Fulvio Pomero

Accuracy of emergency physician-performed ultrasonography in the diagnosis of deep-vein thrombosis: a systematic review and meta-analysis.

Duplex ultrasound is the first-line diagnostic test for detecting lower limb deep-vein thrombosis (DVT) but it is time consuming, requires patient transport, and cannot be interpreted by most physicians. The accuracy of emergency physician-performed ultrasound (EPPU) for the diagnosis of DVT, when performed at the bedside, is unclear. We did a systematic review and meta-analysis of the literature, aiming to provide reliable data on the accuracy of EPPU in the diagnosis of DVT. The MEDLINE and EMBASE databases (up to August 2012) were systematically searched for studies evaluating the accuracy of EPPU compared to either colour-flow duplex ultrasound performed by a radiology department or vascular laboratory, or to angiography, in the diagnosis of DVT. Weighted mean sensitivity and specificity and associated 95% confidence intervals (CIs) were calculated using a bivariate random-effects regression approach. There were 16 studies included, with 2,379 patients. The pooled prevalence of DVT was 23.1% (498 in 2,379 patients), ranging from 7.4% to 47.3%. Using the bivariate approach, the weighted mean sensitivity of EPPU compared to the reference imaging test was 96.1% (95%CI 90.6-98.5%), and with a weighted mean specificity of 96.8% (95%CI:94.6-98.1%). Our findings suggest that EPPU may be useful in the management of patients with suspected DVT. Future prospective studies are warranted to confirm these findings.

Spontaneous dissection of the celiac artery: a pitfall in the diagnosis of acute abdominal pain. Presentation of two cases

Spontaneous visceral artery dissection is an uncommon event with an unpredictable natural history and is rarely considered in the diagnosis of acute abdominal pain. It is frequently asymptomatic and usually diagnosed at autopsy after fatal hemorrhage or ischemia but may be revealed by abdominal angina or acute hemorrhage. Spontaneous resolution, definitive occlusion of the artery, and formation of an aneurysm with severe complications are other possible outcomes. Isolated dissection of the celiac artery (CA) is exceptional and there are only 13 cases in the literature (1). This paper describes two cases recently treated at the Department of Internal Medicine, Molinette Hospital, Turin. The first case was successfully managed by surgical resection of the CA; the second, by close medical surveillance.

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.

Pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations.

Abstract.Aims/hypothesis: Thickening of the basement membrane and selective loss of pericytes are early events in diabetic retinopathy. We aimed at checking whether pericyte interaction with extracellular matrix produced by endothelial cells is influenced by the hexose concentrations in which endothelial cells are cultured. Methods: Conditioned extracellular matrixes were obtained by growing human umbilical vein endothelial cells in media containing 28 mmol/l hexoses (d-glucose, d-galactose, l-glucose), which undergo different intracellular processing, before and after adding the inhibitors of protein glycation thiamine or aminoguanidine. Having removed the endothelium, bovine retinal pericytes were grown on such matrixes and, in separate experiments, on laminin, fibronectin or type IV collagen. Pericyte adhesion was determined by cell counts 18 h after seeding. Results: Reduced adhesion was observed on matrixes produced in high d-glucose, high d-galactose and high l-glucose. Both thiamine and aminoguanidine restored impaired pericyte adhesion when added to high d-glucose and high d-galactose, but not l-glucose. Laminin, fibronectin and type IV collagen did not consistently modify pericyte adhesion. Conclusions/interpretations: Pericyte adhesion is impaired on extracellular matrix produced by endothelium in high hexose concentrations. This could result from excess protein glycation, corrected by aminoguanidine and thiamine, rather than altered glycoprotein composition. [Diabetologia (2002) 45: 416–419]

Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose

Abstract We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation endproducts (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 μM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3% ±5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%±2.4%, p=0.005) or benfotiamine (87.5%±89%, p=0.006), although it was not completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%±38.9% of fluorescence in physiological glucose, p0.003) was reduced by thiamine (113.2%±16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%±49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study.

Bleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59-0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51-0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.

Time trends and case fatality rate of in-hospital treated pulmonary embolism during 11 years of observation in Northwestern Italy

Pulmonary embolism (PE) is a common disorder with high mortality and morbidity rates. However, population-based information on its incidence and prognosis remains limited. We conducted a large epidemiology study collecting data on hospitalisation for PE (from 2002 to 2012) in a population of about 13 million people in Northwestern Italy. Patients were identified using the ICD-9-CM codes: 415.11, 415.19; gender and age specific incidence rate of PE during the study period were estimated using the resident population for each year of the study. Furthermore, time trends in the in-hospital PE-related mortality and case fatality rate were calculated. Results were adjusted for possible confounders. A total of 60,853 patients (mean age 72.8 years, ± 14.1, 59.6% females) with PE were included; the overall crude incidence rate for the entire study period was 55.4 and 40.6 events per year per 100,000 inhabitants for women and men, respectively (p <0.001). However, this difference was completely lost after standardisation for age. The incidence of PE significantly increased in both genders during the study period. In-hospital case fatality rate significantly decreased throughout the study period (p < 0.001) in women (from 15.6% to 10.2%) and in men (from 17.6% to 10.1%). The observed decrease of the in-hospital case-fatality throughout the study period remained significant also after adjustment for possible confounders. In conclusion, time trends over an 11-year period show an increasing incidence of PE, but a significant reduction in mortality during hospitalisation. Reduction in the case fatality rate remained significant after adjustment for these possible confounders.

Major bleeding with vitamin K antagonists or direct oral anticoagulants in real-life

BACKGROUND Limited data are available on major bleeding (MB) occurring during treatment with vitamin K (VKAs) or direct oral anticoagulants (DOACs) outside clinical trials. METHODS Patients hospitalized for MB while on treatment with VKAs or DOACs were included in a multicenter study to compare clinical presentation, management and outcome of bleeding. The primary study outcome was death at 30days. RESULTS Between September 2013 and September 2015, 806 patients were included in the study, 76% on VKAs and 24% on DOACs. MB was an intracranial hemorrhage in 51% and 21% patients on VKAs or DOACs, respectively (Odds Ratio [OR] 3.79; 95% confidence interval [CI] 2.59-5.54) a gastrointestinal bleeding in 46% and 25% patients on DOACs and VKAs, respectively (OR 2.62; 95% CI 1.87-3.68). Death at 30days occurred in 130 patients (16%), 18% and 9% of VKA and DOAC patients (HR 1.95; 95% CI 1.19-3.22, p=0.008). The rate of death at 30days was similar in VKA and DOAC patients with intracranial hemorrhage (26% and 24%; HR 1.05, 95% CI 0.54-2.02) and gastrointestinal bleeding (11% and 7%; HR 1.46, 95% CI 0.57-3.74) and higher in VKA than DOAC patients with other MBs (10% and 3%; HR 3.42, 95% CI 0.78-15.03). CONCLUSIONS Admission for ICH is less frequent for DOAC patients compared with VKA patients. Admission for gastrointestinal MB is more frequent for DOAC as compared to VKA patients. Mortality seems lower in patients with MBs while on DOACs than VKAs but this finding varies across different types of MBs.

Is diabetes a hypercoagulable state? A critical appraisal

Abstract Diabetes mellitus (DM), a chronic disease with an increasing incidence and prevalence worldwide, is an established risk factor for arterial cardiovascular, cerebrovascular and peripheral vascular diseases including acute myocardial infarction, stroke and peripheral artery disease. On the other hand, its role as independent risk factor for venous thromboembolism (VTE) and for cardioembolic stroke or systemic embolism (SE) in patients with atrial fibrillation (AF) is more conflicting. Venous and arterial thromboses have traditionally been regarded as separate diseases, but recent studies have documented an association between these vascular complications. Cardiovascular risk factors may contribute to unprovoked VTE, and VTE may be an early symptomatic event in patients at high cardiovascular risk, including diabetic patients. Compelling evidences suggest that DM is associated with a higher risk of development and progression of AF. Furthermore, in AF patients with a coexisting DM the risk of cardioembolic stroke/SE appeared increased. Thus, DM has been included as one of the items of the CHADS2 score and of the subsequent CHA2DS2-VASc score that have been developed to assess the arterial tromboembolic risk of AF patients. Such a high incidence of thromboembolic events observed in these clinical subsets may be attributable to the DM-related prothrombotic state due to a number of changes in primary and secondary hemostasis. Although of potential clinical interest, unfortunately, to date, no study has properly evaluated the effects of drugs used to control blood glucose levels on the risk of venous thromboembolism and arterial cardioembolic events in patients with DM.

Incidence rates and case fatality rates of portal vein thrombosis and Budd-Chiari Syndrome

Little information is available on the incidence of splanchnic vein thrombosis and on mortality rates during the acute phase of the disease. We performed a large epidemiologic study on hospital admissions for portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BCS) between 2002 and 2012 in Northwestern Italy. Primary and secondary discharge diagnoses of PVT and BCS were identified using the 9th edition International Classification of Diseases codes 453.0, 572.1 and 452. Hospitalisations for recurrent events were not included. Information was collected on age and gender, vital status at discharge, duration of hospitalisation, and up to five secondary discharge diagnoses. Comorbidity was evaluated using the Charlson comorbidity index (CCI). A total of 3535 patients with PVT and 287 with BCS were hospitalized. The overall gender-specific incidence rates for PVT were 3.78 per 100,000 inhabitants in males and 1.73 per 100,000 inhabitants in females; for BCS 2.0 and 2.2 per million inhabitants, respectively. In-hospital case fatality was 7.3 % in patients with PVT and 4.9 % in patients with BCS. Age, non-abdominal solid cancer, and CCI were independently associated with in-hospital mortality in both PVT and BCS after stepwise regression analysis, male gender and haematologic cancer were associated with mortality in BCS patients only. In this large study we confirmed the low incidence of BCS and we found an incidence of PVT higher than previously reported. This incidence was stable during the period of observation. In-hospital mortality is not negligible, in particular in PVT patients.