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Masotti L, Ceccarelli E, Forconi S,Cappelli R (Cecina Hospital, Physical Medicine andRehabilitation, Livorno; and University of Siena,Siena, Italy). Prognostic role of C-reactive protein invery old patients with acute ischaemic stroke.J Intern Med 2005; 258: 145–152.Background and scope. Recent literature hasdemonstrated that inflammation contributes to allphases of atherosclerosis and brain damage causedby stroke. In acute phase of cerebrovascular diseasesbiochemical markers of inflammation, such as C-reactive protein (CRP), could represent an indicatorof severity of stroke, but few studies have verifiedthis hypothesis, especially in very old patients. Theaim of this study was to evaluate the role of CRP onshort- and long-term prognosis in 75-year old andover elderly patients with acute ischaemic stroke.Materials and methods. We retrospectively eval-uated CRP values (nephelometric method), per-formed within 12 h from hospital admission, in196 elderly patients (124 females and 72 males withmean age ± SD 83.32 ± 10.46 years), dischargedwith diagnosis of acute ischaemic stroke, 68 of themwith atherothrombotic large vessel stroke, 38 withlacunar stroke and 90 with cardioembolic stroke.We studied the relationship between CRP valuesand short-term prognosis [30-day mortality,length of hospitalization (LOS) and physicaldisability measured by modified Rankin scale andlong-term prognosis (12-month mortality andre-hospitalization)].Results. Mean values of CRP were significantlyhigher in patients with cardioembolic strokecompared with atherothrombotic large vessel andlacunar stroke, in patients who died in the first30 days from the acute event compared withsurvivors. LOS and physical disability score rosewith increasing values of CRP for all subtypesof stroke. Higher CRP values were associatedwith the 12-month re-hospitalization for cerebro-vascular events, whereas it did not influence the12-month cumulative re-hospitalization and12-month mortality.Conclusions. Elevation of CRP values at hospitaladmission could represent a negative prognosticindex in elderly patients with ischaemic stroke, inparticular, for short-term prognosis.Keywords: C-reactiveprotein,elderly,inflammation,prognosis, stroke.

Aims To study protein S, as an acute phase protein, for its relationships with C4b-BP (C4BP), fibrinogen and Factor VIII:C in a group of patients with solid tumours, without proven metastases. Methods Eighty-one consecutive patients with gastrointestinal or pelvic adenocarcinoma (TNM staging: T1-3, N0-2, M0) and 58 healthy subjects were evaluated for plasma free and total protein S antigen, protein S activity, C4BP, fibrinogen and Factor VIII:C. Results When compared to the control group, the total protein S, the C4BP, the fibrinogen and the Factor VIII:C mean levels were significantly higher in the cancer group, but there was no significant difference for the free and the functional protein S mean concentrations. In both groups the free protein S was correlated with the functional and the total protein S; moreover the latter was significantly correlated with the C4BP, whereas it was significantly correlated with the fibrinogen and the Factor VIII:C only in the cancer group. In addition, a high correlation was found among the C4BP, the fibrinogen and the Factor VIII:C. Conclusions Our data show that in these patients there is an acute phase response and suggest that, in the thrombophilic early cancer screening, determination of free protein S is redundant.

Pulmonary sequestration is a congenital anomaly of lung parenchyma that can be definitively treated only with surgical resection. We report a case of an intralobar sequestration of the right lower pulmonary lobe in an infant successfully treated with video-thoracoscopic surgical removal of the involved lobe at 6 months of age.

The clinical and instrumental manifestations of thoracic outlet syndrome are well known but the therapeutic choices frequently differ in relation to the physician's experience. Thus, there is no univocal opinion regarding the therapy of this complex syndrome. To solve this problem we have attempted to bring together the clinical and instrumental pictures in a single classification that includes the three fundamental aspects of the syndrome, namely nerve, artery and vein injury (NAV). Our goal was to achieve a universally accepted therapy-oriented staging system, as is the case with the TNM system for malignant tumours. From 1984 to 2002, in our institution 156 patients with thoracic outlet syndrome were evaluated. These were grouped in 4 stages depending on their NAV status. Subsequent therapy was in accordance with stage. Our results confirmed the accuracy of NAV. On the basis of our preliminary experience, the NAV staging system is useful for correct patient grouping. Now a prospective multicentre study is needed for universal scientific validation.

Pulmonary embolism (PE) is often underdiagnosed in the elderly for nonspecificity and atypicity of presentation. The aim of this study was to evidence, retrospectively, the clinical, instrumental and laboratory aspects in the diagnosis of elderly patients with suspected PE and to observe the antithrombotic primary prophylaxis, acute antithrombotic treatment and its hemorrhagic side effects in patients with confirmed PE (CPE).We conducted an observational, retrospective, study on 118 hospitalized patientsor = 65 years (49 males and 69 females, mean age 77.76 +/- 7.17 years) during a 5-year period who underwent a scintigraphic lung scan for suspected PE. Clinical, instrumental and laboratory findings of 75 patients with CPE were compared with 43 patients with unconfirmed PE (UCPE).Symptoms of dyspnea and chest pain and all the considered signs, except tachycardia, were significantly more frequent in the CPE group. Bed rest4 days, venous insufficiency, deep vein thrombosis, obesity and stroke were the risk factors significantly more frequent in the CPE group. Sinus tachycardia, incomplete right bundle branch block, ST-T alterations were significantly more present in the CPE group. Cardiomegaly was the only significant more frequent chest X-ray finding in the CPE group, while echocardiography showed a significant involvement of the right ventricle in the CPE group. Plasma D-dimer levels were significantly higher in the CPE group but the mean values were500 micrograms/l in both groups. In arterial blood gas analysis we found more severe hypoxemia, arterial hyposaturation and higher alveolar-oxygen gradient in the CPE group, while we did not find a more frequent respiratory alkalosis in this group. Heart failure, ischemic heart disease and chronic obstructive pulmonary disease were the more frequent diagnoses in the UCPE group. None of the patients received thrombolysis. Seventy percent of the CPE patients received intravenous heparin; 9 hemorrhagic side effects occurred, 3 of them being major with one fatal in one patient treated with subcutaneous unfractionated heparin.Our study shows the diagnostic difficulties of PE in the elderly because of nonspecifcity of clinical, instrumental and laboratory aspects. Although many of these aspects are significantly more frequent in the CPE group, the same are often the main aspects also in the UCPE group. Moreover, our study reveals the low utilization of antithrombotic primary prophylaxis and high risk of hemorrhagic side effects of heparin in this subgroup of patients.

Objective: The localized benign fibrous tumor of the pleura represents 8% of all benign pathologies of the chest and 10% of neoplasms of the pleura. The authors review the literature, and report on 15 cases of localized benign fibrous tumors of the pleura surgically treated over a period of 15 years to further knowledge of this pathology, its therapy and prognosis. Methods: With respect to the well-known diffuse malignant mesothelioma, different etiopathogenesis, prognosis, and therapeutic approaches characterize the localized benign fibrous tumor of the pleura. In our experience, 15 patients underwent thoracotomy with excision of a pathological endothoracic mass, then histologically proved to be a localized benign tumor of the pleura. The whole group underwent pre-operative evaluation and, when clinic suggested, stadiation and post-operative frequent follow-up. Results: The whole group of 15 patients underwent surgical approach well tolerated the surgical treatment with perfect recovery of post-operative respiratory function. There was no relapse of disease in any patients. At the moment all patients are still alive except one dead of heart failure. Conclusion: The differential diagnosis of benign fibrous tumor of the pleura and lung and pleural malignancy depends upon immunohistochemistry of the surgical specimen so that prognosis could be formulated only after surgery. We consider surgery as the treatment of choice in this pathology.

Though associated with substantially prolonged survival, the favourable results of Sugarbaker's trimodality treatment for malignant pleural mesothelioma are controversial and have yet to be extensively reproduced. The aim was to evaluate the prospective medium-term (3-year) reproducibility of the results of trimodality treatment in a significant group of patients staged using the international IMIG classification. Forty-three patients with malignant pleural mesothelioma were candidates for extended pleuropneumonectomy, followed by chemo- and radiotherapy. At thoracotomy, 33 of the 43 surgical candidates underwent extended pleuropneumonectomy and 71% of the 30 evaluable operated patients completed the scheduled course of adjuvant chemotherapy. The perioperative mortality rate was 6% and the major morbidity rate 36%. At 3 years the overall survival of the 30 evaluable patients was 30% and the disease-free survival rate was 25%, with a prevalence of epithelial pI and pII IMIG stages. Clinical understaging was appreciable. Survival was less favourable for stage pIII and for mixed tumours. Most of the disease recurrences were due to incomplete local postsurgical monitoring. This series confirms the reproducibility of trimodality treatment for malignant pleural mesothelioma. The treatment is associated with prolonged survival in the case of early-stage tumours and has an acceptable complication rate. Early diagnosis, accurate staging, preoperative induction and better local monitoring are avenues to be explored when seeking to achieve curability of malignant pleural mesothelioma.

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.

Community-acquired pneumonia (CAP) is a serious social and medical problem in the elderly. Mortality, hospitalization and length of stay increase with age. The aim of this study was to determine the risk factors associated with prolonged hospital stay in elderly patients with CAP. Clinical and laboratory data were collected for 115 community-living patients, 65 years old and over, admitted to the geriatric ward of a University Hospital from 1995 to 1998 because of symptoms and signs of pneumonia confirmed by a pulmonary infiltrate on chest x-ray. We divided the patients into two groups, with length of stay more than 13 days (70 patients, cases), and length of stay less than 13 days (45 patients, controls) according to Diagnosis Related Groups criteria for complicated and uncomplicated pneumonia, respectively. A prolonged hospital stay was associated with a higher fever peak and a higher number of days with fever (p

Abstract 543 Background A recurrence occurs in 15–20% of patients with unprovoked venous thromboembolism (VTE) in the two years after the withdrawal of oral anticoagulant treatment. Extending anticoagulant treatment is effective but associated with increased bleeding risk. We assessed the efficacy and safety of aspirin for the prevention of VTE recurrence after a conventional course of oral anticoagulation. Methods Warfasa was an investigator-initiated double-blind randomized placebo-controlled event-driven study. Patients with a first-ever unprovoked VTE who had completed 6–12 months of oral anticoagulant treatment were randomized to receive aspirin, 100 mg daily, or placebo for at least two years. The primary efficacy outcome was objectively confirmed recurrent symptomatic VTE and VTE-related death. Clinically relevant (major and non-major) bleeding were the main safety outcome. All outcome events were blindly adjudicated by an independent committee. Results A VTE recurrence occurred in 27 of the 205 patients who received aspirin and 42 of the 197 patients who received placebo (6.3% versus 11.0% patient-years; hazard ratio, 0.57, 95% CI 0.35 to 0.93) during the study period (mean 24 months) (Figure A). While on study treatment, 22 and 38 patients who received aspirin or placebo, respectively had a recurrence (5.7% versus 10.7% patient-years; hazard ratio, 0.54, 95% CI 0.32 to 0.91) (mean on-treatment period 22 months) (Figure B). One patient in each treatment group had a major bleeding, with a similar incidence of clinically relevant non-major bleeding. Conclusions Aspirin reduces by about 40% the risk of recurrence in patients with unprovoked VTE without increasing bleeding, when given after a 6–12 month anticoagulant treatment. For its safety, practicality and low cost, aspirin is a valid alternative to oral anticoagulants in the extended treatment of VTE. Disclosures: No relevant conflicts of interest to declare.

Cyclandelate, a vasoactive substance consisting of the mandelic acid ester of 3,3,5-trimethylcyclohexanol, was administered to 10 patients with cerebrovascular and/or peripheral vascular disease. Blood specimens were collected at 1 − 6 h after oral administration of 1600 mg cyclandelate, and the ester and acid were extracted from plasma in acid medium using n-hexane/isopropyl alcohol. The concentrations were determined by a high-performance liquid chromatography isocratic system. The highest plasma cyclandelate concentrations were detected at the third hour, whereas plasma mandelic acid concentrations were still increasing 6 h after administration.

AIM: To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrombin G20210A, in patients with gastric cancer. METHODS: One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects, comparable for age and sex, were investigated. Factor V Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR. RESULTS: Among the 121 cancer patients, factor V Leiden was found in 4 cases (GA genotype: 3.3%) and prothrombin G20210A in 10 cases (GA genotype: 8.3%). Of the 130 control subjects, factor V Leiden was detected in 6 cases (GA genotype: 4.6%) and prothrombin G20210A in 8 cases (GA genotype: 6.1%). No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor V Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects. CONCLUSION: Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.

The chest wall is involved by direct lung tumour extension in approximately 2-8% of the patients. Between 1976 and 1989, 1365 patients underwent resection of non small cell lung cancer and this study is concerned with 73 of these patients (5.3%) who required resection of an area of the chest wall including one or more ribs because of direct tumour invasion (T3). The overall 5-year survival rate was 31.5% (23 patients); 17(74%), were N0,5 (21.7%) were N1 and only 1 (4.3%)was N2. Our experience confirms earlier reports: stage IIIA patients T3N0MO have a better 5-year survival rate than NI and N2, indicating a potentially radical tumour excision even in this stage.

We report our experience in the surgical treatment of lung metastases from 1976 to 1995. Among 2040 patients who underwent pulmonary resection, we observed 102 cases (5%) in which a metastasectomy was performed. All the patients had neither local nor distant recurrence of the neoplasm. There were no intra or perioperative complications. The 5-year survival rate was 35.4%; we report the 5-year survival rate related to the number, the dimension, the site of the metatases and the surgical technique, which all seem not to be negative prognostic factors. On the contrary the histologic type of the neoplasm seems to the affect the survival.

Paraneoplastic syndrome (PS) is sometimes related to lung cancer and often is the first clinical manifestation of the disease. We review our experience from 1967 to 1994: during this period we observed 3012 patients with lung cancer and among them PS was diagnosed in 601 (19.9%). The most frequent clinical manifestations were syndromes involving the bones and the joints (43.4%). We observed a higher incidence of PS (36.7%) in patients with small lung cancer. In 392 patients (13%) PS was the first presenting complaint and in 124 (4.1%) led to correct diagnosis. We studied the relationship between PS and staging of neoplasm, surgical feasibility and 5-year survival rate.

The infusion of isoxsuprine was followed by an increase of heart rate and calf blood flow and by a decrease of arterial diastolic pressure and blood viscosity both in normal controls and patients with peripheral obstructive arterial disease. The pre-treatment with a non-selective beta adrenoceptor blocker (propranolol) canceled all the isoxsuprine-dependent changes, while the pre-treatment with a selective beta adrenoceptor blocker (metoprolol) abolished only tachycardia and did not influence the increase of calf blood flow and the decrease of blood viscosity. These findings indicate the different role of vascular beta receptors in the regulation of muscular blood flow and suggest the pharmacologic possibility to unmask the beta2-dependent vaso dilation.

Deep venous thrombosis is a common disease with significant danger of both acute and chronic complications. Widely accepted therapies are based on anticoagulant (heparin and/or anticoagulant agents) or early fibrinolytic therapy. All these therapies frequently have severe side effects. Defibrotide is a new drug with antithrombotic and profibrinolytic activities but without anticoagulant activity and major side effects. To evaluate the efficacy of this drug against acute thrombophlebitis, we treated a group of 10 patients with 200 mg defibrotide intravenously three times a day for 15 days. Fibrinolysis parameters were monitored every other day. The indices of venous function by strain-gauge plethysmography and venous occlusion were evaluated every 7 days.The drug induced a significant improvement in plethysmographic indices and a significant profibrinolytic activity. Defibrotide-treated patients showed a fast disappearance of clinical and instrumental signs of thrombophlebitis. No side effects were reported during the study.

Peripheral obliterative arterial disease (POAD) is a clinical condition characterized from a pathophysiological point of view by a reduction of nutritional blood flow due to atherosclerotic stenosis or occlusion of great or medium-sized arteries of the legs. In this condition, blood flow supply to the tissue can be insufficient to meet the metabolic needs and ischaemia can occur. The blood flow reduction usually develops slowly and a compensatory mechanism can be activated to antagonize ischaemia.

Periphere obliterierende arterielle Erkrankungen (im weiteren Text als POAD—peripheral obliterative disease —abgekurzt) sind pathophysiologisch durch eine Reduktion der nutritiven Durchblutung gekennzeichnet, die durch arteriosklerotische Stenosen oder Verschlusse der grosen oder mittleren Beinarterien hervorgerufen wird.

Despite the methodological difficulties of evaluating the role of a single rheological component, some clinical situations characterised by an increase of blood viscosity can be identified. These are classified as 'blood hyperviscosity syndromes' and can be divided into 2 groups. The first includes pathophysiological conditions in which a primary blood abnormality causes a decrease of blood flow, as occurs in polycythaemic, sclerocythaemic and seric hyperviscosity syndromes, and may be referred to as 'primary blood hyperviscosity syndromes'. The second group includes pathological conditions in which a primary reduction of blood supply to tissue provokes tissue ischaemia, and an impairment of rheological properties of blood can be observed at microcirculatory level. Thus, these situations have been described as 'secondary blood hyperviscosity syndromes'. Patients with peripheral obliterative arterial disease, ischaemic cardiopathies and cerebrovascular insufficiencies show a diminution in blood fluidity during spontaneous or provoked ischaemic conditions which disappears after reperfusion of the tissue. The pathogenesis of this rheological damage is unclear, but may arise from the complex relationship among blood cells (red cells, leucocytes, platelets), endothelium and plasma components. In addition to these 2 groups of blood hyperviscosity syndromes, several pathological states such as diabetes, shock, surgery, and rheumatic disease have been described in which an increase of blood viscosity can be observed. For these situations, which require much further investigation, the term 'syndromes associated with blood hyperviscosity' could be proposed.

Deep Vein Thrombosis during Varicella in a Child with Factor V Leiden Mutation and Familial Deficiency of Protein S