk patients with submassive PE. Guidelines also clarify the indications for unfractioned and low molecular weight heparins and fondaparinux. Therefore, in the present article, the authors focus on modern risk-based therapeutic guidelines of acute PE. Keywords Pulmonary embolism; Treatment; Prognosis; Biomarkers; Chocardiography; Hemodynamic; Guidelines

Pulmonary embolism in the elderly: a review on clinical, instrumental and laboratory presentation

Objective Diagnosis of pulmonary embolism (PE) remains difficult and is often missed in the elderly due to nonspecific and atypical presentation. Diagnostic algorithms able to rule out PE and validated in young adult patients may have reduced applicability in elderly patients, which increases the number of diagnostic tools use and costs. The aim of the present study was to analyze the reported clinical presentation of PE in patients aged 65 and more. Materials and Methods Prospective and retrospective English language studies dealing with the clinical, instrumental and laboratory aspects of PE in patients more than 65 and published after January 1987 and indexed in MEDLINE using keywords as pulmonary embolism, elderly, old, venous thromboembolism (VTE) in the title, abstract or text, were reviewed. Results Dyspnea (range 59%–91.5%), tachypnea (46%–74%), tachycardia (29%–76%), and chest pain (26%–57%) represented the most common clinical symptoms and signs. Bed rest was the most frequent risk factor for VTE (15%–67%); deep vein thrombosis was detected in 15%–50% of cases. Sinus tachycardia, right bundle branch block, and ST-T abnormalities were the most frequent ECG findings. Abnormalities of chest X-ray varied (less than 50% in one-half of the studies and more than 70% in the other one-half). Arterial blood gas analysis revealed severe hypoxemia and mild hypocapnia as the main findings. D-Dimer was higher than cut-off in 100% of patients in 75% of studies. Clinical usefulness of D-Dimer measurement decreases with age, although the strategies based on D-Dimer seem to be cost-effective at least until 80 years. Conclusion Despite limitations due to pooling data of heterogeneous studies, our review could contribute to the knowledge of the presentation of PE in the elderly with its diagnostic difficulties. A diagnostic strategy based on reviewed data is proposed.