Infección del sitio de salida de los catéteres venosos centrales y su asociación con bacteriemia relacionada con catéter / Infection of the exit site central venous catheters and its association with bacteremia related to catheter

Introducción: Los catéteres venosos centrales (CVC) plantean un alto riesgo de infección. La infección del sitio de salida (ISS-CVC) es la menos estudiada, y se desconoce su asociación con la bacteriemia asociada a catéter (BAC) y su impacto en la evolución del paciente. Objetivo: Evaluar la asociación entre ISS-CVC, BAC y mortalidad. Materiales y métodos: Estudio prospectivo, de observación. Pacientes internados en una Unidad de Terapia Intensiva médico/quirúrgica que requirieron la colocación de CVC desde el 01/06/2010 hasta el 01/04/2012. Se evaluaron datos epidemiológicos, BAC (según criterios de los CDC) y gérmenes. Se utilizaron media ± DE, mediana y rango intercuartílico, y porcentajes. Resultados: Durante este período, ingresaron 575 pacientes, el 98% requirió CVC. Datos de los pacientes: edad 41 ± 26 años, APACHE II 15 ± 7, 96% con ventilación mecánica, días de ventilación mecánica 41 (33-63), días de internación 43 (25-67). Todos los CVC con ISS fueron retirados y cultivados. Se observaron 51 ISS: 5,5/1000-días-catéter: 33% subclavia, 38% yugular, 29% femoral. Seis pacientes con ISS (12%) tuvieron BAC (0,65/1000-días-catéter): 3 subclavias, 2 yugulares, 1 femoral; 2 con halo y 8 con secreción purulenta. Tiempo de permanencia del CVC: 7,5 días (5-10). Clínica al momento de la ISS: shock 50%, fiebre 83%, SOFA 6 ± 3. El 83% de las infecciones fueron monomicrobianas: 83% por bacilos gramnegativos (2 Klebsiella, 2 Pseudomonas, 1 Serratia y 1 Acinetobacter), 17% por enterococos resistentes a vancomicina. La mortalidad fue del 50%. Conclusión: Aunque la ISS provocó una baja incidencia de BAC, la mortalidad fue alta. Al parecer, la ISS no es un factor predictivo de BAC.(AU)

Introduction: Central venous catheters (CVC) are widely used and pose a high risk of infection. There are few studies on insertion site infection (ISI-CVC), and both its association with catheter-associated bloodstream infection (CABSI) and the outcome of patients are unknown. Objective: To determine the association between ISI-CVC, the presence of CABSI and mortality. Materials and methods: Prospective observational study. All patients admitted to a medical/surgical Intensive Care Unit requiring CVC insertion from 06/01/2010 to 04/01/2012 were included. Epidemiological data, CABSI (according to CDC criteria) and microorganisms involved were evaluated. Mean ± SD, median and interquartile range, and percentages were used. Results: During the period study, 575 patients were admitted, 98% required CVC. Patient´s data: age 41 ± 26 years, APACHE II 15 ± 7, 96% on mechanical ventilation, days on mechanical ventilation: 41 (33-63), length of stay 43 (25-67) days. All CVCs with ISI were removed and cultured. Fifty one ISI were observed (5.5/1000-catheter-day). Six patients with ISI (12%) presented CABSI (0.65/1000-catheter-day): 3 in subclavian, 2 in jugular, 1 femoral; 2 with erythema and 8 with purulent secretion. CVC permanence: 7.5 day (5-10). Signs and/or symptoms at the moment of ISI: shock 50%, fever 83%, SOFA 6 ± 3. The 83% of infections were caused by one microorganism: 83% due to gram-negative bacilli (2 Klebsiella, 2 Pseudomonas, 1 Serratia, and 1 Acinetobacter), 17% due to vancomycin-resistant enterococci. The mortality rate was 50%. Conclusion: Although ISI-CVC presented a low incidence of CABSI, mortality rate was high. The ISI-CVC might have a little predictable value for CABSI.(AU)

[Economic and epidemiologic aspects of generalized anxiety disorder: a review of the literature]. / Aspectos económicos y epidemiológicos de los trastornos de ansiedadgeneralizada: una revisión de la literatura.

INTRODUCTION: The objective is to assess the prevalence and treatment patterns of generalized anxiety disorder (GAD) in Spain as well as the cost associated to this disorder in different countries. METHODS: A search in the literature of health and economics databases was conducted. RESULTS: In regards to the 32 references selected, 6 studies had data on the prevalence of GAD and 3 on treatment patterns in Spain and 11 studies on the costs associated to the disease on an international level. The remaining 20 studies were of general interest for methodological or contextual reasons. CONCLUSIONS: GAD is a mental disorder with high prevalence. According to some authors, it is probably underdiagnosed. No appropriate long term treatment is available. High health care and social costs are associated to GAD. The frequent presence of comorbidity, different definitions and methodologies used in the studies limits the comparability and synthesis of the results. It also makes it difficult to obtain valid estimations of prevalence and costs.

Attempts to make sense of the antiphospholipid syndrome.

Many investigators have been intrigued by the paradoxical association of a circulating anticoagulant, first called lupus anticoagulant by Feinstein and Rapaport [1], with a tendency to develop thrombosis, as initially described by Walter Bowie [2]. Work in Leuven on this topic started when Luis Carreras, an Argentinian hematologist, joined the laboratory of blood coagulation at this university in 1979. At that time, the head of the laboratory was Marc Verstraete. Luis had a particular interest in antibody-mediated coagulation disorders, and had prepared reviews on thrombosis and thrombocytopenia induced by heparin [3] and on the lupus inhibitor [4]. In Leuven, he joined Jos Vermylen, senior member of the laboratory, and an internist with particular interest in hemostasis, thrombosis and vascular disease. As such, Professor Vermylen was involved in both laboratory research and patient care.

Link between anti-CD36 antibodies and thrombosis in the antiphospholipid syndrome.

OBJECTIVE: Some studies have previously suggested the involvement of antibodies directed against CD36 (anti-CD36) in the pathogenesis of thrombosis. The aim of this study was to evaluate the prevalence of anti-CD36 in patients with antiphospholipid antibodies (aPL) and its relationship with thrombosis. METHODS: Anti-CD36 were tested using an indirect MAIPA assay in 62 patients with autoimmune aPL but without SLE; there were 38 with and 24 without thrombosis. Nineteen patients with thrombosis served as an aPL(-) control group and 58 healthy subjects as the normal control group. RESULTS: 15 of 62 aPL patients (24.2%) but only 1 of 58 (1.7%) normal controls had anti-CD36 (p < 0.0005). As compared to normal controls, the prevalence of anti-CD36 was significantly higher in aPL patients with (26.3%, p < 0.0005) or without thrombosis (20.8%, p < 0.01). Anti-CD36 were significantly more frequent in aPL patients with thrombosis than in thrombosis aPL(-) subjects (26.3% vs 0%, p = 0.02). The presence of anti-CD36 seems to be more frequent in aPL patients with recurrent thrombosis than in those with a single episode (36.8% vs 15.8%). CONCLUSION: The presence of anti-CD36 is highly prevalent in patients with autoimmune aPL with a trend to being more frequent in patients with recurrent episodes of thrombosis.

Markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with antiphospholipid antibodies.

OBJECTIVE: To evaluate plasma levels of markers of platelet, endothelial cell and blood coagulation activation in leprosy patients with or without antiphospholipid antibodies (aPL) and to compare them to those found in patients with antiphospholipid syndrome (APS). METHODS: 42 patients with leprosy (35 lepromatous and 7 borderline): 29 aPL(+) and 13 aPL(-), as well as 26 healthy subjects as normal controls (NC) and 79 control aPL patients without leprosy (59 with and 20 without APS) were included in the study. Plasma soluble P and E selectin (sPsel and sEsel), and VCAM-1 (sVCAM-1), prothrombin F1 + 2 fragment (F1 + 2), thrombin-antithrombin complexes (TAT) and D dimer (DD) were measured by ELISA. The protein C pathway was assessed by the ProC global test. RESULTS: Leprosy patients with aPL presented increased median levels of sPsel [ng/ml (82.0 vs 36.0, p < 0.001)] and sVCAM-1 [ng/ml (495 vs 335, p < 0.001)] compared to NC, as observed in control aPL patients without leprosy. Levels of sPsel in aPL(+) patients with leprosy were significantly higher than in aPL(-) ones (52.5 ng/ml), p = 0.005. However, plasma markers of thrombin generation were increased in control aPL patients without leprosy but not in those with leprosy. ProcC global test was abnormal in 24.1% of leprosy patients with aPL compared to 4.4% of NC (p < 0.024), and to 57.2% of control patients with aPL without leprosy (p = 0.005). CONCLUSIONS: We demonstrated that although patients with leprosy present a high prevalence of aPL, and platelet and endothelial cell activation in vivo to the same extent than patients with APS, they do not show a procoagulant state.

Major and potential prothrombotic genotypes in a cohort of patients with venous thromboembolism.

Factor V Leiden (FVL) and the prothrombin 20210A (PT-20210A) variant are well-known risk factors for venous thromboembolism (VT). The thermolabile variant (TT) of the methylenetetrahydrofolate reductase (MTHFR) gene, and homozygosity for the 4G allele of the promoter region of the plasminogen activator inhibitor-1 (PAI-1) are potential genetic polymorphisms that have not been consistently associated with increased risk of VT. A case-control study was performed on 192 consecutive unrelated patients referred for evaluation of thrombophilia because of VT and 200 healthy controls. FVL was found in 10.4% of patients compared to 3.0% of controls, while 6.3% of patients were carriers of the PT-20210A allele compared to 2.0% of controls. The adjusted odds ratios (OR) were 5.92 and 4.03 for FVL (P=.001) and the PT-20210A (P=.033), respectively. The prevalence of homozygotes for MTHFR (TT) and PAI-1 (4G/4G) among patients and controls were 13.7% versus 13.0% and 21.6% versus 23.5%, respectively (P=ns). A total of 121 patients underwent a complete screening for FVL, the PT-20210A, protein C (PC), protein S (PS), antithrombin III (ATIII), levels of factor VIII, and antiphospholipid antibodies (aPL). In 59 patients (48.8%) at least one defect was found, being a single defect in 55 and combined defects in 4 patients. Plasma levels of homocysteine (Hcy) were measured in 138 patients and 144 controls. Subjects from both groups carrying the MTHFR-TT variant had higher Hcy levels than those with the normal genotype. Hyperhomocysteinemia (HHcy) by itself is a risk factor for VT (OR 4.92, P<.0001). We conclude that FVL and the PT-20210A are risk factors for VT as well as Hcy levels, but the MTHFR and PAI-1 polymorphisms do not appear to be associated with VT in our country.

Increased lipid peroxidation correlates with platelet activation but not with markers of endothelial cell and blood coagulation activation in patients with antiphospholipid antibodies.

Recent studies have shown that patients with antiphospholipid antibodies (aPL) have increased lipid peroxidation. We evaluated the urinary excretion of 11-dehydro thromboxane B2 (11-DH-TXB(2) and isoprostane F(2alpha)III (IPF(2alpha)III), reflecting platelet activation and lipid peroxidation in vivo, and plasma soluble markers of endothelial cell, platelet and blood coagulation activation: soluble vascular cell adhesion molecule-1 (sVCAM-1), P- and E-selectin (sPsel and sEsel), F1 + 2 fragment of prothrombin (F1 + 2), thrombin-antithrombin complexes (TAT) and D-Dimer (DD). We studied 79 patients with aPL (47 with previous thrombosis), 45 healthy volunteers (normal controls, NC), 12 patients with systemic lupus erythematosus (SLE) without aPL and a thrombosis control group (TCG) without thrombophilia (n = 16). Urinary levels (mean, range) of eicosanoids and isoeicosanoids were significantly increased in 39 patients with aPL compared with 25 NC, 11-DH-TXB(2) 164.0 ng/mmol creatinine (9.5-1162.8) versus 43.4 ng/mmol creatinine (4.2-87.6), P < 0.001; IPF(2alpha)III 56.9 pg/mg creatinine (5.5-388.7) versus 27.0 pg/mg creatinine (4.6-87.6), P = 0.03. Both metabolites were significantly correlated (rho = 0.49, P = 0.014), but none correlated with any clinical manifestation or antibody profile. The aPL group presented increased levels of sPsel, sEsel, sVCAM-1, TAT, F1 + 2 and DD, but any soluble marker correlated with IPF2alphaIII. Urinary 11-DH-TXB(2) correlated with sPsel (rho = 0.39, P = 0.04). Compared with SLE controls, the SLE group with aPL had higher levels of F1 + 2. Plasma levels of F1 + 2 and DD were significantly increased and a trend to higher sPsel was found in aPL patients with thrombosis compared with the TCG. Platelet activation, lipid peroxidation and blood coagulation activation seem to be important in the pathophysiology of antiphospholipid syndrome.

Thrombophilic factors in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTE-PH) is an infrequent cause of pulmonary hypertension that develops in 0.1-0.2% of patients who survive after an acute venous thromboembolic event. According to the largest series so far reported, 15-30% of patients with diagnosis of CTE-PH have an underlying congenital or acquired hypercoagulable state. To determine the prevalence of thrombophilic factors in our population, we analyzed 24 patients admitted to our institution between November 1992 and March 2000 fulfilling criteria for CTE-PH. Eighteen patients disclosed abnormal results in the screening for thrombophilia. The presence of antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) was the abnormality most frequently found (12 out of 24 patients). We found hyperhomocysteinaemia in 7/14, true protein S deficiency in 1/10, protein C deficiency in 1/13, activated protein C resistance in 1/22, antithrombin III deficiency in 1/24, and prothrombin gene G20210A mutation in 1/18 patients. Factor V Leiden was normal in all 18 patients studied. Five patients (20.8%) disclosed more than one thrombophilic abnormality. In conclusion, contrary to the largest series of patients with CTE-PH so far reported, we found that 75% of patients with CTE-PH presented at least one thrombophilic risk factor, being antiphospholipid antibodies in 50% of the cases. We recommend a thorough screening for thrombophilia in all patients with diagnosis of CTE-PH.

The combination of thrombophilic genotypes is associated with definite antiphospholipid syndrome.

BACKGROUND AND OBJECTIVES: Thrombosis and pregnancy morbidity are clinical features of the definite antiphospholipid syndrome (APS). These clinical complications are also associated with the presence of inherited thrombophilias. Interactions between acquired and genetic risk factors are becoming increasingly related to a higher thrombotic risk. The aim of our study was to determine the prevalence of four common gene polymorphisms in patients with antiphospholipid antibodies (aPL). DESIGN AND METHODS: A series of 105 consecutive unselected patients with aPL grouped as having APS (n= 69) and not having APS (n= 36) was studied. A control group of 200 healthy subjects was also investigated for the presence of factor V Leiden (FVL), the 20210A allele of the prothrombin (PT-20210A) gene, the thermolabile variant (677TT) of methylenetetrahydrofolate reductase (MTHFR), and the 4G/4G genotype of the plasminogen activator inhibitor (PAI-1) promoter. RESULTS: Two patients who belong to the APS group carried the FVL while PT-20210A was found in 6 patients with APS (8.7%) and in 1 of the non-APS group (2.8%). The prevalence of FVL was similar to that found in the control group whereas PT-20210A was significantly more frequent in APS patients than in normal controls (2.0%, p=0.02). The MTHFR-677TT was found in 22.0%, 15.1% and 13.0%, and the PAI-1 (4G/4G) in 27.5%, 22.8% and 23.5% of APS, non-APS patients and normal controls, respectively. Furthermore, combinations of PT-20210A or FVL with PAI-1 (4G/4G) were significantly more frequent in APS patients (5.8%) than in normal controls (0.5%, p=0.016). This difference was not found between non-APS patients and normal subjects. INTERPRETATION AND CONCLUSIONS: Present data indicate that testing for heritable thrombophilia would be important to identify aPL subjects with an increased risk of developing APS.

High prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity.

Antiphospholipid antibodies (aPL) have been reported not only in autoimmune disorders but also in various infectious diseases. Accumulating evidence indicates that beta2 glycoprotein I (beta2GPI) and prothrombin are the main proteins to which autoimmune aPL bind. The aim of this study was to evaluate the prevalence of different aPL in patients with leprosy. We included 51 outpatients (42 lepromatous and 9 borderline leprosy) without any clinical feature of the antiphospholipid syndrome (APS). 35 had lupus anticoagulant and 31 had anticardiolipin antibodies (aCL). Anti-beta2GPI antibodies were highly positive in 29/51 and anti- prothrombin antibodies (anti-II) were detected in 23/51. Almost all aCL and anti-beta2GPI were of IgM isotype, while IgG isotype was more frequent among anti-II. No statistical difference was found when aPL were evaluated in patients grouped according to their bacteriological status. Furthermore, patients under treatment (n=33) had a similar frequency of positive aPL compared to patients in vigilance (n=14). Assessing the specificity of antibody binding to CL and beta2GPI in ELISA by means of inhibition studies with cardiolipin-beta2GPI liposomes, leprosy and APS sera showed a similar behaviour. Comparable results were also found in both groups of patients when inhibition experiments with lysate of Mycobacterium leprae were carried out. In summary, leprosy-related aPL resemble those found in patients with APS but the immunoglobulin isotype is different, with IgM much more prevalent in leprosy patients.

Which are the best biological markers of the antiphospholipid syndrome?

The diagnosis of antiphospholipid syndrome (APS) requires the presence of both clinical and biological features. Due to the heterogeneity of anti-phospholipid antibodies (aPL) the laboratory approach for their detection includes clotting-based tests for lupus anticoagulant (LA) as well as solid-phase assays for anticardiolipin antibodies (aCL). In addition, as it has been shown that autoimmune aPL recognize epitopes on phospholipid (PL)-binding plasma proteins, assays detecting antibodies to beta 2-glycoprotein I (beta 2-GPI) or prothrombin have been developed. The association between venous or arterial thrombosis and recurrent fetal loss with the presence of conventional aPL (LA and/or aCL) has been confirmed by many studies. The LA and IgG aCL at moderate/high titre seem to exhibit the strongest association with clinical manifestations of the APS. Several reports indicate that LA is less sensitive but more specific than aCL for the APS. Assays against PLs other than CL as well as the use of mixtures of PLs have been proposed to improve the detection of APS-related aPL. Concerning antibodies to PL-binding proteins (detected in the absence of PLs), there is evidence that anti-beta 2-GPI are closely associated with thrombosis and other clinical features of the APS. Moreover, these antibodies may be more specific in the recognition of the APS and in some cases may be present in the absence of aPL detected by standard tests. Many issues are still under debate and are discussed in this review, such as the problems of standardization of anti-beta 2-GPI assays, detection of the IgA isotype of aCL and anti-beta 2-GPI, the coagulation profiles of LA in the recognition of the thrombotic risk and the association of particular markers with subsets of patients with APS.

Evaluation of red blood cell aggregation in diabetes by computerized image analysis.

Red blood cell (RBC) aggregation has been widely studied and its importance is well established in the rheology of microcirculation. RBC aggregation is a major factor responsible for the flow properties of blood. Increased RBC aggregation has been observed in several pathological states. Therefore, the measurement of erythrocyte aggregation is rheologically important for quantifying flow abnormality in pathological conditions. Normal RBC under low flow or at rest form rouleaux aggregates, while abnormal RBC aggregation may lead to the formation of irregular aggregate structures, which may be induced by cell-associated factors (reduced membrane sialic acid levels) but also by extracellular factors. The main objective of the present investigation was to study RBC aggregate morphology in diabetic patients, using direct microscopic observation and numerical processing of recorded digitized images. Blood samples were obtained from 20 diabetic patients and from 15 normal control subjects. The aggregate morphology was quantified by the so-called Aggregate Shape Parameter (ASP) defined as the ratio of the aggregate projected area to its square perimeter. ASP appeared significantly higher (p < 10(-5)) in diabetic patients (0.65 +/- 0.18) than in normal controls (0.28 +/- 0.15). This rheo-optical method based on the theoretical model for rouleaux aggregates provides a useful reference for measuring deviations of RBC aggregate morphology. Increased aggregation of RBC resulting from a decreased sialylation of glycophorins may be an important factor in the development of vascular diseases and in the microcirculation impairment.