Clinical management and outcome of major bleeding in patients on treatment with vitamin K antagonists.

BACKGROUND: The optimal management of major bleeding associated with vitamin K antagonists remains unclear. OBJECTIVES: The aim of the study was to assess the determinants of outcome of vitamin K antagonists-associated major bleeding and the outcome of bleeding in relation with the therapeutic management. METHODS: Patients hospitalized for major bleeding while on vitamin K antagonists were included in a prospective, cohort study. Major bleeding was defined according to the criteria of the International Society of Thrombosis Haemostasis. The primary study outcome was death at 30days from major bleeding. RESULTS: 544 patients were included in this study, of which 282 with intracranial hemorrhage. Prothrombin complex concentrates were used in 51% and in 23% of patients with intracranial hemorrhage or non-intracranial major bleeding, respectively (p<0.001); fresh frozen plasma was used in 7% and in 17% of patients with intracranial hemorrhage or non-intracranial major bleeding (p<0.001). Death at 30days occurred in 100 patients (18%), 72 patients with intracranial hemorrhage and 28 patients with non-intracranial major bleeding. Age over 85years, low Glasgow Coma Scale score and shock were independent predictors of death at 30days. Invasive procedures were associated with decreased risk of death. CONCLUSIONS: Among the patients hospitalized for major bleeding while on vitamin K antagonists, the risk for death is substantial. The risk for death is associated with the clinical severity of major bleeding as assessed by the GCS score and by the presence of shock more than with the initial localization of major bleeding (ICH vs other sites).

Serum analysis of coagulation factors in IPF and NSIP.

Recent literature and our previous proteomic findings prompted us to study the coagulation system in idiopathic pulmonary fibrosis (IPF), the pathogenesis of which remains unclear. The aim of this study was to compare coagulation factors in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia (NSIP) patients and healthy controls. Thirty-three IPF patients (23 acute exacerbation and 10 stable IPF patients), 7 NSIP patients, and 44 controls were enrolled. Concentrations of D-dimer, homocysteine, functional protein C, protein C antigen, free and total protein S antigen and activity, fibrinogen and factor VIIIc were analyzed in serum of patients and controls. The lupus anticoagulant (LAC) test was also performed. Factor VIIIc levels were significantly higher in acute exacerbation IPF patients than controls (p = 0.0001) and in stable IPF patients than controls (p = 0.002). Factor VIIIc levels were higher and PT levels were lower in acute exacerbation IPF patients who died after exacerbation than in patients who survived (p = 0.04 and p = 0.003, respectively). D-dimer, fibrinogen, and homocysteine levels were also significantly higher in IPF patients than controls (p < 0.01). Protein C activity was increased in acute exacerbation IPF patients than controls (p = 0.005). The LAC test was positive in seven IPF patients and negative in controls. Procoagulant status was demonstrated in IPF patients (mainly in acute exacerbation/IPF) than controls and NSIP patients, probably due to endothelial activation and microvascular injury. These preliminary results are of interest because of their potential implications in the pathogenesis and treatment of this disease.

Fast and Accurate Fingerprint Indexing Based on Ridge Orientation and Frequency.

This paper describes a new fingerprint indexing approach based on vector and scalar features, obtained from ridge-line orientations and frequencies. A carefully designed set of features and ad-hoc score measures allow the proposed indexing algorithm to be extremely effective and efficient, as confirmed by the results of extensive experiments. The new method markedly outperforms competing state-of-the-art techniques over six publicly available data sets. Furthermore, it can scale to large databases without losing accuracy: on a standard PC, a search over one million fingerprints takes less than 1 s.

Geriatric teledermatology: store-and-forward vs. face-to-face examination.

BACKGROUND: Telemedicine could be useful in countries like Italy to meet the needs of elderly patients and in particular in those in precarious general conditions, for whom travelling even short distances can pose considerable practical and economical difficulties. OBJECTIVE: The aim of this study was to determine the efficacy of store-and-forward teledermatology vs face-to-face consultations in elderly patients. METHODS: A total of 130 geriatric patients with skin diseases requiring dermatological examination were enrolled. The patients examined, consisting of 60 men (46.15%) and 70 women (53.85%), were aged between 66 and 97 years (mean age 80.58 years). Three dermatologists of the department, with equal experience took turns in face-to-face examination and teledermatology (store-and-forward). To compare face-to-face dermatological examinations with the asynchronous store-and-forward approach of teledermatology, we considered diagnostic agreement (ICD-9 code), therapeutic agreement and concordance of diagnostic confidence. RESULTS: One hundred and fourteen of 130 patients were diagnosed with the same ICD-9 code, making a total observed agreement of 87.7% with a Cohen's κ estimated of 0.863. Agreement between therapies was 69.6% (Cohen's κ = 0.640). As it concerns diagnostic confidence, dermatologists appeared generally slightly less certain of their diagnosis by telemedicine. CONCLUSIONS: Store-and-forward teledermatology can improve diagnostic and therapeutic care for skin disease in elderly who lack easy and/or direct access to dermatologists.

Fingerprint image reconstruction from standard templates.

A minutiae-based template is a very compact representation of a fingerprint image and for a long time it has been assumed that it did not contain enough information to allow the reconstruction of the original fingerprint. This work proposes a novel approach to reconstruct fingerprint images from standard templates and investigates to what extent the reconstructed images are similar to the original ones (i.e., those the templates were extracted from). The efficacy of the reconstruction technique has been assessed by estimating the success chances of a masquerade attack against nine different fingerprint recognition algorithms. The experimental results show that the reconstructed images are very realistic and that, although it is unlikely they can fool a human expert, there is a high chance to deceive state-of-the-art commercial fingerprint recognition systems.

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

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. MATERIALS AND METHODS: We retrospectively evaluated CRP values (nephelometric method), performed within 12 h from hospital admission, in 196 elderly patients (124 females and 72 males with mean age+/-SD 83.32+/-10.46 years), discharged with diagnosis of acute ischaemic stroke, 68 of them with atherothrombotic large vessel stroke, 38 with lacunar stroke and 90 with cardioembolic stroke. We studied the relationship between CRP values and short-term prognosis [30-day mortality, length of hospitalization (LOS) and physical disability measured by modified Rankin scale and long-term prognosis (12-month mortality and re-hospitalization)]. RESULTS: Mean values of CRP were significantly higher in patients with cardioembolic stroke compared with atherothrombotic large vessel and lacunar stroke, in patients who died in the first 30 days from the acute event compared with survivors. LOS and physical disability score rose with increasing values of CRP for all subtypes of stroke. Higher CRP values were associated with the 12-month re-hospitalization for cerebrovascular events, whereas it did not influence the 12-month cumulative re-hospitalization and 12-month mortality. CONCLUSIONS: Elevation of CRP values at hospital admission could represent a negative prognostic index in elderly patients with ischaemic stroke, in particular, for short-term prognosis.

Protein S in cancer patients with non-metastatic solid tumours.

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.

Vascular Thoracic Outlet Syndrome staging and treatment.

Thoracic Outlet Syndrome (TOS) is a well known lesion. Sophisticated imaging techniques can clearly highlight any anatomical damage and a wide range of therapeutic choices are available. It would seem obvious that any given patient should obtain the same treatment irrespective of the medical institution he contacts, but this is not the case. Instead each specialist may recommend different treatments: physiatrist, neurologist, surgeons (thoracic, vascular, neuro, orthopedic). Everyone preserves his specific language and there is no univocal treatment plan consensus for this complex syndrome. Evidently, the correct staging of TOS is still an unresolved question. In order to solve this problem, we collected all clinical and instrumental aspects of the syndrome into a clear, precise classification. Similar to TNM staging of malignant diseases, we used a grouping model based on the three mainly involved anatomical structures: N (= Nerves; brachial plexus and sympathetic fibers), A (= Artery; subclavian-axillary), V (= Vein; subclavian-axillary). We named it the NAV staging of TOS. A retrospective examination of our case records confirmed a valid and useful correlation between the proposed NAV staging and the therapeutic procedures that were actually applied. It is now essential to perform a multi-centre study to extend the validity of our staging.

Arterial blood gas analysis and alveolar-arterial oxygen gradient in diagnosis and prognosis of elderly patients with suspected pulmonary embolism.

BACKGROUND: Arterial blood gas analysis (BGA) remains a first-step diagnostic approach in patients with suspected pulmonary embolism (PE). The aim of this study was to evaluate BGA parameters in elderly patients with suspected pulmonary embolism for diagnosis and 14-day prognosis. METHODS: We performed a retrospective cohort observational study of 6 years (1994-1999) in a 60-bed acute geriatric ward of University Hospital in Siena, Italy. Room air arterial oxygen partial pressure (pO2), arterial carbon dioxide partial pressure (pCO2), pH, arterial oxyhemoglobin saturation (SO2), and alveolar-arterial oxygen gradient [D(A-a)O2] were performed on hospital admission of 75 patients with confirmed PE (CPE) and were compared with data from 43 patients with unconfirmed PE (UCPE). The same parameters of 54 CPE surviving patients were compared with 21 CPE nonsurviving patients. RESULTS: Significantly lower PO2 and SO2, and higher DA-aO2 were found in CPE patients. Respiratory alkalosis was found in one third of the patients in both groups (no significant difference). In the CPE group, there was a significantly lower SO2 in nonsurviving patients, without significant differences for the other parameters. Metabolic acidosis was significantly more frequent in nonsurviving patients. CONCLUSION: More severe hypoxemia, oxyhemoglobin hyposaturation, and higher D(A-a)O2 are associated with the diagnosis of PE in elderly patients. Respiratory alkalosis is less frequent than in younger patients, and metabolic disorders are negative prognostic indicators.

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 microg/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.

Length of hospitalization in elderly patients with community-acquired pneumonia.

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<0.005), greater comorbidity (p<0.001), urinary catheterization and secondary urinary infections (p<0.001), higher erythrocyte sedimentation rate (p<0.001), dehydration (p<0.005), and caloric-proteic malnutrition (p=0.01). In conclusion, knowledge of the risk factors for prolonged hospital stay in elderly patients with CAP may be used to identify high-risk patients, prevent the risks with prophylactic measures, and contain the costs of hospitalization.

[Critical ischemia in elderly patients. Evaluation of the effect of two different methods of Iloprost therapy on the efficacy, tolerance, modification of quality of life and self-sufficiency]. / L'anziano arteriopatico con ischemia critica. Valutazione del trattamento con iloprost secondo due diverse modalità, sulla efficacia e tollerabilità, sulle modificazioni della qualità di vita e dell'autosufficienza.

BACKGROUND: The use of Iloprost in the treatment of critical leg ischemia in very old patients can lead to tolerability problems, related to the drug used and to the kind of patient treated. The aim of this study was to evaluate the impact of this therapy on the activities of daily living and on the quality of life of the patient together with its efficacy and tolerability. METHODS: We studied 20 subjects (mean age 74 +/- 6.8) divided in 2 groups homogeneous for age, seriousness of the disease and presence of diabetes mellitus. In the first group Iloprost was administered for 6 hours, for 28 consecutive days, in the second group for 6 hours, two times a day for 14 consecutive days. In each group we observed the following parameters before and after treatment: clinical evaluation of pain and use of analgesics, ADL and SK39 questionnaire, ankle/arm index c.w. Doppler, strain gauge plethismography of lower limbs, TcPO2 at the back-feet level. RESULTS: Treatment was well tolerated in both groups where we observed a similar reduction of pain, a reduction in the instrumental indexes which express the microcirculatory activity, an improvement in the quality of life and in the capacity to carry out everyday activities. The double daily administration of Iloprost did not cause any significant side effect in the subjects studied, and a better responsiveness to the pain symptomatology was observed. CONCLUSIONS: Iloprost can be used in the treatment of critical leg ischemia even for very old patients with good tolerability and effectiveness. In the double daily administration no relevant side effect was observed. This approach is to be preferred also in terms of cost-effectiveness.

Haemorheological disturbances and possibility of their correction in cerebrovascular diseases.

The presence of a hemorheological disturbance must be considered in the pathophysiological and therapeutical approach to vascular diseases, including cerebral diseases. A reduction of blood fluidity, due either to increase of hematocrit (polycythemic hyperviscosity) or of fibrinogen concentration (plasmatic hyperviscosity) or of red cell rigidity (sclerocythemic hyperviscosity) is commonly considered a condition of high risk for acute or chronic brain ischemia. So many attempts have been made for improving blood fluidity with the purpose to prevent stroke and to delay cerebral deterioration in chronic condition. This paper will present a review of the literature on this subject and the personal experience of our research group with the use of hemodilution, plasmapheresis and pharmacological agents. In our opinion the possible correction of hyperviscosity is very helpful in the prevention of acute ischemic attacks and in the reduction of their incidence in chronic cerebral ischemia. During the acute phase of stroke, hemorheological disturbance is only a part of the complex hemodynamic situation: a primary blood hyperviscosity can favor the onset of the disease but, because of its secondary increase after stroke, a vicious circle might be set in motion resulting in a further reduction of blood supply to the brain. Considering this, attempts in improving blood fluidity during stroke could be made, but with the caution that is required in this complicated "circulatory storm".

Impact of inherited polymorphisms in glutathione S-transferase M1, microsomal epoxide hydrolase, cytochrome P450 enzymes on DNA, and blood protein adducts of benzo(a)pyrene-diolepoxide.

The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.

Effect of felodipine on arterial blood flow and venous function at rest in patients with mild essential hypertension.

Felodipine is a second-generation dihydropyridine calcium antagonist used to treat mild to moderate arterial hypertension. The authors used venous occlusion plethysmography to study the effect of this drug on lower limb arterial inflow and venous outflow in 10 at rest patients with mild essential hypertension. They also sought correlations between changes in district blood flow and blood pressure. Plethysmography was carried out at 8 AM and 4, 8, and 24 hours later at baseline (after washout), on the first day of treatment with a single daily administration of 10 mg felodipine ER, and after 7 and 30 days of treatment. The drug was given after the 8 AM evaluation. The authors determined rest flow, maximal venous incremental volume (MVIV) at 40 mmHg and 60 mmHg, and gradient of venous volume between 60 and 40 mmHg divided by the pressure difference (DV/DP) as index of venous distensibility. On the days of plethysmographic evaluation, arterial blood pressure and heart rate were measured continuously over 24 hours by the ABPM (Ambulatory Blood Pressure Monitoring). The results were analyzed by ANOVA. Rest flow, MVIV, and DV/DP were stable at the baseline evaluation. On days 1, 7, and 30 of treatment the rest flow after 4 and 8 hours was significantly greater than at 8 AM but had always returned to normal after 24 hours. No other plethysmographic parameters changed significantly; in particular venous outflow remained unchanged. Mean arterial, systolic, and diastolic blood pressure were significantly reduced, compared with baseline, following treatment on the first day and after 7 and 30 days' treatment. There was no effect on heart rate. The authors conclude that felodipine is useful for the treatment of mild essential hypertension, since it reduces arterial resistance without altering venous capacitance or distensibility.