Roberto Cappelli

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.

Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis: A Randomized Controlled Trial

CONTEXT Patients with suspected deep vein thrombosis (DVT) of the lower extremities are usually investigated with ultrasonography either by the proximal veins (2-point ultrasonography) or the entire deep vein system (whole-leg ultrasonography). The latter approach is thought to be better based on its ability to detect isolated calf vein thrombosis; however, it requires skilled operators and is mainly available only during working hours. No randomized comparisons are yet available evaluating the relative values of these 2 strategies. OBJECTIVE To assess if the 2 diagnostic strategies are equivalent for the management of symptomatic outpatients with suspected DVT of the lower extremities. DESIGN, SETTING, AND PATIENTS A prospective, randomized, multicenter study of consecutive symptomatic outpatients (n = 2465) with a first episode of suspected DVT of the lower extremities who were randomized to undergo 2-point or whole-leg ultrasonography. Data were taken from ultrasound laboratories of 14 Italian universities or civic hospitals between January 1, 2003, and December 21, 2006. Patients with normal ultrasound findings were followed up for 3 months, with study completion on March 20, 2007. MAIN OUTCOME MEASURE Objectively confirmed 3-month incidence of symptomatic venous thromboembolism in patients with an initially normal diagnostic workup. RESULTS Of 2465 eligible patients, 345 met 1 or more exclusion criteria and 22 refused to participate; therefore, 2098 patients were randomized to either 2-point (n = 1045) or whole-leg (n = 1053) ultrasonography. Symptomatic venous thromboembolism occurred in 7 of 801 patients (incidence, 0.9%; 95% confidence interval [CI], 0.3%-1.8%) in the 2-point strategy group and in 9 of 763 patients (incidence, 1.2%; 95% CI, 0.5%-2.2%) in the whole-leg strategy group. This met the established equivalence criterion (observed difference, 0.3%;95% CI, -1.4% to 0.8%). CONCLUSION The 2 diagnostic strategies are equivalent when used for the management of symptomatic outpatients with suspected DVT of the lower extremities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00353093.

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.

Prognostic role of C-reactive protein in very old patients with acute ischaemic stroke

Background and scope.  Recent literature has demonstrated that inflammation contributes to all phases of atherosclerosis and brain damage caused by stroke. In acute phase of cerebrovascular diseases biochemical markers of inflammation, such as C‐reactive protein (CRP), could represent an indicator of severity of stroke, but few studies have verified this hypothesis, especially in very old patients. The aim of this study was to evaluate the role of CRP on short‐ and long‐term prognosis in 75‐year old and over elderly patients with acute ischaemic stroke.

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.

Plasma D-Dimer Levels in Elderly Patients with Suspected Pulmonary Embolism

been shown to be a useful aid in the diagnosis of PE. DD, a degradation product of cross-linked fibrin, has high sensitivity (89‐98.8%) and high

Pulmonary embolism in the elderly: clinical, instrumental and laboratory aspects.

Objective: To focus on diagnostic and therapeutic problems of pulmonary embolism in the elderly. Methods: Retrospective analysis of 5 years of clinical, instrumental, and laboratory data (collected at the time of hospital admission) for patients 65 years and older with pulmonary embolism proven by a high-probability scintigraphic lung scan or necropsy. Sixty-eight patients, 46 females and 22 males, 78.61 ± (SD) 7.71 years old, were enrolled in the study. Results: Dyspnea, chest pain, tachycardia, and tachypnea were the most common symptoms and signs; they were present alone or in combination in all patients. Bed rest over 4 days was found in 65% of the patients and deep vein thrombosis in the leg in 35%. Only 7 patients were on anticoagulant therapy which was likely to reduce the incidence of pulmonary embolism. The mortality was 29.5%. Major bleeding due to anticoagulant therapy was observed in 4.4% of the patients; 1 case was fatal. Sinus tachycardia, ST segment and T wave abnormalities in anterior leads, and incomplete bundle branch block were the most frequent electrocardiographic findings. Chest X-ray was normal in 19.5% of the patients and compatible with pulmonary embolism in 10%. A transthoracic two-dimensional echocardiogram was abnormal in 74% of the cases, with involvement of the right ventricle in the majority of them. Many patients had laboratory parameters within the normal range. The value of the latex agglutination D-dimer assay was less than the cutoff value of 500 µg/l in 16% of the patients. Hypoxemia and a high alveolar-arterial oxygen gradient were the most frequent aspects of the arterial blood gas analysis. Respiratory alkalosis was observed in only one third of the patients. Conclusions: Pulmonary embolism is often underdiagnosed in the elderly. Clinical, instrumental, and laboratory findings are nonspecific. Only acute suspicion can increase the number of diagnoses, reduce the time to diagnosis, and improve the prognosis.

Strain Gauge Plethysmography in the Study of Circulation of the Limbs

Plethysmography means registration of spontaneous or provoked volume changes in a segment of the body, with which it is possible to obtain information on the circulation of blood in that segment. This method has been known for a long time and has been applied by physiologists to several circulatory problems. However, the first plethysmographic instruments, water plethysmographs, presented such difficult technical problems that their use was restricted to sophisticated research in animals and only rarely in man. The water-filled plethysmograph was then replaced by the air-filled types, but these instruments also had grave technical problems. The principle of the so-called impedance plethysmography or rheography is based on electric impedance changes when a high-frequency and low-power alternating electric current passes through the body segment under investigation. This method, developed in the 1950s and designed to detect pulse waves in the limb, does not really reflect volume changes, but changes in the electrolyte content of the segment; so it cannot be compared with methods developed to measure blood flow.