Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism

Introduction

We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden.

Materials and Methods

39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.

Results

Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181).

Conclusions

It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.     

Direct microscopic monitoring of initial and dynamic clot lysis using plasmin or rt-PA in an in vitro flow system

Introduction

Plasmin is a direct-acting thrombolytic agent with a favorable safety profile upon intra-arterial delivery in pre-clinical and phase I studies. However, the thrombolytic efficacy of plasmin, relative to that of rt-PA, remains to be established. We have compared the dynamics of clot lysis with plasmin or rt-PA in an in vitro perfusion system, in which thrombolytic agent is administered locally, allowed to induce lysis for short intervals, then washed with plasma in a re-circulation circuit.

Materials and Methods

Whole blood human clots were prepared in observation chambers, exposed to plasmin or rt-PA at equimolar concentrations (1.2/1.0, 1.8/1.5 and 2.4/2.0 mg/ml) for measured intervals of time, followed by perfusion with human plasma. Clot size was monitored by digital analysis of sequential photographs obtained through an optical microscope.

Results

Plasma perfusion after incubation with thrombolytic agent rapidly removed superficial clot fragments. This initial decrease in clot size was greater with plasmin than with rt-PA when tested at the highest concentrations of agent (0.63 ± 0.11 vs. 0.30 ± 0.11, p = 0.001 for clots with non-cross-linked fibrin and 0.53 ± 0.15 vs. 0.14 ± 0.15, p = 0.02, for clots with cross-linked-fibrin). Subsequent clot lysis during plasma flow was greater after prior incubation with rt-PA. Longer incubation times of plasmin resulted in larger portions of the clot being washed free. Repeated plasmin incubations and plasma perfusions of a clot successfully induced stepwise reductions in clot size.

Conclusions

Initial clot lysis is greater with direct exposure using plasmin than rt-PA. During washout and circulation with plasma, rt-PA induced continued clot lysis, while plasmin lysis was curtailed, presumably because of plasmin inhibition.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

Incidental venous thromboembolism detected by PET-CT in patients with cancer: Prevalence and impact on survival rate

Introduction

People with cancer are at increased risk of incidental venous thromboembolism (VTE) and PET-CT imaging is commonly used in this population. However, the prevalence of incidental VTE detected by PET-CT in patients with cancer and its impact on survival are unknown.

Materials and Methods

This retrospective study was approved by the local Institutional Review Board. 1331 consecutive adult patients with cancer who underwent PET-CT examination between 2009 and 2012 were included in the study (mean age: 57 ± 15 years). PET-CT reports were reviewed to identify patients with incidental VTE at the time of examination. Survival rates were assessed with Kaplan-Meier curves. The Cox proportional hazards model was used to determine the association between incidental VTE and overall survival, after controlling for clinical variables.

Results

Incidental VTE was detected in 19 patients (1.4%). Patients with genitourinary malignancies, colorectal cancer and lung cancer had the highest rates of incidental VTE at PET-CT. At multivariate analysis, incidental VTE detected by PET-CT was associated with worse overall survival independently of patient age, hospitalization status at time of PET-CT examination, and the presence of metastatic disease (Hazard ratio = 2.03; 95% confidence interval = 1.08-3.81, p = 0.028).

Conclusion

Incidental VTE was detected in 1.4% of adult patients with cancer undergoing PET-CT imaging. Diagnosis of incidental VTE at PET-CT imaging was associated with worse overall survival in this population.     

Partial versus complete factor VIII inhibition in a mouse model of venous thrombosis

Introduction

Partial inhibition of Factor VIII (FVIII) may provide antithrombotic efficacy whilst avoiding excessive anticoagulation.

Materials and Methods

We studied the anticoagulant effects of a partial (TB-402) and a complete (BO2C11) FVIII-inhibiting monoclonal antibody (MAb) on FVIII, aPTT, thrombin generation and fibrin deposition in a flow chamber model. The antithrombotic efficacy of TB-402 and BO2C11 was compared in a mouse model of venous thrombosis.

Results

Both in vitro and ex vivo, the maximally achievable FVIII inhibition by TB-402 was about 25 to 30%. The degree of inhibition reached a plateau in vitro at 0.316 μg/mL and ex vivo after administering 0.1 mg/kg and higher doses. BO2C11 strongly inhibited FVIII:C, up to 91% at 100 μg/mL in vitro, and by 88% ex vivo 1 hour after administering 1 mg/kg to the mice.Whereas BO2C11 also markedly prolonged the aPTT and completely inhibited thrombin generation in vitro and ex vivo, the effect of TB-402 on the aPTT and on thrombin generation was limited. Similarly, in a dynamic flow chamber model, TB-402 and BO2C11 inhibited tissue factor-induced human fibrin deposition by 40% and 76%, respectively.In a mouse model of FeCl₃-induced venous thrombosis, TB-402 (1 mg/kg) inhibited thrombus formation to the same extent as BO2C11 (2 mg/kg) and enoxaparin (5 mg/kg), with a mean (± SD) occlusion time of 51 ± 13 minutes for TB-402, compared to 28 ± 6 minutes for the controls, 51 ± 13 minutes for BO2C11 and 55 ± 11 minutes for enoxaparin.

Conclusions

In this mouse model of venular thrombosis, partial FVIII inhibition yielded similar antithrombotic effects as nearly complete FVIII inhibition. These preclinical data are indicative of a therapeutic potential of partial FVIII inhibition in the management of venous thromboembolism.     

Thromboprophylaxis use and concordance with guidelines among medical and surgical patients in Morocco

Introduction

No data are available on thromboprophylaxis use in Morocco. Our aim was to characterize patients at risk of venous thromboembolism and assess the rate of appropriate thromboprophylaxis.

Materials and Methods

This was a national, observational, multicentre survey of venous thromboembolism risk and thromboprophylaxis use in hospitalized patients. Data were collected on a predefined date in three university hospitals in Morocco using a standardized pre-printed form. Thromboembolic risk was assessed according to the American College of Chest Physicians (ACCP) 2008 guidelines. Patients were classified as “thromboprophylaxis indicated” or “thromboprophylaxis not indicated”.

Results

784 patients were analysed: 307 (39.2%) medical and 477 (60.8%) surgical. 421 (53.7%) were female. Medical patients were older than surgical patients (57.6 ± 11.5 vs. 46.2 ± 16.9 years, p < 0.0001) and were more likely to have risk factors for thromboembolism (50.5% vs. 45.7% of patients, p = NS). 57% of patients without contraindications or bleeding risk were at risk of thromboembolism according to ACCP guidelines and thromboprophylaxis was prescribed to 42.8% of these patients. In contrast, 7.4% of patients with no thromboembolic risk also received thromboprophylaxis (proportion agreement: 61.0%; Kappa = 0.296). Over half (54.5%) of medical patients at risk of thromboembolism did not receive thromboprophylaxis whereas 6.3% of those with no risk did receive it (proportion agreement: 76.4%; Kappa = 0.433). These figures were 57.9% and 9.2%, respectively, for surgical patients (proportion agreement: 52.7%; Kappa = 0.191). Thromboprophylaxis was given to 19.2% of patients with contraindications or a bleeding risk.

Conclusions

Educational initiatives are imperative to inform doctors about appropriate thromboprophylaxis.     

Surfactant impairs coagulation in-vitro: A risk factor for pulmonary hemorrhage?

Background

Pulmonary hemorrhage (PHEM) complicates the hospital course of 3-5% of preterm infants with respiratory distress syndrome (RDS), and bears a high mortality rate. Impaired thrombin generation and poor clot formation in premature neonates affect PHEM severity.

Objectives

We evaluated the impact of surfactant upon in-vitro clot formation in order to assess the role of surfactant in the pathogenesis of PHEM.

Methods

Blood samples were obtained from healthy volunteers for measuring complete blood count, PT, PTT, and platelet function. Surfactant at increasing concentrations was added to blood samples, and whole blood clotting assays were performed using rotation thromboelastogram (ROTEM®, Pentapharm Munich, Germany) and whole blood platelet adhesion and aggregation (Impact-R®, Diamed, Switzerland).

Results

The mean PT level increased from 10.05 ± 033 to 11.64 ± 0.85 sec (p = 0.06) in the presence of surfactant. Platelet aggregation with the agonists adenosine diphosphate and epinephrine significantly decreased with escalating surfactant concentration (p < 0.001). Adhesion, manifested by surface coverage (SC), significantly decreased with increasing surfactant concentration: mean SC 9.25 ± 2.96 compared to 6.1 ± 0.96 and 0.05 ± 0.058 with 0/0.1/5 mg/ml surfactant, respectively, p < 0.001 Whole blood ROTEM studies showed a trend towards lengthening of clotting time with increased surfactant concentration and lower clot strength.

Conclusion

The presence of surfactant impairs coagulation in-vitro. The risk of PHEM may therefore be greater in extremely premature infants. Future studies are required to assess the clinical significance and relevance of our preliminary findings.     

Ginsenoside Rg1 inhibits platelet activation and arterial thrombosis

Introduction

Derived from the root of Panax ginseng C.A.Mey, Panax notoginsenosides (PNS) is a widely used herbal medicine to treat atherothrombotic diseases in Asian medicine. Ginsenoside Rg1 is one of the main compounds responsible for the pharmaceutical actions of PNS. As platelets play pivotal roles in atherothrombogenesis, we therefore studied the effect of Rg1 on platelet activation and its underlying mechanisms.

Materials and Methods

Human platelets are obtained from healthy subjects. Platelet activation and the inhibition of Rg1 were assessed by Born aggregometer, flow cytmetry, flow chamber and western blot. The in vivo thrombosis model was induced by 10% FeCl₃ on mesenteric arterioles of wild type B57/b6 mice.

Results

Rg1 significantly inhibited platelet aggregation induced by thrombin, ADP, collagen and U46619, e.g., aggregation rate stimulated by 0.1 U mL^- 1 thrombin was decreased 46% by Rg1. Rg1 also reduced thrombin (0.1 U mL^- 1)-enhanced fibrinogen binding and P-selectin expression of single platelet by 81% and 66%, respectively. Rg1 affected αIIbβ3-mediated outside-in signaling as demonstrated by diminished platelet spreading on immobilized fibrinogen. Rg1 also decreased the rate of clot retraction in platelet rich plasma. Furthermore, Rg1 decreased platelet adhesion on collagen surface under a shear rate correlated to the arterial flow (1000 s^- 1) by approximately 70%. Western blot showed that Rg1 potently inhibited ERK phosphrylation. The in vitro findings were further evaluated in the mouse model of in vivo arterial thrombosis, and Rg1 was found to prolong the mesenteric arterial occlusion time (34.9 ± 4.1 min without and 64.3 ± 4.9 min with Rg1; p < 0.01).

Conclusions

Rg1 inhibits platelet activation via the inhibition of ERK pathway, and attenuates arterial thrombus formation in vivo.     

Prothrombotic alterations in plasma fibrin clot properties in thyroid disorders and their post-treatment modifications

Introduction

Available data on fibrin clot properties and fibrinolysis in hyperthyroidism and hypothyroidism are inconsistent. Our objective was to assess the impact of effective treatment of hyper- and hypothyroidism on fibrin clot characteristics.

Material and Methods

In a case-control study, ex vivo plasma fibrin clot permeability (K_s) and efficiency of fibrinolysis were assessed in 35 consecutive hyperthyroid and 35 hypothyroid subjects versus 30 controls. All measurements were performed before and after 3 months of thyroid function normalizing therapy.

Results

At baseline, hyperthyroid, but not hypothyroid, patients had lower K_s than controls (p < 0.0001). Hyperthyroid and hypothyroid groups compared with controls had prolonged clot lysis time (CLT), and lower rate of D-dimer release from clots (D-D_rate) (all p < 0.05). The regression analysis adjusted for fibrinogen showed that in hyperthyroid patients, pre-treatment thyroid stimulating hormone (TSH) independently predicted K_s, while thrombin activatable fibrinolysis inhibitor (TAFI) antigen predicted CLT. In hypothyroid individuals a similar regression model showed that TSH independently predicts CLT. After 3 months of thyroid function normalizing therapy, 32 (91.4%) hyperthyroid and 30 (85.7%) hypothyroid subjects achieved euthyroidism and had improved fibrin clot properties (all p < 0.05), with normalization of K_s in hyperthyroid and lysability in hypothyroid patients.

Conclusions

Both hyper- and mild-to-moderate hypothyroidism are associated with prothrombotic plasma fibrin clot phenotype and restoration of euthyroidism improves clot phenotype. Abnormal fibrin clot phenotype might contribute to thromboembolic risk in thyroid disease.     

Differentiation of pure vasogenic edema and tumor-infiltrated edema in patients with peritumoral edema by analyzing the relationship of axial and radial diffusivities on 3.0T MRI

Object

The purpose of this study was to analyze the relationship of axial diffusivity (AD) and radial diffusivity (RD) in peritumoral edema of high grade glioma, metastasis, and meningioma, and to differentiate tumor-infiltrated edema from pure vasogenic edema.

Materials and methods

Twenty patients with high-grade glioma and 16 with meningioma or metastatic tumor were enrolled in our study. All cases were confirmed by histopathological study. Diffusion tensor imaging (DTI) was performed in all patients. Peritumoral edema of high-grade glioma was considered tumor-infiltrated edema, and edema of meningioma or metastasis was considered pure vasogenic edema. Fractional anisotropy (FA), mean diffusivity (MD), AD, RD, regression coefficient of RD to AD (RC_RD–AD), and tumor infiltration index (TII) in tumor-infiltrated edema and pure vasogenic edema were analyzed and compared. Receiver operating characteristic (ROC) curve analysis was conducted to demonstrate their differential effectiveness.

Results

RC_RD–AD in tumor-infiltrated edema (0.724 ± 0.125) was significantly higher than that in pure vasogenic edema (0.571 ± 0.111) (P = 0.001). FA of tumor-infiltrated edema (0.175 ± 0.025) was significantly lower than that of pure vasogenic edema (0.203 ± 0.035) (P = 0.007). Other parameters showed no significant difference between the 2 types of edema. ROC curve analysis showed RC_RD–AD was the most effective parameter in distinguishing tumor-infiltrated edema from pure vasogenic edema. Using a threshold of 0.6, a sensitivity of 0.85 and specificity of 0.69 can be achieved with RC_RD–AD.

Conclusion

Analysis of the AD and RD relationship may reflect differences in diffusion characteristics of edema surrounding high-grade glioma and meningioma or metastasis, and may be helpful in detecting peritumoral infiltration in high-grade glioma.     

Volumetric differences in the pituitary between drug-naïve and medicated male patients with obsessive–compulsive disorder

Objective

Obsessive–compulsive symptoms are induced or aggravated by stress, and the pituitary is a key component of the hypothalamic-pituitary-adrenal axis. We examined pituitary volume in drug-naïve and medicated male patients with obsessive–compulsive disorder (OCD).

Methods

Volumetric magnetic resonance imaging studies were conducted on 62 male control subjects, medicated male patients (N = 50) and drug-naïve male patients (N = 12) with OCD.

Results

Pituitary volume was significantly smaller in drug-naïve patients with OCD (464.97 ± 55.82 mm³) compared to medicated patients (577.84 ± 129.11 mm³, P = 0.004) and control subjects (543.04 ±113.70 mm³, P = 0.027), and no difference between control subjects and medicated patients (P = 0.174).

Conclusion

The results indicate that drug-naïve male patients with OCD exhibit decreased pituitary volume. This finding suggests that dysregulation of the HPA axis in OCD may influence pituitary volume. In addition, the increased pituitary volume in medicated patients may reflect the effect of drugs on the pituitary.     

CVD risk factors are related to plasma fibrin clot properties independent of total and or γ’ fibrinogen concentration

Introduction

Cardiovascular disease (CVD) risk factors are associated with total fibrinogen concentration and/or altered clot structure. It is however, unclear whether such associations with clot structure are ascribed to fibrinogen concentration or other independent mechanisms. We aimed to determine whether CVD risk factors associated with increased total and/or γ’ fibrinogen concentration, were also associated with altered fibrin clot properties and secondly whether such associations were due to the fibrinogen concentration or through independent associations.

Materials and methods

In a plasma setting CVD risk factors (including total and γ’ fibrinogen concentration) were cross-sectionally analysed in 2010 apparently healthy black South African participants. Kinetics of clot formation (lag time, slope and maximum absorbance) as well as clot lysis times were calculated from turbidity curves.

Results

Of the measured CVD risk factors age, metabolic syndrome, C-reactive protein (CRP), high density lipoprotein (HDL)-cholesterol and homocysteine were significantly associated with altered fibrin clot properties after adjustment for total and or γ’ fibrinogen concentration. Aging was associated with thicker fibres (p = 0.004) while both metabolic syndrome and low HDL-cholesterol levels were associated with lower rates of lateral aggregation (slope), (p = 0.0004 and p = 0.0009), and the formation of thinner fibres (p = 0.007 and p = 0.0004). Elevated CRP was associated with increased rates of lateral aggregation (p = 0.002) and consequently thicker fibres (p < 0.0001). Hyperhomocysteinemia was associated with increased rates of lateral aggregation (p = 0.0007) without affecting fibre thickness.

Conclusion

Final clot structure may contribute to increased CVD risk in vivo through associations with other CVD risk factors independent from total or γ’ fibrinogen concentration.     

Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation

Background

The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis.

Material/Methods

Prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23–25 until 8–10 weeks postpartum.

Results

Prothrombin fragments 1 + 2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5 mg/l were found in about 30% and 20% of the heterozygous carriers at 4–5 and 8–10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies.

Conclusion

Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5 mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation.     

Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: Studies of spatial dynamics of fibrin clot formation in hemophilia A

Background

In recent years, a number of tissue factor pathway inhibitor (TFPI) antagonists have been developed to serve as bypassing agents to improve hemostasis in hemophilia A. Since TFPI antagonists and FVIII concentrates are procoagulants, their combined effect on spatial clot formation could be potentially pro-thrombotic.

Objective

To investigate the cooperative effect of TFPI inhibition and supplementation of FVIII in hemophilia A in a spatial, reaction-diffusion experiment in vitro.

Methods

Plasma was collected at different time points from hemophilia A patients undergoing prophylaxis and was supplemented in vitro with TFPI inhibitor BAX499 (formerly ARC19499) at concentrations from 0 up to 600 nM. Clotting propagation in recalcified plasma activated by a surface with immobilized tissue factor (TF) was monitored by videomicroscopy.

Results

Increasing concentration of BAX499 improved coagulation for all hemophilia A plasma samples activated with TF at 1.6 pmole/m² by shortening lag time and increasing initial clot growth velocity and clot size. In contrast, plasma concentration of FVIII had little effect on lag time, but increased spatial clot growth velocity. There was a decrease in the BAX499 efficiency as FVIII concentration increased (lag time shortened by 50% if FVIII:C < 5%, but the effect was only 25% if FVIII:C > 30%).

Conclusions

The results indicate that BAX499 has an effect on clotting in hemophilia A plasma at low FVIII concentrations, however has little effect at high FVIII concentrations.     

Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers

Objective

Diffusion tensor imaging (DTI) recently identified structural abnormalities of corticomotoneurons in asymptomatic copper/zinc superoxide-dismutase-1 (SOD-1) gene mutation carriers. The potential existence of longstanding corticomotoneuronal dysfunction would clearly have consequences for the medical management of asymptomatic SOD-1 mutation carriers. To clarify this unexpected finding, DTI techniques were combined with threshold tracking transcranial magnetic stimulation (TMS) to assess the anatomical and functional integrity of corticomotoneurons in asymptomatic SOD-1 mutation carriers.

Methods

TMS studies were undertaken using a 90 mm circular coil on seven asymptomatic SOD-1 mutation carriers and results were compared to 62 healthy controls. DTI studies were carried out using a 3 T magnetic resonance device in the same asymptomatic SOD-1 mutation carriers. Results were compared to age-matched healthy controls.

Results

In contrast to previous findings, there were no significant differences in fractional anisotropy (SOD-1 mutation carriers, 0.62 ± 0.01; controls, 0.61 ± 0.02, P = 0.2) and trace apparent diffusion coefficient (SOD-1 mutation carriers, 0.003 ± 0.0001; controls, 0.003 ± 0.0001) in asymptomatic SOD-1 mutation carriers. Of further relevance, there were no significant differences in short-interval intracortical inhibition (SOD-1 mutation carriers, 7.9 ± 3.4%; controls, 8.5 ± 1.1%, P = 0.26), intracortical facilitation (P = 0.5), MEP amplitude (P = 0.44), resting motor threshold (P = 0.36) and cortical silent period duration (P = 0.29).

Conclusions

Combined anatomical and functional modalities established normal integrity of corticomotoneurons in asymptomatic SOD-1 mutation carrier subjects.

Significance

Additional factors other than simply SOD-1 mutation expression are required to trigger cortical hyperexcitability and neurodegeneration in FALS.     

Calculating the tumor volume of acoustic neuromas: Comparison of ABC/2 formula with planimetry method

Objective

The ABC/2 equation is commonly applied to measure the volume of intracranial hematoma. However, the precision of ABC/2 equation in estimating the tumor volume of acoustic neuromas is less addressed. The study is to evaluate the accuracy of the ABC/2 formula by comparing with planimetry method for estimating the tumor volumes.

Methods

Thirty-two patients diagnosed with acoustic neuroma received contrast-enhanced magnetic resonance imaging of brain were recruited. The volume was calculated by the ABC/2 equation and planimetry method (defined as exact volume) at the same time. The 32 patients were divided into three groups by tumor volume to avoid volume-dependent overestimation (<3 ml, 3–6 ml and >6 ml).

Results

The tumor volume by ABC/2 method was highly correlated to that calculated by planimetry method using linear regression analysis (R² = 0.985). Pearson correlation coefficient (r = 0.993, p < 0.001) demonstrates nearly perfect association between two methods.

Conclusions

The ABC/2 formula is an easy method in estimating the tumor volume of acoustic neuromas that is not inferior to planimetry method.     

Venous thromboembolism prophylaxis in patients undergoing abdominal or pelvic surgery for cancer – A real-world,prospective, observational French study: PRéOBS

Introduction

Data on the epidemiology and prevention of venous thromboembolism in patients undergoing abdominal or pelvic cancer surgery in real practice are limited. The primary objective of this observational study was to describe the thromboprophylactic strategy implemented in routine practice. The main secondary objective was to assess the incidence of outcomes.

Materials and Methods

Patients admitted to public or private hospitals for abdominal or pelvic cancer surgery were included between November 2009 and November 2010; endoscopic route for surgery was the only exclusion criterion. Study outcomes were recorded at hospital discharge and at routine follow-up (generally 9 ± 3 weeks).

Results

2380 patients (mean ± SD age: 66.4 ± 11.6 years, women: 36.8%) admitted to hospital for abdominal (47.8%), urological (41%), or gynaecological (11.2%) cancer surgery were included in the analysis. Of these, 2179 had data available at study end. Perioperative antithrombotic prophylaxis, consisting mainly of low-molecular-weight heparin, was given to 99.5% of patients. At hospital discharge, thromboprophylaxis was continued in 91.7% of patients, 57.4% receiving a 4-6 week prophylaxis. This management strategy was associated with an overall venous thromboembolic event rate of 1.9%, 34.7% of events occurring after discharge. Incidences of fatal bleeding, bleeding in a critical organ and bleeding necessitating re-intervention were 0.1%, 0.3% and 1.7%, respectively. Overall mortality was 1.5%.

Conclusions

Thromboprophylaxis is routinely used in French patients undergoing major cancer surgery. For more than a third of patients, however, treatment duration did not comply with best-practice recommendations, which might explain the non-negligible rate of thromboembolic complications still observed in this patient population.     

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study

Objectives

To evaluate patients with “clinically established” psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism.

Patients and methods

Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n = 5) and healthy control subjects (n = 5).

Results

The mean age (years-old) at first evaluation in the PsyP group was 37.4 ± 3.7, and the mean disease duration (years) was 3.9 ± 1.2. DAT BPs (means ± standard deviations) on right/left caudate were, respectively, 0.69 ± 0.18 and 0.70 ± 0.18 in the PD group versus 1.17 ± 0.06 and 1.12 ± 0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48 ± 0.10 and 0.45 ± 0.06 in the PD group versus 1.10 ± 0.10 and 1.21 ± 0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (≤0.70) for controls, implying pre-synaptic dopaminergic deficit.

Conclusions

Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.     

Reproducibility of contact heat evoked potentials (CHEPs) over a 6 months interval

Objective

Contact heat evoked potentials (CHEPs) mediated by primary afferent Aδ-fibers can be recorded at the vertex. CHEPs are reduced in small fibre neuropathy and considered as a noninvasive measure of small fibre function. As long-term stability of CHEPs has not been examined, it is presently not clear if CHEPs may also be useful for following the course of small fibre neuropathy.

Methods

Here, we analyzed CHEPs from 60 healthy subjects recorded at two occasions separated by 6 months.

Results

There was a systematic shift towards larger amplitudes (from 40.2 ± 13.8 μV to 53.3 ± 17.5 μV, p < 0.001) and towards shorter latencies (from 425.0 ± 28.8 ms to 387.2 ± 30.3 ms, p < 0.001) after six months, while CHEP areas were more constant over time.

Conclusions

The present results show that systematic changes of CHEP amplitudes and latencies may occur over time. Possible reasons include seasonal differences in skin conductivity for heat and psychological effects.

Significance

CHEP areas seem to be more stable over time than amplitudes or latencies, however, it remains to be determined if CHEP areas differentiate between subjects with lesions of the nociceptive system and healthy controls as reliably as CHEP amplitudes.