Pathologies mimicking deep venous thrombosis of the legs : pictorial review of US findings : P27

Purpose: Precise diagnosis of DVT of the legs is a challenging problem, not only in front of suspicion of PE, but also in all status of leg pain, warmth and swelling. Clinical diagnosis has a low accuracy and further investigations are mandatory in order to diagnose DVT. Amongst the possible investigations, US has a high specificity and a good NPV. However, many pathologies unrelated to the veins may mimic the signs and symptoms of DVT and have to be recognized in order to make the correct diagnosis. The purpose of this paper is to review the results of the US investigations of the legs performed in our Department during the last three years for a suspicion of DVT and describe alternative diagnoses mimicking DVT. Methods and materials: Through a RIS-based search, we retrospectively reviewed all the cases of US of the legs performed in our Department between January 2006 and December 2008 for a suspicion of DVT. We selected the cases of positive findings unrelated to the veins and illustrated these findings with characteristic images. Results: 419 US of the legs were performed between December 2006 and December 2008 for a suspicion of DVT. Among these, 75 were positive for DVT, and 79 for alternative diagnosis. The most common alternative diagnosis was edema of the legs (31%), followed by hematoma (23%). Other findings were Baker cysts (13%), cellulitis (10%) and lymphoceles (5%). Rare diagnoses were arterio-venous malformations, pseudoaneurysms, pelvic masses, necrosing fasciitis, intramuscular abscesses, subcutaneous seromas, sarcoma and ganglion cysts. Conclusion: A greater knowledge of the US appearance of the pathologies mimicking DVT may help to make the correct diagnosis, avoiding further expensive investigations or inappropriate anticoagulant therapy.

Portal vein embolization: what do we know?

Portal vein embolization (PVE) has been developed to increase the size of the future remnant liver (FRL) left in place after major hepatectomy, thus reducing the risk of postoperative liver insufficiency. PVE consist in embolizing preoperatively portal branches of the segments that will be resected. Indication is based on preoperative measurements of the FRL by computed tomography and its ratio with either the theoretical liver volume or by direct measurement of the functional liver volume. After PVE, the volume and function of the FRL increases in 3 to 6 weeks, permitting extensive resections in patients otherwise contraindicated for liver resection. The PVE technique is variable from one center to another; however n-butyl-cyano-acrylate provides an interesting compromise between hypertrophy rate and procedure risk.

The vasodilatory effect of juxta-arteriolar microinjection of endothelinA receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas.

Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

Detection of coronary thrombosis after multi-phase postmortem CT-angiography.

The aim of this study was to compare postmortem angiography-based, autopsy-based and histology-based diagnoses of acute coronary thrombosis in a series of medicolegal cases that underwent postmortem angiographies according to multiphase CT-angiography protocol. Our study included 150 medicolegal cases. All cases underwent native CT-scan, postmortem angiography, complete conventional autopsy and histological examination of the main organs and coronary arteries. In 10 out of the 150 investigated cases, postmortem angiographies revealed coronary arterial luminal filling defects and the absence of collateral vessels, suggesting acute coronary thromboses. Radiological findings were confirmed by autopsy and histological examinations in all cases. In 40 out of 150 cases, angiograms revealed complete or incomplete coronary arterial luminal filling defects and the presence of collateral vessels. Histological examinations did not reveal free-floating or non-adherent thrombi in the coronary arteries in any of these cases. Though postmortem angiography examination has not been well-established for the diagnosis of acute coronary thrombosis, luminal filling defects in coronary arteries suggesting acute thromboses can be observed through angiography and subsequently confirmed by autopsy and histological examinations.

Predictors of the Indefinite Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved.Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment.Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Vascular postpneumonectomy syndrome: inferior vena cava and pulmonary vein compression as unusual cause for platypnea-orthodeoxia following pneumonectomy

Background: Excessive mediastinal shift into the vacated thoracic cavity after pneumonectomy can result in dyspnea without hypoxemia by compression of the tracheobronchial tree, a phenomenon called postpneumonectomy syndrome. More rarely hypoxemia in upright position (platypnea-orthodeoxia syndrome, POS) after pneumonectomy can result from re-opening of an atrial right-to-left shunt through a patent foramen ovale (PFO) due to mediastinal distorsion. Review of literature also shows a unique report of pulmonary veins stenosis resulting in POS without intracardiac shunt after pneumonectomy. Methods: We report the case of a 32-year-old woman who presented POS 6 months after right pneumonectomy for destroyed lung post tuberculosis. Results: The patient described severe dyspnea disappearing when lying. SpO2 decreased from 94% when lying to 60% sitting. Transthoracic echocardiography (TTE) suspected a possible PFO. We first tried to highlight clinical repercussions of PFO by noninvasive exams. Hyperoxia shunt quantification was not tolerated because of increased dyspnea in sitting position. Contrast bubbles TTE was difficult because of the important mediastinal shift but identified only rare left heart bubbles with/without Valsalva both in lying and sitting position, excluding a significant right-to-left shunt. A lung perfusion scintigraphy (injection while sitting) confirmed the absence of systemic isotope uptake. Computed tomographic pulmonary angiography (angio-CT) revealed a stretched but not stenosed left main bronchus, while the shift of the heart into the right cavity was major. Pulmonary angiography did not show embolism but revealed compression of the inferior vena cava (IVC) with impaired venous return to the right heart, as well as compression of the left pulmonary veins. There was no arteriovenous shunt. Cardiac MRI showed torsion of IVC at the level of the diaphragm, and strong atrial contraction contributing to a passive filling of the RV, while the right ventricle was normal. Right catheterism showed major hemodynamic disturbances with negative diastolic pressure in right heart cavities (atrium -12 mm Hg ventricle pressure -7 mm Hg). SaO2 measured in the pulmonary artery decreased from 58% when lying to 45% sitting. Conclusion: We described here an exceedingly rare and complex mechanism explaining POS after right pneumonectomy. Mediastinal repositioning with a silicone breast implant of appropriate size has been scheduled.

Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion.

Objective-Inflammation and proteolysis crucially contribute to myocardial ischemia and reperfusion injury. The extracellular matrix metalloproteinase inducer EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) may be involved in both processes. The aim of the study was to characterize the role of the CD147 and CyPA interplay in myocardial ischemia/reperfusion (I/R) injury.Methods and Results-Immunohistochemistry showed enhanced expression of CD147 and CyPA in myocardial sections from human autopsies of patients who had died from acute myocardial infarction and from mice at 24 hours after I/R. At 24 hours and 7 days after I/R, the infarct size was reduced in CD147(+/-) mice vs CD147(+/+) mice (C57Bl/6), in mice (C57Bl/6) treated with monoclonal antibody anti-CD147 vs control monoclonal antibody, and in CyPA(-/-) mice vs CyPA(+/+) mice (129S6/SvEv), all of which are associated with reduced monocyte and neutrophil recruitment at 24 hours and with a preserved systolic function at 7 days. The combination of CyPA(-/-) mice with anti-CD147 treatment did not yield further protection compared with either inhibition strategy alone. In vitro, treatment with CyPA induced monocyte chemotaxis in a CD147-and phosphatidylinositol 3-kinase-dependent manner and induced monocyte rolling and adhesion to endothelium (human umbilical vein endothelial cells) under flow in a CD147-dependent manner.Conclusion-CD147 and its ligand CyPA are inflammatory mediators after myocardial ischemia and reperfusion and represent potential targets to prevent myocardial I/R injury.

Benefits of endoscopic vein harvesting.

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 +/- 6.6 vs. 31.2 +/- 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 +/- 24 vs. 100 +/- 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p = 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.

Palliative portal vein stent placement in malignant and symptomatic extrinsic portal vein stenosis or occlusion.

This article evaluates the results of portal vein (PV) stent placement in patients with malignant extrinsic lesions stenosing or obstructing the PV and causing symptomatic PV hypertension (PVHT). Fourteen patients with bile duct cancer (n = 7), pancreatic adenocarcinoma (n = 4), or another cancer (n = 3) underwent percutaneous transhepatic portal venous stent placement because of gastroesophageal or jejunal varices (n = 9), ascites (n = 7), and/or thrombocytopenia (n = 2). Concurrent tumoral obstruction of the main bile duct was treated via the transhepatic route in the same session in four patients. Changes in portal venous pressure, complications, stent patency, and survival were evaluated. Mean +/- standard deviation (SD) gradient of portal venous pressure decreased significantly immediately after stent placement from 11.2 mmHg +/- 4.6 to 1.1 mmHg +/- 1.0 (P < 0.00001). Three patients had minor complications, and one developed a liver abscess. During a mean +/- SD follow-up of 134.4 +/- 123.3 days, portal stents remained patent in 11 patients (78.6%); stent occlusion occurred in 3 patients, 2 of whom had undergone previous major hepatectomy. After stent placement, PVHT symptoms were relieved in four (57.1%) of seven patients who died (mean survival, 97 +/- 71.2 days), and relieved in six (85.7%) of seven patients still alive at the end of follow-up (mean follow-up, 171.7 +/- 153.5 days). Stent placement in the PV is feasible and relatively safe. It helped to relieve PVHT symptoms in a single session.

Expressed isolated integrin beta1 subunit cytodomain induces endothelial cell death secondary to detachment.

Expression of isolated beta integrin cytoplasmic domains in cultured endothelial cells was reported to induce cell detachment and death. To test whether cell death was the cause or the consequence of cell detachment, we expressed isolated integrin beta1 cytoplasmic and transmembrane domains (CH1) in cultured human umbilical vein endothelial cells (HUVEC), and monitored detachment, viability, caspase activation and signaling. CH1 expression induced dose-dependent cell detachment. At 24 h over 90% of CH1-expressing HUVEC were detached but largely viable (>85%). No evidence of pro-caspase-8,-3, and PARP cleavage or suppression of phosphorylation of ERK, PKB and Ikappa-B was observed. The caspase inhibitor z-VAD did not prevent cell detachment. At 48 h, however, CH1-expressing cells were over 50% dead. As a comparison trypsin-mediated detachment resulted in a time-dependent cell death, paralleled by caspase-3 activation and suppression of ERK, PKB and Ikappa-B phosphoyrylation at 24 h or later after detachment. HUVEC stimulation with agents that strengthen integrin-mediated adhesion (i.e. PMA, the Src inhibitor PP2 and COMP-Ang1) did not prevent CH1-induced detachment. Expression of CH1 in rat carotid artery endothelial cells in vivo caused endothelial cell detachment and increased nuclear DNA fragmentation among detached cells. A construct lacking the integrin cytoplasmic domain (CH2) had no effect on adhesion and cell viability in vitro and in vivo. These results demonstrate that isolated beta1 cytoplasmic domain expression induces caspase-independent detachment of viable endothelial cells and that death is secondary to detachment (i.e. anoikis). They also reveal an essential role for integrins in the adhesion and survival of quiescent endothelial cells in vivo.

Peri-operative management of antiplatelet therapy in patients with coronary artery disease. Joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society for Cardiology (ESC).

An increasing number of patients suffering from cardiovascular disease, especially coronary artery disease (CAD), are treated with aspirin and/or clopidogrel for the prevention of major adverse events. Unfortunately, there are no specific, widely accepted recommendations for the perioperative management of patients receiving antiplatelet therapy. Therefore, members of the Perioperative Haemostasis Group of the Society on Thrombosis and Haemostasis Research (GTH), the Perioperative Coagulation Group of the Austrian Society for Anesthesiology, Reanimation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society of Cardiology (ESC) have created this consensus position paper to provide clear recommendations on the perioperative use of anti-platelet agents (specifically with semi-urgent and urgent surgery), strongly supporting a multidisciplinary approach to optimize the treatment of individual patients with coronary artery disease who need major cardiac and non-cardiac surgery. With planned surgery, drug eluting stents (DES) should not be used unless surgery can be delayed for ≥12 months after DES implantation. If surgery cannot be delayed, surgical revascularisation, bare-metal stents or pure balloon angioplasty should be considered. During ongoing antiplatelet therapy, elective surgery should be delayed for the recommended duration of treatment. In patients with semi-urgent surgery, the decision to prematurely stop one or both antiplatelet agents (at least 5 days pre-operatively) has to be taken after multidisciplinary consultation, evaluating the individual thrombotic and bleeding risk. Urgently needed surgery has to take place under full antiplatelet therapy despite the increased bleeding risk. A multidisciplinary approach for optimal antithrombotic and haemostatic patient management is thus mandatory.