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BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Thrombotic thrombocytopenic purpura (TTP) is a rare and unpredictable disease with a high mortality rate (90%) if untreated. It results from systemic microvascular thrombosis and leads to profound thrombocytopenia, hemolytic anemia and organ failure of varying severity. However, macrovascular thrombosis has been described in very rare cases. Caplacizumab has emerged as a promising new drug for the management of TTP. We report the case of a patient with idiopathic refractory TTP treated with caplacizumab who developed thrombotic complications upon discontinuation of treatment.

OBJECTIVES: COVID-19 predisposes patients to thrombotic disease. The aim of this guidance document is to provide Belgian health-care workers with recommendations on anticoagulation management in COVID-19 positive patients. METHODS: These recommendations were based on current knowledge and a limited level of evidence. RESULTS: We formulated recommendations for the prophylaxis and treatment of COVID-related venous thromboembolism in ambulatory and hospitalised patients, as well as recommendations for the use of antithrombotic drugs in patients with prior indication for anticoagulation who develop COVID-19. CONCLUSIONS: These recommendations represent an easy-to-use practical guidance that can be implemented in every Belgian hospital and be used by primary care physicians and gynaecologists. Of note, they are likely to evolve with increased knowledge of the disease and availability of data from ongoing clinical trials. ispartof: ACTA CLINICA BELGICA vol:77 issue:2 pages:280-285 ispartof: location:England status: published

Le Groupe d’intérêt en hémostase périopératoire (GIHP) et le Groupe français d’études sur l’hémostase et la thrombose (GFHT), en collaboration avec la Société française d’anesthésie et de réanimation (SFAR) ont fait des propositions de gestion des agents antiplaquettaires (AAP) pour une procédure invasive programmée. Ces propositions ont été discutées et validées par vote ; toutes sauf une ont fait l’objet d’un accord fort. La gestion des AAP dépend de leur indication et de la procédure considérée. Le risque hémorragique lié à la procédure invasive peut être divisé en bas, intermédiaire ou élevé, selon la possibilité ou non de réaliser la procédure sous traitement (sous respectivement bithérapie antiplaquettaire, aspirine en monothérapie ou aucun AAP). Si une interruption des AAP est indiquée avant la procédure, une dernière prise d’aspirine, clopidogrel, ticagrélor et prasugrel 3, 5, 5 et 7 jours avant la procédure est proposée. Le risque thrombotique associé à l’interruption des AAP doit être évalué en fonction de l’indication des AAP. Il est plus élevé chez les patients traités par bithérapie pour un stent coronaire que chez ceux traités par monothérapie pour une prévention cardiovasculaire, un antécédent d’accident vasculaire cérébral ischémique ou une artériopathie oblitérante des membres inférieurs. Ces propositions concernent aussi le rôle potentiel des tests fonctionnels plaquettaires, la gestion des AAP pour l’anesthésie locorégionale, centrale et périphérique, et pour la chirurgie cardiaque coronaire.

Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic disease characterised by its potential severity, mainly related to thrombosis, and by difficulties regarding its diagnosis and management of affected patients. In 2002, a conference of experts mobilised by the French Society of Anaesthesia and Intensive Care Medicine (Société française d’anesthésie et de réanimation [SFAR]) drafted recommendations for the management of HIT [...]

Resume Le Groupe d’interet en hemostase perioperatoire (GIHP) et le Groupe francais d’etudes sur l’hemostase et la thrombose (GFHT), en collaboration avec la Societe francaise d’anesthesie-reanimation (SFAR) ont fait des propositions de gestion des agents antiplaquettaires (AAP) pour une procedure invasive programmee. Ces propositions ont ete discutees et validees par vote ; toutes sauf une ont fait l’objet d’un accord fort. La gestion des AAP depend de leur indication et de la procedure consideree. Le risque hemorragique lie a la procedure invasive peut etre divise en bas, intermediaire ou eleve, selon la possibilite ou non de realiser la procedure sous traitement (sous respectivement bitherapie antiplaquettaire, aspirine en monotherapie ou aucun AAP). Si une interruption des AAP est indiquee avant la procedure, une derniere prise d’aspirine, clopidogrel, ticagrelor et prasugrel 3, 5, 5 et 7 jours avant la procedure est proposee. Le risque thrombotique associe a l’interruption des AAP doit etre evalue en fonction de l’indication des AAP. Il est plus eleve chez les patients traites par bitherapie pour un stent coronaire que chez ceux traites par monotherapie pour une prevention cardiovasculaire, un antecedent d’accident vasculaire cerebral ischemique ou une arteriopathie obliterante des membres inferieurs. Ces propositions concernent aussi le role potentiel des tests fonctionnels plaquettaires, la gestion des AAP pour l’anesthesie locoregionale, centrale et peripherique, et pour la chirurgie cardiaque coronaire.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Background: Prostate biopsy is a rather frequent procedure, mostly performed in outpatient settings. Bleeding complications following this procedure require precise and delicate management of pre-, peri- and post-procedure anti-coagulation treatments. New oral anti-coagulation drugs (NOACs) are increasingly used. However, the management of such treatments is feared and not yet well known to urologists. A protocol for prostate biopsy management of NOACs seems mandatory. Materials and methods: A review of the literature, using Pubmed and Cochrane databases, together with analysis of several medical associations’ recommendations in urology, anaesthesiology, cardiology, oncology and drug safety agency, was performed. Results: There are no recommendations about NOAC management for prostate biopsy available from scientific societies. There is also a lack of specific urological studies. However, several panels of expert recommendations could be helpful in establishing standardized protocols adapted from surgery to prostate biopsy. With the growing use of NOACs, recommendations have shifted to continue anti-coagulant treatment without bridging NOACs for low bleeding risk procedures such as prostate biopsy, in carefully selected groups of patients. Conclusion: Extensive indications coupled with the ease of use of NOACs contribute significantly to the widespread replacement of traditional vitamin K antagonist. Knowing that heparin bridging leads to more bleeding, and in the pursuit of more autonomy and safety, urologists should be able to propose dedicated anti-coagulant management using NOACs adapted to carefully selected patients before the prostate biopsy procedure. Further studies and guidelines specific to the concept of non-bridging for anti-coagulant-requiring patients are mandatory for this routine procedure., SCOPUS: re.j, info:eu-repo/semantics/published

International audience

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery., SCOPUS: ar.j, info:eu-repo/semantics/published

The objective of this study was to estimate the total hospital cost per patient admitted through the emergency department with a primary diagnosis of pulmonary embolism (PE), and to identify the main components and predictors of costs.Actual costs of care of 652 consecutive patients hospitalised in 10 general hospitals in Belgium, including 31 outlier patients in terms of length of stay (4.8%), were obtained by aggregating all cost components contributing to care of each patient.In both inlier and outlier patients, the mean total cost per patient increased linearly with the degree of severity of illness classes related to the All Patient Refined Diagnosis Related Group (pAn increasing burden of comorbid illness was strongly associated with increasing actual cost for caring hospitalised patients for PE. Increasing age was associated with an increase in all main cost components.

Background: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients agedMethods: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (kappa = 0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively.Conclusion: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm. (C) 2015 Elsevier Ltd. All rights reserved.

SUMMARY Many patients receiving regular oral anticoagulation will need to undergo surgery at some point. However, the optimal management of such patients is uncertain. Various approaches have been suggested, but the strategy adopted must take into account each patient’s risk factors for thromboembolism as well as the type and likely duration of the surgical procedure. The objective of this review is to summarize the possible approaches to the management of orally anticoagulated patients requiring surgery and, in so doing, to provide a practical perioperative anticoagulation management scheme that can be used in daily practice.

To describe risk assessment models that have been developed to stratify patients into different risk levels of postoperative venous thromboembolism (VTE) and then to review the different methods of prophylaxis and to outline the evidence supporting their effectiveness and safety.Our review of the literature is focused on consensus documents, recent large randomized trials and meta-analyses.The risk of VTE is determined by the type of surgery and underlying patient factors. Risk assessment models are useful in stratifying patients into different VTE risk levels. However, multiple risk factors are often present in the same patient and in practice the evaluation of their relative contribution to the overall risk remains difficult. A variety of prophylactic strategies including physical and pharmacological methods have been shown to be effective in different patient groups. Patients with a moderate or high risk of VTE should receive prophylaxis consisting of an antithrombotic agent, unless contraindicated, used alone or in combination with a mechanical method. Recommendations concerning which prophylaxis to use and how intensive it should be are based mainly on data from trials using surrogate endpoints, and do not translate easily into practical decisions aiming to reduce the incidence of symptomatic events.Although risk assessment models and recommendations provided by consensus documents are of practical assistance, a decision concerning any patient is best made by combining recommendations of the literature with clinical judgment, including individual patient risk factors for thrombosis and bleeding.

Background Forty to 50 % of hospitalized patients with an acute medical illness have risk factors for venous thromboembolism (VTE) and it has been shown that VTE prophylaxis reduced the incidence of VTE events in these patients. However, a large multinational survey, the ENDORSE study, showed that only 37 % of medical patients with VTE risk factors actually received VTE prophylaxis. Objective To evaluate the impact over time of pharmacist-driven interventions aiming at increasing the appropriate use of VTE prophylaxis in acutely ill medical hospitalized patients. Setting A Belgian urban academic hospital. Method First, during 1 month, medical and nurse reports of all hospitalized medical patients were reviewed to evaluate the proportion of patients who were on prophylaxis according to clinical practice guidelines. Second, interventions were conducted and included unit-specific physician and nurse education, diffusion of educational tools summarizing VTE prophylaxis guidelines, and reminders. Third, the impact of the interventions on the proportion of patients receiving VTE prophylaxis according to clinical practice guidelines was evaluated after 3 months and 1 year. Main outcome measure Proportion of hospitalized medical patients receiving VTE prophylaxis according to clinical practice guidelines. Results The baseline evaluation showed that 36 % (26/72) of the patients at risk of VTE received VTE prophylaxis according to clinical practice guidelines. Three months and one year after the interventions, 68 % (55/81), and 72 % (58/81) of the patients at risk of VTE received VTE prophylaxis according to clinical practice guidelines. Among patients not at risk of VTE, 15 % (21/141), 8 % (24/290), and 8 % (27/330) respectively at baseline evaluation, 3 months and 1 year after the interventions, received VTE prophylaxis. Conclusion Pharmacist-driven interventions improved the proportion of acutely ill medical patients receiving VTE prophylaxis according to clinical practice guidelines and the benefit of the interventions was maintained after 1 year.

Abdominal aortic coarctation is found in only 2% of aortic coarctation and is usually manifested by renovascular hypertension. Splanchnic arterial occlusive lesions occur in 22% of these patients and are exceptionally symptomatic. We present a case report of a young patient with abdominal aortic coarctation causing hypertension and visceral angina. The aetiopathogeny and treatment are discussed.

Purpose: To describe an exclusion endoluminal technique for management of abdominal aortic aneurysms among high-risk patients with complex anatomic features. Methods: From January 1995 to December 1996, among 143 patients with infrarenal abdominal aortic aneurysm treated by means of endograft placement, 9 (6.3%) had complex aortic or aortoiliac morphologic features. For these patients, the endograft was delivered through a femoral cutdown in an occluding aortoiliac configuration. The contralateral iliac artery was occluded with an iliac endograft. Axillofemoral bypass grafting was performed. Computed tomographic scans were obtained regularly. Results: There was 1 postoperative death of severe arrhythmia. All aneurysms were found to be affected by thrombosis on immediately postoperative computed tomographic scans, except in 1 patient with a proximal leak, which was managed successfully with angiographic embolization. The mean follow-up time was 12 months. Aortic aneurysm diameter decreased from 2 mm at 6 months (2 patients) to 6 mm at 12 months (6 patients). All axillofemoral bypass grafts are patent. Conclusions: Placement of an occluding endograft associated with axillofemoral bypass grafting is a good alternative for patients at high risk with complex anatomic features. Longer-term follow-up study is needed to evaluate this endoluminal technique. (J Vasc Surg 1998;28:651-6.)

We describe the case of a patient with adventitial cystic disease of the popliteal artery in which a direct anatomic communication between the cysts and the nearby knee joint was demonstrated by magnetic resonance imaging and confirmed by surgery. This unusual observation could shed some light on the much debated question of the cause, the pathogenesis, and the management of the affection. Moreover, it emphasizes the importance and the role of magnetic resonance imaging in the diagnosis of adventitial cystic disease of the popliteal artery.

We report two cases of septic arthritis of the knee caused by Aspergillus: one by Aspergillus terreus in a cirrhotic patient and the other by Aspergillus fumigatus after vascular graft infection. The recovery of these organisms in synovial fluid should be considered as pathogenic, particularly in immunocompromised hosts. The pathogenic mechanism is discussed and the literature is reviewed.

The number of hospitalizations for atrial fibrillation has increased dramatically. This increase, in the number of hospital stays will continue, given the growth projections based on epidemiological data, and will contribute to significantly increase expenses for the social security system.The objective of this study was to evaluate the length of hospital stay, the average cost borne by social security, and the types of hospital stay expenditures for patients admitted through the emergency department for atrial fibrillation.Patients were identified by using the minimal clinical summaries of seven general hospitals in Belgium in 2008. Only hospitalized patients having as primary diagnosis code ICD-9-CM 42731 'atrial fibrillation'were selected for this study. Hospital billing files were analysed in order to isolate the costs borne by social security. Outliers were isolated in order not to have results influenced by patients having an atypical length of stay.Results show that the mean length of stay was 8.6 days and the mean cost charged to social security was euro 3,066.02 per hospital stay.The mean cost of care was strongly associated with the degree of severity index related to the APR-DRG. Approximately 85% of the total cost was related to the cost of hospital days and medical procedures with medical imaging and laboratory tests being the two main cost inductors. 18% of patients had cardioversion during their hospital stay, including 4% who had only that treatment. 19% of patients used amiodarone. Flecainide and propafenone were also used, but less frequently.The mean cost of care for AF patients admitted via the emergency department is strongly associated with the degree of severity. Approximately 85% of the total cost is related to the cost of hospital days and medical procedures. Hypertension is the most common secondary diagnosis. An optimal treatment of this risk factor could help to reduce the risk of atrial fibrillation, and thereby reduce the morbidity and costs associated with this disease.

The P2Y4 receptor is a new member of the P2Y family which functionally behaves as a pyrimidinergic receptor. The pharmacological properties of the human P2Y4 receptor have been characterized following its stable expression in 1321N1 astrocytoma cells. UTP induced a biphasic accumulation of inositol trisphosphates, with an early peak at 30 s followed by a smaller but more sustained accumulation. ATP was a pure antagonist at early times and later behaved as a partial agonist. At 20 min, the rank order of potency of various nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP. Diadenosine polyphosphates also stimulated the production of inositol trisphosphates (after 20 min), more potently than ATP, but their maximal effect represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited strongly the UTP response, whereas suramin was inactive and reactive blue 2 had an intermediate effect. Pertussis toxin inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4 receptor can exist in two distinct activation states differing in terms of time-course, specificity for uridine nucleotides and G-protein coupling.

1. Adenine nucleotides stimulate the synthesis and release of prostacyclin and nitric oxide (two potent platelet aggregation inhibitors) by endothelial cells from different origins. These responses are mediated by P2 purinergic receptors, coupled to the production of inositol (1,4,5)trisphosphate (InsP3) and to the increase of intracytoplasmic calcium concentration. 2. In bovine aortic endothelial cells (BAEC), both 2-MeSATP and UTP stimulate the production of InsP3. By experiments of additivity and cross desensitization, we have confirmed the expression of both P2Y/P2Y1 and P2U/P2Y2 receptors on these cells. Moreover, these receptors are not segregated on different subpopulations but are co-localized on the same cells. 3. The action of UTP on InsP3 production was inhibited by pertussis toxin and was unaffected by a pretreatment with phorbol 12-myristate, 13-acetate (PMA). On the other hand, the response induced by 2-MeSATP was inhibited by PMA but insensitive to pertussis toxin. These results suggest that P2Y/P2Y1 and P2U/P2Y2 receptors are respectively coupled to Gq/G11 and G1 proteins. 4. Northern blotting experiments revealed the expression of the P2Y1 (doublet of 2 and 2.2 kb) and of the P2Y2 (2.4 kb) receptor messengers in BAEC. A signal corresponding to the P2Y2 mRNA was also detectable in human umbilical vein endothelial cells. 5. These various results thus demonstrate the expression of the P2Y1 and P2Y2 receptors in vascular endothelial cells.

It has recently been demonstrated that two types of ATP receptors, the P2Y and P2U receptors, are coexpressed on bovine aortic endothelial cells. The aim of the present study was to characterize directly P2Y and P2U subtypes on intact bovine aortic endothelial cells and on membranes prepared from these cells using adenosine 5'-0-(3-thio[35S]triphosphate) ([35S]ATP gamma S), [alpha-32P]ATP and [alpha-32P]UTP as radioligands. [35S]ATP gamma S binding to bovine aortic endothelial cell membranes was saturable and apparently involved a single class of high-affinity binding sites (Kd: 14 +/- 11 nM. Bmax 1.6 +/- 0.7 pmol/mg protein; mean +/- S.D.). A similar class of high-affinity binding sites was identified with [alpha-32P]ATP (Kd: 14 +/- 9 nM; Bmax: 1.7 +/- 1.1 pmol/mg protein; mean +/- S.D.). Competition experiments showed that only one third of these sites bound 2-methylthio-ATP (2-MeSATP) with high affinity (Ki: 21 +/- 5 and 14 +/- 10 nM, mean +/- S.D., for [35S]ATP gamma S and [alpha-32P]ATP, respectively) and might therefore represent the P2Y receptors. UTP did not compete with [35S]ATP gamma S or [alpha-32P]ATP for binding at the remaining sites, indicating that they are not the P2U receptors. No high-affinity UTP binding sites could be detected using [alpha-32P]UTP. [35S]ATP gamma S binding to intact bovine aortic endothelial cells was competed by ATP gamma S (Kd: 1.0 +/- 0.5 microM; mean +/- S.D.), but not by 2-MeSATP and UTP, indicating that these binding sites are neither the P2Y nor the P2U receptors.

We used polymerase chain reaction (PCR) to detect cytomegalovirus (CMV) deoxyribonucleic acid (DNA) in the bronchoalveolar lavages (BAL) of 16 CMV-infected patients with active disease. We also tested PCR on a control group of 20 patients including latently infected patients without evidence of active CMV infection. Results were compared with those of CMV culture and of a rapid method of diagnosis which detects CMV in BAL cells by nucleic acid hybridization. PCR allowed the diagnosis in 93% of the actively infected patients compared to 73% for the CMV culture. Among the 20 control patients without evidence of active CMV infection, PCR was negative in all the 24 BAL tested. Hybridization on BAL cells with the CMV probe detected nine out of 10 actively infected patients, but the specificity of the test was only 68.5%. In our experience, PCR appears to be at least as sensitive as CMV culture, it provides results faster and it performs better than the detection of the virus by hybridization on BAL cells. Only active CMV infection was detected with the PCR conditions used in our study. This suggests that the PCR can be applied to bronchoalveolar lavage fluids as a rapid method to detect CMV lung infection.

Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP receptors might coexist on endothelial cells. To evaluate this hypothesis, we examined the effects of P2y receptor agonists 2-methylthioadenosine 5'-triphosphate (2MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) and of UTP on the accumulation of inositol phosphates in bovine aortic endothelial cells. BzATP, 2MeSATP, and UTP produced a smaller maximal effect than ATP. The effects of 2MeSATP and UTP were additive, whereas the effects of ATP and either UTP or 2MeSATP were not. Prior exposure to UTP reduced the subsequent response to UTP to 12% of the control response, whereas the response to 2MeSATP was decreased to 61%. Reciprocally, preincubation with 2MeSATP reduced the subsequent response to 2MeSATP to 23% of the control response, whereas the response to UTP was reduced to 73%. Pertussis toxin pretreatment decreased the response to both ATP and UTP (65% and 70% inhibition, respectively), whereas the response to 2MeSATP was not modified. Our data support the hypothesis that two classes of receptors recognizing ATP are expressed on bovine aortic endothelial cells.

We report an unusual case of vascular graft infection caused by Aspergillus fumigatus that began with a false aneurysm, major arterial emboli, and septic arthritis. Successful treatment included resection of the infected graft, restoration of circulation by extraanatomic bypass, and administration of amphotericin B and itraconazole, a new antifungal agent. Graft infection in the case reported herein most likely occurred during surgery and took place during an insidious outbreak of postoperative infection.

INTRODUCTION: The Wells score is widely used in the assessment of pretest probability of pulmonary embolism (PE). The revised Geneva score is a fully standardized clinical decision rule that was recently validated and further simplified. We compared the predictive accuracy of these two scores. METHODS: Data from 339 patients clinically suspected of PE from two prospective management studies were used and combined. Pretest probability of PE was assessed prospectively by the Wells score. The simplified revised (SR) Geneva score was calculated retrospectively. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The overall prevalence of PE was 19%. Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4% (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81). The Wells score performed better than the simplified revised Geneva score in patients with a high suspicion of PE (p

The P2 purinoceptors were initially defined as a family of receptors responsive to extracellular adenine nucleotides. In the late 1980s, it became clear that extracellular uridine nucleotides are also able to modulate cell function. The existence of a nucleotide receptor, common to ATP and UTP, was suggested by indirect pharmacological arguments (for instance the lack of additivity and the cross-desensitization of the responses to the two nucleotides) and later demonstrated by the cloning of a P2U receptor equally responsive to ATP and UTP. Vascular endothelial cells are a paradigm of cells on which both ATP and UTP exert physiologically relevant effects (stimulation of prostacyclin and nitric oxide release). Their response to nucleotides is mediated by two distinct receptors, both coupled to phospholipase C: a specific purinoceptor responsive to ATP and ADP (P2Y) and a nucleotide receptor responsive to ATP and UTP (P2U). We have recently cloned from the human genome a new subtype of receptor (tentatively called P2Y4), which is structurally related to the P2U receptor. Functional expression revealed its coupling to phospholipase C and its selective responsiveness to UTP and UDP. According to the new nomenclature, the P2 receptors that are coupled to G proteins belong to the P2Y family. It now appears that this family encompasses specific purinoceptors (P2Y1, formerly called P2Y), nucleotide receptors common to ATP and UTP (P2Y2, previously P2U) and selective pyrimidinoceptors (P2Y4). The existence of these pyrimidinoceptors suggests that uridine nucleotides may play a role as intercellular mediators, independently from adenine nucleotides.

To describe the drugs used to treat venous thromboembolism (VTE) and to review particular aspects of the management (elastic stockings, thrombolysis, thrombectomy, vena cava filter).Our review of the literature is focused on consensus documents and recent large randomized trials.Subcutaneous low molecular weight heparins (LMWH) have been shown to be both safe and effective for the initial treatment of VTE and have largely replaced unfractionated heparin, unless there is a contraindication to LMWH such as severe renal insufficiency. Low molecular weight heparins or unfractionated heparin are usually administered for five to seven days. Treatment is gradually switched from heparin to oral vitamin K antagonists (VKA) which are usually started the same day as heparin. The duration of oral anticoagulation must be tailored to the individual patient according to the presence of reversible or continuing risk factors. In patients with active cancer, long-term treatment of VTE with LMWH has been shown to be more effective than oral anticoagulation and is recommended for the first three to six months of long-term anticoagulant therapy as an alternative approach to VKA. Elastic stockings are recommended because they have been shown to prevent postthrombotic syndrome. Thrombolysis is, usually, not justified for the treatment of deep venous thrombosis, but is used in cases of massive pulmonary embolism with arterial hypotension and/or shock. Vena cava filter placement is mainly indicated in patients with a proximal deep venous thrombosis and an absolute contraindication to anticoagulation.The initial management of patients with acute VTE has largely been simplified due to the use of LMWH. Early conversion to VKA is recommended for the great majority of patients. New agents, such as anti-Xa or oral thrombin inhibitors, are promising alternatives to heparins or VKA.

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The earliest papers reporting a stimulatory effect of extracellular nucleotides on inositol phosphate formation were published in 1985–1987 (Charest et al., 1985; Horstman et al., 1986; Pirotton et al., 1987; Forsberg et al., 1987). Since then the number of organs and cells in which nucleotides have been shown to produce an accumulation of inositol phosphates has been growing. A list which is not claimed to be exhaustive is provided in Table 1. These actions are mediated by at least two distinct receptors, P2Y and P2U, which have been identified according to the rank order of potency of various natural and synthetic agonists and on the basis of cross-desensitization experiments. Basically, the P2Y receptor is characterized by the high potency of 2-Methylthio ATP (2MeSATP) and related agonists (Burnstock et al., 1994), similar potencies of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) (the ratio being somewhat variable from one system to the other) and the lack of activity of UTP. It became apparent in the late eighties that, in many tissues and cells, not only ATP but also UTP is able to induce inositol phosphate formation. At that time it was proposed that the action of UTP is mediated by specific pyrimidinoceptors distinct from the purinoceptors (Seifert and Schultz, 1989). The existence of nucleotide or P2U receptors common to ATP and UTP constituted an alternative possibility, in favor of which experimental evidence started to accumulate: mainly the lack of additivity and the cross-desensitization of the responses to the two nucleotides (Brown et al., 1991; O’Connor et al., 1991; O’Connor, 1992).

The role of ATP and ADP as intercellular mediators is now well established. The presence of the nucleotides in extracellular fluids can result from several mechanisms: cell lysis, selective permeabilization of the plasma membrane and exocytosis of secretory vesicles, such as platelet dense bodies. Extracellular adenine nucleotides are rapidly degraded by ectonucleotidases expressed inter alia on the surface of endothelial cells. They act on cells via the family of P2 receptors which encompasses more than 5 subtypes, some of which have been cloned recently. The P2T, P2U and P2Y receptors belong to the superfamily of receptors coupled to G proteins, whereas the P2X receptor is a cation channel and the P2Z receptor a non-selective pore. ATP and ADP stimulate the endothelial production of prostacyclin (PGI2) and nitric oxide (NO), two vasodilators and inhibitors of platelet aggregation, via an increase in cytosolic Ca2+. This action of adenine nucleotides is believed to limit the extent of intravascular platelet aggregation and to help localize thrombus formation to areas of endothelial damage. The endothelial response to nucleotides is mediated by at least two distinct subtypes of P2 receptors, P2Y and P2U, both coupled to phospholipase C.

It is generally considered that patients with rest pain and/or ulceration have a bad prognosis independent of the type of treatment given. Many factors can reasonably explain this evolution; the main ones are: multifocal atherosclerotic disease in most instances with a high death frequency secondary to myocardial infarction and stroke, morbidity and mortality secondary to amputations, and higher risk of both arterial and venous thromboembolic disease.

1. The response of bovine aortic endothelial cells to adenosine 5'-triphosphate (ATP) is mediated by both P2y and nucleotide/P2u receptors. In order to determine which form of the nucleotide is the true ligand of these receptors, we have investigated the effects of divalent cations on ATP-, uridine 5'-triphosphate (UTP)- and 2 methylthioadenosine 5'-triphosphate (2MeSATP)-induced inositol phosphate accumulation in these cells. 2. Omisson of Mg2+ from a calcium-free incubation buffer caused a shift to the left of the ATP concentration-action curve. 3. In the presence of EDTA (1 mM), the basal level of inositol trisphosphate (InsP3) was markedly increased and the absolute maximal response to ATP was decreased; however, the response to low concentrations of ATP was enhanced. 4. When the results were plotted in terms of calculated ATP4- concentrations, the concentration-response curves obtained in the presence of 1.25 mM Mg2+ lay closer to the respective curves obtained when Mg2+ was omitted from the medium or when Mg2+ was omitted and EDTA (1 mM) was added. The curves became almost superimposable when the baseline value was subtracted. 5. A similar shift to the left of the concentrations-action curves was also observed with both UTP and 2MeSATP. 6. Our data provide evidence that a form of ATP uncomplexed with divalent cation is the preferential agonist of both the nucleotide/P2u and the P2y receptors expressed on bovine aortic endothelial cells.

The purpose of this study was to identify patients who were more likely to experience septicemia after endoscopic biliary drainage. In an attempt to determine the relative importance of each risk factor and their possible interdependancy to more precisely identify high-risk patients and to deduce some guidelines for prevention, a discriminant regression analysis of risk factors for septicemia was used. Clinical, biological, and radiological data of 34 consecutive patients who experienced septicemia within 3 days after endoscopic biliary stenting were reviewed retrospectively and compared with data of a group of 71 patients without any septic complication. If only data available before the procedure were used in the discriminant analysis, prior cholangitis and leucocytosis appeared as significant risk factors, but the linear combination of these data could not predict septicemia in 50% of cases. When information concerning the quality of drainage after the procedure was introduced into the analysis, 91% of the septicemic patients were identified, and other expected risk factors such as the nature of the stricture, the type of drainage, or prior cholangitis and leukocytosis had no or marginal predictive values. Patients referred from centers where duodenoscopes might have been poorly disinfected appeared to be at higher risk for Pseudomonas aeruginosa septicemia. These results emphasize the crucial role of the quality of drainage as a risk for septicemia. Regarding the prevention of infection, it is concluded from this study that (a) pure diagnostic endoscopic retrograde cholangiopancreatography should be avoided in obstructed patients if drainage cannot be performed during the same procedure; (b) drainage should be as complete as possible; (c) antibiotics should be administered before ERCP to every patient with suspected obstructive jaundice and should cover P. aeruginosa if local epidemiological data suggest that there is a problem with disinfection of the endoscopes; and (d) the quality of drainage should guide the duration of antibiotic prophylaxis.

Because of their antimicrobial activity and pharmacologic properties, fluoroquinolones should be particularly suitable for the treatment of lower respiratory tract infections, although they might be less efficient in pneumococcal diseases. In fact, the overall clinical success rate of enoxacin, ofloxacin, pefloxacin, and ciprofloxacin is greater than 85%, and their efficacy compares favorably with that of other antibiotics. For acute exacerbation of chronic bronchitis, however, beta-lactam or macrolide agents probably remain a first choice unless sputum reveals gram-negative pathogens; in the same way, drugs other than quinolones seem better indicated in community-acquired pneumonia because of the prevalence of Streptococcus pneumoniae in these infections. In contrast, nosocomial pulmonary infections due to gram-negative pathogens should be excellent candidates for therapy with new quinolones. These drugs, used with or without erythromycin and rifampin, might be useful in the treatment of legionnaires' disease.

Resume L'implantation des corps etrangers les plus divers (protheses, catheters vasculaires et urinaires, …) s'est largement devaloppee ces dernieres annees. L'infection de protheses — « sanctuaire privilegie de l'infection— d'incidence faible pour la plupart d'entre elles est cependant de consequences cliniques souvent desastreuses. Les differents modes de contamination du materiel prothetique (souillure per-operatoire, ensemencement hematogene) sont discutes, de meme que les principes de prevention de greffe septique lors d'une bacteriemie au niveau du bioimplant. Le caractere insidieux de l'infection de certaines protheses est souligne, de meme que l'interpretation parfois difficile de prelevements bacteriologiques au site presume de l'infection. Enfin, quelques methodes experimentales de prevention de l'infection sur corps etrangers sont brievement evoquees.

After massive alcohol intake, a patient under disulfiram therapy developed a severe cardiovascular collapse unresponsive to dopamine but successfully reversed with norepinephrine. Resistance to dopamine could be related to norepinephrine depletion caused by disulfiram. Norepinephrine could, therefore, represent the treatment of choice of these life-threatening conditions.

Glomerular filtration rate (GFR) may be computed using the kinetics of the renal distribution volume curve Vt = Rt/Pt and a power fit of the plasma curve Pt = Pot-B. It can be demonstrated that GFR = d(Vt)/d(t)(1-B). The method is largely independent of background subtraction, allowing nonequivocal renal function determination in all cases. In a preliminary series of 20 patients, the linear regression coefficient of computed GFR with true clearance measurement by multiple blood samples method was 0.97 with a standard error on the estimate of the clearance of 5.5 ml.